Eli Lilly's Oral Weight Loss Drug Shows Promise, But Safety Concerns Linger

Eli Lilly's oral weight loss candidate, orforglipron, has shown significant promise in recent clinical trials, but some analysts remain concerned about its safety profile. The pharmaceutical giant presented data from its Phase III ACHIEVE-1 trial at the American Diabetes Association (ADA) conference, simultaneously publishing results in The New England Journal of Medicine.

Efficacy and Liver Safety Data Impress Analysts

Orforglipron demonstrated strong efficacy in lowering blood sugar levels in type 2 diabetes patients, setting a positive precedent for its potential in obesity treatment. Contrary to initial concerns, liver enzyme data showed no signs of organ damage. In fact, liver markers decreased from baseline by two to four points, according to Jefferies analysts.

Lilly's management addressed the liver enzyme issue during an investor event, stating that the FDA is encouraging the inclusion of patients with higher baseline liver enzymes to better represent the typical patient population. Patients with elevated baseline levels did not experience further increases, and their enzymes normalized or returned to baseline during the trial.

Persistent Gastrointestinal Side Effects Raise Eyebrows

While many analysts praised the overall safety profile of orforglipron, William Blair expressed concerns about the persistence of gastrointestinal adverse events. At the highest dose, symptoms such as nausea, vomiting, and constipation did not appear to taper off as typically observed with GLP-1 drugs like Novo Nordisk's semaglutide (Wegovy) and Lilly's own tirzepatide (Zepbound).

Jeff Emmick, Lilly's senior vice president of product development, countered this characterization during an investor call. He noted geographic variabilities in the study, with higher rates of diarrhea observed in patients from India and China, and extremely low rates in Japan. Emmick compared the gastrointestinal adverse events to those of tirzepatide, emphasizing that less than 6% of patients at the highest dose discontinued due to these side effects.

Future Outlook and Market Segmentation

Lilly plans to file for approval of orforglipron in obesity by the end of this year, followed by a type 2 diabetes application in 2026. The company is also exploring the drug's potential in sleep apnea and hypertension, mirroring the approach taken with Zepbound.

Ken Custer, Lilly's newly appointed president of cardiometabolic health, predicts that patient preference will drive the future of the obesity market. He anticipates segmentation based on factors such as preferred route of administration, dosing frequency, tolerability, and desired weight loss outcomes.

As the pharmaceutical industry eagerly awaits the results of the Phase III ATTAIN trial, which will provide crucial weight loss data for orforglipron, Eli Lilly continues to position itself as a major player in the evolving landscape of obesity and diabetes treatment.