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Data on Eli Lilly’s Weight Loss Pill Haven’t Thrilled Investors. New Updates Are Complicating the Picture.

Sep 17, 2025 10:35:00 -0400 by Josh Nathan-Kazis | #Biotech and Pharma

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The drugmaker Eli Lilly’s reign as the undisputed king of the weight loss trade came under threat in early August, after disappointing preliminary data on its closely watched experimental weight loss pill set off a 14% single-day selloff.

This week, an avalanche of new data on the pill isn’t dramatically improving the picture.

Investors had hoped that Lilly’s experimental pill, orforglipron, would work better as an obesity treatment than Novo Nordisk’s injection Wegovy, and that patients looking for a more convenient option might choose it instead.

That didn’t pan out in early August, when Lilly said patients on their pill lost 12.4% of their weight on average over 72 weeks, short of the 15% weight loss Wegovy delivered in earlier trials. An oral version of Wegovy, now under Food and Drug Administration review, has also demonstrated 15% weight loss.

Lilly shares fell sharply on the day the company released the preliminary data, closing at $640.86. Since then, the picture has grown more complicated. While Lilly’s orforglipron may not be as effective in obese patients as investors had hoped, it returned a surprisingly good result in a trial previewed in late August, showing that patients with both obesity and Type 2 diabetes, a more difficult-to-treat group, lost 10% on orforglipron.

Late Tuesday and early Wednesday, Lilly reported more data on orforglipron, which together don’t seem strengthen the case for the drug as an alternative to Novo’s drugs for patients only seeking weight loss—but do continue to suggest it could be an important tool for patients with Type 2 diabetes.

Lilly shares were up 0.9% on Wednesday morning.

The orforglipron updates started late Tuesday, when Lilly published the full results of the weight loss trial previewed in early August in the New England Journal of Medicine. The article showed that patients on all doses had stopped losing weight after 48 weeks, erasing hopes that the underwhelming body weight reductions might have continued if the trial persisted.

Side effects had also been a worry when Lilly announced the preliminary results in August. At the time, the company had said that 10.3% of patients on the highest dose had stopped taking the pill because of side effects, compared with 2.6% of patients on the placebo. The New England Journal paper published Tuesday said that 7% of the patients in the highest dose group stopped taking the drug because of a gastrointestinal disorder, compared with 0.4% in the placebo group.

In the high-dose group, 23.1% reported diarrhea, while 24% reported vomiting. In a note late Tuesday, Citi Research analyst Geoff Meacham noted that vomiting and diarrhea remained “relatively persistent” over the course of the study.

Still, Meacham said that the tolerability wouldn’t be an issue for the drug’s uptake. “We think the tolerability profile is mostly benign and continue to believe orforglipron’s data support use in a broad, commercial setting,” Meacham wrote.

On Wednesday morning, Lilly rolled out more orforglipron data. In a trial of patients with Type 2 diabetes, Lilly said that patients who received orforglipron saw more weight loss and a greater reduction in blood sugar than patients on an oral version of Novo’s semaglutide, the drug sold under the brand names Wegovy and Ozempic. Novo sells oral semaglutide under the brand name Rybelsus as a Type 2 diabetes treatment. Novo has asked the Food and Drug Administration to approve a higher-dose version as a weight loss treatment. Lilly’s trial tested orforglipron against the lower dose version now sold as Rybelsus.

In the trial, patients on the higher dose of orforglipron saw a 2.2% reduction in A1C levels after 52 weeks, while patients on a higher dose of Rybelsus saw a 1.4% reduction. Weight loss after 52 weeks was 9.2% on orforglipron, and 5.3% on Rybelsus.

“These results, combined with orforglipron’s once-daily oral dosing and broad scalability, reinforce its potential as a foundational treatment for Type 2 diabetes,” Lilly’s president of cardiometabolic health, Kenneth Custer, said in a statement.

Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com