Wilding JPH et al. – Dapagliflozin improves glycemic control, stabilizes insulin dosing, and reduces weight without increasing major hypoglycemic episodes in patients with inadequately controlled type 2 diabetes mellitus.

• 126 centers in Europe and North America from 30 April 2008 to 19 November 2009.
• 808 patients with inadequately controlled type 2 diabetes mellitus receiving at least 30 U of insulin daily, with or without up to 2 oral antidiabetic drugs.
• Patients were randomly assigned in a 1:1:1:1 ratio and allocated with a computer–generated scheme to receive placebo or 2.5, 5, or 10 mg of dapagliflozin, once daily, for 48 weeks.
• The primary outcome was change in hemoglobin A1c from baseline to 24 weeks.
• Secondary outcomes included changes in body weight, insulin dose, and fasting plasma glucose level at 24 weeks and during the 24–week extension period.
• Adverse events were evaluated throughout both 24–week periods.
• 800 patients were analyzed.

• After 24 weeks, mean hemoglobin A1c decreased by 0.79% to 0.96% with dapagliflozin compared with 0.39% with placebo (mean difference, –0.40% [95% CI, –0.54% to –0.25%] in the 2.5–mg group, –0.49% [CI, –0.65% to –0.34%] in the 5–mg group, and –0.57% [CI, –0.72% to –0.42%] in the 10–mg group).
• Daily insulin dose decreased by 0.63 to 1.95 U with dapagliflozin and increased by 5.65 U with placebo (mean difference, –7.60 U [CI, –10.32 to –4.87 U] in the 2.5–mg group, –6.28 U [CI, –8.99 to –3.58 U] in the 5–mg group, and –6.82 U [CI, –9.56 to –4.09 U] in the 10–mg group).
• Body weight decreased by 0.92 to 1.61 kg with dapagliflozin and increased by 0.43 kg with placebo (mean differences, –1.35 kg [CI, –1.90 to –0.80 kg] in the 2.5–mg group, –1.42 kg [CI, –1.97 to –0.88 kg] in the 5–mg group, and –2.04 kg [CI, –2.59 to –1.48 kg] in the 10–mg group).
• These effects were maintained at 48 weeks.
• Compared with the placebo group, patients in the pooled dapagliflozin groups had a higher rate of hypoglycemic episodes (56.6% vs. 51.8%), events suggesting genital infection (9.0% vs. 2.5%), and events suggesting urinary tract infection (9.7% vs. 5.1%).