For people following the rise of GLP-1 medications, the names can blur together: Wegovy, Zepbound, Saxenda, Ozempic, Mounjaro. But a new review suggests the medications approved for weight loss do not all lead to the same average results.
In a systematic review and network meta-analysis published in Obesity, researchers compared randomized clinical trial evidence for three medications used for weight loss in adults without diabetes: tirzepatide, semaglutide and liraglutide. Tirzepatide was associated with the greatest average weight loss across the reviewed trials, followed by semaglutide and then liraglutide.
The finding does not mean tirzepatide is the best choice for every person. These medications differ in dosing, side effects, access, cost, insurance coverage and how they fit into a person’s medical history. The study also compared trial averages, not individual outcomes.
The review included 15 phase 3 randomized controlled trials with 14,059 adults who had overweight or obesity but did not have diabetes. Researchers compared the medications with placebo and with one another using a network meta-analysis, a method that allows researchers to compare treatments across studies, even when not every drug has been tested head-to-head in the same trial.
Across the included studies, tirzepatide led to the largest average reduction in body weight. The University of Georgia release reported that tirzepatide helped patients lose more than 20% of their starting body weight across the reviewed studies. Semaglutide was associated with about 15% weight loss and liraglutide with about 8%.
That difference may be partly explained by how the medications work. Semaglutide and liraglutide are GLP-1 receptor agonists, meaning they mimic the effects of a hormone involved in appetite, digestion and blood sugar regulation. Tirzepatide is often discussed alongside GLP-1 medications, but it works on two hormone pathways: GLP-1 and GIP.
All three medications were associated with more weight loss than placebo. Higher-dose tirzepatide, especially 10- and 15-milligram doses, had the largest effect in the analysis. Liraglutide had the smallest effect and is injected daily, while tirzepatide and semaglutide are weekly injections.
The review also looked at side effects, including gastrointestinal symptoms such as nausea, diarrhea and vomiting. According to the university release, tirzepatide appeared to produce greater average weight loss without higher rates of common gastrointestinal side effects compared with the other medications. Still, tolerability can vary widely from person to person, and side effects are one of the main reasons some people stop these medications.
The study focused on adults without diabetes who were using these medications for weight loss. That distinction matters because these drugs are also used in diabetes care, where blood sugar management, cardiovascular risk and other health goals may factor into treatment decisions.
It’s also important to separate weight loss during treatment from what happens after treatment stops. The study did not evaluate weight regain after discontinuing GLP-1 or related medications. Other research has raised concerns that many people regain weight after stopping treatment, which is one reason clinicians often discuss these medications as part of long-term obesity care rather than a short-term fix.
The review also reflects the medication landscape at the time of its analysis. GLP-1 and related medications are changing quickly, including new formulations, new indications and ongoing research into long-term outcomes. Direct head-to-head trials can provide clearer comparisons than indirect analyses, but systematic reviews can help summarize the evidence available at a given moment.
For readers, the most useful message is not that one medication “wins.” It’s that weight-loss medications are not interchangeable, and average results from clinical trials do not answer every question that matters in real life.
A person’s best option may depend on medical history, other medications, side effects, pregnancy plans, digestive conditions, cost, insurance coverage and whether long-term treatment is realistic. Diet quality, protein intake, strength training and follow-up care also matter, especially as people lose weight and work to preserve muscle and maintain nutrition.
These medications have changed the conversation around obesity treatment because they can produce meaningful weight loss for many people. But they’re still prescription medications, not wellness shortcuts. Anyone considering them should work with a qualified health care professional who can explain the likely benefits, risks and trade-offs in the context of their own health.
The authors reported no funding for the study and declared no conflicts of interest.