A Randomized Controlled, Double-Masked, Crossover Study of a GPR119 Agonist on Glucagon Counterregulation During Hypoglycemia in Type 1 Diabetes

Hypoglycemia is the limiting factor for optimal glycemic control in people with type 1 diabetes (T1D). Activation of α-cell GPR119 receptors increases glucagon counterregulatory responses to hypoglycemia in preclinical studies. We assessed the effect of MBX-2982, a GPR119 agonist, on glucagon counterregulatory responses to experimental hypoglycemia in participants with T1D. Activation of GPR119 with MBX-2982 did not improve glucagon counterregulatory responses to hypoglycemia in participants with T1D, though increases in fasting glucagon-like peptide 1 and responses during a mixed-meal test demonstrated appropriate target engagement. GPR119 agonists are unlikely to be effective agents to mitigate hypoglycemia risk in people with T1D.