Lilly’s Foundayo shows cardiovascular safety and durable A1C and weight benefits in ACHIEVE‑4
- Foundayo met non‑inferiority for MACE‑4 versus insulin glargine (HR 0.84; 95% CI 0.59–1.20) and reduced MACE‑3 risk (HR 0.77; 95% CI 0.52–1.13).
- Pre‑planned analyses showed lower cardiovascular death (HR 0.47; 95% CI 0.25–0.90) and all‑cause death (HR 0.43; 95% CI 0.25–0.75) versus insulin glargine.
- At 52 weeks A1C fell by 1.6% with Foundayo versus 1.0% with insulin glargine (treatment difference −0.66%; 95% CI −0.74 to −0.58) and mean body weight declined 8.1 kg vs a 1.4 kg gain (treatment difference −10.42%).
- At 104 weeks 54.6% reached A1C ≤6.5% (versus 23.8%) and 35.9% achieved ≥10% weight loss (versus 3.4%); most common adverse events were gastrointestinal and 10.6% discontinued due to adverse events.
Trial design and primary outcome
ACHIEVE‑4 randomized 2,749 adults with type 2 diabetes and BMI ≥25 kg/m² to escalating doses of Foundayo (up to a 17.2 mg equivalent investigational formulation) or titrated insulin glargine. The primary endpoint was time to first MACE‑4 event. Foundayo met the prespecified non‑inferiority criterion for MACE‑4 (HR 0.84; 95% CI 0.59–1.20) and showed a lower point estimate for MACE‑3 (HR 0.77; 95% CI 0.52–1.13).
Cardiovascular, renal and inflammatory signals
Pre‑planned analyses reported lower cardiovascular death (HR 0.47; 95% CI 0.25–0.90) and lower all‑cause mortality (HR 0.43; 95% CI 0.25–0.75) with Foundayo versus insulin glargine. At week 52 Foundayo reduced waist circumference by 7.0 cm, systolic blood pressure by 4.4 mmHg, triglycerides by 18.9%, non‑HDL cholesterol by 6.6% and hsCRP by 38.9%. Kidney measures showed a 2.8 mL/min/1.73 m² smaller eGFR decline and a 27.1% greater reduction in albuminuria versus insulin glargine.
Glycaemic control and weight outcomes
At 52 weeks mean A1C fell from 8.22% by 1.6% on Foundayo versus 1.0% on insulin glargine (estimated treatment difference −0.66%; p<0.001). Mean body weight declined 8.1 kg (−8.8%) on Foundayo versus a 1.4 kg gain (+1.7%) on insulin glargine (treatment difference −10.42%; p<0.001). At 104 weeks 54.6% of Foundayo patients achieved A1C ≤6.5% (23.8% on glargine) and 35.9% achieved ≥10% weight reduction (3.4% on glargine).
Safety and next steps
Adverse events were consistent with incretin therapies, predominantly nausea, vomiting, diarrhea, decreased appetite and constipation; 10.6% discontinued Foundayo for adverse events during the 52‑week minimum treatment period. Lilly is conducting ATTAIN‑OUTCOMES, an ongoing Phase 3 study to evaluate cardiovascular and kidney outcomes with Foundayo in a broader population with established cardiovascular or kidney disease.
Source: Lilly