Phentermine

updated

Phentermine is an FDA-approved short-term adjunct for weight reduction in exogenous obesity (generic label, initial U.S. approval 1959), and it is a Schedule IV drug related to the amphetamines. The label's own trial summary calls the added weight loss over placebo only a fraction of a pound a week, the one placebo-controlled phentermine-alone trial found enrolled 68 adults, and modern phase 3 data exist only for the phentermine and topiramate combination (CONQUER, 2,487 adults). The label warns of rare pulmonary hypertension, rare valvular disease, and abuse and dependence, and the 24-month LEAP trial (870 adults) has no results yet.

Appetite suppressant, chemically and pharmacologically related to the amphetamines

  • The generic label indicates phentermine as a short-term (a few weeks) adjunct in exogenous obesity for a BMI of 30 or more, or 27 or more with risk factors, and gives an initial U.S. approval year of 1959.
  • The label's clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks.
  • In 68 obese Korean adults, weight fell by 6.7 +/- 2.5 kg (P < 0.001), and dry mouth and insomnia were the only adverse events significantly more common on phentermine.
  • LEAP (870 adults, 24 months) is active, not recruiting, with no posted results, and its design paper says long-term efficacy and safety have never been tested in a randomized trial.
  • In CONQUER (2,487 adults, 56 weeks), phentermine plus topiramate cut weight by 7.8% and 9.8% versus 1.2% on placebo.
  • The label contraindicates cardiovascular disease and warns of rare primary pulmonary hypertension, rare valvular disease, tolerance, and abuse and dependence; phentermine is Schedule IV.

What is phentermine approved to do?

The generic phentermine label (initial U.S. approval 1959) indicates it as a short-term adjunct to a weight-reduction regimen in exogenous obesity, for a BMI of 30 or more, or 27 or more with risk factors. Phentermine is a Schedule IV drug.

The generic phentermine hydrochloride 37.5 mg tablet label (version effective 10 June 2026) indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. It states that phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines.

The label gives an initial U.S. approval year of 1959, but the original 1959 application was not found in openFDA. In the openFDA Drugs@FDA records, ADIPEX-P tablets (Teva) are ANDA 085128, approved 22 October 1980, and ADIPEX-P capsules (Teva, now discontinued) are ANDA 088023, approved 2 August 1983. Among the 21 applications whose generic name includes phentermine, the earliest original approval date is ANDA 083923 (Chartwell, 1 July 1976). LOMAIRA, an 8 mg phentermine hydrochloride tablet, is ANDA 203495, approved 12 September 2016, and its label (version effective 19 December 2023) states it is not recommended for patients 16 years old or younger. The combination product QSYMIA, which adds topiramate, is NDA 022580, approved 17 July 2012.

Phentermine free base is C10H15N (149.23 g/mol, CAS 122-09-8, PubChem CID 4771). The tablets contain phentermine hydrochloride (C10H16ClN, 185.69 g/mol, CAS 1197-21-3, CID 70969), and label strengths are in the hydrochloride, so 37.5 mg of phentermine hydrochloride equals 30 mg of phentermine base. LOMAIRA's 8 mg tablet is equivalent to 6.4 mg of phentermine base.

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source
Drugs@FDA: phentermine applications from 1976 to 2016; QSYMIA approved 17 July 2012

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application records for ANDA 085128 (ADIPEX-P tablets), ANDA 088023 (ADIPEX-P capsules), ANDA 083923, ANDA 203495 (LOMAIRA) and NDA 022580 (QSYMIA). Dates read from the openFDA Drugs@FDA records.

The generic label gives an initial U.S. approval year of 1959. In the openFDA Drugs@FDA records, ADIPEX-P tablets (Teva) are ANDA 085128, approved 22 October 1980; ADIPEX-P capsules (Teva, now discontinued) are ANDA 088023, approved 2 August 1983; among the 21 applications whose generic name includes phentermine, the earliest original approval date is ANDA 083923 (Chartwell, 1 July 1976); LOMAIRA is ANDA 203495, approved 12 September 2016; and the combination QSYMIA is NDA 022580, approved 17 July 2012. The original 1959 application itself was not found in openFDA.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Applications from 1976 to 2016
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels, and the 1959 original application was not found.

Read the original source
LOMAIRA label, version effective 19 December 2023: 8 mg tablet, not for ages 16 and under

FDA prescribing information

DailyMed, U.S. National Library of Medicine. LOMAIRA (phentermine hydrochloride) 8 mg oral tablets, prescribing information, label version effective 19 December 2023. Set ID cde9fb09-e5af-434d-8874-e4f9f974d893.

LOMAIRA is an 8 mg phentermine hydrochloride tablet (equivalent to 6.4 mg phentermine base). Its label states it is not recommended for patients 16 years old or younger, and its patient counseling section lists primary pulmonary hypertension and serious valvular heart disease among the risks.

Participants / model
Adults with obesity
Treatment
LOMAIRA 8 mg oral tablets
Follow-up
Label version effective 19 December 2023
Study design
FDA prescribing information
Funding
not stated in the source

A second phentermine hydrochloride product with a different tablet strength.

Read the original source
PubChem: phentermine and phentermine hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 4771 (phentermine) and CID 70969 (phentermine hydrochloride).

Phentermine free base: PubChem CID 4771, C10H15N, 149.23 g/mol, CAS 122-09-8. Phentermine hydrochloride, the salt in the tablets: CID 70969, C10H16ClN, 185.69 g/mol, CAS 1197-21-3. Label doses are in the hydrochloride, so 37.5 mg of phentermine hydrochloride equals 30 mg of phentermine base.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the weight-loss studies find?

