Eli Lilly released a new analysis on September 29, 2026, at the 62nd EASD Annual Meeting in Milan, comparing its tirzepatide-based Zepbound against Novo Nordisk's higher-dose Wegovy HD (semaglutide 7.2 mg). The company reported that Zepbound produced significantly more weight loss, but the comparison came with an important asterisk: the two drugs were never tested against each other directly.

What the Analysis Found

Using a covariate-adjusted indirect treatment comparison (ITC), Lilly's researchers found that Zepbound 15 mg was associated with 4.5 percentage points more weight loss than Wegovy HD at 72 weeks, and Zepbound 10 mg was associated with 3.2 percentage points more weight loss. Participants on the 15 mg dose also had more than three times the odds of losing at least 20% of their body weight compared with those on Wegovy HD. Lilly reported that rates of treatment discontinuation due to adverse events were comparable between the two drugs.

Why "Indirect" Matters

An indirect treatment comparison doesn't put two drugs in the same trial. Instead, it pulls results from two separate studies, here Zepbound's SURMOUNT-1 trial and Wegovy HD's STEP UP trial, and uses statistical adjustment to account for differences between the two trial populations, in this case gender, age, baseline weight, and baseline A1C. That adjustment can narrow some of the gap between trials that enrolled different people under different conditions at different times, but it can't fully close it. Differences in how weight loss was measured, how closely patients were followed, and who dropped out and why can all still skew the comparison in ways statistical adjustment doesn't fully correct for.

This site's guide to real-world evidence versus randomized controlled trials covers the general hierarchy of evidence; an indirect comparison sits in an awkward middle ground. It uses data from two randomized trials, but the comparison between those trials isn't itself randomized.

Who Funded It, and Why That's Worth Noting

The analysis was conducted and funded by Eli Lilly, the maker of the drug that came out ahead. That doesn't make the underlying numbers wrong, but sponsor-funded indirect comparisons are, almost by definition, selected and framed by the company with the most to gain from a favorable result. A comparison funded by Novo Nordisk using different trials, different adjustment variables, or a different weight-loss endpoint could plausibly produce a different picture. Neither company has published a jointly designed, head-to-head randomized trial directly comparing Zepbound against Wegovy HD specifically.

Regulatory and Safety Context

Both drugs are FDA-approved for chronic weight management: tirzepatide as Zepbound, and semaglutide as Wegovy, including its higher-dose 7.2 mg formulation. Both carry the same class-wide boxed warning regarding thyroid C-cell tumors seen in rodent studies, along with labeling around gastrointestinal side effects, pancreatitis, and allergic reactions. Nothing in this new analysis changes either drug's approved indication or safety labeling.

The Bottom Line

An indirect comparison showing one GLP-1-class drug outperforming another is a real data point, not a fabricated one. But it's a weaker form of evidence than a head-to-head randomized trial, and it was produced by the company whose drug won the comparison. Anyone weighing one of these medications against the other should treat this result as one input, not a verdict, and should discuss their individual health history with a prescribing physician rather than choosing a drug based on a single company-sponsored analysis.