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Research · Medication

Phentermine

Phentermine-topiramate produced about 8 to 9 kg more weight loss than placebo at one year, the largest of the older obesity drugs in two network meta-analyses. Phentermine alone was tested in short trials. Tingling, altered taste, dry mouth and attention problems rose. Heart rate rose. Topiramate in pregnancy raises the risk of oral clefts.

Add to Bio HackChecked 2026-11-09
Status
Prescription drug in the US and a Schedule IV controlled substance. Phentermine alone is FDA-approved as a short-term (a few weeks) adjunct to diet and exercise for obesity. Phentermine-topiramate extended release (Qsymia) is FDA-approved for chronic weight management and is dispensed under a REMS program because of birth defect risk.
Also called
Adipex-P, Lomaira, phentermine hydrochloride, phentermine-topiramate, phentermine/topiramate, Qsymia, PHEN/TPM
Taken for
weight loss, appetite suppression, fat loss, energy

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

Shown to help3

Reported risks5

What people take it for, and what was found

Shown to help3

StrongVery common

Weight loss with phentermine-topiramate

Shown to cut about 8 to 9 kg more weight than placebo over a year with phentermine-topiramate, rising with dose, alongside lifestyle programs.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
At 56 weeks, weight changed by -1.4 kg on placebo, -8.1 kg on 7.5/46 mg and -10.2 kg on 15/92 mg. A loss of at least 5% occurred in 21%, 62% and 70%, and a loss of at least 10% in 7%, 37% and 48% [1]. Across obesity drug trials of at least a year, phentermine-topiramate produced 8.8 kg (95% CrI 7.42 to 10.20) more loss than placebo, the largest of the five drugs compared [2]. A second network meta-analysis found 7.98 percentage points (95% CI 6.69 to 9.27) more loss than lifestyle change alone [3]. A meta-analysis of phentermine-topiramate trials found 7.73 kg (95% CI 6.60 to 8.85) more loss than placebo, rising with dose from 3.55 kg at 3.75/23 mg to 8.25 kg at 15/92 mg [4].
Population
2,487 adults with BMI 27 to 45 and two or more weight-related conditions [1]; 28 RCTs with 29,018 adults [2]; 132 RCTs with 48,209 adults [3]; RCTs of phentermine-topiramate to April 2020 [4].
Sources
[1], [2], [3], [4]
Caveats
CONQUER was funded by Vivus, the maker [1]. Trials paired the drug with lifestyle programs. Attrition across obesity drug trials ran 30 to 45% [2]. Neither network meta-analysis included semaglutide 2.4 mg in its main ranking, and [3] reports semaglutide separately as larger.
Limited

Weight held at two years on phentermine-topiramate

One extension trial found weight held about 9 to 10.5% below baseline at 2 years on phentermine-topiramate, against 1.8% on placebo.

The numbers and sources
Effect
At week 108, weight changed from baseline by -1.8% on placebo, -9.3% on 7.5/46 mg and -10.5% on 15/92 mg. Incident diabetes was lower on treatment than placebo. Adverse event rates were lower in weeks 56 to 108 than in weeks 0 to 56 [5].
Population
676 of 866 eligible CONQUER participants who chose to continue, 84% completing [5].
Sources
[5]
Caveats
One extension trial at selected sites, with participants who chose to continue. Last observation carried forward.
Limited

Weight loss with phentermine alone

One 12-week trial found 8.1 kg lost on phentermine against 1.7 kg on placebo. No year-long review of phentermine alone was sourced.

The numbers and sources
Effect
Over 12 weeks, people on phentermine 30 mg lost 8.1 kg and people on placebo 1.7 kg. A loss of 5% or more occurred in 95.8% and 20.8%. Blood pressure did not differ between groups [6]. In health records, people who used phentermine continuously for more than 12 months had lost 7.4% more weight at 24 months than people who used it for 3 months or less [7].
Population
74 Korean adults with obesity and controlled diabetes, hypertension or dyslipidemia [6]; 13,972 adults with a first phentermine fill, 84% women [7].
Sources
[6], [7]
Caveats
[6] is a small 12-week trial. [7] is observational, and duration of use was not randomized. No meta-analysis of phentermine alone over a year or more was sourced.

Doses studied

CONQUER and SEQUEL used once-daily oral phentermine 7.5 mg plus topiramate 46 mg, or phentermine 15 mg plus topiramate 92 mg [1][5]. The phentermine-topiramate meta-analysis also included 3.75/23 mg arms [4]. The phentermine-alone trial used 30 mg once daily in a controlled-release form [6].

