Aims/Objectives: Obesity and prediabetes are risk factors for developing T2D. 5-10% weight-loss can reduce risk of developing T2D by >50%. This phase-3 trial investigated effects of liraglutide 3.0mg, as adjunct to diet+exercise, on delaying onset of T2D over 3 years (primary endpoint), body-weight and cardiometabolic risk factors.
Methods: Individuals (BMI ≥30kg/m2, or ≥27kg/m2 with ≥1 comorbidity) were randomised 2:1 to once-daily subcutaneous liraglutide 3.0mg (n=1505) or placebo (n=749) and advised on a 500-kcal/day deficit diet and 150-min/week exercise. Efficacy data are observed means, with last-observation-carried-forward (LOCF) imputation. Clinicaltrials.gov NCT01272219.
Results: Baseline characteristics were (mean±SD): age 47.5±11.7 years, 76.0% female, weight 107.6±21.6kg, BMI 38.8±6.4kg/m2. With continued treatment over 160 weeks, time to T2D onset was 2.7-fold longer with liraglutide 3.0mg than placebo [95%CI 1.9;3.9, p<0.0001], corresponding to a hazard ratio of 0.2; 3% vs 11% of patients, respectively were diagnosed with T2D. More individuals on liraglutide (66%) than placebo (36%) regressed from prediabetes (ADA2010 criteria) to normoglycaemia by week 160 (OR 3.6 [3.0;4.4], p<0.0001). Individuals on liraglutide 3.0 mg lost more weight than on placebo (6.1% vs 1.9%; estimated treatment difference [ETD] -4.3% [95%CI ‑4.9;-3.7]), accompanied by greater mean reductions in waist circumference (ETD ‑3.5 [‑4.2;‑2.8] cm), SBP (ETD ‑2.8 [-3.8;-1.8] mmHg), triglycerides (ETD -6%[‑9;-3]) and high-sensitivity C-reactive protein (ETD 29% [-34;-23]) (all p<0.001). Mean pulse increased with liraglutide 3.0mg vs placebo (ETD 2.0 [1.2;2.7] beats/min, p<0.0001). AE incidence was 94.7% with liraglutide 3.0mg vs 89.4% with placebo, SAEs 15.1% vs 12.9%. Adjudicated major adverse cardiovascular events (non-fatal myocardial infarction, stroke, cardiovascular death) were low overall (0.19 vs 0.20 events/100 patient-years-of-observation for liraglutide 3.0mg vs placebo).
Conclusion: Liraglutide 3.0mg, as adjunct to diet+exercise, delayed the onset and reduced the risk of T2D over 3 years in adults with prediabetes, reduced body weight and improved cardiometabolic risk factors.
Supported by Novo Nordisk.