Eli Lilly’s oral GLP-1 outperforms oral semaglutide in head-to-head diabetes trial
The findings add to competitive pressure on Novo Nordisk’s GLP-1 portfolio and come days after the Danish drugmaker reported that its next-generation obesity drug, CagriSema, did not meet its primary endpoint in a head-to-head study against Lilly’s tirzepatide.
- Feb 26, 2026,
- Updated Feb 26, 2026 7:11 PM IST
Eli Lilly’s investigational oral GLP-1 drug, orforglipron, delivered stronger blood sugar reduction and greater weight loss than oral semaglutide in a 52-week head-to-head Phase 3 trial in adults with type 2 diabetes, according to results published in The Lancet on Thursday.
The findings add to competitive pressure on Novo Nordisk’s GLP-1 portfolio and come days after the Danish drugmaker reported that its next-generation obesity drug CagriSema did not meet its primary endpoint in a head-to-head study against Lilly’s tirzepatide. Together, the developments points at an intensifying contest in one of the fastest-growing segments of metabolic medicine.
The ACHIEVE-3 study enrolled 1,698 adults with type 2 diabetes inadequately controlled on metformin. Participants received either orforglipron (12 mg or 36 mg) or oral semaglutide (7 mg or 14 mg), which is marketed by Novo Nordisk.
At the highest dose, orforglipron reduced HbA1c by 2.2 percentage points from a baseline of 8.3 per cent, compared with a 1.4 percentage point reduction with oral semaglutide 14 mg. The 12 mg dose achieved a 1.9 percentage point decline.
Weight loss outcomes also favoured Lilly’s candidate. Participants receiving orforglipron 36 mg lost 9.2 per cent of body weight, compared with 5.3 per cent with oral semaglutide 14 mg. A greater proportion of patients on orforglipron achieved HbA1c below 7 per cent at week 52.
“Orforglipron 12 mg and 36 mg doses outperformed oral semaglutide 7 mg and 14 mg diabetes-related doses on every key endpoint we measured, including A1C and weight loss,” said Dr Julio Rosenstock, lead investigator of the study.
Orforglipron is a once-daily, small-molecule oral GLP-1 receptor agonist that can be taken without food or water restrictions, potentially offering a convenience advantage over existing oral GLP-1 options.
The safety profile was consistent with the GLP-1 class, with gastrointestinal side effects most commonly reported. Discontinuation rates due to adverse events were higher with orforglipron than with oral semaglutide.
Lilly has submitted orforglipron to regulators in more than 40 countries, with potential US regulatory action for obesity expected in the second quarter of 2026. A submission for type 2 diabetes in the US is planned later this year. If approved, orforglipron could further reform competition in the GLP-1 segment, where Novo Nordisk’s semaglutide franchise has been a key growth driver.
Eli Lilly’s investigational oral GLP-1 drug, orforglipron, delivered stronger blood sugar reduction and greater weight loss than oral semaglutide in a 52-week head-to-head Phase 3 trial in adults with type 2 diabetes, according to results published in The Lancet on Thursday.
The findings add to competitive pressure on Novo Nordisk’s GLP-1 portfolio and come days after the Danish drugmaker reported that its next-generation obesity drug CagriSema did not meet its primary endpoint in a head-to-head study against Lilly’s tirzepatide. Together, the developments points at an intensifying contest in one of the fastest-growing segments of metabolic medicine.
The ACHIEVE-3 study enrolled 1,698 adults with type 2 diabetes inadequately controlled on metformin. Participants received either orforglipron (12 mg or 36 mg) or oral semaglutide (7 mg or 14 mg), which is marketed by Novo Nordisk.
At the highest dose, orforglipron reduced HbA1c by 2.2 percentage points from a baseline of 8.3 per cent, compared with a 1.4 percentage point reduction with oral semaglutide 14 mg. The 12 mg dose achieved a 1.9 percentage point decline.
Weight loss outcomes also favoured Lilly’s candidate. Participants receiving orforglipron 36 mg lost 9.2 per cent of body weight, compared with 5.3 per cent with oral semaglutide 14 mg. A greater proportion of patients on orforglipron achieved HbA1c below 7 per cent at week 52.
“Orforglipron 12 mg and 36 mg doses outperformed oral semaglutide 7 mg and 14 mg diabetes-related doses on every key endpoint we measured, including A1C and weight loss,” said Dr Julio Rosenstock, lead investigator of the study.
Orforglipron is a once-daily, small-molecule oral GLP-1 receptor agonist that can be taken without food or water restrictions, potentially offering a convenience advantage over existing oral GLP-1 options.
The safety profile was consistent with the GLP-1 class, with gastrointestinal side effects most commonly reported. Discontinuation rates due to adverse events were higher with orforglipron than with oral semaglutide.
Lilly has submitted orforglipron to regulators in more than 40 countries, with potential US regulatory action for obesity expected in the second quarter of 2026. A submission for type 2 diabetes in the US is planned later this year. If approved, orforglipron could further reform competition in the GLP-1 segment, where Novo Nordisk’s semaglutide franchise has been a key growth driver.