The label's own trial summary says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks. In a placebo-controlled trial in 68 obese Korean adults, weight fell by 6.7 +/- 2.5 kg and more people reached 5% and 10% weight loss on phentermine, and dry mouth and insomnia were the only adverse events significantly more common.

The clinical studies section of the generic label says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

A randomized double-blind placebo-controlled trial in 68 relatively healthy obese Korean adults in Seoul (BMI 25 kg/m2 or more) gave phentermine or placebo with behavioral therapy. Weight fell by 6.7 +/- 2.5 kg (P < 0.001) and waist circumference by 6.2 +/- 3.5 cm (P < 0.001), and more people reached 5% and 10% weight loss on phentermine. Blood pressure did not differ (systolic P = 0.122), and dry mouth and insomnia were the only adverse events significantly more common. The placebo-group change is not given in the figures used here, and the abstract does not state the trial length beyond calling it short-term.

This is the one placebo-controlled trial of phentermine alone found here, so the monotherapy efficacy numbers rest on it and on the label's qualitative statement. The 1959 original application and any originator trial data were not found.

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source
68 obese Korean adults: weight fell 6.7 kg, dry mouth and insomnia the adverse events

Randomized controlled trial

Kim KK et al. Yonsei Med J. 2006;47(5):614-25. PMID 17066505.

Weight fell by 6.7 +/- 2.5 kg (P < 0.001) and waist circumference by 6.2 +/- 3.5 cm (P < 0.001), with more people reaching 5% and 10% weight loss on phentermine. Blood pressure did not differ (systolic P = 0.122), and dry mouth and insomnia were the only adverse events significantly more common. The placebo-group change is not given in the figures used here.

Participants / model
68 relatively healthy obese Korean adults (BMI 25 kg/m2 or more) in Seoul
Treatment
Oral phentermine or placebo, with behavioral therapy
Follow-up
Short-term; length not stated in the abstract
Study design
Randomized double-blind placebo-controlled trial
Funding
not stated in the source

The one placebo-controlled trial of phentermine alone found here. Endpoints were body weight, waist circumference, blood pressure and adverse events.

Read the original source

Has long-term phentermine use been tested in a randomized study?

Not with results. The LEAP design paper says long-term efficacy and safety of phentermine have never been evaluated in a randomized trial, and LEAP (870 adults, 24 months) has no posted results. An observational cohort of 13,972 adults found more weight loss at 24 months with continuous use for more than 12 months, but it compares users with other users.

The LEAP design paper states that phentermine's long-term efficacy and safety have never been evaluated in a randomized trial, because its approval predates such requirements. LEAP randomized 870 adults with BMI 27 to 44.9 kg/m2 to phentermine 24 mg daily or placebo for 24 months, with an online lifestyle program for all. The primary outcomes are 24-month percent weight loss, systolic blood pressure change and adverse events. The registry (NCT05176626) lists the trial as active, not recruiting, with no posted results, so no result exists yet.

An electronic health record cohort of 13,972 adults (84% female, mean BMI 37.8 kg/m2) who filled phentermine between 2010 and 2015 found that people using it continuously for more than 12 months lost 7.4% more weight than the group using it for 3 months or less at 24 months (P < 0.001). The composite of cardiovascular disease or death was rare (0.3%, 41 events), with no significant difference between duration groups. The authors note the observational design and say it supports longer-term use for low-risk individuals.

The cohort is not a placebo-controlled result, and the label limits use to a few weeks. The cohort shows how the drug is used, not that long-term use is tested or safe.

LEAP design paper: 870 adults, 24 months, no posted results

Trial registry record

Young CB et al. Contemp Clin Trials. 2026;161:108219. PMID 41519431.

The design paper states that phentermine's long-term efficacy and safety have never been evaluated in a randomized trial, because its approval predates such requirements. LEAP randomized 870 adults with BMI 27 to 44.9 kg/m2 to phentermine 24 mg daily or placebo for 24 months, with an online lifestyle program for all. The primary outcomes are 24-month percent weight loss, systolic blood pressure change and adverse events. The registry (NCT05176626) lists the trial as active, not recruiting, with no posted results, so no result exists yet.

Participants / model
870 adults with overweight or obesity (design and baseline paper)
Treatment
Oral phentermine 24 mg daily or placebo, with an online lifestyle program
Follow-up
24 months
Study design
Trial design paper and registry record
Funding
not stated in the source

A design paper and registry entry with no posted results. It reports no efficacy or safety outcome.

Read the original source
13,972 adults: 7.4% more weight loss with more than 12 months of continuous use, observational

Human study

Lewis KH et al. Obesity (Silver Spring). 2019;27(4):591-602. PMID 30900410.

People using phentermine continuously for more than 12 months lost 7.4% more weight than the group using it for 3 months or less at 24 months (P < 0.001). The composite of cardiovascular disease or death was rare (0.3%, 41 events), with no significant difference between duration groups. The authors note the observational design and say it supports longer-term use for low-risk individuals.

Participants / model
13,972 adults (84% female, mean BMI 37.8 kg/m2) with a first phentermine fill between 2010 and 2015
Treatment
Oral phentermine, usual outpatient use
Follow-up
Percent weight loss at 6, 12 and 24 months
Study design
Electronic health record observational cohort
Funding
not stated in the source

Not a placebo-controlled result: it compares users with other users. Endpoints were percent weight loss at 6, 12 and 24 months and a composite of cardiovascular disease or death.

Read the original source
Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source

Does the phentermine and topiramate combination differ from phentermine alone?

