Review of 56 trials finds only semaglutide and tirzepatide top 10% weight loss

A network meta-analysis of 56 randomized controlled trials covering 60,307 adults found that only two of six obesity medications studied produced average total body weight loss above 10%: semaglutide and tirzepatide. The review also found that the two drugs have evidence for different obesity-related conditions, and its authors concluded the results "support the need to individualize the selection of OMMs," or obesity management medications ^[1].

The review searched Medline and Embase for trials published up to January 31, 2025, comparing obesity medications with placebo or an active comparator in adults. The primary measure was percentage of total body weight lost by the end of each study. Secondary measures included weight loss at one, two and three or more years, lipid profile, blood pressure, hemoglobin A1c, fasting plasma glucose, mental health, serious adverse events, quality of life, cardiovascular illness and death, remission of obesity-related complications, and death from any cause ^[1].

The 56 trials enrolled 60,307 patients: 32,598 taking a medication and 27,709 taking placebo. By drug, the trials were orlistat (22), semaglutide (14), liraglutide (11), tirzepatide (6), naltrexone/bupropion (5) and phentermine/topiramate (2). Every medication produced significantly greater total body weight loss than placebo (P < 0.0001), but the average exceeded 10% only for semaglutide and tirzepatide ^[1]. In the United States, semaglutide is sold as Ozempic, Wegovy and Rybelsus; tirzepatide is sold as Mounjaro and Zepbound.

The two drugs had some benefits in common. Both showed restoration of normal blood sugar, remission of type 2 diabetes, and fewer hospitalizations for heart failure. Beyond that, the evidence split. Semaglutide was effective at reducing major adverse cardiovascular events and at reducing pain in knee osteoarthritis. Tirzepatide was effective at producing remission of obstructive sleep apnea syndrome and metabolic dysfunction-associated steatohepatitis, or MASH ^[1].

Several specifics are not in the published report. It does not give average weight-loss percentages for each drug beyond the 10% threshold, and it does not report how semaglutide and tirzepatide compare with each other directly. Results for serious adverse events, quality of life and all-cause death were listed as outcomes of interest but no figures for them appear in the report ^[1].

Many of the review's authors disclosed financial ties to the companies that make these drugs. Disclosures list speaking or advisory fees from Novo Nordisk, which makes semaglutide, and Eli Lilly, which makes tirzepatide, as well as from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Sanofi, Novartis, Regeneron and others. Two authors declared no conflicts of interest ^[1].

Why it matters for patients

For most people choosing among these medications, weight loss is the headline. This analysis suggests the bigger practical difference may be which complications each drug has been shown to affect. Someone whose main concern is cardiovascular events or knee osteoarthritis pain is looking at a body of trial evidence for semaglutide that does not exist for the other drugs in this review. Someone whose main concern is sleep apnea or MASH is looking at the reverse. Both drugs carry evidence for diabetes remission and fewer heart failure hospitalizations ^[1].

The numbers behind that are averages across tens of thousands of trial participants, not predictions for any one person, and individual results vary in ways this review does not describe. The report also does not rank the drugs against each other, so it does not establish that either semaglutide or tirzepatide is more effective overall ^[1]. Which medication is appropriate, and whether a person's insurance covers it, are separate questions the review does not address ^[1].