To investigate the effects of Sitagliptin on blood glucose control, insulin sensitivity and pancreatic α-and β-cell function in drug-naïve type 2 diabetes mellitus (T2DM).

Eighty four drug-naïve patients with duration of diabetes less than 3 years were treated with Sitagliptin for 12 weeks. Hyperinsulinemic-euglycemic clamp technique was used to evaluate insulin sensitivity, the glucose infusion rate (GIR), before and after Sitagliptin treatment. The early-phase insulin secretion and glucagon secretion after a standard meal were used to estimate β-and α-cell function. Paired t test or rank sum test were used to compare the differences before and after treatment, and multivariate regression analysis was used to evaluate the correlation.

After Sitagliptin treatment for 12 weeks, HbA_1c decreased from (7.70±1.22) % to (6.63±0.58) %, decreased by (1.08±0.13) % in T2DM patients (t=-8.12, P<0.01). Accordingly, the fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2 h PG) levels were also significantly reduced ［(6.33±0.92) and (7.71±1.70) mmol/L, (8.44±1.62) and (13.27±2.74) mmol/L,P<0.01］. The GIR increased from 4.39 to 5.71 mg·kg^-1·min^-1 without significant weight reduction(P<0.01). The early-phase insulin secretion index (ΔI₃₀/ΔG₃₀) increased from 2.42(1.09, 4.42) to 5.17(3.44, 8.56) mU/mmol (P<0.05). The insulin-AUC was also significantly improved (P<0.01), but there was no significant change in glucagon-AUC (P>0.05). Multivariate regression analysis showed that baseline insulin sensitivity (β=-0.070, P=0.03) and HbA_1c (β=0.192, P=0.001) were positively associated with the HbA_1cafter treatment.

A 12-week sitagliptin treatment reduced HbA_1c by more than 1.0% in T2DM patients, and not only significantly improved pancreatic β-cell function, but also significantly improved insulin sensitivity.

Diabetes mellitus， type 2; Insulin sensitivity; Hyperinsulinemic-euglycemic clamp technique; Insulin secretion; Sitagliptin