In indirect comparisons of clinical trials, semaglutide and tirzepatide produced larger average placebo-subtracted weight-loss estimates than orlistat, naltrexone/bupropion and liraglutide. Phentermine/topiramate also showed substantial average efficacy. These trial averages are not predictions for an individual, and the drugs were not all compared with one another in a single head-to-head trial.
How do the average weight-loss estimates compare?
The American Diabetes Association’s 2025 standards summarize a network meta-analysis comparing results across groups of randomized trials. The estimates below are the average weight reduction attributable to treatment beyond placebo at each study’s endpoint; they do not show how much a particular person will lose.
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| Medicine | Placebo-subtracted weight reduction at study endpoint |
|---|---|
| Orlistat | 3.1% (22 trials) |
| Phentermine/topiramate | 8.8% (5 trials) |
| Naltrexone/bupropion | 4.8% (2 trials) |
| Liraglutide | 4.5% (10 trials) |
| Semaglutide | 11.9% (13 trials) |
| Tirzepatide | 16.2% (6 trials) |
All figures and trial counts are estimates reported in the American Diabetes Association’s 2025 standards. The underlying trials differed in their participants, treatment periods and designs. Network meta-analysis combines direct and indirect evidence across studies, so the figures are useful for comparing average efficacy but are not a direct ranking from one trial that randomized participants to every medicine.
What is different about the newer medicines?
Semaglutide and liraglutide
Semaglutide and liraglutide act at the GLP-1 receptor. In the network estimates, semaglutide had a larger average placebo-subtracted weight reduction than liraglutide, but that comparison is across separate trial groups rather than a single head-to-head study.
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Tirzepatide
Tirzepatide is not a GLP-1-only medicine: it activates both the GIP and GLP-1 receptors. Its estimate was the largest among the medicines listed, but the same limits on interpreting indirect trial comparisons apply.
Older treatment options
Orlistat and naltrexone/bupropion had smaller average estimates in this analysis. Phentermine/topiramate showed substantial efficacy, with an estimate between those for the newer medicines and the other older options listed. Efficacy alone does not establish which medicine is the right or safest choice for a particular person.
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- Diabetic Travel Case with Cool Packs: Insulin cooling travel case with 2 Ice Packs 180g reusable ice packs, this diabetic travel cooler maintains critical temperatures for 10-24 hours (varies by climate). ice packs freeze solid in 2-3 hours, for flights, road trips, or daily use
- Diabetic Medicine Cooling Bag: Crafted from pressure-resistant EVA shell and lined with high-density PE compartments, this refrigerated medicine organizer bag protects insulin pens, syringes, and glucose monitors from impacts, spills, and humidity. Watertight design preserves contents even in rainy conditions
- Diabetic Refrigerated Travel Case: Optimized interior holds 4-8 insulin pens + diabetic supplies (alcohol pads, test strips, etc.) in dedicated zones. Compact yet spacious enough for 24-hour medical needs, it doubles as a discreet diabetic travel cooling box for clinics, offices, or vacations
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How should the numbers be used?
These percentages are group-level differences from placebo at trial endpoints. They are not a promise of total weight loss, an estimate of what any one patient will experience, or a guarantee that two medicines will differ by exactly the amount shown. Trial duration and participant characteristics varied, and individual outcomes depend on clinical circumstances and treatment.
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A separate, broader estimate from the National Institute of Diabetes and Digestive and Kidney Diseases says adults taking prescription weight-loss medicines alongside a lifestyle program lose, on average, 3% to 12% more of their starting weight after one year than people using lifestyle treatment alone. This is a class-level comparison, not a result for any one of the medicines in the table. NIDDK also notes that prescription medicines work best with lifestyle measures and do not replace healthy eating and physical activity. See its guidance on prescription medicines for overweight and obesity.
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What else matters besides efficacy?
The best option depends on treatment goals, health conditions, the medicine’s current prescribing information and a person’s preferences. Route and frequency of administration, treatment duration, follow-up, availability and affordability may also matter. For people with type 2 diabetes and overweight or obesity, the ADA’s 2025 standards give particular weight to glucose and cardiometabolic benefits and prefer semaglutide or tirzepatide among options with greater weight-loss efficacy. That guidance is for this clinical group; it is not a universal recommendation for everyone seeking weight loss. The ADA’s 2025 standards on obesity and weight management in type 2 diabetes provide that context.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.What safety information is established here?
Safety warnings should be checked for the specific medicine rather than inferred from another drug in the comparison. The FDA’s 2025 U.S. prescribing information for semaglutide used for weight reduction says acute pancreatitis has been observed in patients treated with GLP-1 receptor agonists and that acute gallbladder disease occurred in clinical trials. It advises stopping semaglutide at least two months before a planned pregnancy. These are semaglutide-label statements, not a complete safety comparison or warnings that can automatically be applied to every medicine in the table. Consult the FDA’s 2025 WEGOVY prescribing information and current U.S. prescribing information for any medicine being considered.
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This comparison is U.S.-focused. FDA approvals, labels and availability can change, and the evidence summarized here does not establish every comparator’s current contraindications, interactions or access conditions. Discuss individual suitability, risks and pregnancy plans with a qualified healthcare professional.
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