Lilly’s oral GLP-1 Foundayo outperforms comparators across three pivotal type 2 diabetes trials in A1C control and weight reduction

Three Phase 3 trials from the ACHIEVE programme have added substantial weight to the case for Foundayo (orforglipron), Lilly’s small molecule oral GLP-1 therapy that places no restrictions on food or water intake. Taken together, the trials evaluated the therapy in adults managing type 2 diabetes and were presented at the American Diabetes Association (ADA) 86th Scientific Sessions, with ACHIEVE-3 published in The Lancet and ACHIEVE-2 and ACHIEVE-5 appearing in The Lancet and JAMA respectively.

The standout finding came from ACHIEVE-3, the first trial ever to pit two oral GLP-1 receptor agonists directly against one another in a Phase 3 setting. Over 52 weeks, those on Foundayo 17.2 mg saw their A1C fall by an average of 2.2%, nearly double the 1.4% recorded among those taking the highest approved dose of oral semaglutide. At the same dose comparison, Foundayo produced 73.6% greater relative weight loss, with participants shedding an average of 19.7 lbs against 11.0 lbs with oral semaglutide. More than a third of those on the highest Foundayo dose reached an A1C below 5.7%, the marker for normal blood sugar, compared to just 12.5% on oral semaglutide.

Turning to ACHIEVE-2, Foundayo went up against dapagliflozin over 40 weeks in participants with an average baseline A1C of 8.1%. Those on the highest dose brought their A1C down by an average of 1.7%, more than double the 0.8% reduction seen with dapagliflozin, and nearly seven in ten reached an A1C at or below 6.5%. Weight loss with Foundayo scaled with dose, reaching up to 15.0 lbs at the highest dose against 6.0 lbs with dapagliflozin.

In ACHIEVE-5, Foundayo was placed alongside titrated insulin glargine and measured against placebo added to the same regimen over 40 weeks. Starting from an average baseline A1C of 8.5%, those on Foundayo 9 mg achieved an average reduction of 2.1% versus 0.8% with placebo, and 69.1% reached an A1C at or below 6.5% compared to just 11.1% in the placebo group. While placebo recipients gained an average of 1.1 lbs over the course of the trial, those on Foundayo lost up to 11.5 lbs.

“When we look across the ACHIEVE program, Foundayo consistently demonstrated superior A1C control and weight loss, giving us real confidence in what it could deliver for patients,” said Thomas Seck, M.D., Senior Vice President of Product Development, Lilly Cardiometabolic Health. “ACHIEVE-3 marks the first time two oral GLP-1 therapies have been tested head-to-head in a Phase 3 study, and Foundayo clearly outperformed oral semaglutide on the outcomes that matter most to patients with type 2 diabetes. For the millions of people with type 2 diabetes who want an oral treatment they can take any time of day, Foundayo has the potential to be an attractive first-line therapy option in primary care.”

“ACHIEVE-3 provides the first head-to-head data on oral GLP-1s in type 2 diabetes, with orforglipron showing greater A1C and weight reductions than oral semaglutide, which was tested at approved diabetes doses,” said Dr. Julio Rosenstock, clinical professor of medicine at the University of Texas Southwestern Medical Center and ACHIEVE-3 lead investigator. “That level of efficacy is reinforced in ACHIEVE-2 and ACHIEVE-5, demonstrating a consistent and robust treatment effect across a wide spectrum of patient populations. These results support a potential shift toward using oral GLP-1 receptor agonist therapies like orforglipron earlier as a foundation of type 2 diabetes care.”

Across all three trials, Foundayo generated clinically meaningful improvements in a broad set of cardiovascular risk markers from baseline, covering areas including cholesterol fractions, systolic blood pressure, and triglyceride levels.

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Related Topics and Keywords

A1C control, Foundayo, GLP-1, glp1, Lilly's oral GLP-1 Foundayo, type 2 diabetes