GLP-1 medicines are not the only approved way to treat obesity. People look for alternatives for plain reasons — cost, supply, side effects, a contraindication, or not wanting a weekly injection — and the alternatives have labels, trial results and warnings of their own. This page reads them, as of 26 September 2026, and places them next to the GLP-1 results.
It reports what the documents say. Which option fits one person depends on their health, their other medicines and their coverage, and it is a decision for their clinician. The oral GLP-1 tablets are still GLP-1 medicines and are on our GLP-1 pills page; how the injectable GLP-1 drugs compare with one another is on which drugs are GLP-1s.
The approved medicines at a glance
| Medicine (label) | How it works, per label | Weight result in its label's trials | Duration of use in the label |
|---|---|---|---|
| Phentermine (generic, several makers) | sympathomimetic appetite suppressant | no long-term trial in the label | short-term, "a few weeks" |
| Qsymia (phentermine/topiramate) | appetite suppressant plus an anti-seizure drug | −10.9% vs −1.6% (Study 1) and −9.8% vs −1.2% (Study 2) at 15 mg/92 mg, 56 weeks | long-term, with a 12-week check |
| Contrave (naltrexone/bupropion) | opioid antagonist plus an antidepressant | −5.4% vs −1.3% (COR-I), 56 weeks | long-term, with a 12-week check |
| Xenical (orlistat 120 mg) | blocks absorption of dietary fat | about 3 points more than placebo at 1 year | long-term |
| Imcivree (setmelanotide) | MC4 receptor agonist | reported by BMI in rare genetic conditions | long-term, specific diagnoses only |
For comparison, from the GLP-1 labels: Wegovy 2.4 mg −15.5% and 7.2 mg −18.8% against −3.9% on placebo at 72 weeks; Foundayo 17.2 mg −11.1% against −2.1% at 72 weeks. Every label warns that results from different trials cannot be directly compared — different people, lengths and placebo responses — so the table is a guide to scale, not a ranking.
Phentermine
The oldest and cheapest, and the most restricted. Its label calls it "a short-term (a few weeks) adjunct" to diet, exercise and behaviour change, for adults with a BMI of 30 or more, or 27 or more with another risk factor. It also states, unusually for a weight-loss label, that "tolerance to the anorectic effect usually develops within a few weeks." It is a Schedule IV controlled substance and is contraindicated in people with a history of heart disease, including coronary artery disease, stroke, arrhythmias and heart failure.
Qsymia (phentermine/topiramate)
The strongest of the non-GLP-1 options on its own label. In its two one-year trials, the top dose gave −10.9% and −9.8% against −1.6% and −1.2% on placebo; the lower doses gave −5.1% and −7.8%. The label builds in a checkpoint: after 12 weeks, if an adult has not lost at least 3%, the dose is raised, and if after a further 12 weeks at the top dose they have not lost at least 5%, the drug is stopped. It is contraindicated in pregnancy (topiramate can harm a fetus), in glaucoma, in hyperthyroidism and with MAO inhibitors, and its phentermine component is a Schedule IV controlled substance.
Contrave (naltrexone/bupropion)
In its main trial, COR-I, weight fell 5.4% against 1.3% on placebo over 56 weeks, and 42% of people lost at least 5% against 17%. Results were larger with an intensive behaviour programme (−8.1% against −4.9% in COR-BMOD) and smaller in type 2 diabetes (−3.7% against −1.7%). It carries a boxed warning on suicidal thoughts and behaviours, from its bupropion component, and is contraindicated in uncontrolled high blood pressure, seizure disorders, eating disorders and chronic opioid use. Its label says to stop if a person has not lost at least 5% after 12 weeks at the maintenance dose.
Xenical (orlistat)
Orlistat works in the gut rather than the brain: it stops part of the fat in a meal from being absorbed. Its label reports a mean difference of about 3 percentage points over placebo after one year; among people who completed that year, 57% on Xenical and 31% on placebo lost at least 5%. The label's longer trials also measured regain after a diet — for example 26% of the lost weight regained on Xenical against 52% on placebo in one study. It is contraindicated in pregnancy, chronic malabsorption and cholestasis, and the label notes that doses above 120 mg three times a day add nothing.
Imcivree (setmelanotide)
Not a general alternative. It is approved only for obesity caused by specific genetic conditions — POMC, PCSK1 or LEPR deficiency confirmed by a genetic test, Bardet-Biedl syndrome — and, since a 2026 label change, acquired hypothalamic obesity. The label states it would not be expected to work where the gene variants are benign. For the small number of people with those diagnoses, it is the medicine designed for the cause.
Surgery
Metabolic and bariatric surgery has its own criteria. The 2022 guideline from the American Society for Metabolic and Bariatric Surgery and the International Federation for the Surgery of Obesity replaced the 1991 NIH thresholds: surgery is recommended for adults with a BMI of 35 or more, whatever their other conditions, and considered for a BMI of 30 to 34.9 with metabolic disease. A 2026 analysis of survey data from 37 settings estimated that the new thresholds cover nearly three times as many adults as the old ones. NIDDK notes that teenagers may be candidates too, evaluated by a specialist team. Insurers often apply their own criteria. We do not report surgical weight-loss figures here; the procedures differ, and so do their risks.
What is not an alternative
Several things sold as GLP-1 alternatives are not approved medicines:
- Supplements and patches marketed as "GLP-1". None is FDA-approved to treat obesity; what their ingredients have been tested for is on our natural GLP-1, supplements and patches pages.
- Compounded GLP-1 products are the same molecules, not alternatives, and have their own regulatory history on our compounded semaglutide page.
What this page cannot tell you
- Which option suits one person. Contraindications alone rule several of these out for many people, and the choice belongs to a clinician.
- A head-to-head ranking. No trial has compared all of these directly.
- Current prices or coverage, which change often; the GLP-1 cost picture is on our GLP-1 cost page.
Sources
- Phentermine hydrochloride tablets prescribing information (generic), SPL effective 2026-08-17 — DailyMed, sections 1, 4, 5 and 9.
- QSYMIA (phentermine and topiramate extended-release) prescribing information, Vivus, effective 2026-04-22 — DailyMed, sections 2, 4, 9 and 14.
- CONTRAVE (naltrexone/bupropion extended-release) prescribing information, effective 2025-11-10 — DailyMed, boxed warning, sections 2, 4 and 14.
- XENICAL (orlistat) prescribing information, H2-Pharma, effective 2026-01-09 — DailyMed, sections 2, 4 and 14.
- IMCIVREE (setmelanotide) prescribing information, Rhythm Pharmaceuticals, effective 2026-04-01 — DailyMed, section 1.
- WEGOVY (semaglutide) prescribing information, Novo Nordisk, SPL effective 2026-06-18 — DailyMed, Table 12; FOUNDAYO (orforglipron) prescribing information, Eli Lilly, effective 2026-07-29 — DailyMed, section 14.
- Eisenberg D, et al. 2022 ASMBS and IFSO: indications for metabolic and bariatric surgery. Surg Obes Relat Dis 2022;18:1345-1356 — PubMed 36280539; Vera-Ponce VJ. Population meeting thresholds for metabolic and bariatric surgery evaluation under the 1991 NIH and 2022 ASMBS/IFSO criteria across 37 settings. Obes Pillars 2026 — PubMed 42729328.
- NIDDK, Potential candidates for bariatric surgery — niddk.nih.gov, read 2026-09-26.