Yes. QSYMIA (phentermine plus topiramate extended release) is a separate FDA-approved product with its own label, a REMS and embryo-fetal toxicity warnings, and it has the modern phase 3 data: in CONQUER (2,487 adults, 56 weeks), weight fell 7.8% and 9.8% on the two combinations versus 1.2% on placebo.

QSYMIA (NDA 022580, approved 17 July 2012) is indicated with a reduced-calorie diet and increased physical activity to reduce excess weight and maintain weight reduction in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight and at least one weight-related comorbidity. The effect on cardiovascular morbidity and mortality has not been established. The label version used here took effect on 22 April 2026, and the adolescent indication is label-level only.

CONQUER randomized 2,487 overweight or obese adults at 93 US centers (BMI 27 to 45 kg/m2, two or more comorbidities) to placebo or one of two phentermine plus topiramate controlled-release combinations for 56 weeks (NCT00553787). Weight change was -1.4 kg (-1.2%) on placebo and -8.1 kg (-7.8%) and -10.2 kg (-9.8%) on the two combinations (P < 0.0001), and at least 5% weight loss was reached by 21%, 62% and 70%.

A network meta-analysis of 28 randomized trials (29,018 patients, drugs given for at least 1 year) found phentermine/topiramate gave the most excess weight loss at 1 year (8.8 kg versus placebo, 95% credible interval -10.20 to -7.42), with 75% reaching at least 5% weight loss versus a median 23% on placebo (OR 9.22, 95% CrI 6.63 to 12.85). Attrition was 30 to 45% in all trials, which lowers confidence. Phentermine alone is not one of the drugs analyzed.

These results describe the combination, not phentermine alone, and they come with topiramate's fetal toxicity warnings.

QSYMIA label, version effective 22 April 2026: indication, REMS, embryo-fetal toxicity

FDA prescribing information

DailyMed, U.S. National Library of Medicine. QSYMIA (phentermine and topiramate extended-release) oral capsules, prescribing information, label version effective 22 April 2026. Set ID 40dd5602-53da-45ac-bb4b-15789aba40f9.

QSYMIA is indicated with a reduced-calorie diet and increased physical activity to reduce excess weight and maintain weight reduction in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight and at least one weight-related comorbidity. The effect on cardiovascular morbidity and mortality has not been established. The label warns of possible seizure if the highest dose is stopped abruptly. Warnings include embryo-fetal toxicity (topiramate exposure in the first trimester raises the risk of oral clefts, and a REMS program applies), suicidal behavior and ideation, and acute myopia with secondary angle-closure glaucoma.

Participants / model
Adults and adolescents 12 and older with obesity; adults with overweight and a comorbidity
Treatment
QSYMIA extended-release oral capsules
Follow-up
Label version effective 22 April 2026
Study design
FDA prescribing information
Funding
not stated in the source

A separate product from phentermine alone. The adolescent indication is label-level only.

Read the original source
CONQUER: 2,487 adults, 56 weeks, weight down 7.8% and 9.8% versus 1.2% on placebo

Randomized controlled trial

Gadde KM et al. Lancet. 2011;377(9774):1341-52. PMID 21481449.

Weight change was -1.4 kg (-1.2%) on placebo and -8.1 kg (-7.8%) and -10.2 kg (-9.8%) on the two combinations (P < 0.0001), and at least 5% weight loss was reached by 21%, 62% and 70%. Dry mouth (2%, 13%, 21%), paresthesia (2%, 14%, 21%), constipation and insomnia were the common adverse events.

Participants / model
2,487 randomized overweight or obese adults (BMI 27 to 45 kg/m2, two or more comorbidities) at 93 US centers
Treatment
Oral phentermine plus topiramate controlled release at two dose levels, or placebo
Follow-up
56 weeks
Study design
Randomized placebo-controlled trial (NCT00553787)
Funding
not stated in the source

This is the combination product, not phentermine alone. Endpoints were percent weight change and the proportion losing 5% or more.

Read the original source
Network meta-analysis: 28 trials, 29,018 patients, phentermine/topiramate 8.8 kg versus placebo

Systematic review and meta-analysis

Khera R et al. JAMA. 2016;315(22):2424-34. PMID 27299618.

Phentermine/topiramate gave the most excess weight loss at 1 year (8.8 kg versus placebo, 95% credible interval -10.20 to -7.42), with 75% reaching at least 5% weight loss versus a median 23% on placebo (OR 9.22, 95% CrI 6.63 to 12.85). Attrition was 30 to 45% in all trials, which lowers confidence. Phentermine alone is not one of the drugs analyzed.

Participants / model
29,018 patients with overweight or obesity in 28 randomized trials
Treatment
Oral orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate or liraglutide versus placebo
Follow-up
Drugs given for at least 1 year
Study design
Systematic review and network meta-analysis
Funding
not stated in the source

Phentermine alone was not analyzed. Endpoints were the proportion with 5% weight loss, weight change and discontinuation for adverse events.

Read the original source

Is phentermine an effective short-term weight-loss drug?

Within the label's limits, modestly. Phentermine is an FDA-approved short-term adjunct, and the label itself says the extra weight loss over placebo is only a fraction of a pound a week. Longer-term use has no randomized phentermine-alone result, and the combination product is a different drug.

Phentermine is described as an FDA-approved short-term appetite suppressant for weight loss. The label supports short-term use as an adjunct to diet, exercise and behavioral modification, which is the use being claimed.

The effect is modest. The label's own trial summary says the extra weight loss over placebo is only a fraction of a pound a week, and the one placebo-controlled trial of phentermine alone found here enrolled 68 adults. The stretch to longer-term use is not supported by randomized phentermine-alone data, and the stretch to the combination product is a different drug with its own label and warnings.

Products from unregulated sellers were not examined, so nothing on this page describes their content.

