Network meta-analysis of 56 obesity drug trials published

Researchers pooled 56 randomized trials of obesity medications covering 60,307 adults and found that only two drugs — semaglutide and tirzepatide — produced average total body weight loss above 10%. The analysis, published in early October 2025, also found the two drugs have different track records on obesity-related complications ^[1].

The authors searched Medline and Embase through January 31, 2025, for randomized controlled trials comparing obesity management medications against placebo or an active comparator in adults. The main measure was percentage of total body weight loss at the end of each study. Secondary measures included weight loss at 1, 2 and 3 or more years, cholesterol levels, blood pressure, hemoglobin A1c, fasting blood sugar, mental health, serious adverse events, quality of life, cardiovascular events and deaths, remission of obesity-related conditions, and all-cause death ^[1].

What the trials covered

The 56 trials broke down as follows: orlistat (22 trials), semaglutide (14), liraglutide (11), tirzepatide (6), naltrexone/bupropion (5) and phentermine/topiramate (2). Of the 60,307 participants, 32,598 received an obesity medication and 27,709 received placebo ^[1].

Every drug studied beat placebo on weight loss by a statistically significant margin (P < 0.0001). But the size of that effect separated the newer incretin drugs from the rest: average total body weight loss exceeded 10% only for semaglutide, sold as Wegovy and Ozempic, and tirzepatide, sold as Zepbound and Mounjaro ^[1]. The abstract does not list the exact percentage for each individual drug, so the precise gaps between them are not given in the material available here ^[1].

Different drugs, different proven benefits

Beyond weight, the analysis found overlap and divergence. Both semaglutide and tirzepatide were linked to restoring normal blood sugar, remission of type 2 diabetes, and fewer hospitalizations for heart failure ^[1].

After that, the two split. Semaglutide was effective at reducing major adverse cardiovascular events — the standard trial bundle of heart attack, stroke and cardiovascular death — and at reducing pain from knee osteoarthritis. Tirzepatide was effective at producing remission of obstructive sleep apnea and at treating metabolic dysfunction-associated steatohepatitis, or MASH, a form of fatty liver disease ^[1].

The authors concluded that these differences "support the need to individualize the selection" of obesity medications ^[1].

Why it matters for patients

This kind of analysis is the closest thing available to a side-by-side comparison when most of these drugs have never been tested head-to-head in a single trial. It suggests the choice among obesity drugs is not only about how much weight comes off, but about which other health problems a person already has ^[1].

One important caveat: a drug showing a benefit here means a trial measured that benefit and found it. It does not necessarily mean the other drug lacks that benefit — it may simply mean no trial has tested it. For example, the analysis credits semaglutide with a cardiovascular benefit and tirzepatide with a sleep apnea benefit, which reflects how each company designed its outcome trials ^[1]. Readers weighing options with a clinician may find it useful to ask which conclusions rest on direct trial evidence versus absence of testing.

The search cutoff of January 31, 2025, also means newer agents are not included. The six drugs analyzed do not include orforglipron, the oral GLP-1 branded Foundayo, or other medications whose trials reported later ^[1].

Many of the authors disclosed speaking, advisory or research funding ties to Novo Nordisk, which makes semaglutide, and Eli Lilly, which makes tirzepatide; several disclosed both. Two authors reported no relevant conflicts ^[1].

What happens next

The analysis itself sets no future milestones. What is not yet known from this work: how these drugs compare directly against one another in a randomized head-to-head trial, and whether the complication-specific benefits found for one drug will eventually be demonstrated for the other. Those answers depend on trials that were not part of this review ^[1].