Risks

Reported risks5

StrongVery common

Tingling, altered taste, dry mouth and attention problems

Shown to raise tingling, altered taste and dry mouth on phentermine-topiramate, each in about 10 to 21% at the top dose against 1 to 2% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In CONQUER, dry mouth occurred in 2%, 13% and 21% on placebo, 7.5/46 mg and 15/92 mg. Paresthesia (tingling) occurred in 2%, 14% and 21%, altered taste in 1%, 7% and 10%, and insomnia in 5%, 6% and 10% [1]. Pooled against placebo, odds were 8.86 for altered taste, 8.51 for paresthesia, 6.71 for dry mouth, 4.48 for disturbance in attention and 4.10 for irritability [4]. Odds of stopping for adverse events were 2.40 (95% CI 1.68 to 3.44) times those on lifestyle change alone [3].
Population
Trial participants in [1], [3] and [4].
Sources
[1], [3], [4]
Caveats
Most of these effects are attributed to the topiramate component.
LimitedVery common

Faster heart rate and cardiovascular events

Limited evidence: Qsymia raised average heart rate about 3.6 bpm, while observational data did not find more major cardiovascular events.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In an 8-week ambulatory study, Qsymia raised 24-hour average heart rate by 3.6 bpm (95% CI 2.1 to 5.2) against placebo. In trials up to one year, a rise of more than 10 bpm at a single visit occurred in 42.1% on placebo and 56.1% on 15/92 mg [8]. In insurance claims, the rate of major cardiovascular events during current use against unexposed former use was 0.57 (95% CI 0.19 to 1.78) for phentermine plus topiramate and 0.56 (95% CI 0.34 to 0.91) for phentermine alone [9]. In health records, cardiovascular disease or death occurred in 0.3% (41 events), with no difference by length of phentermine use [7].
Population
Qsymia trial participants [8]; US MarketScan claims [9]; 13,972 phentermine users [7].
Sources
[8], [9], [7]
Caveats
[9] and [7] are observational with few events and wide intervals. [9] was funded by Vivus. No cardiovascular outcome trial of phentermine or phentermine-topiramate was sourced.
LimitedCommon

Depression and anxiety

One trial found depression and anxiety events rose at the top dose, 7% and 8% against 4% and 3% on placebo. The label warns of mood disorders.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Depression-related adverse events occurred in 4% on placebo, 4% on 7.5/46 mg and 7% on 15/92 mg. Anxiety-related events occurred in 3%, 5% and 8% [1]. The Qsymia label carries warnings on suicidal behavior and ideation and on mood and sleep disorders [8].
Population
2,487 adults [1]; label [8].
Sources
[1], [8]
Caveats
One trial reports these rates by arm.
LimitedStudied in pregnancyHow often is not known

Birth defects from topiramate

The label states first-trimester topiramate exposure raises the risk of major birth defects, including cleft lip and palate, and requires pregnancy testing.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The Qsymia label states that first-trimester topiramate exposure increases the risk of major congenital malformations, including cleft lip and cleft palate, and of being small for gestational age, based on pregnancy registries and epidemiologic studies. Qsymia is available only through a REMS program, and the label calls for a negative pregnancy test before starting and monthly during use [8].
Population
Pregnancy registries and epidemiologic studies of topiramate, summarized in the label [8].
Sources
[8]
Caveats
The underlying registry data are summarized in the label, not reported here study by study.
LimitedHow often is not known

Abuse potential, tolerance, and heart and lung warnings

The label classifies phentermine as a Schedule IV controlled substance and states tolerance to the appetite effect usually develops within a few weeks.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The phentermine label classifies it as a Schedule IV controlled substance related to the amphetamines. It states that tolerance to the appetite effect usually develops within a few weeks. It lists rare reported cases of primary pulmonary hypertension and of serious regurgitant heart valve disease. The valve cases were reported with phentermine combined with fenfluramine or dexfenfluramine, and the label states the role of phentermine itself has not been established [10].
Population
Postmarketing reports and pharmacology summarized in the label [10].
Sources
[10]
Caveats
These are label statements and case reports, not trial rates.

Sources

  1. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. The Lancet. 2011. https://doi.org/10.1016/S0140-6736(11)60205-5
  2. Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events. JAMA. 2016. https://doi.org/10.1001/jama.2016.7602
  3. Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. The Lancet. 2024. https://doi.org/10.1016/S0140-6736(24)00351-9
  4. Lei X, Ruan J, Lai C, et al. Efficacy and Safety of Phentermine/Topiramate in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis. Obesity. 2021. https://doi.org/10.1002/oby.23152
  5. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. The American Journal of Clinical Nutrition. 2012. https://doi.org/10.3945/ajcn.111.024927
  6. Kang JG, Park C, Kang JH, et al. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes, Obesity and Metabolism. 2010. https://doi.org/10.1111/j.1463-1326.2010.01242.x
  7. Lewis KH, Fischer H, Ard J, et al. Safety and Effectiveness of Longer-Term Phentermine Use: Clinical Outcomes from an Electronic Health Record Cohort. Obesity. 2019. https://doi.org/10.1002/oby.22430
  8. U.S. Food and Drug Administration. QSYMIA (phentermine and topiramate extended-release capsules), prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40dd5602-53da-45ac-bb4b-15789aba40f9
  9. Ritchey ME, Harding A, Hunter S, et al. Cardiovascular Safety During and After Use of Phentermine and Topiramate. The Journal of Clinical Endocrinology & Metabolism. 2018. https://doi.org/10.1210/jc.2018-01010
  10. U.S. Food and Drug Administration. Phentermine hydrochloride tablets, prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02b8f684-b1ca-4ab7-9567-bcacc6a92779

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