Hemoglobin A1c (HbA1c)
HbA1c reflects long-term blood sugar. US bodies place prediabetes at 5.7 to 6.4% and diabetes at 6.5% or above, while WHO and an international committee publish other cut points. Higher values go with more diabetes, heart disease and diabetic complications. In one trial, aiming below 6.0% in type 2 diabetes raised deaths. Iron deficiency and some hemoglobin variants distort results.
- Status
- A blood test ordered by a clinician, run on point-of-care devices in clinics, or bought as a home collection kit. FDA regulates hemoglobin A1c test systems intended as an aid in diagnosing diabetes as class II devices with special controls, which include yearly standardization verification by a certifying glycohemoglobin standardization organization. Its product classification also lists over-the-counter glycosylated hemoglobin tests [1].
- Measures
- The percentage of hemoglobin in blood that has glucose attached (hemoglobin A1c), which reflects long-term blood glucose exposure, not the level at the moment of the draw [1][2].
- Also called
- HbA1c, A1C, A1c, hemoglobin A1c, haemoglobin A1c, glycated hemoglobin, glycosylated hemoglobin, glycohemoglobin, HgbA1c, Hb A1c, hemoglobin A1c percent
- Tested for
- diabetes diagnosis, prediabetes screening, blood sugar control, average blood sugar, metabolic health, heart disease risk
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research4
- StrongLinked to more coronary heart disease from 5.5% upward in adults without diabetes, though adding HbA1c to standard risk factors barely improved risk prediction.
- StrongShown in trials: intensive glucose control that lowered HbA1c about 0.9 points cut kidney events 20% and eye events 13% in type 2 diabetes.
- ModerateLinked to future diabetes in a graded way: 25 to 50% of people at 6.0 to 6.5% developed diabetes within 5 years.
- ModerateLinked to more deaths at both ends: above 6.0% and below 5.0% in people without diabetes, and above 9.0% and below 6.0% in people with diabetes.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in %. Where sources differ, each is shown.
American Diabetes Association Standards of Care, 2026
People being tested for diabetes or prediabetes, outside pregnancy · [3]
| Range | What the source calls it |
|---|---|
| below 5.7 % | No name given |
| 5.7 to 6.4 % | "prediabetes" |
| 6.5 or above % | "diabetes" One to see a doctor about |
The criteria state that the test is to be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay, and that without unequivocal hyperglycemia a diagnosis requires two abnormal results. The Standards name no category below 5.7% in their criteria tables. They direct that plasma glucose criteria be used in conditions that alter the relationship between HbA1c and glucose, such as some hemoglobin variants, pregnancy, glucose-6-phosphate dehydrogenase deficiency and HIV. They print 5.7% as 39 mmol/mol, 6.4% as 47 mmol/mol and 6.5% as 48 mmol/mol. The two scales are linked by an equation, not a single multiplier, so this page gives no conversion factor [3].
National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health
Adults being tested for type 2 diabetes or prediabetes · [4]
| Range | What the source calls it |
|---|---|
| below 5.7 % | "normal" |
| 5.7 to 6.4 % | "prediabetes" |
| 6.5 or above % | "diabetes" One to see a doctor about |
The same cut points as the American Diabetes Association, with the lowest band named. The institute states that a repeat test can read slightly higher or lower, and gives the example that 6.8% on one test could be reported anywhere from 6.4 to 7.2% on a repeat test of the same blood sample. Page last reviewed April 2018 [4].
International Expert Committee, 2009
Nonpregnant people being tested for diabetes · [2]
| Range | What the source calls it |
|---|---|
| below 6 % | No name given |
| 6 to 6.4 % | "highest-risk group for diabetes" |
| 6.5 or above % | "diabetes" One to see a doctor about |
The committee set 6.5% from pooled data on about 28,000 people in which moderate retinopathy rose in prevalence at and above that level, and chose to favor specificity over sensitivity. It prints the middle band as 6.0 to under 6.5%, and states that people below 6.0% may still be at risk, so the cut point is not an absolute dividing line [2].
World Health Organization consultation, 2011
People being tested for diabetes, where quality-assured and standardized assays are available · [5]
| Range | What the source calls it |
|---|---|
| below 6.5 % | No name given |
| 6.5 or above % | "diabetes" One to see a doctor about |
WHO recommends 6.5% as the cut point for diagnosing diabetes and states that a value below 6.5% does not exclude diabetes diagnosed using glucose tests. The expert group concluded there was insufficient evidence to make any formal recommendation on interpreting levels below 6.5%, so WHO publishes no prediabetes band. The recommendation was graded conditional on moderate-quality evidence [5].
Laboratory reference interval, as described in the 2023 laboratory guideline of the American Association for Clinical Chemistry and American Diabetes Association
The reference interval printed on laboratory reports · [6]
| Range | What the source calls it |
|---|---|
| below 4 % | No name given |
| 4 to 6 % | "reference interval" |
| above 6 % | No name given |
The guideline reports that HbA1c reference intervals were 4% to 6% for many years, and that many organizations and laboratories have since lowered the upper limit to 5.6%. It states that reference intervals for certified methods are not expected to deviate by more than about 0.5% from a mean of 5%, and that treatment targets and diagnostic cutoffs, not reference intervals, are used to evaluate glucose control. A reference interval describes the spread of results in people tested, which is a different thing from the diagnostic cut points above [6].
What has been shown to move it
Shown to lower it45
Blood sugar
Shown to lower fasting blood sugar and HbA1c in adults with type 2 diabetes. In apparently healthy participants, fasting glucose rose instead.
The numbers and sources
- Effect
- In 7 controlled trials in type 2 diabetes, ACV lowered fasting blood sugar by 21.9 mg/dL (95% CI -29.19 to -14.67) and HbA1c by 1.53 (95% CI -2.65 to -0.41), with no change in HOMA-IR [1]. Across 9 studies in adults, ACV lowered fasting glucose by 7.97 mg/dL (95% CI -13.74 to -2.21) and HbA1c by 0.50 (95% CI -0.90 to -0.09), with no change in fasting insulin or HOMA-IR [2]. A review of 6 studies in 317 people with type 2 diabetes found lower fasting glucose and HbA1c with vinegar [3].
- Population
- Adults with type 2 diabetes [1][3]. Adults with and without diabetes [2].
- Sources
- [1], [2], [3]
- Caveats
- Heterogeneity for HbA1c was high (I² 91%) [2]. Vinegar content varied across studies and samples were small [3]. In apparently healthy participants, fasting glucose rose [2].
Blood sugar in type 2 diabetes
Shown to lower fasting glucose and HbA1c in adults with type 2 diabetes, with HbA1c about 0.6 points lower. Many trials were small and low quality.
The numbers and sources
- Effect
- Across 37 trials (3,048 patients), berberine lowered fasting glucose by 0.82 mmol/L (95% CI -0.95 to -0.70), HbA1c by 0.63% (95% CI -0.72 to -0.53) and 2-hour glucose by 1.16 mmol/L, with larger effects at higher baseline glucose [1]. Against placebo in 20 trials (1,761 participants), it lowered fasting glucose by 0.52 mmol/L (95% CI -0.72 to -0.33) and HOMA-IR by 0.85 [2].
- Population
- Adults with type 2 diabetes [1]. Adults with and without diabetes [2].
- Sources
- [1], [2]
- Caveats
- Effects on fasting glucose were larger in people with diabetes and in Asian participants [2]. Many trials were small and of low methodological quality [3].
Blood sugar
Shown to lower fasting glucose by about 10 mg/dL and HbA1c by about 0.6 points in adults.
The 2025 review also reported improved fasting glucose, HbA1c and post-meal glucose.
The numbers and sources
- Effect
- In 17 RCTs, fasting glucose fell 9.93 mg/dL (95% CI -13.44 to -6.41), post-meal glucose 14.79 mg/dL and HbA1c 0.57 percentage points (95% CI -0.77 to -0.37). Oil lowered fasting glucose more than powder [3]. The 2025 review also reported improved fasting glucose, HbA1c and post-meal glucose [2].
- Population
- Adults in clinical trials [2][3].
- Sources
- [3], [2]
- Caveats
- The authors call for longer, stronger trials [3].
Blood sugar in type 2 diabetes
Shown to lower HbA1c by about 0.6 points and lower fasting glucose in people with type 2 diabetes, with larger effects in poorer-quality trials.
The numbers and sources
- Effect
- HbA1c fell 0.6 points (95% CI -0.9 to -0.2) and fasting glucose 1.0 mmol/L (95% CI -1.4 to -0.5) on chromium [1]. A 2014 analysis found HbA1c -0.55 points (95% CI -0.88 to -0.22) and fasting glucose -1.15 mmol/L [2]. A 2020 analysis found HbA1c -0.71 points (95% CI -1.19 to -0.23) and fasting glucose -19.0 mg/dL (95% CI -36.2 to -1.9) [3].
- Population
- 41 trials, almost half poor quality [1]; 25 trials in diabetes [2]; 28 trials in type 2 diabetes [3].
- Sources
- [1], [2], [3], [4]
- Caveats
- Sources disagree on what this means. Larger effects came more often from poor-quality trials [1]. Heterogeneity for fasting glucose was 99.8% [3]. A 2016 review found few of 20 trials reached clinical treatment goals, with HbA1c falling 0.5 points or more in 5 of 14 [4]. FDA ranked the evidence for preventing insulin resistance or diabetes at its lowest level for a qualified claim [5].
Blood sugar in diabetes
Shown to lower fasting glucose by about 1 mmol/L and HbA1c by about 0.85% in people with diabetes, only at medium or high doses.
A 2023 meta-analysis of 10 RCTs (706 participants) with type 2 diabetes or prediabetes also reported lower fasting glucose, 2-hour glucose and HbA1c, and no change in HOMA-IR.
The numbers and sources
- Effect
- Across 10 trials, fenugreek seed changed fasting glucose by -0.96 mmol/L (95% CI -1.52 to -0.40, I² 80%), 2-hour glucose by -2.19 mmol/L and HbA1c by -0.85% (95% CI -1.49 to -0.22, 3 trials). Significant effects appeared only at medium or high doses in people with diabetes [1]. A 2023 meta-analysis of 10 RCTs (706 participants) with type 2 diabetes or prediabetes also reported lower fasting glucose, 2-hour glucose and HbA1c, and no change in HOMA-IR [2].
- Population
- People with and without diabetes [1]; type 2 diabetes and prediabetes [2].
- Sources
- [1], [2]
- Caveats
- Most trials in [1] were of low methodological quality. The 2023 abstract does not report effect sizes [2].
Blood sugar in type 2 diabetes
Shown to lower HbA1c about 1.2 to 1.9 points in adults with type 2 diabetes, more than placebo, oral semaglutide or dapagliflozin. Not US approved for diabetes.
Meta-analyses reported pooled HbA1c reductions of 1.07 points and 1.29 points.
