INDIANAPOLIS, April 16, 2026

Eli Lilly and Company announced positive results from its ACHIEVE-4 Phase 3 clinical trial, demonstrating that Foundayo (orforglipron) achieved cardiovascular safety and significant cardiometabolic benefits in adults with type 2 diabetes and elevated cardiovascular risk. The study, which enrolled over 2,700 patients across 15 countries, confirmed that the once-daily oral therapy met its primary endpoint of non-inferiority versus insulin glargine in major adverse cardiovascular events (MACE), while also delivering superior improvements in blood sugar control and body weight reduction.

Phase 3 Trial Demonstrates Cardiovascular Safety Advantage

The ACHIEVE-4 trial, the largest and longest study of Foundayo to date, demonstrated a 16% lower risk of major cardiovascular events (MACE-4) and a 23% lower risk of MACE-3 events compared to insulin glargine, confirming its cardiovascular safety profile in high-risk patients. Notably, a pre-planned analysis showed a 57% reduction in all-cause mortality, highlighting the potential of Foundayo to provide broader health benefits beyond glucose control.

The trial’s primary endpoint was successfully met, with Foundayo demonstrating non-inferiority in cardiovascular outcomes, a critical requirement for diabetes therapies. This reinforces confidence in the drug’s ability to safely manage patients with both metabolic and cardiovascular comorbidities, a growing concern in global healthcare systems.

Superior Glycemic Control and Weight Reduction

Advertisement

cGxPJobs Banner

In addition to cardiovascular outcomes, Foundayo delivered clinically meaningful improvements in glycemic control, with a 1.6% reduction in A1C levels compared to 1.0% with insulin glargine, demonstrating statistically significant superiority. Furthermore, patients treated with Foundayo experienced substantial weight loss of 8.8%, while those receiving insulin glargine gained weight, resulting in a treatment difference exceeding 10%.

The therapy also showed improvements across several cardiometabolic risk factors, including reductions in non-HDL cholesterol, systolic blood pressure, triglycerides, and inflammatory markers, supporting its role as a comprehensive metabolic treatment.

As a non-peptide oral GLP-1 receptor agonist, Foundayo offers a significant advantage over injectable therapies, providing once-daily dosing without food or water restrictions, improving patient convenience and adherence.

Regulatory Pathway and Future Outlook

Based on these results, Lilly plans to submit Foundayo for FDA approval in type 2 diabetes by the end of Q2 2026, leveraging its strong clinical profile across multiple Phase 3 trials involving more than 11,000 patients globally. The drug is already approved for chronic weight management, further supporting its versatility as a dual-benefit therapy for obesity and diabetes.

The broader ACHIEVE clinical program continues to evaluate Foundayo across multiple indications, including hypertension, sleep apnea, and cardiovascular disease, reflecting its potential to become a multi-indication metabolic therapy.

With the increasing global burden of type 2 diabetes and obesity, therapies that address both glycemic control and cardiovascular risk are becoming essential in modern treatment paradigms. Foundayo’s strong clinical performance positions it as a next-generation oral GLP-1 therapy capable of transforming diabetes care.

The ACHIEVE-4 Phase 3 results reinforce Foundayo’s potential as a safe, effective, and convenient oral therapy for patients with type 2 diabetes. With robust cardiovascular outcomes, significant weight loss, and improved metabolic health markers, Lilly is advancing a promising treatment that could reshape the future of diabetes management and cardiometabolic care.

Source: Eli Lilly press release