Eli Lilly presented indirect-comparison analyses at EASD showing Zepbound (15 mg and 10 mg) achieved greater weight loss than Wegovy HD at 72 weeks, with 15 mg linked to a 4.5-point larger reduction and fourfold higher odds of ≥20% weight loss. Separately, Foundayo (17.2 mg) produced 1.5 points more weight loss and a 0.3% greater A1C reduction versus 25 mg oral semaglutide over 52 weeks. All comparisons adjusted for baseline factors, but results are from indirect analyses and should be confirmed in head-to-head trials.
Eli Lilly Data: Zepbound Outperforms Wegovy — Foundayo Shows Greater Weight Loss and A1C Reduction Versus Oral Semaglutide
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Eli Lilly presented new indirect-comparison analyses at the Annual Meeting of the European Association for the Study of Diabetes showing that its investigational medicines Zepbound and Foundayo produced larger weight reductions and improved glycemic control than semaglutide-based therapies from Novo Nordisk in pooled trial comparisons.
Key Findings for Zepbound (Obesity)
The obesity analysis combined patient-level and aggregate data from the SURMOUNT-1 and STEP UP trials. At 72 weeks, participants receiving 15 mg Zepbound lost on average 4.5 percentage points more body weight than those treated with Wegovy HD (treatment-regimen estimand). The 10 mg Zepbound group experienced a 3.2 percentage-point greater mean weight reduction versus Wegovy HD.
The analysis also examined substantial weight-loss thresholds: the 15 mg Zepbound group had approximately four times the odds of losing ≥20% of body weight compared with Wegovy HD, while the 10 mg group had more than double the odds. Rates of treatment discontinuation due to adverse events were reported as comparable between Zepbound doses and Wegovy HD. Eli Lilly noted these indirect results are consistent with prior randomized Phase 3b SURMOUNT-5 data.
Key Findings for Foundayo (Type 2 Diabetes)
For adults with type 2 diabetes, Eli Lilly compared Foundayo 17.2 mg with 25 mg oral semaglutide using data from the ACHIEVE-3 and PIONEER PLUS trials over 52 weeks. Foundayo produced 1.5 percentage points greater mean weight loss and an additional 0.3% A1C reduction. Alternative statistical approaches reported consistent effects, with differences up to 2.4 percentage points more weight loss and up to 0.6% additional A1C reduction in some analyses.
Analysis Notes and Limitations
All reported comparisons were adjusted for baseline covariates including sex, age, baseline weight and baseline A1C to account for differences between trial populations. These were indirect treatment comparisons that pooled data across separate trials rather than randomized, head-to-head studies. While informative, indirect comparisons can be affected by residual confounding and should be interpreted with caution; direct randomized comparisons remain the gold standard for confirming superiority.
Bottom line: The presented analyses suggest Zepbound may offer greater weight loss than Wegovy HD at the evaluated doses and that Foundayo may deliver modestly larger weight and A1C improvements than oral semaglutide in the examined trial datasets, but confirmation in head-to-head trials would strengthen these conclusions.
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