The numbers and sources
- Effect
- In early type 2 diabetes treated with diet and exercise, HbA1c fell 1.24 to 1.48 points across doses from a baseline of 8.0% at 40 weeks, against 0.41 on placebo, a difference of -1.07 points on 36 mg (95% CI -1.33 to -0.81) [7]. In people taking metformin, HbA1c fell 1.91 points on orforglipron 36 mg and 1.47 on oral semaglutide 14 mg at 52 weeks, a difference of -0.44 (95% CI -0.62 to -0.26) [8]. Against dapagliflozin it fell 1.56 points on 36 mg and 0.81 points, a difference of -0.75 (95% CI -0.96 to -0.55) [9]. Added to insulin glargine, it fell 1.82 points on 36 mg and 0.79 on placebo, a difference of -1.03 (95% CI -1.28 to -0.77) [10]. Meta-analyses reported pooled HbA1c reductions of 1.07 points [5] and 1.29 points [4].
- Population
- 559 adults with early type 2 diabetes [7]; 1,698 adults on metformin [8]; 962 adults on metformin [9]; 546 adults on insulin glargine [10].
- Sources
- [7], [8], [9], [10], [4], [5]
- Caveats
- Type 2 diabetes is not an approved use in the US. The label covers weight management only [6]. The comparisons with oral semaglutide and dapagliflozin were open-label [8][9]. ACHIEVE-1, ACHIEVE-2 and ACHIEVE-3 were funded by Eli Lilly [7][8][9]. HbA1c is a blood marker, not a measure of diabetes complications.
Blood sugar in type 2 diabetes
Shown to lower HbA1c by about 0.66 points more than placebo in adults with type 2 diabetes, and about as much as other diabetes drugs.
Against other diabetes drugs in 13 studies HbA1c was 0.06 points lower (95% CI 0.18 lower to 0.05 higher), and the risk of low blood sugar was similar.
The numbers and sources
- Effect
- Against placebo in 45 studies, SGLT2 inhibitors lowered HbA1c by 0.66 percentage points (95% CI 0.58 to 0.73). Against other diabetes drugs in 13 studies HbA1c was 0.06 points lower (95% CI 0.18 lower to 0.05 higher), and the risk of low blood sugar was similar [14]. In a network meta-analysis of trials of at least 24 weeks, canagliflozin, dapagliflozin and empagliflozin each lowered HbA1c and fasting glucose against placebo. Canagliflozin 300 mg lowered HbA1c by 0.2 points (95% CI 0.1 to 0.3) more than dapagliflozin 10 mg or empagliflozin 25 mg [15].
- Population
- 11,232 participants in placebo-controlled studies and 5,175 in active-comparator studies [14]; 23,997 participants in 38 trials [15].
- Sources
- [14], [15]
- Caveats
- Most trials in the first review were rated at high risk of bias for missing data [14]. The glucose-lowering effect depends on kidney filtration and shrinks as kidney function falls.
HbA1c and fasting glucose in type 2 diabetes
Shown to lower HbA1c by about 0.4% to 0.6% with resistance training in type 2 diabetes in pooled trials, more at high intensity, without a clear fasting glucose change.
Compared with control groups in randomized trials [6][7][8]; aerobic training [6]
The numbers and sources
- Effect
- Resistance training lowered HbA1c by 0.39% against controls (95% CI -0.60 to -0.18), more when strength rose more, and did not differ from aerobic training [6]. High-intensity training lowered HbA1c by 0.61% and low to moderate intensity by 0.23%. Fasting blood glucose fell only as a nonsignificant trend across 15 trials [7]. A third review found a 0.57% fall (95% CI -1.14% to -0.01%) [8].
- Population
- 1,172 adults with type 2 diabetes in 20 trials [6]. 962 patients in 24 trials, 443 in the fasting glucose analysis [7]. Patients with type 2 diabetes in trials of at least 12 weeks [8].
- Sources
- [6], [7], [8]
- Caveats
- Heterogeneity was high (I² 69.2% [6], 92.5% [8]).
Blood sugar in type 2 diabetes
Shown to lower HbA1c by about 1.5 points more than placebo as single therapy in type 2 diabetes, with no added drop at higher doses.
The numbers and sources
- Effect
- Across nine trials, sulfonylurea monotherapy lowered HbA1c by 1.51 percentage points more than placebo (95% CI 1.25 to 1.78). Added to other oral treatment it lowered HbA1c by 1.62 points (95% CI 1.0 to 2.24), and added to insulin by 0.46 points (95% CI 0.24 to 0.69). Higher doses did not lower HbA1c more than lower doses [1]. Added to maximal metformin, the drug classes studied lowered HbA1c by a similar 0.64 to 0.97 points against placebo [2]. In a 14-week label trial, glimepiride 1 mg, 4 mg and 8 mg lowered HbA1c by 1.2, 1.8 and 1.8 points against placebo, and in a 22-week trial by 1.1 points [3]. Over 10 years, intensive treatment with a sulfonylurea or insulin held HbA1c at 7.0% against 7.9% on diet [4].
- Population
- 31 trials with a median length of 16 weeks [1]; 11,198 participants in 27 trials of drugs added to metformin [2]; 304 and 249 adults in two glimepiride trials [3]; 3,867 newly diagnosed patients [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- Most trials were short. Trial length, drug and duration of diabetes contributed to differences between trials [1].
Blood sugar and blood lipids
Shown to lower fasting glucose about 6 mg/dL and triglycerides about 14 to 18 mg/dL, mostly in people with obesity, diabetes or metabolic syndrome. HDL did not change.
A second meta-analysis found fasting glucose 5.9 mg/dL lower, HbA1c 0.21% lower, triglycerides 14.4 mg/dL lower and LDL cholesterol 5.1 mg/dL lower.
The numbers and sources
- Effect
- Fasting glucose fell by 5.9 mg/dL (95% CI -10.7 to -1.0) and triglycerides by 18.3 mg/dL (95% CI -25.6 to -11.0). HDL cholesterol did not change [4]. A second meta-analysis found fasting glucose 5.9 mg/dL lower, HbA1c 0.21% lower, triglycerides 14.4 mg/dL lower and LDL cholesterol 5.1 mg/dL lower [5].
- Population
- 25 RCTs, 1,024 participants [4]; 34 RCTs [5].
- Sources
- [4], [5]
- Caveats
- Most trials were short and enrolled people with obesity, diabetes or metabolic syndrome. Neither review measured hard outcomes such as heart attacks or diabetes onset.
Weight loss
Shown to lower weight by about 5.3 kg more than placebo in adults with overweight or obesity, and 3.4 kg in adults with type 2 diabetes, with more adverse events.
Compared with placebo [7][8][3]
In adults with obesity and type 2 diabetes, topiramate alone lowered weight 3.4 kg more than placebo (95% CI -3.79 to -3.04) and HbA1c by 0.4 points (95% CI -0.58 to -0.32), with more serious adverse events (RR 1.69, 95% CI 1.00 to 2.87).
The numbers and sources
- Effect
- Across 10 trials of at least 16 weeks, topiramate lowered weight 5.34 kg more than placebo (95% CI -6.12 to -4.56), and 6.58 kg in trials longer than 28 weeks at 96 to 200 mg a day. Withdrawal for adverse events was more likely (OR 1.94, 95% CI 1.64 to 2.29) [7]. In adults with obesity and type 2 diabetes, topiramate alone lowered weight 3.4 kg more than placebo (95% CI -3.79 to -3.04) and HbA1c by 0.4 points (95% CI -0.58 to -0.32), with more serious adverse events (RR 1.69, 95% CI 1.00 to 2.87) [8]. In the label's migraine trials, mean weight fell 2% at 50 mg, 3% at 100 mg and 4% at 200 mg, against 0% on placebo [3].
- Population
- 3,320 adults with overweight or obesity in 10 trials [7]; adults with obesity and type 2 diabetes in 5 trials [8]; adults in migraine trials [3].
- Sources
- [7], [8], [3]
- Caveats
- Topiramate alone is not approved for weight loss. All but one diabetes trial had high risk of bias [8].
Blood sugar
Shown to lower fasting glucose about 6 to 10 mg/dL and HbA1c about 0.3 points in adults with prediabetes or type 2 diabetes.
The numbers and sources
- Effect
- Across 34 RCTs in adults with prediabetes or type 2 diabetes, curcumin or turmeric lowered fasting glucose by 10.15 mg/dL (95% CI -12.59 to -7.72), HbA1c by 0.32% (95% CI -0.43 to -0.21) and HOMA-IR by 0.46 against control [6]. A meta-analysis of 63 trials drawn from 13 earlier reviews (3,706 participants) found fasting glucose 6.30 mg/dL lower (95% CI -9.33 to -3.27) and HbA1c 0.31% lower (95% CI -0.57 to -0.05) [7]. With piperine added, 15 RCTs (1,020 participants) showed fasting glucose 5.89 mg/dL lower, while HbA1c, fasting insulin and HOMA-IR did not differ significantly [8].
- Population
- Adults with prediabetes or type 2 diabetes [6][7]; adults, many overweight with metabolic disorders [8].
- Sources
- [6], [7], [8], [9]
- Caveats
- Heterogeneity was significant [6] and high [7]. GRADE certainty was low for fasting glucose and HbA1c in the piperine review [8]. In a network meta-analysis of 24 RCTs in prediabetes, turmeric extract was linked to fewer new cases of type 2 diabetes (RR 0.05, 95% CI 0.00 to 0.78), with low certainty and short trials [9].
Blood sugar in type 2 diabetes
Shown to lower HbA1c about 0.3 to 0.4 points against comparison diets in adults with type 2 diabetes.
Compared with comparator diets the source does not describe [1]; control diets the source does not describe [2]
The numbers and sources
- Effect
- In 6 controlled trials (255 participants), vegetarian diets lowered HbA1c by 0.39 points (95% CI -0.62 to -0.15), and fasting glucose did not change significantly [1]. In 9 RCTs (664 participants), HbA1c fell 0.29 points (95% CI -0.45 to -0.12) and fasting glucose 0.56 mmol/L, at moderate certainty, with no change in fasting insulin [2].
- Population
- Adults with type 2 diabetes, mean age 42.5 in [1]; adults with diabetes in trials of 3 weeks or more [2].
- Sources
- [1], [2]
- Caveats
- Both reviews pooled lacto-ovo and vegan diets. Trials were small and short.
Blood sugar
Mixed results: one large review found lower fasting glucose and HbA1c, while a review of overweight adults and neuropathy trials found no change.
The numbers and sources
- Effect
- Across 63 trials, fasting glucose fell 5.28 mg/dL (95% CI -7.21 to -3.35), HbA1c 0.40% (95% CI -0.66 to -0.14), fasting insulin 1.70 mU/mL and HOMA-IR 0.74 against control [8]. In 11 trials of 704 overweight or obese adults, fasting glucose (SMD 0.13, 95% CI -0.16 to 0.41) and HOMA-IR (SMD -0.23, 95% CI -0.60 to 0.15) did not differ from control [9]. In diabetic neuropathy trials, HbA1c did not change [5].
- Population
- 63 randomized trials [8]; adults with a BMI of 25 or more [9]; people with diabetic neuropathy [5].
