Could orforglipron reshape the GLP-1 market?

In the run-up to one of the most highly anticipated FDA approvals of the year, Eli Lilly is trumpeting a study that suggests its oral GLP-1 is a better drug than its rival in treating patients with diabetes.

With a PDUFA goal date of April 10, 2026, orforglipron is a once-daily oral glucagon-like peptide-1 receptor agonist that is developed by Chugai Pharmaceutical Co. and licensed to Lilly in 2018.

If approved, orforglipron will join a GLP-1 market that is changing rapidly. It will compete against Novo Nordisk’s oral semaglutide, Wegovy, for weight loss, which was approved in December 2025. Novo Nordisk also markets an oral semaglutide as Rybelsus for diabetes and as an injection (Ozempic for diabetes and Wegovy for weight loss). For cash-paying patients, oral Wegovy sells for $149 a month for the 1.5 mg and 4 mg tablets, but the 4 mg offer is only available until April 15, 2026, then it is $199 per month for 4 mg. The higher doses of Wegovy are $299 a month.

Oral GLP-1 therapies, especially for weight loss, are expected to be a “major inflection point in obesity medication accessibility and patient preference,” according to leaders at IQVIA. In a blog post from January 2026, they said the oral GLP-1 medications for weight could improve adherence, provide convenience and potentially provide broader access.

The GLP-1 pipeline continues to provide innovation in obesity treatment, with new combinations such as Novo Nordisk's CagriSema, the first once-weekly combination of semaglutide 2.4 mg and an amylin analogue, and an oral GLP-1/amylin agonist combination. Additionally, long-acting injectables are also being studied, including MET-097i from Metsera, which Pfizer acquired in November 2025. In all, IQVIA estimates there are about 193 therapies in development throughout the pipeline for obesity.

For payers and employers, the near-term impact of new oral approvals is expected to be small. A Mercer analyst suggests the population that would likely seek to use the oral weight loss medications overlaps the injectable population. Mercer suggests that the direct-to-consumer sales are putting pressure on prices of GLP-1s, but new expanding indications (such as liver disease) will also drive demand and cost pressures.

New data on orforglipron

Orforglipron is being studied in a head-to-head phase 3 trial comparing it with oral semaglutide in adults with type 2 diabetes inadequately controlled with metformin as the primary endpoint. The secondary endpoint compared the two products for weight loss.

Investigators found that orforglipron 36 mg lowered A1C by 2.2% compared with 1.4% with oral semaglutide 14 mg. Additionally, patients who received orforglipron 36 mg lost 19.7 pounds compared with 11.0 pounds with oral semaglutide 14 mg, representing a 73.6% greater relative weight loss. Orforglipron also showed clinically meaningful improvements from baseline across key cardiovascular risk factors, including non-HDL cholesterol, HDL cholesterol, VLDL cholesterol, total cholesterol, systolic blood pressure and triglycerides.

Results from the 52-week ACHIEVE-3 open-label study were recently published in The Lancet.

Lead investigator Julio Rosenstock, M.D., said in a news release that these differences were clinically meaningful. He is director of the Dallas Diabetes Research Center at Medical City, and clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas.

“The results of ACHIEVE-3 highlight the potential advantages of orforglipron over oral semaglutide for type 2 diabetes: greater A1C reduction, more weight loss, and the ability to take it without food or water timing restrictions — that’s a combination that could matter significantly to people managing their disease day in and day out,” said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health, in a news release.

The overall safety and tolerability profile of orforglipron in ACHIEVE-3 was consistent with previous trials. The incidence of gastrointestinal events, discontinuations due to adverse events, and mean increase in pulse rate were higher with orforglipron than with oral semaglutide. For orforglipron and oral semaglutide, the most common adverse events were nausea, diarrhea, vomiting, dyspepsia, and decreased appetite. Treatment discontinuation rates were 8.7% (12 mg) and 9.7% (36 mg) for orforglipron compared with 4.5% (7 mg) and 4.9% (14 mg) for oral semaglutide.

The ACHIEVE-3 study enrolled 1,698 patients across the United States, Argentina, China, Japan, Mexico, and Puerto Rico to receive either 12 mg or 36 mg of orforglipron or 7 mg or 14 mg of oral semaglutide. All patients in the oral semaglutide arms started the study at a dose of 3 mg once daily and then increased the dose in a stepwise approach at four-week intervals until receiving a maintenance dose of 7 mg or 14 mg.

Orforglipron is also being studied as a potential treatment for obstructive sleep apnea (OSA) and hypertension in adults with obesity.