Lilly presents fuller ACHIEVE-4 cardiovascular dataset for Foundayo at EASD

Eli Lilly is detailing results from ACHIEVE-4, the longest Phase 3 study of its oral GLP-1 pill Foundayo (orforglipron), at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD), held September 28 to October 2, 2026 in Milan, Italy ^[2]. The company's Foundayo symposium, which covers Phase 3 results across the ACHIEVE type 2 diabetes program, is scheduled for Thursday, October 1 ^[2].

The fuller presentation builds on topline results Lilly released on April 16, 2026 ^[1]. ACHIEVE-4 randomized 2,749 adults with type 2 diabetes and obesity or overweight (BMI of 25 kg/m² or higher) who were at increased risk of cardiovascular events, across the U.S., Puerto Rico and more than a dozen other countries ^[1]. It was an event-driven, open-label trial comparing escalating doses of Foundayo with insulin glargine, a long-acting insulin ^[1].

What the trial found

The primary goal was to show that Foundayo was not worse than insulin glargine on MACE-4 — a combined count of cardiovascular death, heart attack, stroke or hospitalization for unstable and sudden chest pain ^[1]. Foundayo met that bar: risk was 16% lower than with insulin glargine (hazard ratio 0.84; 95% confidence interval 0.59 to 1.20; p=0.336), inside the prespecified non-inferiority margin, which required the upper limit of the confidence interval to fall below 1.8 ^[1][2]. A narrower three-part measure, MACE-3, showed a 23% lower risk (hazard ratio 0.77; 95% CI 0.52 to 1.13; p=0.181) ^[2]. Because both confidence intervals cross 1.0, those reductions were not statistically significant on their own; Lilly describes the findings as suggesting "the potential to provide cardiovascular benefits" ^[2].

In a pre-planned analysis that was not controlled for multiple comparisons, the risk of death from any cause was 57% lower with Foundayo (hazard ratio 0.43; 95% CI 0.25 to 0.75; nominal p=0.002) ^[1]. Lilly flags that this endpoint, along with lipids, blood pressure and hsCRP, was not adjusted for family-wise error, which means the result is considered supportive rather than definitive ^[1].

On blood sugar and weight, Foundayo beat insulin. From a mean baseline A1C of 8.22%, A1C fell 1.6% with Foundayo versus 1.0% with insulin glargine at 52 weeks (treatment difference −0.66; p<0.001) ^[1]. From a mean baseline weight of 90.9 kg (200.4 lbs), Foundayo users lost 8.8% of body weight (8.1 kg, or 17.9 lbs) while insulin glargine users gained 1.7% (1.4 kg, or 3.1 lbs), a difference of 10.42 percentage points (p<0.001) ^[1]. Both effects persisted through 104 weeks ^[1].

Side effects were in line with the GLP-1 class: nausea, vomiting, diarrhea, decreased appetite and constipation were most common, and 10.6% of Foundayo patients stopped treatment because of adverse events during the 52-week minimum treatment period ^[1]. A detailed liver analysis found no hepatic safety signal, consistent with earlier ACHIEVE and ATTAIN studies ^[1].

Why it matters for patients

Foundayo is already FDA-approved in the U.S. for chronic weight management in adults with obesity, or with overweight plus weight-related medical problems ^[1]. It is not yet approved for type 2 diabetes. ACHIEVE-4 is the cardiovascular safety study regulators typically expect for a new diabetes drug, and it compares the pill against insulin rather than a placebo — a comparison closer to what many people with longer-standing type 2 diabetes face.

Practically, the trial tested a once-daily pill that can be taken at any time of day without food or water restrictions ^[1][2]. Participants started at a 1 mg capsule (equal to 0.8 mg in tablet form) and increased every four weeks up to a maximum tolerated dose of 36 mg capsule / 17.2 mg tablet ^[1]. Whether the mortality and MACE numbers hold up in other trials has not been established.

What happens next

Lilly said in April it would submit Foundayo for type 2 diabetes to the FDA by the end of the second quarter of 2026 using the Commissioner's National Priority Review Voucher ^[1]. Whether that filing has been accepted, and any FDA decision date, has not been reported. Also at EASD, Lilly is presenting an ACHIEVE-2/ACHIEVE-3 analysis indicating Foundayo 17.2 mg helped patients reach A1C and weight goals faster than dapagliflozin and oral semaglutide 7 mg and 14 mg, based on median time ^[2].