- Sources
- [8], [9], [5]
- Caveats
- The reviews disagree. The overweight review rated 8 of its 11 trials at low risk of bias [9].
Blood sugar and blood lipids
Shown to lower fasting glucose by about 16 mg/dL and triglycerides in people with prediabetes or type 2 diabetes. Reviews disagree on LDL and total cholesterol.
The numbers and sources
- Effect
- In prediabetes and type 2 diabetes, astaxanthin lowered fasting glucose by 16.1 mg/dL (95% CI -29.0 to -3.3), HbA1c by 0.34 points, triglycerides by 20.9 mg/dL, total cholesterol by 12.2 mg/dL and LDL by 9.4 mg/dL, and raised HDL by 3.0 mg/dL. HOMA-IR, weight and BMI did not change [4]. At 6 to 20 mg a day, a second meta-analysis found higher HDL and lower triglycerides, with no change in LDL or total cholesterol [5]. In adults at risk of metabolic syndrome, effects on total cholesterol and systolic pressure were marginal, and LDL fell [6].
- Population
- 403 patients in 9 RCTs [4]; 8 studies with 11 results [5]; 321 adults in 7 RCTs [6].
- Sources
- [4], [5], [6]
- Caveats
- The reviews disagree on LDL and total cholesterol. All pooled small trials.
Compared with metformin and other diabetes drugs
Shown to lower blood sugar about as much as metformin and other oral diabetes drugs in adults with type 2 diabetes, in mostly low-quality trials.
In 36 adults with new type 2 diabetes, 0.5 g of berberine or metformin three times a day for 3 months gave similar glucose lowering, with HbA1c falling from 9.5% to 7.5% on berberine.
The numbers and sources
- Effect
- In 14 trials (1,068 participants), berberine did not give better glucose control than metformin, glipizide or rosiglitazone, and added to the same drug it gave better control than the drug alone [3]. A 27-trial meta-analysis (2,569 patients) found no significant difference between berberine and oral diabetes drugs [4]. In 36 adults with new type 2 diabetes, 0.5 g of berberine or metformin three times a day for 3 months gave similar glucose lowering, with HbA1c falling from 9.5% to 7.5% on berberine [5]. In 89 women with PCOS, berberine reduced waist-to-hip ratio and LDL more than metformin over 3 months [6].
- Population
- Adults with type 2 diabetes [3][4][5]. Chinese women with PCOS and insulin resistance [6].
- Sources
- [3], [4], [5], [6]
- Caveats
- Methodological quality was generally low [3]. The 36-person comparison was a pilot [5]. An integrity review rated every PCOS trial it found at high risk of compromised integrity [7].
Blood sugar control in type 2 diabetes
Shown to lower HbA1c by about 1.0 to 1.2 points against almost no change on placebo in adults with type 2 diabetes, with 62% reaching under 7% against 22%.
Compared with placebo [1]; sitagliptin, metformin, exenatide and insulin glargine [1]; other diabetes drugs in a network meta-analysis [2]
In other placebo-controlled trials, dulaglutide lowered HbA1c more than placebo when added to glimepiride, to metformin with pioglitazone, and to SGLT2 inhibitors.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Added to metformin, HbA1c changed by -1.0 points on 0.75 mg, -1.2 on 1.5 mg, -0.6 on sitagliptin and +0.1 on placebo at 26 weeks. HbA1c under 7% was reached by 56%, 62%, 39% and 22%, and fasting glucose fell 35, 41, 18 and 9 mg/dL. In other placebo-controlled trials, dulaglutide lowered HbA1c more than placebo when added to glimepiride, to metformin with pioglitazone, and to SGLT2 inhibitors [1]. A network meta-analysis of 453 trials found that specific GLP-1 receptor agonists added to metformin, with insulin regimens, produced the largest HbA1c reductions [2].
- Population
- 972 adults on metformin in one trial and other placebo-controlled trials described in the label [1]; 453 trials of 21 glucose-lowering treatments [2].
- Sources
- [1], [2]
- Caveats
- The trials were funded by the manufacturer. The network meta-analysis abstract does not give a dulaglutide estimate [2].
Blood sugar
Shown to lower fasting glucose, and HbA1c by about 0.5 points, more in people with type 2 diabetes. Insulin did not change.
Fructosamine and HbA1c were lower at 12 and 24 weeks.
The numbers and sources
- Effect
- In 9 RCTs (768 patients with type 2 diabetes), fasting glucose was lower with garlic at 1 to 2, 3 to 4, 12 and 24 weeks. Fructosamine and HbA1c were lower at 12 and 24 weeks. Complications did not differ [5]. A 2026 GRADE-assessed meta-analysis of 27 RCTs (1,619 adults) found fasting glucose fell 2.76 mg/dL (95% CI -5.11 to -0.41) and HbA1c 0.53 percentage points (95% CI -0.86 to -0.20). Insulin and HOMA-IR did not change significantly [6]. In 8 trials in type 2 diabetes, fasting glucose fell 12.41 mg/dL and HbA1c 0.5 points [7]. The 108-trial review found fasting glucose 2.77 mg/dL lower [4].
- Population
- Adults with type 2 diabetes [5][7]. Adults in 27 RCTs [6] and 108 trials [4].
- Sources
- [4], [5], [6], [7]
- Caveats
- The reviews pooled different populations, and the fasting glucose drop in the type 2 diabetes review [7] is more than four times that in the all-adult reviews. The pooled standardized differences in [5] are very large (SMD -21.02 at 24 weeks), which points to small, varied trials. Heterogeneity in [7] was very high (I² 99.2% for fasting glucose), and its authors rate the included trials as low quality.
Blood sugar
Shown to lower fasting glucose, HbA1c and insulin resistance modestly with EGCG supplements in adults, with HbA1c down about 0.18 points.
The numbers and sources
- Effect
- In a 2025 meta-analysis of 41 RCTs, EGCG supplements lowered fasting glucose, HbA1c and HOMA-IR by modest amounts. HbA1c fell 0.18 percentage points (95% CI -0.35 to -0.02), and fasting insulin did not change significantly (95% CI -1.46 to 0.47) [6].
- Population
- Adults in 41 RCTs of EGCG [6].
- Sources
- [6]
- Caveats
- The authors describe the HbA1c and insulin effects as modest and possibly not clinically meaningful for most people [6].
HbA1c in type 2 diabetes
Shown to lower HbA1c about 0.5% more than standard-protein diets within 6 months in type 2 diabetes, in one meta-analysis of nine small trials.
Compared with diets with less protein
The numbers and sources
- Effect
- Against diets with 15% to 20% of energy from protein, diets with 25% to 32% lowered weight 2.08 kg more (95% CI 0.90 to 3.25) and HbA1c 0.52% more (95% CI 0.14 to 0.90). Fasting glucose and blood lipids did not differ [8].
- Population
- 418 adults with type 2 diabetes in 9 trials lasting 4 to 24 weeks [8].
- Sources
- [8]
- Caveats
- Two studies had a large influence on the weight and HbA1c results [8]. The indexed abstract prints minus signs as the digit 2. The figures here follow its text, which reports reductions.
Blood sugar and complications in type 2 diabetes
Shown to lower HbA1c in type 2 diabetes, to 7.0% against 7.9% on diet over 10 years in one trial, with 25% fewer small-vessel complications.
An HbA1c of 7.0% or higher was reached at 26.5 per 100 participant-years on glargine, 26.1 on liraglutide, 30.4 on glimepiride and 38.1 on sitagliptin.
The numbers and sources
- Effect
- In newly diagnosed type 2 diabetes, intensive treatment with insulin or a sulfonylurea held HbA1c at 7.0% against 7.9% on diet over 10 years, with no difference between agents. The risk of any diabetes-related endpoint was 12% lower (95% CI 1 to 21) and of microvascular endpoints 25% lower (95% CI 7 to 40) [3]. Added to metformin, glargine kept HbA1c below 7.0% for longer than glimepiride or sitagliptin. An HbA1c of 7.0% or higher was reached at 26.5 per 100 participant-years on glargine, 26.1 on liraglutide, 30.4 on glimepiride and 38.1 on sitagliptin [4]. In a 52-week label trial of glargine added to oral drugs, HbA1c fell by 0.5 points from a baseline of 9.0% [5]. In a network meta-analysis, drug classes added to metformin were associated with similar HbA1c levels [6].
- Population
- 3,867 newly diagnosed patients, median age 54 [3]; 5,047 participants on metformin followed a mean of 5.0 years [4]; 570 adults in the label trial [5]; 301 trials of glucose-lowering drugs [6].
- Sources
- [3], [4], [5], [6]
- Caveats
- The 10-year trial pooled insulin with sulfonylureas in its intensive group, and found no drop in diabetes-related death or death from any cause [3]. A meta-analysis of 20 trials found no effect of insulin on any clinical outcome in type 2 diabetes [7].
HbA1c in type 2 diabetes
Shown to lower HbA1c about 0.6 points more than comparison diets at 3 to 6 months in type 2 diabetes, with mixed results at 12 months.
Compared with diets that did not restrict carbohydrates to the level of ketosis
The numbers and sources
- Effect
- Against guideline diabetes diets, HbA1c fell 0.61% more at 3 months (95% CI 0.40 to 0.82, moderate certainty) and 0.58% more at 6 months (95% CI 0.32 to 0.85, low certainty), with no difference at 12 months. Diabetes medication use fell more for up to 12 months [4]. Across 29 trials, HbA1c fell 0.29% (95% CI 0.14 to 0.44) [7]. At 12 months, four studies showed a difference of 0.01% (95% CI -0.22 to 0.25) and two showed 0.65% lower (95% CI 0.31 to 0.99) [6].
- Population
- 648 adults with type 2 diabetes in 8 RCTs of 12 weeks or more [4]; 606 adults with pre-diabetes or type 2 diabetes in 8 RCTs of 6 months or more [6]; 29 trials in type 2 diabetes [7].
- Sources
- [4], [6], [7]
- Caveats
- The authors of [4] name poor adherence to carbohydrate restriction as a major limitation. The 12-month results disagree between analyses [6]. Review [7] pooled clinical trials, not only randomized ones.
HbA1c and remission in type 2 diabetes
Shown to lower HbA1c and raise remission rates at 3 to 6 months in type 2 diabetes, with no clear difference at 12 to 24 months.
Compared with diets with more carbohydrate
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- At 6 months, 57% on low-carbohydrate diets reached HbA1c under 6.5% against 31% on control diets (risk difference 0.32, 95% CI 0.17 to 0.47, 8 studies, 264 people, I² 58%). With remission defined as HbA1c under 6.5% without medication, the effect was smaller and not significant. At 12 months, remission data were sparse [6]. Diets under 26% of energy from carbohydrate lowered HbA1c 0.47% more at 3 months (95% CI 0.23 to 0.71) and 0.36% more at 6 months (95% CI 0.09 to 0.62), with no difference at 12 or 24 months. Moderate restriction at 26% to 45% of energy did not differ from higher-carbohydrate diets [7]. Over 1 to 2 years, HbA1c showed little to no difference against balanced-carbohydrate diets [1].
