GLP-1RAs help improve blood glucose control, but have differing effects on body weight

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) help improve glycated haemoglobin (HbA1c) levels in patients with type 2 diabetes (T2D), though different drugs work through different mechanisms of action, particularly in terms of lowering body weight, a new study has found.

Researchers performed a single-arm, prospective, observational study including 18 T2D patients taking the following GLP-1RAs, either alone or in combination with other treatments: lixisenatide (n=7), liraglutide (n=6), and dulaglutide (n=5). Meal tolerance tests were performed at baseline and at 2 and 12 weeks after GLP-1RA initiation.

After 12 weeks, GLP-1RA led to a significant drop in HbA1c (8.58±0.28 percent to 6.45±0.16 percent), body weight (86.1±5.1 to 81.9±4.7 kg), and body mass index (BMI; 29.9±1.2 to 28.5±1.1 kg/m²; p<0.05 for all). Across all groups, fasting plasma glucose was likewise decreased (139.4±5.4 to 121.3±6.4 mg/dL p<0.05).

Meanwhile, C-peptide index and the homeostatic minimal model of assessment for β-cell function both increased significantly after 12 weeks (p<0.05 for both).

Stratifying according to the three different types of GLP-1RA, the researchers saw that all agents were able to significantly reduce HbA1c, while only lixisenatide and liraglutide led to reductions in body weight and BMI.

“Questions remain as to why there are differences in body weight reduction among the different GLP-RAs,” the researchers said, adding that differences in molecular weight may explain these discrepancies.

“Further studies are required to understand the differing effects of the various GLP-1RAs on appetite suppression and body weight reduction,” they added.