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source
68 obese Korean adults: weight fell 6.7 kg, dry mouth and insomnia the adverse events

Randomized controlled trial

Kim KK et al. Yonsei Med J. 2006;47(5):614-25. PMID 17066505.

Weight fell by 6.7 +/- 2.5 kg (P < 0.001) and waist circumference by 6.2 +/- 3.5 cm (P < 0.001), with more people reaching 5% and 10% weight loss on phentermine. Blood pressure did not differ (systolic P = 0.122), and dry mouth and insomnia were the only adverse events significantly more common. The placebo-group change is not given in the figures used here.

Participants / model
68 relatively healthy obese Korean adults (BMI 25 kg/m2 or more) in Seoul
Treatment
Oral phentermine or placebo, with behavioral therapy
Follow-up
Short-term; length not stated in the abstract
Study design
Randomized double-blind placebo-controlled trial
Funding
not stated in the source

The one placebo-controlled trial of phentermine alone found here. Endpoints were body weight, waist circumference, blood pressure and adverse events.

Read the original source
LEAP design paper: 870 adults, 24 months, no posted results

Trial registry record

Young CB et al. Contemp Clin Trials. 2026;161:108219. PMID 41519431.

The design paper states that phentermine's long-term efficacy and safety have never been evaluated in a randomized trial, because its approval predates such requirements. LEAP randomized 870 adults with BMI 27 to 44.9 kg/m2 to phentermine 24 mg daily or placebo for 24 months, with an online lifestyle program for all. The primary outcomes are 24-month percent weight loss, systolic blood pressure change and adverse events. The registry (NCT05176626) lists the trial as active, not recruiting, with no posted results, so no result exists yet.

Participants / model
870 adults with overweight or obesity (design and baseline paper)
Treatment
Oral phentermine 24 mg daily or placebo, with an online lifestyle program
Follow-up
24 months
Study design
Trial design paper and registry record
Funding
not stated in the source

A design paper and registry entry with no posted results. It reports no efficacy or safety outcome.

Read the original source
QSYMIA label, version effective 22 April 2026: indication, REMS, embryo-fetal toxicity

FDA prescribing information

DailyMed, U.S. National Library of Medicine. QSYMIA (phentermine and topiramate extended-release) oral capsules, prescribing information, label version effective 22 April 2026. Set ID 40dd5602-53da-45ac-bb4b-15789aba40f9.

QSYMIA is indicated with a reduced-calorie diet and increased physical activity to reduce excess weight and maintain weight reduction in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight and at least one weight-related comorbidity. The effect on cardiovascular morbidity and mortality has not been established. The label warns of possible seizure if the highest dose is stopped abruptly. Warnings include embryo-fetal toxicity (topiramate exposure in the first trimester raises the risk of oral clefts, and a REMS program applies), suicidal behavior and ideation, and acute myopia with secondary angle-closure glaucoma.

Participants / model
Adults and adolescents 12 and older with obesity; adults with overweight and a comorbidity
Treatment
QSYMIA extended-release oral capsules
Follow-up
Label version effective 22 April 2026
Study design
FDA prescribing information
Funding
not stated in the source

A separate product from phentermine alone. The adolescent indication is label-level only.

Read the original source

How does phentermine work, and what does the body do with it?

The label describes phentermine as chemically and pharmacologically related to the amphetamines and places it in Schedule IV. The sources reviewed give no receptor-level mechanism, and the label gives a peak concentration 3 to 4.4 hours after a dose with no half-life.

The generic label states that phentermine is chemically and pharmacologically related to the amphetamines and is a Schedule IV drug. The appetite-suppressant description is how the drug is promoted. The sources reviewed do not describe its receptor-level mechanism, so none is stated here.

The label gives peak concentration 3 to 4.4 hours after a dose. No half-life, clearance or bioavailability figure appears in the sources reviewed, and the label reports that tolerance can develop within a few weeks.

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source

What risks do the labels and reports describe?

The phentermine label contraindicates a history of cardiovascular disease, MAO inhibitor use, hyperthyroidism, glaucoma, agitated states, a history of drug abuse, and pregnancy or nursing. It warns of rare primary pulmonary hypertension, rare serious valvular disease, tolerance, and abuse and dependence, and the combination product adds embryo-fetal toxicity with a REMS.

The generic label's contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, a history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (the label says a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV. The LOMAIRA label lists primary pulmonary hypertension and serious valvular heart disease among the risks in its patient counseling section.

In 1997, a Mayo Clinic case series described valvular heart disease in 24 previously healthy women treated with fenfluramine plus phentermine, 12.3 +/- 7.1 months after starting; 8 also had newly documented pulmonary hypertension and 5 needed cardiac surgery. The valves had a plaque-like appearance identical to carcinoid or ergotamine valve disease. This concerns the drug pair, not phentermine alone, and matches the label's valve warning, which describes the same combination.

In the 68-adult Korean trial, dry mouth and insomnia were the only adverse events significantly more common on phentermine, and blood pressure did not differ. In the 13,972-adult cohort, the composite of cardiovascular disease or death was rare (0.3%, 41 events) with no significant difference between duration groups, but that comparison was observational. The label-level warnings for phentermine alone are not tested by a long-term randomized trial.

For the combination, the QSYMIA label warns of embryo-fetal toxicity (topiramate exposure in the first trimester raises the risk of oral clefts, and a REMS program applies), suicidal behavior and ideation, and acute myopia with secondary angle-closure glaucoma, and of possible seizure if the highest dose is stopped abruptly. In CONQUER, dry mouth (2%, 13%, 21%), paresthesia (2%, 14%, 21%), constipation and insomnia were the common adverse events.