- Population
- 1,357 adults with type 2 diabetes in 23 trials [6]; 2,412 adults with diabetes in 25 RCTs [7]; adults with type 2 diabetes and overweight [1].
- Sources
- [1], [6], [7]
- Caveats
- Remission fell markedly in studies that included people using insulin [6]. Certainty was moderate to low [6], and the authors of [7] note issues with evidence quality.
Blood sugar and insulin resistance
Mixed results: most reviews found lower insulin resistance but disagreed on fasting glucose, and one review in people with diabetes found no significant change.
The numbers and sources
- Effect
- One meta-analysis found magnesium lowered HOMA-IR (WMD -0.67, 95% CI -1.20 to -0.14) but not fasting glucose (WMD -0.20 mmol/L, 95% CI -0.45 to 0.05) or HbA1c overall. Trials of 4 months or longer showed lower fasting glucose and HOMA-IR [3]. A 2021 meta-analysis of double-blind trials reported lower fasting glucose in people with diabetes and improved glucose and insulin-sensitivity markers in people at high risk [4]. A 2026 meta-analysis of 78 RCTs found lower HOMA-IR (WMD -0.48, 95% CI -0.79 to -0.18), fasting glucose (WMD -3.60 mg/dL) and HbA1c (WMD -0.15%) [5]. A 2026 meta-analysis of 15 RCTs (1,085 people with diabetes or prediabetes) found no significant change in insulin (MD -1.73) or HOMA-IR (MD -0.74, 95% CI -1.58 to 0.09). Baseline insulin and HOMA-IR modified the effect [6].
- Population
- People with and without diabetes [3][5]; people with or at high risk of diabetes [4][6].
- Sources
- [3], [4], [5], [6]
- Caveats
- The sources disagree on fasting glucose and on HOMA-IR in people with diabetes. The 2021 abstract does not report effect sizes [4]. The authors of [5] rated certainty as variable across outcomes.
Blood pressure, cholesterol and blood sugar markers
Shown to lower blood pressure about 3/2 mmHg and LDL cholesterol and HbA1c slightly in adults, at low to moderate certainty.
Compared with no or minimal intervention, and another dietary intervention the abstract does not name [2]; a low-fat diet, a low-carbohydrate diet and the American Diabetes Association diet [7]; control diets the source does not describe [10]
In 9 RCTs (1,337 people at raised risk of diabetes or heart disease), HbA1c fell 0.18 points (95% CI -0.35 to -0.01), LDL 0.10 mmol/L and triglycerides 0.20 mmol/L.
The numbers and sources
- Effect
- Against no or minimal intervention, systolic blood pressure fell 2.99 mmHg (95% CI -3.45 to -2.53) and diastolic 2.0 mmHg (95% CI -2.29 to -1.71) at moderate quality, with little or no effect on LDL or HDL. Against other diets, LDL fell 0.15 mmol/L (95% CI -0.27 to -0.02) and triglycerides 0.09 mmol/L, with little or no effect on blood pressure [2]. In 9 RCTs (1,337 people at raised risk of diabetes or heart disease), HbA1c fell 0.18 points (95% CI -0.35 to -0.01), LDL 0.10 mmol/L and triglycerides 0.20 mmol/L. Fasting glucose, insulin, insulin resistance and HDL did not change [10]. Over 12 months or more, blood pressure and lipids changed about as much as on comparator diets [7].
- Population
- Healthy adults and adults at high cardiovascular risk [2]; adults at increased risk of type 2 diabetes and heart disease [10]; adults with overweight or obesity [7].
- Sources
- [2], [7], [10]
- Caveats
- The Cochrane review rated the lipid evidence low or very low quality for most comparisons [2]. The changes are small next to drug effects.
Blood sugar in type 2 diabetes
Shown to lower HbA1c about 1.1 points more than placebo in people with diabetes, and more at higher doses.
The numbers and sources
- Effect
- Across 35 trials of at least 12 weeks, metformin alone lowered HbA1c by 1.12 points more than placebo (95% CI 0.92 to 1.32). Added to other oral diabetes drugs it lowered HbA1c 0.95 points more than placebo (95% CI 0.77 to 1.13), and added to insulin 0.60 points more than insulin alone (95% CI 0.30 to 0.91). Higher doses lowered HbA1c more than lower doses, with no significant rise in side effects [6]. A Cochrane review of 29 trials found a strong benefit for HbA1c against placebo and against diet [7].
- Population
- People with diabetes in trials of at least 12 weeks [6]; 5,259 people with type 2 diabetes [7].
- Sources
- [6], [7]
- Caveats
- Heterogeneity was high (I² 77 to 80%) [6]. The Cochrane abstract gives no pooled effect size, so the grade rests on one review with numbers. These are people with diabetes. For people without it, see diabetes prevention above.
Blood sugar in type 2 diabetes
Shown to lower fasting glucose about 27 mg/dL and HbA1c about 1 point in adults with type 2 diabetes, in low quality trials.
The numbers and sources
- Effect
- In 5 trials (270 patients), silymarin lowered fasting blood glucose by 26.86 mg/dL (95% CI -35.42 to -18.30) and HbA1c by 1.07 points (95% CI -1.73 to -0.40). Lipids did not change [9]. A 2025 network meta-analysis of 17 studies (1,337 people with type 2 diabetes) found silymarin lowered fasting glucose, HOMA-IR and HbA1c against placebo (P < 0.05) [10]. Across 6 RCTs (673 participants), HOMA-IR fell by 2.29 (95% CI -4.55 to -0.03) with no change in fasting insulin. The fall was seen in type 2 diabetes but not in fatty liver disease [11].
- Population
- Adults with type 2 diabetes [9][10]; adults with type 2 diabetes, alcoholic cirrhosis or fatty liver disease in Iran, Egypt and Italy [11].
- Sources
- [9], [10], [11]
- Caveats
- The authors of [9] rated the evidence as low quality, with high heterogeneity. The network meta-analysis abstract reports p-values for silymarin against placebo without effect sizes [10]. The authors of [11] called the evidence limited.
Blood sugar in type 2 diabetes
Shown to lower HbA1c by 0.07 percentage points and fasting glucose slightly in people with type 2 diabetes, in one meta-analysis of short trials.
Compared with diets with the same calories without tree nuts [12]
The numbers and sources
- Effect
- A median 56 g a day of tree nuts lowered HbA1c (MD -0.07%, 95% CI -0.10 to -0.03) and fasting glucose (MD -0.15 mmol/L, 95% CI -0.27 to -0.02). Fasting insulin and HOMA-IR did not change significantly [12].
- Population
- 450 people with diabetes in 12 randomized trials of 3 weeks or more [12].
- Sources
- [12]
- Caveats
- The reviewers describe most trials as short and of poor quality [12].
Blood sugar in people with type 2 diabetes
Shown to lower HbA1c by 0.27 points and fasting glucose by 0.44 mmol/L in people with type 2 diabetes, in pooled trials against control groups.
Compared with control groups in the trials pooled [8]
The numbers and sources
- Effect
- In people with type 2 diabetes, olive oil lowered HbA1c (mean difference -0.27%, 95% CI -0.37 to -0.17) and fasting plasma glucose (-0.44 mmol/L, 95% CI -0.66 to -0.22) more than in control groups [8].
- Population
- People with type 2 diabetes in trials among the 29 pooled [8].
- Sources
- [8]
- Caveats
- The abstract does not describe the control groups. The authors note the finding applies to olive oil as a food, not its single components [8].
HbA1c in people with type 2 diabetes
Shown to lower HbA1c by 0.67% with structured exercise training in type 2 diabetes, and by 0.89% with more than 150 minutes a week.
Compared with control groups in randomized trials [7]
The numbers and sources
- Effect
- Structured exercise training lowered HbA1c by 0.67% (95% CI -0.84% to -0.49%) against control groups. Aerobic training lowered it 0.73%, resistance training 0.57% and both combined 0.51%. More than 150 minutes a week lowered it 0.89%, and 150 minutes or less 0.36%. Activity advice lowered HbA1c only when combined with diet advice (-0.58%) [7].
- Population
- 8,538 patients with type 2 diabetes in 47 randomized trials of at least 12 weeks [7].
- Sources
- [7]
- Caveats
- Heterogeneity was very high (I² 91.3%) [7].
Blood sugar in type 2 diabetes
Shown to lower HbA1c about 0.9 to 1.1 points more than placebo in adults with type 2 diabetes, with no severe low blood sugar reported.
Pooling 3 RCTs in adults with obesity, with or without diabetes, HbA1c fell 0.91% more than on placebo.
The numbers and sources
- Effect
- At 40 weeks, HbA1c changed by -1.69% on 4 mg, -1.86% on 9 mg and -1.94% on 12 mg, against -0.81% on placebo. Differences from placebo were -0.88 (95% CI -1.18 to -0.59), -1.04 (95% CI -1.32 to -0.76) and -1.12 (95% CI -1.39 to -0.85) points. No severe hypoglycemia was reported [6]. A meta-analysis of 8 studies found HbA1c fell 1.04% (95% CI -1.42 to -0.67). Doses of 8 mg or less lowered it more (-1.39%) than doses of 12 mg or more (-0.65%) [7]. Pooling 3 RCTs in adults with obesity, with or without diabetes, HbA1c fell 0.91% more than on placebo [3].
- Population
- 537 adults with type 2 diabetes, baseline HbA1c 7.9%, mean diabetes duration 2.5 years [6]; 8 studies in people with diabetes, obesity or both, framed around chronic kidney disease [7]; 3 RCTs with 878 adults [3].
- Sources
- [6], [7], [3]
- Caveats
- The 40-week trial tested retatrutide as a single drug rather than added to others [6]. The abstract of [7] does not say how many participants had kidney disease. [3] mixed people with and without diabetes.
Type 1 diabetes, added to insulin
Shown to lower HbA1c by about 0.38 points when added to insulin in adults with type 1 diabetes, while about doubling the risk of ketoacidosis.
The numbers and sources
- Effect
- Added to insulin, SGLT2 inhibitors lowered HbA1c by 0.38 points, raised time in range by 8.6 percentage points, and lowered insulin use by 4.7 units a day and body weight by 2.5 kg. The risk of diabetic ketoacidosis rose (RR 2.19, 95% CI 1.16 to 4.17) [19]. The US labels state that the drugs are not for blood sugar control in type 1 diabetes and may raise the risk of ketoacidosis in these patients [20].
- Population
- Adults with type 1 diabetes in a meta-analysis of 90 studies of two drug classes [19].
- Sources
- [19], [20]
- Caveats
- Not an approved use in the US. The review pooled trials with other study designs. See the ketoacidosis block below.
Long-term programs to cut sitting
Shown to cut sitting by about an hour a day and lower HbA1c 0.17%, body fat and waist size in trials of people with chronic conditions.
Compared with control interventions [9]; control offices whose workers were told to behave as usual [10]
HbA1c fell 0.17% (95% CI -0.30 to -0.04), body fat 0.66 percentage points and waist circumference 1.52 cm against control groups.
