Eli Lilly's oral GLP-1 drug Foundayo (orforglipron) demonstrates cardiovascular safety in the Phase 3 ACHIEVE-4 trial of 2,749 adults with type 2 diabetes and obesity. Foundayo meets non-inferiority criteria against insulin glargine, showing a 16% lower risk of major adverse cardiovascular events (MACE-4). While achieving superior A1C reductions of 1.6% and weight loss of 8.8% at 52 weeks, Foundayo causes gastrointestinal side effects in 62.1% of patients, leading to a 10.6% treatment discontinuation rate.
Cardiovascular safety and mortality outcomes
- ▪In the Phase 3 ACHIEVE-4 trial, Eli Lilly and Company's oral GLP-1 receptor agonist Foundayo (orforglipron) demonstrated non-inferiority for cardiovascular safety compared to titrated insulin glargine over a median of 2 years.
- ▪In pre-planned analyses of the ACHIEVE-4 trial, Foundayo was associated with a 53% lower risk of cardiovascular death and a 57% lower risk of all-cause mortality compared to insulin glargine.
- ▪Participants taking Foundayo in the ACHIEVE-4 trial experienced a 16% lower risk of MACE-4 (cardiovascular death, heart attack, stroke, or hospitalization for unstable chest pain) compared to those taking insulin glargine.
Glycemic control and A1C reduction
- ▪At 52 weeks in the ACHIEVE-4 trial, participants treated with Foundayo showed a mean A1C reduction of 1.6% from an 8.22% baseline, compared to a 1.0% reduction for insulin glargine.
- ▪At 104 weeks in the ACHIEVE-4 trial, 54.6% of participants in the Foundayo group achieved an A1C of 6.5% or lower, compared to 23.8% of participants in the insulin glargine group.
Body weight reduction
- ▪At 104 weeks in the ACHIEVE-4 trial, a body weight reduction of 10% or more was achieved by 35.9% of Foundayo participants compared to 3.4% of insulin glargine participants.
- ▪At 52 weeks in the ACHIEVE-4 trial, body weight decreased by 8.8% with Foundayo from a mean baseline of 90.9 kg, compared to a 1.7% weight increase with insulin glargine.
Adverse events and treatment discontinuation
- ▪Gastrointestinal adverse events were the most common reason for participants discontinuing Foundayo treatment during the ACHIEVE-4 trial.
- ▪During the minimum 52-week treatment period of the ACHIEVE-4 trial, 10.6% of participants discontinued Foundayo treatment due to adverse events.
- ▪The most common adverse events reported for Foundayo in the ACHIEVE-4 trial were nausea, vomiting, diarrhea, decreased appetite, and constipation.
- ▪Gastrointestinal adverse events in the ACHIEVE-4 trial were more frequent in the Foundayo group compared to the insulin glargine group, occurring in 62.1% versus 14.2% of participants.
Novo Nordisk oral GLP-1s
- ▪Novo Nordisk debuted its Wegovy pill for obesity in January 2026.
- ▪Novo Nordisk markets an oral semaglutide pill for type 2 diabetes in the United States, which was rebranded from Rybelsus to the Ozempic pill in May 2026.
Hengrui Pharma licensing deals
- ▪Novo Nordisk agreed to pay Hengrui Pharma $300 million up front and up to $2.6 billion in milestones for rights outside of China to HRS-1596, a weekly oral obesity drug candidate.
- ▪Hengrui Pharma has signed six licensing deals with U.S. or European drugmakers since the start of 2025, the most of any China-based biopharmaceutical company.
Debatable claims
- ▪Foundayo is a superior alternative to insulin glargine for type 2 diabetes
- ▪Physicians should wait for superiority trials before prescribing Foundayo for heart protection
- ▪Foundayo's clinical benefits outweigh its high rate of gastrointestinal side effects
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