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source
LOMAIRA label, version effective 19 December 2023: 8 mg tablet, not for ages 16 and under

FDA prescribing information

DailyMed, U.S. National Library of Medicine. LOMAIRA (phentermine hydrochloride) 8 mg oral tablets, prescribing information, label version effective 19 December 2023. Set ID cde9fb09-e5af-434d-8874-e4f9f974d893.

LOMAIRA is an 8 mg phentermine hydrochloride tablet (equivalent to 6.4 mg phentermine base). Its label states it is not recommended for patients 16 years old or younger, and its patient counseling section lists primary pulmonary hypertension and serious valvular heart disease among the risks.

Participants / model
Adults with obesity
Treatment
LOMAIRA 8 mg oral tablets
Follow-up
Label version effective 19 December 2023
Study design
FDA prescribing information
Funding
not stated in the source

A second phentermine hydrochloride product with a different tablet strength.

Read the original source
1997 case series: 24 women on fenfluramine plus phentermine with valve disease

Case report

Connolly HM et al. N Engl J Med. 1997;337(9):581-8. PMID 9271479.

Valvular heart disease appeared in 24 previously healthy women treated with fenfluramine plus phentermine, 12.3 +/- 7.1 months after starting; 8 also had newly documented pulmonary hypertension and 5 needed cardiac surgery. The valves had a plaque-like appearance identical to carcinoid or ergotamine valve disease.

Participants / model
24 women with no prior cardiac disease
Treatment
Oral fenfluramine plus phentermine
Follow-up
12.3 +/- 7.1 months after starting
Study design
Case series
Funding
not stated in the source

This concerns the drug pair, not phentermine alone, and matches the label's valve warning, which describes the same combination.

Read the original source
68 obese Korean adults: weight fell 6.7 kg, dry mouth and insomnia the adverse events

Randomized controlled trial

Kim KK et al. Yonsei Med J. 2006;47(5):614-25. PMID 17066505.

Weight fell by 6.7 +/- 2.5 kg (P < 0.001) and waist circumference by 6.2 +/- 3.5 cm (P < 0.001), with more people reaching 5% and 10% weight loss on phentermine. Blood pressure did not differ (systolic P = 0.122), and dry mouth and insomnia were the only adverse events significantly more common. The placebo-group change is not given in the figures used here.

Participants / model
68 relatively healthy obese Korean adults (BMI 25 kg/m2 or more) in Seoul
Treatment
Oral phentermine or placebo, with behavioral therapy
Follow-up
Short-term; length not stated in the abstract
Study design
Randomized double-blind placebo-controlled trial
Funding
not stated in the source

The one placebo-controlled trial of phentermine alone found here. Endpoints were body weight, waist circumference, blood pressure and adverse events.

Read the original source
13,972 adults: 7.4% more weight loss with more than 12 months of continuous use, observational

Human study

Lewis KH et al. Obesity (Silver Spring). 2019;27(4):591-602. PMID 30900410.

People using phentermine continuously for more than 12 months lost 7.4% more weight than the group using it for 3 months or less at 24 months (P < 0.001). The composite of cardiovascular disease or death was rare (0.3%, 41 events), with no significant difference between duration groups. The authors note the observational design and say it supports longer-term use for low-risk individuals.

Participants / model
13,972 adults (84% female, mean BMI 37.8 kg/m2) with a first phentermine fill between 2010 and 2015
Treatment
Oral phentermine, usual outpatient use
Follow-up
Percent weight loss at 6, 12 and 24 months
Study design
Electronic health record observational cohort
Funding
not stated in the source

Not a placebo-controlled result: it compares users with other users. Endpoints were percent weight loss at 6, 12 and 24 months and a composite of cardiovascular disease or death.

Read the original source
QSYMIA label, version effective 22 April 2026: indication, REMS, embryo-fetal toxicity

FDA prescribing information

DailyMed, U.S. National Library of Medicine. QSYMIA (phentermine and topiramate extended-release) oral capsules, prescribing information, label version effective 22 April 2026. Set ID 40dd5602-53da-45ac-bb4b-15789aba40f9.

QSYMIA is indicated with a reduced-calorie diet and increased physical activity to reduce excess weight and maintain weight reduction in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight and at least one weight-related comorbidity. The effect on cardiovascular morbidity and mortality has not been established. The label warns of possible seizure if the highest dose is stopped abruptly. Warnings include embryo-fetal toxicity (topiramate exposure in the first trimester raises the risk of oral clefts, and a REMS program applies), suicidal behavior and ideation, and acute myopia with secondary angle-closure glaucoma.

Participants / model
Adults and adolescents 12 and older with obesity; adults with overweight and a comorbidity
Treatment
QSYMIA extended-release oral capsules
Follow-up
Label version effective 22 April 2026
Study design
FDA prescribing information
Funding
not stated in the source

A separate product from phentermine alone. The adolescent indication is label-level only.

Read the original source
CONQUER: 2,487 adults, 56 weeks, weight down 7.8% and 9.8% versus 1.2% on placebo

Randomized controlled trial

Gadde KM et al. Lancet. 2011;377(9774):1341-52. PMID 21481449.

Weight change was -1.4 kg (-1.2%) on placebo and -8.1 kg (-7.8%) and -10.2 kg (-9.8%) on the two combinations (P < 0.0001), and at least 5% weight loss was reached by 21%, 62% and 70%. Dry mouth (2%, 13%, 21%), paresthesia (2%, 14%, 21%), constipation and insomnia were the common adverse events.

