Lilly’s GLP-1 Receptor Agonist Cuts Weight by Almost 15% in Mid-Stage Trial

Pictured: Person stepping onto a weighing scale/iStock

Pictured: Person stepping onto a weighing scale/Getty Images

Friday, Eli Lilly revealed new Phase II findings for orforglipron showing that the investigational oral non-peptide GLP-1 receptor agonist can induce statistically significant and clinically meaningful weight reductions in overweight or obese adults.

The data, published the same day in the New England Journal of Medicine and presented at the American Diabetes Association’s 83rd Scientific Sessions, demonstrated that participants who took orforglipron lost 8.6% to 12.6% of their body weight at the 26-week follow-up. Meanwhile, placebo counterparts only saw a 2.0% body weight reduction. Higher doses of orforglipron led to greater weight loss.

Orforglipron’s weight loss effects persisted until 36 weeks. Study participants treated with Lilly’s candidate showed weight loss ranging from 9.4% to 14.7%, whereas placebo comparators only achieved 2.3% weight loss.

Lilly’s oral drug also outperformed placebo at lowering the participants’ body mass index and waist circumference.

Orforglipron belongs to a class of drugs called GLP-1 receptor agonists, which work by inducing the pancreas to release insulin into the bloodstream. Other medicines in this group include Novo Nordisk’s Wegovy and Ozempic, both carry the active ingredient semaglutide, as well as Lilly’s own Mounjaro (tirzepatide).

Unlike most GLP-1 receptor agonists, however, orforglipron is a small molecule drug that can survive in the gastrointestinal tract and can thus be taken orally.

“These study results support the continued development of orforglipron in Phase III,” Jeff Emmick, Lilly’s senior vice president for product development, said in a statement. The company has already launched the Phase III ATTAIN development program for orforglipron in obesity and overweight patients, and the ACHIEVE trials for Type 2 diabetes.

Lilly’s Phase II randomized, double-blinded and placebo-controlled study enrolled 272 adults who at baseline had a mean body weight of 240 pounds and who had at least one weight-related comorbidity except Type 2 diabetes. Orforglipron was given as an oral capsule in the morning at four different doses: 12 mg, 24 mg, 36 mg and 45 mg. The study did not impose any dietary or water restrictions.

Aside from efficacy, the study also assessed orforglipron’s safety and found a safety profile comparable with that of other incretin-based treatments. The most common adverse events were gastrointestinal toxicities, which were generally mild or moderate in severity.

Going up against Lilly’s orforglipron is Boehringer Ingelheim’s and Zealand’s survodutide, which also strongly induced weight loss in overweight or obese adults, according to a Phase II data drop Friday during the 2023 American Diabetes Association’s 83rd Scientific Sessions.

After 46 weeks of treatment, participants given the 4.8-mg dose of survodutide saw an almost 19% weight reduction, while 67% of treated adults achieved weight reduction of at least 15%. Survodutide was also safe and did not demonstrate unexpected signals.

Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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