Endocrine Abstracts

Aims/objectives: Obesity and prediabetes are risk factors for developing T2D. 5–10% weight-loss can reduce risk of developing T2D by >50%. The 3-year part of this phase 3 trial investigated effects of liraglutide 3.0 mg, as adjunct to diet+exercise, in delaying onset of T2D over 3 years, body-weight and cardiometabolic risk factors in adults with obesity or overweight with comorbidities, and diagnosed with prediabetes at screening.

Methods: Individuals (BMI ≥30 kg/m², or ≥27 kg/m² with ≥1 comorbidity) were randomised 2:1 to once-daily subcutaneous liraglutide 3.0 mg (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. (NCT01272219).

Results: Baseline characteristics were (mean±S.D.): age 47.5±11.7 years, 76.0% female, weight 107.6±21.6 kg, BMI 38.8±6.4 kg/m². With continued treatment over 160 weeks, estimated time to onset of diabetes was 2.7 times longer with liraglutide 3.0 mg than with placebo (95% CI, 1.9–3.9, P<0.001), corresponding to a HR of 0.2. Based on the Kaplan-Meier plot of cumulative probability of a diagnosis of diabetes, 3% of patients in the liraglutide group vs 11% in the placebo group were diagnosed with diabetes by week 160 while on treatment. More individuals on liraglutide (66%) vs placebo (36%) regressed to normoglycaemia by week 160 (OR 3.6 [3.0;4.4], P<0.001). Individuals on liraglutide 3.0 mg lost more weight than on placebo (6.1% vs 1.9%; 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 3.0 mg vs placebo (ETD 2.0 [1.2;2.7] beats/min, P<0.0001). AE incidence was 94.7% with liraglutide 3.0 mg vs 89.4% with placebo, SAEs 15.1% vs 12.9%. Adjudicated major adverse CV events (non-fatal MI, stroke, cardiovascular death) were low overall (0.19 vs 0.20 events/100 patient-years-of-observation for liraglutide 3.0 mg vs placebo).

Conclusion: Liraglutide 3.0 mg for 3 years, as an adjunct to diet+exercise, was associated with lower risk of T2D and greater weight loss, and improved cardiometabolic risk factors compared with placebo.