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Orforglipron Noninferior to Insulin Glargine for CV Outcomes in T2D
Developing
In Short: A phase 3 trial found orforglipron noninferior to insulin glargine for cardiovascular outcomes in people with type 2 diabetes.
In a phase 3 trial presented at the European Association for the Study of Diabetes (EASD) conference in Milan, the once-daily nonpeptide small molecule GLP-1 receptor agonist orforglipron was found to be noninferior to insulin glargine for cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) at increased CV risk.
Although the trial did not demonstrate superiority for CV outcomes, it showed an association of lower risk for major CV events and death with orforglipron.
Insulin glargine was chosen as the comparator due to its established efficacy in glucose-lowering, long-term safety profile, and neutral effect on CV risk and overall mortality.
The trial involved 1,000 participants who were randomized to receive either orforglipron at a maximum tolerated dose (up to 36 mg capsule) daily or daily injected titrated insulin glargine.
Severe hypoglycemia was reported in one individual on orforglipron who was also taking metformin and a sulfonylurea, compared to 12 individuals on insulin glargine.
The safety profile of orforglipron was consistent with previous studies, according to Dr. Klein, who noted that the drug was approved for both weight loss and T2D in the UK in August 2026, but not yet for either indication in the European Union.
An upcoming trial, ATTAIN-OUTCOMES, will be specifically powered to assess CV outcomes for orforglipron.
What's still developing
- The safety profile was consistent with that seen for orforglipron in the previously-reported ACHIEVE-1 and ATTAIN-1 studies for glycemic control and weight management, respectively, Klein said.