Participants / model
2,487 randomized overweight or obese adults (BMI 27 to 45 kg/m2, two or more comorbidities) at 93 US centers
Treatment
Oral phentermine plus topiramate controlled release at two dose levels, or placebo
Follow-up
56 weeks
Study design
Randomized placebo-controlled trial (NCT00553787)
Funding
not stated in the source

This is the combination product, not phentermine alone. Endpoints were percent weight change and the proportion losing 5% or more.

Read the original source

Why does phentermine sit in S tier?

S fits an approved drug used for its labeled purpose, even when the effect is modest. Phentermine is FDA-approved for short-term weight loss, which is the use being sought, but the grade does not extend to long-term or combination use.

The S applies to label-adherent short-term use. The label itself calls the extra weight loss over placebo only a fraction of a pound a week, and the placebo-controlled phentermine-alone data are one 68-adult trial, with LEAP (870 adults, 24 months) not yet reported.

Modern phase 3 evidence exists only for the phentermine and topiramate combination (CONQUER, 2,487 adults, 7.8 to 9.8% weight loss at 56 weeks), which carries topiramate's fetal toxicity warnings and a REMS. The harms to keep in view are the label's pulmonary hypertension, valvular disease, and abuse and dependence warnings (Schedule IV), and a contraindication list that includes cardiovascular disease.

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source
68 obese Korean adults: weight fell 6.7 kg, dry mouth and insomnia the adverse events

Randomized controlled trial

Kim KK et al. Yonsei Med J. 2006;47(5):614-25. PMID 17066505.

Weight fell by 6.7 +/- 2.5 kg (P < 0.001) and waist circumference by 6.2 +/- 3.5 cm (P < 0.001), with more people reaching 5% and 10% weight loss on phentermine. Blood pressure did not differ (systolic P = 0.122), and dry mouth and insomnia were the only adverse events significantly more common. The placebo-group change is not given in the figures used here.

Participants / model
68 relatively healthy obese Korean adults (BMI 25 kg/m2 or more) in Seoul
Treatment
Oral phentermine or placebo, with behavioral therapy
Follow-up
Short-term; length not stated in the abstract
Study design
Randomized double-blind placebo-controlled trial
Funding
not stated in the source

The one placebo-controlled trial of phentermine alone found here. Endpoints were body weight, waist circumference, blood pressure and adverse events.

Read the original source
LEAP design paper: 870 adults, 24 months, no posted results

Trial registry record

Young CB et al. Contemp Clin Trials. 2026;161:108219. PMID 41519431.

The design paper states that phentermine's long-term efficacy and safety have never been evaluated in a randomized trial, because its approval predates such requirements. LEAP randomized 870 adults with BMI 27 to 44.9 kg/m2 to phentermine 24 mg daily or placebo for 24 months, with an online lifestyle program for all. The primary outcomes are 24-month percent weight loss, systolic blood pressure change and adverse events. The registry (NCT05176626) lists the trial as active, not recruiting, with no posted results, so no result exists yet.

Participants / model
870 adults with overweight or obesity (design and baseline paper)
Treatment
Oral phentermine 24 mg daily or placebo, with an online lifestyle program
Follow-up
24 months
Study design
Trial design paper and registry record
Funding
not stated in the source

A design paper and registry entry with no posted results. It reports no efficacy or safety outcome.

Read the original source
CONQUER: 2,487 adults, 56 weeks, weight down 7.8% and 9.8% versus 1.2% on placebo

Randomized controlled trial

Gadde KM et al. Lancet. 2011;377(9774):1341-52. PMID 21481449.

Weight change was -1.4 kg (-1.2%) on placebo and -8.1 kg (-7.8%) and -10.2 kg (-9.8%) on the two combinations (P < 0.0001), and at least 5% weight loss was reached by 21%, 62% and 70%. Dry mouth (2%, 13%, 21%), paresthesia (2%, 14%, 21%), constipation and insomnia were the common adverse events.

Participants / model
2,487 randomized overweight or obese adults (BMI 27 to 45 kg/m2, two or more comorbidities) at 93 US centers
Treatment
Oral phentermine plus topiramate controlled release at two dose levels, or placebo
Follow-up
56 weeks
Study design
Randomized placebo-controlled trial (NCT00553787)
Funding
not stated in the source

This is the combination product, not phentermine alone. Endpoints were percent weight change and the proportion losing 5% or more.

Read the original source
QSYMIA label, version effective 22 April 2026: indication, REMS, embryo-fetal toxicity

FDA prescribing information

DailyMed, U.S. National Library of Medicine. QSYMIA (phentermine and topiramate extended-release) oral capsules, prescribing information, label version effective 22 April 2026. Set ID 40dd5602-53da-45ac-bb4b-15789aba40f9.

QSYMIA is indicated with a reduced-calorie diet and increased physical activity to reduce excess weight and maintain weight reduction in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight and at least one weight-related comorbidity. The effect on cardiovascular morbidity and mortality has not been established. The label warns of possible seizure if the highest dose is stopped abruptly. Warnings include embryo-fetal toxicity (topiramate exposure in the first trimester raises the risk of oral clefts, and a REMS program applies), suicidal behavior and ideation, and acute myopia with secondary angle-closure glaucoma.

Participants / model
Adults and adolescents 12 and older with obesity; adults with overweight and a comorbidity
Treatment
QSYMIA extended-release oral capsules
Follow-up
Label version effective 22 April 2026
Study design
FDA prescribing information
Funding
not stated in the source

A separate product from phentermine alone. The adolescent indication is label-level only.

Read the original source

Studies and sources

Generic phentermine label, version effective 10 June 2026: indication, contraindications, warnings, trial summary

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Phentermine hydrochloride 37.5 mg oral tablets, prescribing information (generic label, Initial U.S. Approval 1959), label version effective 10 June 2026. Set ID 5927e0f6-3de3-4885-a633-5b92003f6fe4.