The numbers and sources
- Effect
- Lifestyle programs cut sedentary time by 64 minutes a day (95% CI -91 to -38). HbA1c fell 0.17% (95% CI -0.30 to -0.04), body fat 0.66 percentage points and waist circumference 1.52 cm against control groups [9]. In office workers, a workplace program cut sitting by 71 minutes per 8-hour workday at 1 month and 48 minutes at 3 months, and body fat was 0.61 percentage points lower at 3 months [10].
- Population
- 18 randomized trials in people with overweight, type 2 diabetes, heart, neurological or musculoskeletal disease [9]. 317 office workers in 19 offices, cluster randomized [10].
- Sources
- [9], [10]
- Caveats
- Programs often added counseling and activity, so the effect of less sitting alone cannot be separated out. Follow-up was months, not years.
Blood sugar
Shown to lower HbA1c by about 0.18 points against control diets in adults with overweight or type 2 diabetes.
Compared with the participants' habitual diet, unchanged, in 3 trials in US and New Zealand adults, and in 8 trials a National Cholesterol Education Program diet, American Diabetes Association and Korean Diabetes Association diets, a portion-controlled diet, a Mediterranean diet, a low-fat diet, a healthy omnivorous diet or a high-carbohydrate lacto-ovo vegetarian diet [1]
The numbers and sources
Blood sugar in trials
Shown to lower the rise in blood sugar after a meal against refined foods. Longer trials found no change in fasting glucose, and one review found HbA1c fell.
Compared with similar refined foods [12]; refined grains or placebo [9]
Another review found whole grains lowered HbA1c (SMD -0.33, 95% CI -0.61 to -0.04).
The numbers and sources
- Effect
- In 14 single-meal trials, whole grain foods reduced the 2-hour glucose response by 29.71 mmol·min/L (95% CI -43.57 to -15.85) and the insulin response. In 16 trials lasting weeks to months, fasting glucose, fasting insulin and HOMA-IR did not change significantly [12]. Another review found whole grains lowered HbA1c (SMD -0.33, 95% CI -0.61 to -0.04) [9].
- Population
- Healthy adults in 30 trials [12]. 25 trials of adults with or without cardiovascular risk factors [9].
- Sources
- [12], [9]
- Caveats
- Most longer trials enrolled healthy people with normal blood sugar [12].
Blood sugar and blood fats in type 2 diabetes
Shown in one meta-analysis to lower HbA1c by 0.47 points and fasting glucose by 24 mg/dL in adults with type 2 diabetes, with high heterogeneity.
Compared with control groups including usual care or standard treatment [12]
The numbers and sources
- Effect
- Pooled differences were -23.72 mg/dL for fasting blood glucose (95% CI -37.78 to -9.65, I² 82%), -0.47% for HbA1c (95% CI -0.87 to -0.07, I² 82%), -17.38 mg/dL for glucose after meals, -18.50 mg/dL for total cholesterol, +4.30 mg/dL for HDL cholesterol and -12.95 mg/dL for LDL cholesterol. Triglycerides did not differ (-12.57 mg/dL, 95% CI -29.91 to 4.76) [12].
- Population
- 864 adults with type 2 diabetes in 12 trials [12].
- Sources
- [12]
- Caveats
- The authors note limited methods and heterogeneity, and long-term effects were not studied [12].
Blood sugar
Shown to lower fasting glucose about 14 mg/dL and HbA1c about 0.55% in people with and without diabetes.
The numbers and sources
- Effect
- Across 32 placebo-controlled interventions (1,700 participants, 14 countries), zinc lowered fasting glucose by 14.15 mg/dL (95% CI -17.36 to -10.93), 2-hour glucose by 36.85 mg/dL, HbA1c by 0.55% (95% CI -0.84 to -0.27) and hs-CRP by 1.31 mg/L [3]. Across 18 RCTs (1,023 participants) with diabetes, gestational diabetes or prediabetes, zinc lowered serum insulin (MD -2.50, 95% CI -4.69 to -0.31) and HOMA-IR (MD -1.10, 95% CI -2.05 to -0.15), and LDL cholesterol rose slightly (MD 3.46, 95% CI 1.48 to 5.43) [4].
- Population
- People with and without diabetes [3]; people with diabetes or prediabetes [4].
- Sources
- [3], [4]
- Caveats
- The fasting glucose effect depended on diabetes status and on the zinc formulation [3].
Blood sugar in insulin-treated type 2 diabetes
One trial found 3 fasting days a week lowered HbA1c by 7.3 mmol/mol against control over 12 weeks in insulin-treated type 2 diabetes.
Compared with eating every day, with no fasting days or daily fasting window
The numbers and sources
- Effect
- HbA1c fell 7.3 mmol/mol (SD 12.0) on fasting against 0.1 mmol/mol in controls (P 0.012). Eight people on fasting and none in control reached the combined goal of 2% weight loss, 10% lower insulin dose and a 3 mmol/mol HbA1c drop [10].
- Population
- 46 adults with insulin-treated type 2 diabetes, with dietary counseling and continuous glucose monitoring [10].
- Sources
- [10]
- Caveats
- One small 12-week trial, published as a brief report [10].
Blood sugar
Small trials found HbA1c fell about 0.5 points. Pooled trials found no change in fasting glucose.
Compared with usual diets, and for fasting glucose also low-antioxidant and weight-loss diets, behavioral programs alone and usual gestational diabetes care [7]
The numbers and sources
- Effect
- A meta-analysis of 2 controlled trials (65 participants) found HbA1c fell 0.53 points (95% CI -0.62 to -0.43). Fasting insulin fell slightly, and fasting glucose and insulin resistance did not change [7].
- Population
- Adults with and without diabetes [7].
- Sources
- [7]
- Caveats
- Two small trials. Certainty ranged from very low to moderate across secondary outcomes [7].
Higher doses of 3 mg and 4.5 mg
One trial found 4.5 mg lowered HbA1c 0.24 points more and weight 1.6 kg more than 1.5 mg over 36 weeks, with more nausea and vomiting.
Compared with dulaglutide 1.5 mg [3]
The numbers and sources
- Effect
- At 36 weeks, HbA1c fell 1.77 points on 4.5 mg and 1.54 on 1.5 mg (difference -0.24, P under 0.001). The 3 mg dose beat 1.5 mg only in the on-treatment analysis (-0.17 points). Weight fell 4.6 kg on 4.5 mg and 3.0 kg on 1.5 mg. Nausea occurred in 13.4%, 15.6% and 16.4%, and vomiting in 5.6%, 8.3% and 9.3%, on 1.5, 3 and 4.5 mg [3].
- Population
- 1,842 adults with type 2 diabetes on metformin, mean HbA1c 8.6% and BMI 34.2, over 52 weeks [3].
- Sources
- [3]
- Caveats
- One trial with no placebo arm, funded by the manufacturer.
- Why limited
- This rests on one trial, of 1,842 people. Strength counts independent studies that agree, so one trial is limited at any size.
Compared with semaglutide
One head-to-head trial found semaglutide lowered HbA1c about 0.4 points more and weight 2.3 to 3.6 kg more than dulaglutide at matched dose levels over 40 weeks.
Compared with semaglutide [4]
The numbers and sources
- Effect
- HbA1c fell 1.4 points on dulaglutide 1.5 mg and 1.8 on semaglutide 1.0 mg (difference -0.41), and 1.1 on dulaglutide 0.75 mg against 1.5 on semaglutide 0.5 mg (difference -0.40). Weight fell 3.0 kg against 6.5 kg (difference -3.55 kg) and 2.3 kg against 4.6 kg. Gastrointestinal disorders occurred in 48% on dulaglutide 1.5 mg and 44% on semaglutide 1.0 mg [4].
- Population
- 1,201 adults with type 2 diabetes on metformin in 16 countries [4].
- Sources
- [4]
- Caveats
- Open label, funded by the maker of semaglutide. Dulaglutide still lowered HbA1c and weight from baseline in both arms [4].
- Why limited
- This rests on one trial, of 1,201 people. Strength counts independent studies that agree, so one trial is limited at any size.
Blood sugar in children and teenagers with type 2 diabetes
One trial in youths with type 2 diabetes found dulaglutide lowered HbA1c by 0.9 points while it rose 0.6 on placebo, with no difference in BMI.
Compared with placebo [5]
The numbers and sources
- Effect
- At 26 weeks, HbA1c rose 0.6 points on placebo and fell 0.6 on 0.75 mg and 0.9 on 1.5 mg. HbA1c under 7% was reached by 51% on dulaglutide against 14% on placebo. Fasting glucose rose 17.1 mg/dL on placebo and fell 18.9 mg/dL on dulaglutide. BMI change did not differ [5].
- Population
- 154 youths aged 10 to under 18 with type 2 diabetes, on lifestyle changes alone or with metformin, with or without basal insulin [5].
- Sources
- [5]
- Caveats
- One small trial, funded by the manufacturer. Gastrointestinal adverse events were more frequent than on placebo [5].
Blood sugar
Limited evidence: psyllium lowered fasting glucose and HbA1c in type 2 diabetes but not in normal blood sugar. Other fiber results were small or inconsistent.
The numbers and sources
- Effect
- In people treated for type 2 diabetes, psyllium taken before meals lowered fasting glucose by 37.0 mg/dL and HbA1c by 0.97%. There was no glucose lowering in people with normal blood sugar and a modest effect in prediabetes [5]. Across 12 RCTs in overweight and obese adults, isolated soluble fiber lowered fasting glucose by 0.17 mmol/L (95% CI -0.28 to -0.06) and fasting insulin by 15.88 pmol/L [6]. A 2026 meta-analysis of 11 glucomannan trials in adults with insulin resistance-related conditions found fasting glucose 7.02 mg/dL lower (95% CI -13.56 to -0.49), an effect that lost significance under an alternative correlation assumption [7]. In a 4-week trial of 131 adults, inulin lowered 1-hour and 2-hour glucose on a glucose tolerance test in overweight or obese participants but not in healthy-weight ones, and fructooligosaccharides did not change glucose in either group [8].
- Population
- 35 psyllium RCTs across three groups [5]; 609 overweight and obese adults [6]; 11 glucomannan trials [7]; 131 adults in China [8].
- Sources
- [5], [6], [7], [8]
- Caveats
- Reference [5] searched clinical records held by Procter & Gamble, a psyllium supplement maker, as well as published studies, and its abstract does not report confidence intervals. The glucomannan result was not robust to the analysis method [7]. In the inulin trial, fasting insulin rose [8].
Weight and blood sugar in type 2 diabetes
One trial found more weight loss, 5.0% against 1.8%, and a larger HbA1c drop than placebo in adults with type 2 diabetes.
HbA1c fell 0.6 points against 0.1 points, and 44.1% against 26.3% reached an HbA1c under 7%.
The numbers and sources
Neonatal diabetes from potassium channel mutations
One study found 90% of patients with diabetes from Kir6.2 mutations stopped insulin on a sulfonylurea, with HbA1c falling from 8.1% to 6.4%.
