Lilly’s Orforglipron Demonstrates Semaglutide-Like Efficacy in Phase 3 Type 2 Diabetes Trial

Eli Lilly’s oral GLP-1 receptor agonist orforglipron has met its primary efficacy endpoint in a Phase 3 trial, showing reductions in A1C and body weight on par with injectable semaglutide (Ozempic), Novo Nordisk’s leading single-acting GLP-1 therapy.
In a recent earnings call, Daniel Skovronsky, M.D., Ph.D., Lilly’s Chief Scientific Officer, stated the company aimed to develop an oral therapy with an “efficacy, safety and tolerability profile that is similar to that of an injectable single-acting GLP-1.”
In the 40-week study, individuals with Type 2 diabetes were randomized to receive one of three doses of orforglipron or placebo. A1C reductions ranged from 1.3% to 1.6% across the orforglipron groups, compared to a 0.1% decrease in the placebo arm, meeting the primary endpoint.

Novo Nordisk previously reported A1C reductions of 1.4% to 1.6% after 30 weeks of dosing with semaglutide. In Lilly’s Phase 2 trial, orforglipron achieved reductions of up to 2.1% at 26 weeks, though the highest dose used in that study was not carried into Phase 3.
Weight loss was a key secondary endpoint. Patients on orforglipron lost between 4.7% and 7.9% of their body weight after 40 weeks, with the highest dose group losing an average of 7.3 kg from a mean baseline of 90.2 kg. In comparison, patients on semaglutide in Novo’s trial lost up to 4.7 kg from baseline weights up to 96.9 kg.
Skovronsky previously noted that Lilly anticipates less weight loss in people with diabetes compared to those with obesity, a trend observed across the GLP-1 class. The Phase 2 study for orforglipron reported weight loss of up to 10.1 kg in 26 weeks.
Regarding safety, the most common adverse events reported were diarrhea (up to 26%), nausea (18%), and indigestion (20%). For comparison, Novo’s Phase 3 trial of semaglutide showed rates of nausea and diarrhea at 20% and 9%, respectively.

This Phase 3 readout is the first in a broader clinical program for orforglipron. Lilly anticipates additional data from five Type 2 diabetes studies and two obesity trials. Two of the obesity trials are expected to read out in the third quarter of 2025. The company plans to seek regulatory approval for obesity this year, with Type 2 diabetes submissions targeted for 2026.