While Foundayo’s insulin-matching potential in type 2 diabetes had been established in a topline readout earlier this year, Eli Lilly on Wednesday unveiled the fullest picture yet of its oral GLP-1’s ability to keep blood sugar in check, cut weight and, crucially, demonstrate cardiovascular safety in patients with compounding metabolic conditions.
In a deep dive into the Indianapolis drugmaker’s late-stage Achieve-4 trial, which compared Foundayo (orforglipron) with titrated insulin glargine in adults with type 2 diabetes and obesity or overweight who were at increased cardiovascular risk, Lilly’s drug proved noninferior to insulin on the risk of major adverse cardiovascular events (MACE) while delivering greater reductions in A1C and weight.
The comprehensive results were presented as part of Lilly’s showing at the European Association for the Study of Diabetes (EASD) annual meeting in Milan this week and simultaneously published in The Lancet.
Beyond the 16% lower risk of cardiovascular death, heart attack, stroke or hospitalization for unstable sudden chest pain (MACE-4) for Foundayo versus insulin glargine that Lilly reported in April, the study drug was associated with a 23% lower risk of MACE-3, which specifically encompasses cardiovascular death, heart attack or stroke.
Meanwhile, Foundayo was tied to a 53% lower risk of cardiovascular death and a 57% lower risk of all-cause mortality compared with insulin glargine in prespecified analyses, Lilly said.
The trial’s primary endpoint revolved around the time to first occurrence of MACE-4, while key secondary endpoints concerned the timing of patients’ first MACE-3 event, change in A1C from baseline at one year and change in body weight from baseline over that same span.
Trial participants in the Foundayo arm reported a 1.6% reduction in A1C from an 8.22% baseline at 52 weeks, compared with a 1% reduction on insulin glargine. On weight, those who received Foundayo lost an average of 8.8% of their body weight, or nearly 18 pounds, by the one-year mark, versus a 1.7% weight increase among those in the study’s control cohort.
Other reported Foundayo boons included improvements in waist circumference, systolic blood pressure and non-HDL cholesterol that topped insulin, and the drug was further “associated with a slower decline in kidney function,” per Lilly.
The efficacy across cardiometabolic health measures in Achieve-4 “reinforces our confidence that Foundayo could change how physicians and patients approach the treatment of type 2 diabetes,” said Thomas Seck, M.D., SVP of product development for Lilly Cardiometabolic Health, in a statement.
Lilly first trumpeted results from Achieve-4 back in April, knocking out two birds with one stone via a reported cardiovascular safety win that also had the potential to appease the FDA’s desire for additional safety information on the drug.
When Foundayo was approved for obesity in the U.S. earlier that same month, the FDA’s approval letter called on the company to accrue more data on the med’s potential link to MACE and drug-induced liver injury, alongside additional information about delayed gastric emptying and its potential effects in lactating women.
At the time of that readout, Lilly noted that it planned to file for FDA approval of Foundayo in type 2 diabetes by the end of the second quarter, though Lilly has not provided a specific update on its regulatory progress since then.
Meanwhile, when the drug won its second green light in the United Kingdom in August, regulators there signed off on Lilly’s GLP-1 pill as a daily treatment for both chronic weight management and improved glycemic control in patients struggling to keep their type 2 diabetes in check.
Oral GLP-1s have become an increasingly significant part of Lilly’s and Novo’s metabolic medicine businesses, with Novo also debuting its Wegovy pill for obesity back in January. The company also markets the Ozempic pill, reformulated and rebranded from the now-retired Rybelsus in May, as an approved oral semaglutide offering for patients with type 2 diabetes in the U.S.
Since the kickoff of EASD early this week, Lilly and Novo have unleashed a slew of data on their incretin drugs, from injectables like tirzepatide and semaglutide to oral and next-generation offerings, including Lilly’s experimental triple agonist retatrutide.
Detailed data on that latter candidate, which acts on GIP, GLP-1 and glucagon receptors, revealed additional wins beyond a topline weight loss victory in July, including the fact that nearly 35% of patients on the highest 12-mg dose of retatrutide lost at least 25% of their body weight.
In a separate communique Thursday, Lilly used a post-hoc analysis of another study to further tie Foundayo at 17.2 mg to an estimated 57% reduction in predicted type 2 diabetes risk, alongside an estimated 18% reduction in cardiovascular disease risk, both compared with placebo.
That analysis came courtesy of Lilly’s Attain-1 study, which assessed Foundayo in patients without diabetes who had obesity or were overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease.
The new look at the data “gives us real optimism about what long-term Foundayo use could mean, both for patients and for the broader healthcare system,” Seck added in a separate Lilly release.