Effects of Dapagliflozin, a Sodium-Glucose Cotransporter-2 Inhibitor, on Hemoglobin A1c, Body Weight, and Hypoglycemia Risk in Patients With Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy
Diabetes Care, 03/30/2012
Rosenstock J et al. – In patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone–related weight gain without increasing hypoglycemia risk.
Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone.
They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone.
The primary objective compared hemoglobin A1c (HbA1c) change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24.
Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis.
At week 24, the mean reduction from baseline in HbA1c was -0.42% for placebo versus -0.82 and -0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P < 0.0001 versus placebo).
Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7–1.4 kg) at week 48.
Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6–9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0–8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1–4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare.
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