HbA1c improved in everyone who switched, from 8.1% before treatment to 6.4% after 12 weeks, and the improvement was sustained at one year.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Of 49 patients with diabetes caused by Kir6.2 mutations, 44 (90%) stopped insulin after starting a sulfonylurea. HbA1c improved in everyone who switched, from 8.1% before treatment to 6.4% after 12 weeks, and the improvement was sustained at one year [11].
- Population
- 49 consecutive patients with Kir6.2 (KCNJ11) mutations [11].
- Sources
- [11]
- Caveats
- Not an approved use. An uncontrolled study in a rare genetic form of diabetes.
Shown to raise it1
Blood sugar
Mixed results: sweeteners did not raise blood sugar after intake in pooled trials, while against water, sweetened drinks raised HbA1c 0.21 percentage points in one review.
Compared with blood sugar before intake, in the same people [10]; no or lower sweetener intake [8]; water [5]
Replacing water with sweetened drinks was associated with higher HbA1c (0.21 percentage points, 95% CI 0.02 to 0.40) and lower systolic blood pressure (-2.63 mmHg).
The numbers and sources
- Effect
- Across 29 trials of aspartame, saccharin, steviosides and sucralose, blood glucose did not rise after intake and gradually declined over the observation period [10]. In 2 small studies of 52 adults, sweeteners lowered fasting glucose by 0.16 mmol/L (95% CI -0.26 to -0.06) against no sweetener, with very low to low certainty [8]. Replacing water with sweetened drinks was associated with higher HbA1c (0.21 percentage points, 95% CI 0.02 to 0.40) and lower systolic blood pressure (-2.63 mmHg) [5].
- Population
- 741 participants in 29 randomized trials [10]. 52 adults in 2 studies [8]. 974 adults in 9 trials of sweetened drinks against water [5].
- Sources
- [10], [8], [5]
- Caveats
- The glucose trials measured short-term responses [10]. Each finding rests on few or small trials.
Studies disagree2
HbA1c in people with type 2 diabetes using step counters
Mixed results: two meta-analyses found no change in HbA1c with step counters in type 2 diabetes, and a later one of 24 trials found a 0.22% drop.
Compared with control groups in randomized trials [10]; control groups in controlled trials [12]; control participants [13]
The numbers and sources
- Effect
- Step counter use did not change HbA1c (WMD 0.02%, 95% CI -0.08 to 0.13), with or without a goal [10]. A review of 12 trials found no differences in HbA1c, BMI, blood pressure or lipids [12]. A review of 24 randomized trials found HbA1c fell 0.22% (95% CI -0.4 to -0.05, I² 77%) and triglycerides fell 13.11 mg/dL (95% CI -25.21 to -1.02) against control participants [13].
- Population
- 1,423 participants in 10 trials [10]. 1,458 participants in 12 trials [12]. 1,969 patients in 24 trials [13].
- Sources
- [10], [12], [13]
- Caveats
- All participants had type 2 diabetes. Heterogeneity was high in the positive review [13].
Blood sugar in trials
Mixed results: pooled trials of green tea and extracts found small falls in fasting glucose and HbA1c, while a trial of a catechin-rich drink found no difference.
Compared with control groups in randomized trials [7]; a green tea drink with 96.3 mg of catechins a day [8]
The numbers and sources
- Effect
- Across 17 trials, green tea lowered fasting glucose by 0.09 mmol/L (95% CI 0.03 to 0.15) and HbA1c by 0.30% (95% CI 0.22 to 0.37), and fasting insulin in higher-quality trials [7]. In people with type 2 diabetes, a drink with 582.8 mg of catechins a day for 12 weeks showed no apparent difference in glucose or HbA1c from a low-catechin drink, except in people on insulin-releasing drugs [8].
- Population
- 1,133 participants in 17 randomized trials of green tea or green tea extract [7]. 43 adults with type 2 diabetes not on insulin [8].
- Sources
- [7], [8]
- Caveats
- The pooled trials included extracts, and the abstract gives no separate result for the drink [7].
Tested, and not shown to change it15
Weight loss compared with no diet or brief advice
Shown to lower body weight against control diets in adults with overweight or obesity. As one-off self-help instructions, it matched standard brief advice at one year.
Compared with a daily energy-restricted diet or a routine diet [7]; standard brief weight-management advice [8]
Visceral fat, total cholesterol, triglycerides, HDL, diastolic pressure, fasting glucose and HbA1c did not differ.
The numbers and sources
- Effect
- In 20 articles with 1,393 participants, 5:2 lowered body weight, BMI, waist circumference, body fat percentage, fat mass, fat-free mass, LDL cholesterol, systolic blood pressure and HOMA-IR against control groups. Visceral fat, total cholesterol, triglycerides, HDL, diastolic pressure, fasting glucose and HbA1c did not differ [7]. One-off 5:2 self-help instructions lost 1.9 kg at one year against 1.8 kg with standard brief advice (p 0.79), and 18% against 15% lost at least 5% of body weight [8].
- Population
- Adults with overweight or obesity in 20 trials [7]; 300 UK adults with obesity followed for one year [8].
- Sources
- [7], [8]
- Caveats
- The meta-analysis abstract reports significance without effect sizes [7]. Adherence to self-help 5:2 fell over the year [8].
Diabetic nerve symptoms, oral treatment
Shown to lower nerve symptom scores in people with diabetic neuropathy over 5 weeks. Over 4 years, the main combined measure did not change.
HbA1c and two nerve conduction measures did not change.
The numbers and sources
- Effect
- Over 5 weeks, total symptom scores fell 51% on 600 mg a day, 48% on 1,200 mg and 52% on 1,800 mg, against 32% on placebo (all P < 0.05) [2]. Over 4 years, 600 mg a day did not change the primary composite of impairment and nerve tests (P = 0.105). Impairment scores improved on secondary measures (NIS, P = 0.028) [3]. A 2026 network meta-analysis ranked oral alpha-lipoic acid first for lower-limb impairment scores (NIS-LL, SUCRA 97.4%, I² 0%). IV ranked first for symptom scores, and both routes raised global satisfaction [4]. A 2026 meta-analysis found lower paresthesia (SMD -1.04, 95% CI -1.24 to -0.84) and numbness (SMD -0.23, 95% CI -0.44 to -0.01) scores, mostly at 600 mg a day. HbA1c and two nerve conduction measures did not change [5].
- Population
- 181 people with diabetic polyneuropathy in Russia and Israel [2]; 460 people with mild to moderate diabetic polyneuropathy [3]; 9 randomized trials of 600 to 1,800 mg a day for 3 to 208 weeks [4]; 15 studies in diabetic neuropathy [5].
- Sources
- [2], [3], [4], [5]
- Caveats
- In the 4-year trial, the placebo group did not worsen, so the trial could not test prevention of decline as designed [3]. The abstract of [5] does not separate oral from IV use, and some comparisons were against other treatments.
Blood sugar in people without diabetes
Not shown to change fasting glucose or insulin resistance against control or daily calorie restriction in adults without diabetes.
Compared with eating every day, with no fasting days or daily fasting window
HbA1c did not differ between intermittent fasting, continuous restriction and unrestricted diets.
The numbers and sources
- Effect
- Fasting glucose (p 0.09) and HOMA-IR (p 0.55) did not differ from control [2]. Fasting glucose, fasting insulin and insulin resistance did not differ from daily calorie restriction at 6 or 12 months [3]. HbA1c did not differ between intermittent fasting, continuous restriction and unrestricted diets [6].
- Population
- 269 adults [2]; 100 adults with obesity [3]; 99 trials [6].
- Sources
- [2], [3], [6]
- Caveats
- Few participants had diabetes in these trials.
Blood pressure and other heart risk markers
Shown to lower systolic blood pressure by about 1.6 mmHg for plant sterols and stanols as a class. HDL, blood sugar and weight did not change.
HDL cholesterol, fasting glucose, HbA1c, body weight, waist and fat mass did not change.
The numbers and sources
- Effect
- Plant sterols and stanols lowered systolic blood pressure by 1.55 mmHg (95% CI 0.42 to 2.67), diastolic by 0.84 mmHg, apoB by 0.06 g/L and hs-CRP by 0.25 mg/L. HDL cholesterol, fasting glucose, HbA1c, body weight, waist and fat mass did not change [5].
- Population
- Adults of mixed health status in trials pooled across 14 meta-analyses. Blood pressure came from one of them [5].
- Sources
- [5]
- Caveats
- Class-level evidence, not beta-sitosterol alone. These are risk markers, not heart attacks or strokes. Certainty was moderate to high for most outcomes, downgraded for inconsistency, imprecision or publication bias [5].
Insulin resistance
Shown to lower HOMA-IR and fasting insulin slightly in overweight adults and women with PCOS. Fasting glucose and HbA1c did not change significantly.
Fasting glucose (-1.60 mg/dL, 95% CI -3.28 to 0.07) and HbA1c (-0.05 points, 95% CI -0.19 to 0.07) did not change significantly.
The numbers and sources
- Effect
- In 20 trials in overweight and obese adults, HOMA-IR fell 0.26 (95% CI -0.48 to -0.03) and fasting insulin 12.55 pmol/L (95% CI -23.62 to -1.47). Fasting glucose (-1.60 mg/dL, 95% CI -3.28 to 0.07) and HbA1c (-0.05 points, 95% CI -0.19 to 0.07) did not change significantly [6]. In 10 RCTs in 683 women with polycystic ovary syndrome, chromium lowered fasting insulin (p 0.01) and raised the insulin sensitivity index QUICKI (p 0.02) against placebo. Against metformin, HOMA-IR fell more on chromium (p < 0.00001) [7].
- Population
- Overweight and obese adults, with trial sizes of 1 to 137 [6]; women with polycystic ovary syndrome [7].
- Sources
- [6], [7]
- Caveats
- The two reviews studied different populations. The PCOS abstract gives p-values without effect sizes [7]. The overweight analysis abstract calls the fasting glucose fall significant though its interval crosses zero [6]. In 2005 FDA ranked the evidence for chromium picolinate and insulin resistance at its lowest level for a qualified claim [5].
Blood sugar
Mixed results: one review found fasting glucose about 0.3 mmol/L lower, and a larger review found no significant effect on blood sugar.
Fasting insulin, HbA1c and HOMA-IR did not change overall.
The numbers and sources
- Effect
- Across 16 trials of 30 days or longer, ginseng lowered fasting blood glucose by 0.31 mmol/L (95% CI -0.59 to -0.03). Fasting insulin, HbA1c and HOMA-IR did not change overall [5]. A 2025 meta-analysis of 70 studies (4,506 participants) on cardiovascular risk factors found no significant effect on the glycemic profile, with a dose-response association for fasting glucose and fasting insulin [6].
- Population
- 770 people with and without diabetes [5]. 4,506 participants in 70 studies [6].
- Sources
- [5], [6]
- Caveats
- The two reviews disagree on fasting glucose. Two thirds of trials in [5] ran under 12 weeks, and most participants already had well-controlled glucose [5].