The label indicates phentermine as a short-term (a few weeks) adjunct to a weight-reduction regimen of exercise, behavioral modification and caloric restriction in exogenous obesity, for patients with a BMI of 30 kg/m2 or more, or 27 or more with risk factors such as controlled hypertension, diabetes or hyperlipidemia. Contraindications include a history of cardiovascular disease, use during or within 14 days of an MAO inhibitor, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and pregnancy or nursing. Warnings cover coadministration with other weight-loss drugs (safety and efficacy not established), rare primary pulmonary hypertension (a possible association with phentermine alone cannot be ruled out), rare serious regurgitant valvular disease, tolerance within a few weeks, and abuse and dependence. Phentermine is Schedule IV and is chemically and pharmacologically related to the amphetamines. Peak concentration comes 3 to 4.4 hours after a dose. The clinical studies section says the extra weight loss over placebo is only a fraction of a pound a week in trials lasting a few weeks, and that the total impact over diet alone must be considered clinically limited.

Participants / model
Adults with obesity or overweight with risk factors
Treatment
Phentermine hydrochloride 37.5 mg oral tablets (equivalent to 30 mg phentermine base)
Follow-up
Label version effective 10 June 2026
Study design
FDA prescribing information
Funding
not stated in the source

The label limits use to a few weeks. The pulmonary hypertension and valve statements are label-level for phentermine alone.

Read the original source
LOMAIRA label, version effective 19 December 2023: 8 mg tablet, not for ages 16 and under

FDA prescribing information

DailyMed, U.S. National Library of Medicine. LOMAIRA (phentermine hydrochloride) 8 mg oral tablets, prescribing information, label version effective 19 December 2023. Set ID cde9fb09-e5af-434d-8874-e4f9f974d893.

LOMAIRA is an 8 mg phentermine hydrochloride tablet (equivalent to 6.4 mg phentermine base). Its label states it is not recommended for patients 16 years old or younger, and its patient counseling section lists primary pulmonary hypertension and serious valvular heart disease among the risks.

Participants / model
Adults with obesity
Treatment
LOMAIRA 8 mg oral tablets
Follow-up
Label version effective 19 December 2023
Study design
FDA prescribing information
Funding
not stated in the source

A second phentermine hydrochloride product with a different tablet strength.

Read the original source
Drugs@FDA: phentermine applications from 1976 to 2016; QSYMIA approved 17 July 2012

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application records for ANDA 085128 (ADIPEX-P tablets), ANDA 088023 (ADIPEX-P capsules), ANDA 083923, ANDA 203495 (LOMAIRA) and NDA 022580 (QSYMIA). Dates read from the openFDA Drugs@FDA records.

The generic label gives an initial U.S. approval year of 1959. In the openFDA Drugs@FDA records, ADIPEX-P tablets (Teva) are ANDA 085128, approved 22 October 1980; ADIPEX-P capsules (Teva, now discontinued) are ANDA 088023, approved 2 August 1983; among the 21 applications whose generic name includes phentermine, the earliest original approval date is ANDA 083923 (Chartwell, 1 July 1976); LOMAIRA is ANDA 203495, approved 12 September 2016; and the combination QSYMIA is NDA 022580, approved 17 July 2012. The original 1959 application itself was not found in openFDA.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Applications from 1976 to 2016
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels, and the 1959 original application was not found.

Read the original source
68 obese Korean adults: weight fell 6.7 kg, dry mouth and insomnia the adverse events

Randomized controlled trial

Kim KK et al. Yonsei Med J. 2006;47(5):614-25. PMID 17066505.

Weight fell by 6.7 +/- 2.5 kg (P < 0.001) and waist circumference by 6.2 +/- 3.5 cm (P < 0.001), with more people reaching 5% and 10% weight loss on phentermine. Blood pressure did not differ (systolic P = 0.122), and dry mouth and insomnia were the only adverse events significantly more common. The placebo-group change is not given in the figures used here.

Participants / model
68 relatively healthy obese Korean adults (BMI 25 kg/m2 or more) in Seoul
Treatment
Oral phentermine or placebo, with behavioral therapy
Follow-up
Short-term; length not stated in the abstract
Study design
Randomized double-blind placebo-controlled trial
Funding
not stated in the source

The one placebo-controlled trial of phentermine alone found here. Endpoints were body weight, waist circumference, blood pressure and adverse events.

Read the original source
LEAP design paper: 870 adults, 24 months, no posted results

Trial registry record

Young CB et al. Contemp Clin Trials. 2026;161:108219. PMID 41519431.

The design paper states that phentermine's long-term efficacy and safety have never been evaluated in a randomized trial, because its approval predates such requirements. LEAP randomized 870 adults with BMI 27 to 44.9 kg/m2 to phentermine 24 mg daily or placebo for 24 months, with an online lifestyle program for all. The primary outcomes are 24-month percent weight loss, systolic blood pressure change and adverse events. The registry (NCT05176626) lists the trial as active, not recruiting, with no posted results, so no result exists yet.

Participants / model
870 adults with overweight or obesity (design and baseline paper)
Treatment
Oral phentermine 24 mg daily or placebo, with an online lifestyle program
Follow-up
24 months
Study design
Trial design paper and registry record
Funding
not stated in the source

A design paper and registry entry with no posted results. It reports no efficacy or safety outcome.

Read the original source
13,972 adults: 7.4% more weight loss with more than 12 months of continuous use, observational

Human study

Lewis KH et al. Obesity (Silver Spring). 2019;27(4):591-602. PMID 30900410.

