Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER)

Design

• Population: 9,340 adults with type 2 diabetes and high cardiovascular risk on standard care
• Arms: liraglutide vs placebo; double-blind
• Primary outcome: time to first CV death, nonfatal MI, or nonfatal stroke
• Median follow-up: 3.8 years
• Registry: NCT01179048
• Sponsorship: Novo Nordisk with NIH involvement—read conflicts-of-interest tables in the primary paper

Principal efficacy signals (published primary analysis)

• Primary 3-point MACE: HR 0.87 (95% CI 0.78–0.97); P < 0.001 for noninferiority; P = 0.01 for superiority (13.0% vs 14.9%)
• CV death: HR 0.78 (95% CI 0.66–0.93; P = 0.007)
• All-cause mortality: HR 0.85 (95% CI 0.74–0.97; P = 0.02)
• Nonfatal MI, nonfatal stroke, HF hospitalization: directionally lower on liraglutide but not reported as individually significant in the primary manuscript framing

Safety / tolerance (headline)

• Gastrointestinal adverse events commonly led to discontinuation on liraglutide
• Pancreatitis: incidence did not differ significantly between liraglutide and placebo arms in the published comparison

Evidence hygiene for this wiki

• Molecule-specific: applies to liraglutide in this eligibility definition—do not treat as a class-wide guarantee for semaglutide, dulaglutide, tirzepatide, etc.
• Endpoint family: MACE / mortality complement—but do not replace—short-term wearable autonomic work such as Grosicki et al. 2025 on this protocol page