Reduction in the risk of developing type 2 diabetes (T2D) with liraglutide 3.0 mg in people with prediabetes from the SCALE Obesity and Prediabetes randomized, double-blind, placebo-controlled trial

This 3-year trial investigated the effect of liraglutide 3.0 mg, as an adjunct to diet and exercise (D&E), in delaying the onset of T2D (primary endpoint) in adults with prediabetes and obesity (BMI ≥30 kg/m²) or overweight (≥27 kg/m²) with comorbidities.

Participants were randomised 2:1 to once-daily subcutaneous liraglutide 3.0 mg or placebo; all were advised on D&E. Efficacy data are observed means, with last observation carried forward for missing values.

Of 2254 randomised individuals (n = 2254) with prediabetes (age 47.5 ± 11.7 years, 76.0% female, weight 107.6 ± 21.6 kg, BMI 38.8 ± 6.4 kg/m², mean ± SD), 1128 completed 160 weeks (52.6% liraglutide 3.0 mg; 45.0% placebo). At week 160, mean weight loss (WL) was 6.1% with liraglutide 3.0 mg vs. 1.9% with placebo (estimated treatment difference -4.3% [95% CI -4.9; -3.7], p < 0.0001). Comparing liraglutide 3.0 mg and placebo, 49.6% vs. 23.7% of individuals achieved ≥5% WL (estimated odds ratio [OR] 3.2 [2.6; 3.9]) and 24.8% vs. 9.9% achieved > 10% WL (OR 3.1 [2.3; 4.1]), both p < 0.0001. Time to T2D onset was 2.7 times longer with liraglutide 3.0 mg vs. placebo (95% CI 1.9; 3.9) and the risk of developing T2D (1.8% vs. 6.2%, respectively) was reduced by 79.3% with liraglutide 3.0 mg (p < 0.0001). Withdrawal rates due to adverse events were 13.3% (liraglutide 3.0 mg) vs. 6.2% (placebo); serious events were 15.1% vs. 12.9%. Gallbladder-related events and cases of confirmed pancreatitis were low, but more frequent with liraglutide 3.0 mg vs. placebo.

Liraglutide 3.0 mg, with exercise D&E, delayed the onset and reduced the risk of developing T2D over 3 years versus placebo, provided greater sustained WL, and was generally well tolerated.