People using phentermine continuously for more than 12 months lost 7.4% more weight than the group using it for 3 months or less at 24 months (P < 0.001). The composite of cardiovascular disease or death was rare (0.3%, 41 events), with no significant difference between duration groups. The authors note the observational design and say it supports longer-term use for low-risk individuals.

Participants / model
13,972 adults (84% female, mean BMI 37.8 kg/m2) with a first phentermine fill between 2010 and 2015
Treatment
Oral phentermine, usual outpatient use
Follow-up
Percent weight loss at 6, 12 and 24 months
Study design
Electronic health record observational cohort
Funding
not stated in the source

Not a placebo-controlled result: it compares users with other users. Endpoints were percent weight loss at 6, 12 and 24 months and a composite of cardiovascular disease or death.

Read the original source
1997 case series: 24 women on fenfluramine plus phentermine with valve disease

Case report

Connolly HM et al. N Engl J Med. 1997;337(9):581-8. PMID 9271479.

Valvular heart disease appeared in 24 previously healthy women treated with fenfluramine plus phentermine, 12.3 +/- 7.1 months after starting; 8 also had newly documented pulmonary hypertension and 5 needed cardiac surgery. The valves had a plaque-like appearance identical to carcinoid or ergotamine valve disease.

Participants / model
24 women with no prior cardiac disease
Treatment
Oral fenfluramine plus phentermine
Follow-up
12.3 +/- 7.1 months after starting
Study design
Case series
Funding
not stated in the source

This concerns the drug pair, not phentermine alone, and matches the label's valve warning, which describes the same combination.

Read the original source
QSYMIA label, version effective 22 April 2026: indication, REMS, embryo-fetal toxicity

FDA prescribing information

DailyMed, U.S. National Library of Medicine. QSYMIA (phentermine and topiramate extended-release) oral capsules, prescribing information, label version effective 22 April 2026. Set ID 40dd5602-53da-45ac-bb4b-15789aba40f9.

QSYMIA is indicated with a reduced-calorie diet and increased physical activity to reduce excess weight and maintain weight reduction in adults and pediatric patients aged 12 and older with obesity, and in adults with overweight and at least one weight-related comorbidity. The effect on cardiovascular morbidity and mortality has not been established. The label warns of possible seizure if the highest dose is stopped abruptly. Warnings include embryo-fetal toxicity (topiramate exposure in the first trimester raises the risk of oral clefts, and a REMS program applies), suicidal behavior and ideation, and acute myopia with secondary angle-closure glaucoma.

Participants / model
Adults and adolescents 12 and older with obesity; adults with overweight and a comorbidity
Treatment
QSYMIA extended-release oral capsules
Follow-up
Label version effective 22 April 2026
Study design
FDA prescribing information
Funding
not stated in the source

A separate product from phentermine alone. The adolescent indication is label-level only.

Read the original source
CONQUER: 2,487 adults, 56 weeks, weight down 7.8% and 9.8% versus 1.2% on placebo

Randomized controlled trial

Gadde KM et al. Lancet. 2011;377(9774):1341-52. PMID 21481449.

Weight change was -1.4 kg (-1.2%) on placebo and -8.1 kg (-7.8%) and -10.2 kg (-9.8%) on the two combinations (P < 0.0001), and at least 5% weight loss was reached by 21%, 62% and 70%. Dry mouth (2%, 13%, 21%), paresthesia (2%, 14%, 21%), constipation and insomnia were the common adverse events.

Participants / model
2,487 randomized overweight or obese adults (BMI 27 to 45 kg/m2, two or more comorbidities) at 93 US centers
Treatment
Oral phentermine plus topiramate controlled release at two dose levels, or placebo
Follow-up
56 weeks
Study design
Randomized placebo-controlled trial (NCT00553787)
Funding
not stated in the source

This is the combination product, not phentermine alone. Endpoints were percent weight change and the proportion losing 5% or more.

Read the original source
Network meta-analysis: 28 trials, 29,018 patients, phentermine/topiramate 8.8 kg versus placebo

Systematic review and meta-analysis

Khera R et al. JAMA. 2016;315(22):2424-34. PMID 27299618.

Phentermine/topiramate gave the most excess weight loss at 1 year (8.8 kg versus placebo, 95% credible interval -10.20 to -7.42), with 75% reaching at least 5% weight loss versus a median 23% on placebo (OR 9.22, 95% CrI 6.63 to 12.85). Attrition was 30 to 45% in all trials, which lowers confidence. Phentermine alone is not one of the drugs analyzed.

Participants / model
29,018 patients with overweight or obesity in 28 randomized trials
Treatment
Oral orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate or liraglutide versus placebo
Follow-up
Drugs given for at least 1 year
Study design
Systematic review and network meta-analysis
Funding
not stated in the source

Phentermine alone was not analyzed. Endpoints were the proportion with 5% weight loss, weight change and discontinuation for adverse events.

Read the original source
PubChem: phentermine and phentermine hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 4771 (phentermine) and CID 70969 (phentermine hydrochloride).

Phentermine free base: PubChem CID 4771, C10H15N, 149.23 g/mol, CAS 122-09-8. Phentermine hydrochloride, the salt in the tablets: CID 70969, C10H16ClN, 185.69 g/mol, CAS 1197-21-3. Label doses are in the hydrochloride, so 37.5 mg of phentermine hydrochloride equals 30 mg of phentermine base.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

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Why is Phentermine in S tier?

S fits an FDA-approved drug used for its labeled purpose, even when the effect is modest. Phentermine is labeled for short-term weight loss, which is the use being sought, but the label calls the added weight loss clinically limited, long-term use has no randomized phentermine-alone result yet, and the combination product is a different drug with its own warnings.