Lilly's Oral GLP-1 Drug Matches Ozempic in Phase 3 Diabetes Trial

Eli Lilly has made significant strides in developing an oral GLP-1 drug, orforglipron, which shows promise in treating Type 2 diabetes with efficacy that rivals Novo Nordisk's injectable semaglutide. In a recent Phase 3 clinical trial, orforglipron demonstrated notable reductions in blood glucose levels and body weight, similar to results achieved by Novo Nordisk's Ozempic, though slightly less than Lilly's earlier mid-phase data.

The Phase 3 study involved randomizing Type 2 diabetes patients to receive one of three doses of orforglipron or a placebo for a period of 40 weeks. The research findings revealed that A1C levels, a critical measure of blood sugar control, decreased between 1.3% and 1.6% for those on orforglipron, compared to a marginal 0.1% reduction in the placebo group. These outcomes ensured that the trial met its primary endpoint, with comparisons showing similar A1C reductions of 1.4% to 1.6% after 30 weeks in a previous Phase 3 trial of Ozempic. However, it's worth noting that Lilly observed a more significant A1C drop of 2.1% in its Phase 2 trial, where higher doses were administered.

Weight loss emerged as a pivotal secondary endpoint in Lilly's study of orforglipron. After 40 weeks, participants experienced weight reductions ranging from 4.7% to 7.9%, with those on the highest dose achieving the most significant weight loss. Patients receiving the top dose lost an average of 7.3 kilograms from an initial weight of 90.2 kilograms. Comparatively, Novo Nordisk's Phase 3 trial with Ozempic showed weight loss of up to 4.7 kilograms from starting weights as high as 96.9 kilograms. During Lilly's Phase 2 trial, more substantial weight loss was observed, with patients losing up to 10.1 kilograms over 26 weeks.

Eli Lilly also provided insights into the safety and tolerability of orforglipron. The most frequently reported adverse events included diarrhea, nausea, and indigestion, affecting up to 26%, 18%, and 20% of participants on the oral GLP-1 drug, respectively. For context, Novo Nordisk reported nausea and diarrhea rates of 20% and 9%, respectively, in its Phase 3 semaglutide trial.

This data release marks the beginning of a series of forthcoming reports on orforglipron. Lilly anticipates results from as many as five studies focused on Type 2 diabetes and two trials addressing obesity, with two Phase 3 obesity results expected in the third quarter. The company aims to leverage these findings to seek regulatory approval for obesity treatment later this year, with plans to apply for Type 2 diabetes approval by 2026.

Analysts at Citi noted that the trial results surpassed market expectations of 5-6% weight loss for orforglipron. Additionally, the absence of liver toxicity was a relief, especially in light of Pfizer's recent discontinuation of its oral GLP-1 candidate due to liver-related concerns. Following the announcement, Eli Lilly's stock surged by 15%, reaching $844.69 in early trading hours on Thursday, compared to a closing price of $734.90 on Wednesday.