Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Glycated hemoglobin (HbA1c) and measures of short-term glycemia do not fully capture daily patterns in plasma glucose dynamics. This study evaluated 24-h glycemic profiles in patients with type 2 diabetes (T2D) initiated on dapagliflozin treatment using continuous glucose monitoring (CGM).

METHODS: This randomized double-blind placebo-controlled multicenter parallel-design 4-week study compared dapagliflozin (10 mg/d; n = 50) with placebo (n = 50) in adult patients with T2D uncontrolled (HbA1c 7.5%-10.5%) on either stable doses of metformin monotherapy (≥1500 mg/d) or insulin (≥30 U/d with or without up to two oral antidiabetes drugs). CGM was used to measure 24-h glycemic profiles for 7 days pretreatment and during week 4 of treatment. The primary outcome was change from baseline in 24-h mean glucose (MG) at week 4.

RESULTS: The 24-h MG decreased 18.2 mg/dL with dapagliflozin and increased 5.8 mg/dL with placebo (P < 0.001). The proportion of time spent in the target glucose range (70-180 mg/dL) increased significantly with dapagliflozin versus placebo (69.6% vs. 52.9%; P < 0.001), with a small (0.3%) increase in time spent in the hypoglycemic range (<70 mg/dL), driven by those on background insulin therapy. Dapagliflozin reduced postprandial glucose and significantly decreased overall glucose variability. Few events of symptomatic hypoglycemia occurred. The most common adverse event was urinary tract infection (6% in each treatment arm).

CONCLUSIONS: Compared with placebo, dapagliflozin improved measures of glycemic control and variability as assessed by CGM. Glycemic improvements were more pronounced in the group on background metformin than those receiving basal insulin.