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Aim: This randomized, double-blind, placebo-controlled parallel-group study assessed the effects of sodium glucose cotransporter 2 inhibition by dapagliflozin on insulin sensitivity and secretion in subjects with type 2 diabetes mellitus (T2DM), who had inadequate glycemic control with metformin (with or without an insulin secretagogue). Subjects and Methods: Forty-four subjects were randomized to receive dapagliflozin 5 mg or matching placebo once daily for 12 weeks. Subjects continued stable doses of background antidiabetes medication throughout the study. Insulin sensitivity was assessed by measuring the glucose disappearance rate (G DR ) during the last 40 min of a 5-h hyperinsulinemic, euglycemic clamp. Insulin secretion was determined as the acute insulin response to glucose (AIR g ) during the first 10 min of a frequently sampled intravenous glucose tolerance test. Where noted, data were adjusted for baseline values and background antidiabetes medication. Results: An adjusted mean increase from baseline in G DR (last observation carried forward), at Week 12, was observed with dapagliflozin (7.98%) versus a decrease with placebo (−9.99%). The 19.97% (95% confidence interval 5.75–36.10) difference in G DR versus placebo was statistically significant ( P =0.0059). A change from baseline in adjusted mean AIR g of 15.39 mU/L min was observed with dapagliflozin at Week 12, versus −12.73 mU/L min with placebo ( P =0.0598). Over 12 weeks, numerical reductions from baseline in glycosylated hemoglobin (HbA 1c ), fasting plasma glucose, and body weight were observed with dapagliflozin (−0.38%, −0.39 mmol/L, and −1.58%, respectively) versus slight numerical increases with placebo (0.03%, 0.26 mmol/L, and 0.62%, respectively). Conclusions: In patients with T2DM and inadequate glycemic control, dapagliflozin treatment improved insulin sensitivity in the setting of reductions in HbA 1c and weight.
Mudaliar et al. (Fri,) studied this question.