Blood sugar
Mixed results: one 90-day trial found no HbA1c change in type 2 diabetes, while 4 of 11 studies reported lower insulin sensitivity or higher glucose.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In a 90-day RCT in people with type 2 diabetes, 1,500 mg glucosamine with 1,200 mg chondroitin did not change HbA1c compared with placebo [7]. A systematic review of 11 studies found 4 reporting lower insulin sensitivity or higher fasting glucose. Studies including people with impaired glucose tolerance or insulin resistance were more likely to detect an effect [10].
- Population
- Adults with well-controlled type 2 diabetes [7]; mixed human studies [10].
- Sources
- [7], [10]
- Caveats
- The review calls the evidence mixed [10]. The diabetes trial tested one branded product, Cosamin DS from Nutramax Laboratories [7].
Blood sugar
Shown to lower fasting glucose slightly in adults across 50 trials, with no change in HbA1c.
HbA1c did not change.
Blood pressure and triglycerides
Mixed results: triglycerides fell more on higher-protein diets in two meta-analyses, while blood pressure fell slightly in one and did not differ in another.
Compared with diets with less protein
Total and LDL cholesterol, C-reactive protein and HbA1c did not change.
The numbers and sources
- Effect
- Across 74 trials, higher-protein diets lowered systolic (SMD -0.21, 95% CI -0.32 to -0.09) and diastolic blood pressure (SMD -0.18, 95% CI -0.29 to -0.06) and triglycerides (SMD -0.51, 95% CI -0.78 to -0.24). Total and LDL cholesterol, C-reactive protein and HbA1c did not change [6]. In energy-restricted trials, triglycerides fell 0.23 mmol/L more (95% CI 0.12 to 0.33), and blood pressure and total, LDL and HDL cholesterol did not differ [1].
- Population
- Adults in 74 trials [6] and in 24 weight-loss trials [1].
- Sources
- [1], [6]
- Caveats
- Restricting to studies at lower risk of bias reduced the triglyceride effect [6]. In type 2 diabetes, blood pressure changes were not significant [8].
Insulin sensitivity and metabolic markers
Not shown to change weight, glucose, HbA1c or lipids across trials. One small trial found better insulin sensitivity in women with prediabetes.
Across 15 trials, NMN did not change body weight, BMI, fasting glucose, HbA1c or lipids.
The numbers and sources
- Effect
- In women with prediabetes and overweight or obesity, insulin-stimulated glucose disposal measured by clamp rose after 10 weeks of NMN and did not change on placebo [7]. Across 15 trials, NMN did not change body weight, BMI, fasting glucose, HbA1c or lipids. HOMA-IR showed a downward trend that was not significant [8]. In the 60-day dose trial, HOMA-IR did not differ from placebo [1].
- Population
- Postmenopausal women with prediabetes [7]; 15 RCTs at 250 to 2,000 mg a day for 14 days to 24 weeks [8]; 80 middle-aged adults [1].
- Sources
- [7], [8], [1]
- Caveats
- The clamp result comes from a single small trial in one population [7]. The pooled trials were short [8].
Blood sugar and insulin
Mixed results: two reviews found lower fasting insulin, while a review against Mediterranean, diabetes and guideline diets found no difference in glucose, insulin or HbA1c.
Compared with control diets the source does not describe [3]; a control group the source does not describe [5]; the Mediterranean diet, a diabetes diet and a diet following Dutch Health Council advice [6]
The numbers and sources
- Effect
- Against Mediterranean, diabetes and Dutch guideline diets, fasting glucose (SMD -0.34, 95% CI -0.87 to 0.18), fasting insulin, HOMA-IR and HbA1c (SMD -0.38, 95% CI -0.87 to 0.11) did not differ [6]. In people with metabolic disorders, HOMA-IR fell 0.39 (95% CI 0.08 to 0.70) and fasting insulin 12.17 μU/mL (95% CI 0.08 to 24.26) [5]. In 19 RCTs, fasting insulin fell 1.01 (95% CI 0.57 to 1.45) [3].
- Population
- 98 people with altered glucose metabolism in 4 studies [6]; adults with metabolic disorders [5]; adults in 19 RCTs [3].
- Sources
- [3], [5], [6]
- Caveats
- The null review was small [6]. The reviews used different comparison diets.
Blood sugar, cholesterol and blood pressure
Not shown to change HbA1c, fasting glucose, cholesterol or blood pressure against placebo, with one spore oil trial finding lower lipids.
The numbers and sources
- Effect
- In a Cochrane review of 5 trials (398 participants), 1.4 to 3 g a day for 12 to 16 weeks did not change HbA1c (WMD -0.10%, 95% CI -1.05 to 0.85), total cholesterol, LDL or BMI against placebo. Fasting glucose, blood pressure and triglycerides did not differ. Post-meal glucose results were inconsistent [2]. A 2025 meta-analysis of 17 RCTs (971 participants) at 200 to 11,200 mg a day for 1 to 24 weeks found no effect on blood pressure, fasting glucose or the lipid profile. BMI fell by 0.43 (95% CI 0.10 to 0.77) and heart rate by 3.92 beats a minute (95% CI 0.40 to 7.45) [3]. In 110 adults with dyslipidemia, a spore oil extract for 12 weeks lowered total cholesterol, triglycerides and LDL and raised HDL compared with placebo. The abstract gives no effect sizes [4].
- Population
- Adults with type 2 diabetes in the analyzed trials [2]. Healthy, at-risk and chronically ill adults [3]. Adults with dyslipidemia [4].
- Sources
- [2], [3], [4]
- Caveats
- Data in [2] came from 3 small trials, and risk of bias was unclear in 4 of 5 [2]. The 2025 review rated the certainty of evidence very low for every outcome [3]. The spore oil trial tested a different product and disagrees with both reviews on lipids [4].
Blood sugar and insulin sensitivity
Mixed results: one review found lower glucose and insulin resistance in people with diabetes, while a later review found no effect. No effect without diabetes.
The numbers and sources
- Effect
- Across 11 RCTs, resveratrol reduced fasting glucose, insulin, HbA1c and HOMA insulin resistance in participants with diabetes. No significant effect on any glycemic measure was found in participants without diabetes [1]. A 2026 umbrella review pooling 10 meta-analyses in type 2 diabetes found no significant effect on fasting glucose, HbA1c, insulin or HOMA insulin resistance [2].
- Population
- 388 participants in 11 RCTs [1]. Meta-analyses of trials in type 2 diabetes [2].
- Sources
- [1], [2]
- Caveats
- The two sources disagree on people with diabetes [1][2]. The pooled effects in people without diabetes did not vary by BMI, dose, duration or trial quality [1]. Heterogeneity was significant in [2].
Raised blood sugar and diabetes
Shown to raise HbA1c into the diabetes range in 5% against 1% on placebo by 26 weeks in adults with HIV. Later glucose measures did not differ.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- In the phase 3 trials, HbA1c reached 6.5% or more by week 26 in 5% on tesamorelin and 1% on placebo, a hazard ratio of 3.3 (CI 1.4 to 9.6) [6]. Fasting glucose rose 7 mg/dL more than placebo at 2 weeks, with no difference at 6 months [7]. Fasting glucose and HbA1c did not differ from placebo at 12 months in the liver trial [8].
- Population
- 806 adults with HIV in the phase 3 program [3][6]; 50 adults [7]; 61 adults [8].
- Sources
- [6], [7], [8]
- Caveats
- Mean baseline HbA1c was 5.3% in the phase 3 trials [6]. The pooled trial report found no clinically meaningful glucose differences [3], and a 2026 meta-analysis of 5 RCTs reported no change in glucose [5].
Long-term blood sugar (HbA1c)
One trial found 6 g a day of oat beta-glucan in bread did not change HbA1c over 16 weeks in adults at risk of type 2 diabetes.
The numbers and sources
- Effect
- In 194 adults at risk of type 2 diabetes, bread enriched to 6 g of oat beta-glucan a day for 16 weeks did not change HbA1c compared with whole-grain wheat bread (difference -0.01%, 95% CI -0.03 to 0.06). Fasting glucose, insulin and LDL cholesterol (-0.11 mmol/L, 95% CI -0.27 to 0.05) did not differ either [6].
- Population
- Adults aged about 58 with a mean BMI of 32 in Germany, Norway and Sweden [6].
- Sources
- [6]
- Caveats
- One trial, run as an effectiveness trial in real-life conditions, against whole-grain wheat bread, not a fiber-free control [6].
How it compares with the reference method
Matched the reference method1
Variation from one test to the next
Limited evidence: guideline reviews put within-person variation of HbA1c below 2%, against 12 to 15% for fasting glucose.
The numbers and sources
- Compared with
- Repeat measurement in the same person, and fasting plasma glucose
- Effect
- An international committee reported day-to-day within-person variance of under 2% for HbA1c against 12 to 15% for fasting plasma glucose [2]. A laboratory guideline describes intraindividual variation in healthy people as very small, under 2%, and sets imprecision goals of under 1.5% within a laboratory and under 2.5% between laboratories [6].
- Population
- Figures quoted by two guideline documents from earlier studies, whose sizes they do not give [2][6].
- Sources
- [2], [6]
- Caveats
- Secondhand figures from guideline text, not a primary study. A federal health institute gives a wider practical range for a single result, 6.4 to 7.2% for a reported 6.8% [4].
Mixed results2
Home test kits against a venous laboratory draw
Mixed results: one study found three home HbA1c tests within 5% of a laboratory result in 82%, 46% and 29% of samples, all short of the 90% accuracy goal.
The numbers and sources
- Compared with
- Paired venous samples measured at central reference laboratories
- Effect
- Among three home-use capillary tests, results fell within 5% of the paired reference value for 82% of Home Access samples, 46% of A1cNow+ samples and 29% of CoreMedica samples, and differed by more than 0.5 percentage points for 8%, 37% and 55%. None met the National Glycohemoglobin Standardization Program goal of at least 90% within 5% [20]. In a separate trial, 97.7% of capillary kit samples analyzed at a central laboratory were within 5% of the paired venous result (R squared 0.95) [21].
- Population
- 219 people aged 4 to 80 with type 1 or type 2 diabetes at four clinical sites [20]. 773 paired samples from 258 trial participants [21].
- Sources
- [20], [21]
- Caveats
- Both studies enrolled people with diabetes. The capillary kits in the second study were mailed to one research laboratory, which differs from a device that reads the result at home [21].
Point-of-care devices against laboratory methods
Mixed results: a meta-analysis of 13 point-of-care devices found nine read lower than the laboratory on average, three significantly, with wide variation within each device.
The numbers and sources
- Compared with
- Laboratory HbA1c methods
- Effect
- A meta-analysis of 61 studies covering 13 point-of-care devices found nine had a negative mean bias against laboratory methods, significant for three, with substantial variability in bias within devices. Bias did not differ between clinical and laboratory operators for the two devices where that was tested [22]. The American Diabetes Association limits point-of-care testing for screening and diagnosis to devices approved for diagnosis [3].
