Efficacy and safety of the glucagon-like peptide-1 receptor agonist lixisenatide versus the dipeptidyl peptidase-4 inhibitor sitagliptin in young (<50 years) obese patients with type 2 diabetes mellitus.

OBJECTIVE: To compare the efficacy and safety of the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide with the dipeptidyl peptidase-4 inhibitor sitagliptin in patients aged <50 years affected by obesity and type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This was a 24-week, double-blind, randomized, parallel-group study. Obese patients with T2DM inadequately controlled on metformin were randomized to lixisenatide 20 μg once-daily injection ( = 158) or once-daily oral sitagliptin 100 mg ( = 161). The primary endpoint was the proportion of patients with a glycated hemoglobin (HbA) <7% and ≥5% weight loss at 24 weeks. RESULTS: The proportion of patients that achieved the primary endpoint was 12.0% for lixisenatide versus 7.5% for sitagliptin; weighted average of proportion difference: 4.6%,  = 0.1696). A total of 40.7% of patients achieved HbA <7% with lixisenatide versus 40.0% with sitagliptin. Lixisenatide produced greater reductions in body weight (LS mean difference: -1.3 kg,  = 0.0006) and postprandial plasma glucose after a standardized meal test (LS mean difference: -34.4 mg/dL [-1.9 mmol/L],  = 0.0001) versus sitagliptin. There was a similar incidence of treatment-emergent adverse events (63.9% vs. 60.9%) and serious treatment-emergent adverse events (1.9% vs. 1.9%), with low rates of symptomatic hypoglycemia (0.6% vs. 1.9%) for lixisenatide and sitagliptin, respectively, and no cases of severe hypoglycemia. CONCLUSION: In obese patients aged <50 years with T2DM, the proportion of patients with an HbA <7% with weight loss ≥5% was similar between groups. Lixisenatide, however, resulted in significantly greater reductions in body weight and postprandial plasma glucose excursions than sitagliptin. Tolerability was similar between groups.