Saxagliptin improves glycemic control by modulating postprandial glucagon and C-peptide levels in Chinese patients with type 2 diabetes

Aims Saxagliptin reduced glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) in Asian patients with type 2 diabetes mellitus (T2DM). To understand the physiology of this effect, indices of α- and β-cell function were measured in a subpopulation of Chinese patients following a noodle mixed-meal tolerance test. Methods Data from Chinese patients were pooled from two phase 3, 24-week studies of saxagliptin 5 mg/d as monotherapy in drug-naive patients and as add-on to metformin in patients inadequately controlled with metformin alone. The end points for β- and α-cell function were change from baseline in C-peptide, insulin, and glucagon areas under the curve from 0 to 180 min (AUC0–180), insulinogenic index, and insulin sensitivity from Matsuda index after a mixed meal. Also glycemic variables, HbA1c, FPG, and PPG (AUC0–180), and homeostasis model assessment (HOMA) 2β were measured. Results At 24 weeks, greater improvements in adjusted mean change from baseline HbA1c (difference vs placebo [95% CI], −0.33% [−0.50%, −0.17%], [−4 (−5.5, −1.9) mmol/mol], P < 0.0001), FPG (−0.41 [−0.78, −0.03] mmol/L, P = 0.03), PPG AUC0–180 (−168 [−245, −91.8] mmol min/L, P < 0.0001), C-peptide AUC0–180 (19.7 [5.2, 34.2] nmol min/L, P = 0.008), insulinogenic index (0.06% [0.02%, 0.09%], P = 0.002), and greater suppression of glucagon secretion (glucagon AUC0–180, −322 [−493.6, −150.7] pmol min/L, P = 0.0003) were observed with saxagliptin versus placebo. Conclusion In Chinese patients with T2DM, saxagliptin as monotherapy or as add-on to metformin improved glycemic control by modulating α- and β-cell function.