Lilly's Oral GLP-1 Drug Shows Promise in Phase 3 Diabetes Trial

Eli Lilly has made significant strides in the development of its oral GLP-1 drug, orforglipron, with recent phase 3 trial results demonstrating efficacy comparable to Novo Nordisk's injectable semaglutide (Ozempic). The study, which focused on patients with type 2 diabetes, marks a potential breakthrough in the quest for more convenient treatment options in the rapidly evolving GLP-1 market.

Efficacy Results and Comparison to Ozempic

The phase 3 trial of orforglipron, involving multiple dosage arms, showed promising results in both blood glucose control and weight loss. After 40 weeks of once-daily dosing:

• A1C reductions ranged from 1.3% to 1.6% across the orforglipron cohorts, compared to a 0.1% drop in the placebo group.
• Weight loss varied between 4.7% and 7.9% of body weight, with the highest dose group losing an average of 7.3 kg from a mean starting weight of 90.2 kg.

These results align closely with previous phase 3 data for Novo Nordisk's Ozempic, which reported A1C reductions of 1.4% to 1.6% after 30 weeks of treatment. However, it's worth noting that Lilly's phase 2 results for orforglipron had shown more substantial improvements, with A1C reductions of up to 2.1% after 26 weeks.

Safety Profile and Next Steps

The safety profile of orforglipron appears consistent with other GLP-1 medications:

• Common adverse events included diarrhea (up to 26% of patients), nausea (up to 18%), and indigestion (up to 20%).
• These rates are comparable to those reported for Ozempic, which saw nausea and diarrhea rates of 20% and 9%, respectively, in its phase 3 trial.

Lilly's Chief Scientific Officer, Daniel Skovronsky, M.D., Ph.D., had previously stated the company's goal of developing an oral drug with efficacy, safety, and tolerability similar to injectable single-acting GLP-1 medications. With these phase 3 results, Lilly appears to be on track to meet this objective.

The company is now poised for a series of data releases, with up to five studies in type 2 diabetes and two trials in obesity expected. Lilly plans to seek approval for orforglipron in obesity this year, with submissions for type 2 diabetes planned for 2026.

As the pharmaceutical industry continues to focus on developing more patient-friendly formulations of GLP-1 drugs, Lilly's progress with orforglipron represents a significant step forward in the potential treatment options for millions of patients with diabetes and obesity.