# Obesity Drugs Ranked Across 262 Trials: Weight Lost vs Side-Effect Dropout A network meta-analysis of 262 trials ranks tirzepatide at -14.9% and CagriSema at -14.8% against lifestyle alone, and finds four top performers also lead on discontinuation. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/the-best-losers-are-the-worst-tolerated Updated: 2026-09-18 Published: 2026-09-17 [← Research](https://thisglp.com/research) Evidence # Obesity Drugs Ranked Across 262 Trials: Weight Lost vs Side-Effect Dropout A network meta-analysis of 262 trials and 99,791 participants produces two rankings, biggest weight loss and highest rate of stopping for side effects. Four drugs appear on both. [This GLP Editorial Team](https://thisglp.com/about)September 20267 min readUpdated September 2026 Weight loss vs lifestyle alone, one year · tirzepatide · 14.9% · CagriSema · 14.8% · ● · oral semaglutide · 10.9% · ● · orforglipron · 9.9% · ● · semaglutide (injected) · 9.8% · phentermine-topiramate · 8.1% · ● · ● also among the highest rates of stopping for side effects. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). ## Key takeaways - A network meta-analysis pooled 262 randomized trials and 99,791 participants across 19 drugs. - At one year against lifestyle modification alone: tirzepatide -14.9%, CagriSema -14.8%, oral semaglutide -10.9%, orforglipron -9.9%, injected semaglutide -9.8%, phentermine-topiramate -8.1%. - Stopping because of adverse events was highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema and oral semaglutide — risk ratios from 1.9 to 4.2. - Four drugs appear on both lists. The efficacy ranking and the tolerability ranking are not independent of each other. This is the largest comparison of obesity drugs assembled so far: 262 randomized trials, 99,791 participants, 19 drugs, 24 outcomes, with certainty of evidence graded throughout[\[1\]](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated#ref-1). It supersedes the pooled figures reported in [the earlier weight-loss averages](https://thisglp.com/research/glp1-weight-loss-pooled-average) on coverage, though not on the caveats. On weight at one year, measured against lifestyle modification alone, tirzepatide led at -14.9% (95% CI -16.0% to -13.9%), followed by cagrilintide-semaglutide at -14.8%, oral semaglutide at -10.9%, orforglipron at -9.9%, injected semaglutide at -9.8%, and phentermine-topiramate at -8.1%. All of those carry moderate to high certainty. The newer agents are a separate category and should be read as one. Ecnoglutide, mazdutide and retatrutide may produce similar or larger reductions, in the range of 13.1% to 14.6%, but the certainty attached is very low to low. A number with low certainty and a number with high certainty are not two entries on the same list, and the drugs that have not yet reached the market are covered in [what is not for sale yet](https://thisglp.com/research/what-new-weight-loss-drugs-are-coming). The two league tables share four names Discontinuation because of adverse events was highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema and oral semaglutide, at risk ratios between 1.9 and 4.2. Gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron and tirzepatide, at 3.1 to 4.2. Oral semaglutide, orforglipron, CagriSema and phentermine-topiramate each sit on both lists. The drug that takes off the most weight is disproportionately likely to be the drug people quit. That overlap is the practical finding, and it reframes what a top-of-table position means. A ranking built on weight loss among the people who completed a trial answers a different question from the one a person starting treatment is asking, which is closer to how much weight they will have lost in a year given some chance of stopping along the way. The tolerability route out of treatment is described from the dosing side in [titration and nausea](https://thisglp.com/research/how-long-does-nausea-last-on-a-glp1). Two structural limits apply to every figure above. The comparator is lifestyle modification, so these are not head-to-head contests, and most differences between two drugs here are inferred through the network rather than measured in a trial that randomized people between them. And trial follow-up ran from 12 to 172 weeks, which for a condition managed over decades is short — the question of what the weight is made of, and what returns, sits outside this analysis entirely and is taken up in [what these drugs do to muscle](https://thisglp.com/research/muscle-loss-on-glp1). ## Frequently asked Which obesity drug produces the most weight loss? Tirzepatide, at -14.9% against lifestyle modification alone at one year, with cagrilintide-semaglutide essentially level at -14.8%. Both carry moderate to high certainty of evidence. Are the newer drugs better? Possibly, but the evidence is weaker. Ecnoglutide, mazdutide and retatrutide showed reductions of 13.1% to 14.6% at very low to low certainty, which is not comparable to a high-certainty estimate. Which drugs do people stop taking? Discontinuation for adverse events was highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema and oral semaglutide, at risk ratios from 1.9 to 4.2 — a list that overlaps heavily with the most effective drugs. ## Sources 1. \[1\] Nong K, Shi Q, Xie X, Wang Y, Agarwal A, Guyatt GH, et al. (2026). Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis BMJ. [PMID 42419792](https://pubmed.ncbi.nlm.nih.gov/42419792/) ## Where to get it ### Best GLP-1 injections Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured. 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