Background: The SCALE Obesity and Prediabetes (NCT01272219) trial randomised adults with prediabetes and obesity (BMI ≥30 kg/m²) or overweight with comorbidities (≥27 kg/m²; dyslipidaemia/hypertension) to liraglutide 3.0 mg (N=1505) or placebo (N=749) as adjunct to diet and exercise for 3 years.
Methods: This post-hoc analysis compared liraglutide 3.0 mg early responders (ERs; ≥5% weight loss [WL] at Week [W] 16) and early non-responders (ENRs; <5% WL at W16), in keeping with EMA and Australian stopping-rule criteria. Efficacy outcomes are estimated means in ERs (n=580) and ENRs (n=210) who completed 160 weeks’ treatment. Development of T2D/regression to normoglycaemia were analysed using the full analysis set with LOCF. Safety was analysed using the safety analysis set. Placebo data are shown only for proportion of ERs/ENRs.
Results: Of those with W16 data, for liraglutide 3.0 mg (n=1302) 68.0% were ERs and 32.0% ENRs; for placebo (n=640), 22.3% were ERs and 77.7% ENRs. At W160, greater WL (–8.6% and –9.1 kg change in ER body-weight versus –2.9% and –3.1 kg for ENRs), reduced proportions of subjects developing T2D (0.5% ERs, 3.2% ENRs) and greater regression to normoglycaemia (69.8% in ERs, 55.4% in ENRs) were observed in ERs to liraglutide 3.0 mg vs ENRs. ERs showed greater clinical improvements (FPG, HbA1c, SBP levels) and patient-reported improvements compared with ENRs (SF-36 score +3.68 vs +1.81 and IWQOL-Lite score +13.40 vs +9.53 for ERs and ENRs, respectively. Increase in score=improvement). Adverse events (AEs) and GI AEs were similar between groups (87.1% and 75.3% for ERs; 95% and 71.6% for ENRs) while serious AEs and gallbladder disorders were more frequent in ERs (17.7% and 6.3% vs 12.7% and 2.2% for ENRs).
Conclusions: Among those treated with liraglutide 3.0 mg for 160 weeks, greater benefits were seen in ERs vs ENRs; overall AE rates were similar.