Lilly touts results for once-daily weight-loss and antidiabetic pill

The race to develop small-molecule alternatives to peptide-based weight-loss and antidiabetes drugs isn’t over, but a leader and a laggard have emerged.

Eli Lilly and Company, which already markets weight-loss and diabetes drugs that must be injected, is a step closer to introducing a once-daily pill for the same conditions.

On April 17, the company announced the results of a Phase 3 clinical trial of orforglipron, a small molecule that it licensed from the Japanese firm Chugai Pharmaceutical in 2018. The molecule functions as a glucagon-like peptide 1 (GLP-1) receptor agonist—using the same mode of action as the peptide-based injectables marketed by both Lilly and Novo Nordisk.

In Lilly’s study, called Achieve-1, the company compared the safety and efficacy of orforglipron to those of a placebo in adults with type 2 diabetes and inadequate glycemic control who were on a diet and exercise regimen. According to Lilly’s press release, the results showed that the pill, which can be taken without food and water restrictions, led to a greater reduction in hemoglobin A1c, a protein indicating high blood sugar levels, and more body weight reduction than the placebo after 40 weeks.

Side effects included nausea, vomiting, and diarrhea. Another arm of the study is evaluating the molecule’s efficacy as a weight-loss candidate.

“The overall safety profile of orforglipron in ACHIEVE-1 was consistent with the established GLP-1 class,” Lilly says in its release.

Lilly CEO David Ricks says in the release that if orforglipron gets approved by the US Food and Drug Administration, it will provide people worldwide with an option that “could be readily manufactured and launched at scale.” Last year, the company’s injectable drugs ran into repeated shortages, opening a loophole for compounding pharmacies to offer lower-priced alternatives.

Lilly expects to ask the FDA to approve the pill for weight loss later this year. The company has already stockpiled bulk orforglipron worth over half a billion dollars, it disclosed in a recent US Securities and Exchange Commission filing.

The results Lilly is reporting for its oral pill come as another big drug company, Pfizer, has decided to discontinue its investigational GLP-1 weight-loss pill, danuglipron, after noting liver toxicity in one of the people enrolled in its clinical trial.

Pfizer says in a press release that an asymptomatic volunteer in the study had experienced “potential drug-induced liver injury” that resolved after stopping the medication.

While Lilly looks likely to bring the first oral GLP-1 pill to market, other firms are working on their own versions. For example, Regor Therapeutics and Terns Pharmaceuticals are testing their drugs in Phase 2 clinical trials and expect to announce results later this year.