- Population
- 61 studies comparing point-of-care devices with laboratory methods [22].
- Sources
- [22], [3]
- Caveats
- The abstract names the devices and gives no bias figures. The searches ran to June 2015, so newer devices are not covered [22].
Did not match the reference method2
Agreement with the oral glucose tolerance test
Shown to miss about half of diabetes found by a glucose tolerance test at the 6.5% cut point, while rarely flagging people without it.
The numbers and sources
- Compared with
- 75 gram oral glucose tolerance test
- Effect
- In a meta-analysis of 17 studies of previously undiagnosed adults, venous HbA1c at 6.5% had a pooled sensitivity of 50% (95% CI 42 to 59) and specificity of 97.3% (95% CI 95.3 to 98.4) for diabetes. The authors estimated that a cut point of 6.03% balanced the two, with sensitivity 73.9% and specificity 87.2%. The authors concluded that at 6.5% the test is more specific and less sensitive [17].
- Population
- 17 studies of HbA1c at 6.5%, within a review of 37 articles on screening tests in community settings [17].
- Sources
- [17]
- Caveats
- The two tests measure different things. An international committee noted that the 2-hour glucose value reproduces less well on repeat testing than fasting glucose, and chose 6.5% for HbA1c to favor specificity [2].
Conditions that shift the result apart from blood glucose
Shown to read higher than glucose predicts in iron deficiency, and about 0.4 points higher in black than white people with type 1 diabetes at the same mean glucose.
The numbers and sources
- Compared with
- Blood glucose measures, including mean glucose from continuous glucose monitoring
- Effect
- A systematic review of 12 studies in adults without diabetes found that iron deficiency, with or without anemia, raised HbA1c against controls with no matching rise in glucose, and that other forms of anemia may lower it [18]. In people with type 1 diabetes wearing glucose monitors for 12 weeks, mean HbA1c was 0.4 percentage points higher in black than in white participants for a given mean glucose (95% CI 0.2 to 0.6) [19]. Guideline bodies and a federal health institute also list some hemoglobin variants, hemolytic anemia, major blood loss, transfusion, erythropoietin treatment and hemodialysis as conditions that alter results [2][3][4].
- Population
- 12 studies of non-pregnant adults not known to have diabetes [18]. 104 black and 104 white people aged 8 or older with type 1 diabetes and HbA1c of 6.0 to 12.0% [19].
- Sources
- [18], [19], [2], [3], [4]
- Caveats
- The review's authors call for more evidence on which types and degrees of anemia matter [18]. The racial comparison had too few participants below 6.5% to apply to that range, and race explained only part of the difference [19]. The American Diabetes Association cautions against using race or ancestry as a proxy for poorly understood genetic differences [3].
What studies tie it to
Linked in research4
Developing diabetes
Linked to future diabetes in a graded way: 25 to 50% of people at 6.0 to 6.5% developed diabetes within 5 years.
The numbers and sources
- Effect
- A systematic review of 16 studies found annualized diabetes incidence ranged from 0.1% at HbA1c below 5.0% to 54.1% at 6.1% or above. Five-year incidence was under 9% at 5.0 to 5.5%, 9 to 25% at 5.5 to 6.0% and 25 to 50% at 6.0 to 6.5% [7]. In US adults without diabetes, hazard ratios for diagnosed diabetes against a reference of 5.0 to under 5.5% were 0.52 (95% CI 0.40 to 0.69) below 5.0%, 1.86 (1.67 to 2.08) at 5.5 to under 6.0%, 4.48 (3.92 to 5.13) at 6.0 to under 6.5% and 16.47 (14.22 to 19.08) at 6.5% or greater [8].
- Population
- 16 prospective studies [7]. 11,092 black or white adults without diabetes or cardiovascular disease in the Atherosclerosis Risk in Communities study [8].
- Sources
- [7], [8]
- Caveats
- Observational. Risk rose steeply across the whole range from 5.0 to 6.5%, not from a single level [7].
Heart disease and stroke in people without diabetes
Linked to more coronary heart disease from 5.5% upward in adults without diabetes, though adding HbA1c to standard risk factors barely improved risk prediction.
The numbers and sources
- Effect
- In US adults without diabetes, hazard ratios for coronary heart disease against 5.0 to under 5.5% were 1.23 (95% CI 1.07 to 1.41) at 5.5 to under 6.0%, 1.78 (1.48 to 2.15) at 6.0 to under 6.5% and 1.95 (1.53 to 2.48) at 6.5% or greater, with similar results for stroke [8]. Across 73 prospective studies, the association with cardiovascular disease was approximately J-shaped. Adding HbA1c to conventional risk factors changed the C-index by 0.0018 (95% CI 0.0003 to 0.0033) and gave a net reclassification improvement of 0.42 (-0.63 to 1.48), which the authors called little incremental benefit [9].
- Population
- 11,092 adults [8]. 294,998 participants without known diabetes or cardiovascular disease in 73 studies, median follow-up 9.9 years, 20,840 cardiovascular events [9].
- Sources
- [8], [9]
- Caveats
- Observational. The association weakened somewhat after adjustment for HDL cholesterol and C-reactive protein [9].
Death from any cause
Linked to more deaths at both ends: above 6.0% and below 5.0% in people without diabetes, and above 9.0% and below 6.0% in people with diabetes.
The numbers and sources
- Effect
- A meta-analysis of observational studies found higher death rates from any cause in people without diabetes at HbA1c above 6.0% (HR 1.74, 95% CI 1.38 to 2.20) and below 5.0% (HR 1.19, 95% CI 1.04 to 1.36). In people with diabetes, rates were higher above 9.0% (HR 1.69, 95% CI 1.09 to 2.66) and below 6.0% (HR 1.57, 95% CI 1.14 to 2.17). Results for cardiovascular death were similar [10]. A US cohort of adults without diabetes also found a J-shaped association with death from any cause [8].
- Population
- 46 observational studies in the meta-analysis, of 74 reviewed [10]. 11,092 adults [8].
- Sources
- [10], [8]
- Caveats
- Observational. The excess at low values may reflect illness or conditions that lower HbA1c, not an effect of low blood sugar itself, and the studies cannot separate the two.
Eye, kidney and nerve complications of diabetes
Shown in trials: intensive glucose control that lowered HbA1c about 0.9 points cut kidney events 20% and eye events 13% in type 2 diabetes.
The numbers and sources
- Effect
- In an individual-participant meta-analysis of 4 trials in type 2 diabetes, more intensive control left HbA1c 0.90 percentage points lower (95% CI 0.58 to 1.22) and reduced kidney events (HR 0.80, 95% CI 0.72 to 0.88) and eye events (HR 0.87, 95% CI 0.76 to 1.00), with no reduction in nerve events (HR 0.98, 95% CI 0.87 to 1.09) [11]. In type 1 diabetes, intensive therapy reduced the development of retinopathy by 76% (95% CI 62 to 85) and clinical neuropathy by 60% (95% CI 38 to 74) [12]. In an observational analysis of people with type 2 diabetes, each 1% lower updated mean HbA1c went with 37% fewer microvascular complications (95% CI 33 to 41), with no threshold [13]. In pooled data from nine studies, diabetes-specific retinopathy was rare below 6.0% and its threshold fell at 6.3 to 6.7% [14].
- Population
- 27,049 adults with type 2 diabetes in 4 trials, median follow-up 5.0 years [11]. 1,441 people with type 1 diabetes followed a mean 6.5 years [12]. 3,642 people with type 2 diabetes [13]. 28,010 people with HbA1c and retinal photographs [14].
- Sources
- [11], [12], [13], [14]
- Caveats
- The trials tested treatment strategies, not HbA1c itself. Intensive therapy raised severe hypoglycemia two to threefold in the type 1 diabetes trial [12].
Mixed results1
Heart attack and death in trials that lowered HbA1c in type 2 diabetes
Mixed results: pooled trials of intensive glucose lowering found 9% fewer major cardiovascular events and no fewer deaths, and one trial aiming below 6.0% found more deaths.
The numbers and sources
- Effect
- A prospectively planned meta-analysis found that more intensive glucose control reduced major cardiovascular events by 9% (HR 0.91, 95% CI 0.84 to 0.99) and heart attack by 15% (HR 0.85, 95% CI 0.76 to 0.94). Death from any cause (HR 1.04, 95% CI 0.90 to 1.20) and cardiovascular death (HR 1.10, 95% CI 0.84 to 1.42) were not reduced, and major hypoglycemia rose (HR 2.48, 95% CI 1.91 to 3.21) [15]. In one of the pooled trials, a strategy targeting HbA1c below 6.0% reached a median of 6.4% against 7.5% with standard therapy. Deaths were higher in the intensive group (257 against 203, HR 1.22, 95% CI 1.01 to 1.46), and the intensive strategy was stopped after a mean 3.5 years [16].
- Population
- 27,049 participants with type 2 diabetes and 2,370 major vascular events over 4.4 years [15]. 10,251 patients, mean age 62, with cardiovascular disease or risk factors and a median HbA1c of 8.1% [16].
- Sources
- [15], [16]
- Caveats
- A marker that tracks risk is not always one whose lowering reduces it. These trials used the drugs and insulin regimens of their time in older, high-risk people with long-standing diabetes, and do not describe people without diabetes.
Sources
- US Food and Drug Administration. 21 CFR 862.1373, Hemoglobin A1c test system, and 21 CFR 864.7470, Glycosylated hemoglobin assay. Electronic Code of Federal Regulations, with the FDA product classification entries for hemoglobin A1c test systems (product code PDJ) and over-the-counter glycosylated hemoglobin tests (product code NGB). https://www.ecfr.gov/current/title-21/section-862.1373
- International Expert Committee. International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care. 2009. https://doi.org/10.2337/dc09-9033
- American Diabetes Association Professional Practice Committee for Diabetes. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2026. Diabetes Care. 2026. https://doi.org/10.2337/dc26-S002
- National Institute of Diabetes and Digestive and Kidney Diseases. The A1C Test and Diabetes. US National Institutes of Health. Last reviewed April 2018. https://www.niddk.nih.gov/health-information/diagnostic-tests/a1c-test
- World Health Organization. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. WHO/NMH/CHP/CPM/11.1. Geneva: World Health Organization, 2011. https://www.who.int/publications/i/item/use-of-glycated-haemoglobin-(-hba1c)-in-diagnosis-of-diabetes-mellitus
- Sacks DB, Arnold M, Bakris GL, et al. Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Diabetes Care. 2023. https://doi.org/10.2337/dci23-0036
- Zhang X, Gregg EW, Williamson DF, et al. A1C Level and Future Risk of Diabetes: A Systematic Review. Diabetes Care. 2010. https://doi.org/10.2337/dc09-1939
- Selvin E, Steffes MW, Zhu H, et al. Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults. New England Journal of Medicine. 2010. https://doi.org/10.1056/NEJMoa0908359
- Emerging Risk Factors Collaboration. Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease. JAMA. 2014. https://doi.org/10.1001/jama.2014.1873
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