Effects of Dapagliflozin, an SGLT2 Inhibitor, on HbA1c, Body Weight, and Hypoglycemia Risk in Patients With Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy

Abstract

OBJECTIVETo examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone.RESEARCH DESIGN AND METHODSTreatment-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 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.RESULTSAt 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.CONCLUSIONSIn 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.

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

“…Data were sorted by first author, year of publication, country of the study, design, age range of the participants, total sample size, SGLT2 inhibitor, comparator, number of patients, dosage, and follow‐up duration (Table 1). 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 …”

Glucuretics: A New Class of Drug for the Treatment of Type 2 Diabetes

“…Dapagliflozin also decreased the effect of pioglitazone-associated weight gain and edema. Overall, dapagliflozin was well tolerated; however, the incidence of genital infections was increased compared with placebo 40 . A total of 800 patients with T2DM who were inadequately controlled on 30 units or more of insulin were evaluated in a double-blind, placebo-controlled RCT that investigated the effects of 24 weeks of dapagliflozin or placebo on A1C.…”

Dapagliflozin: a new adjunct in the treatment of Type 2 diabetes mellitus

“…12 Patients on a stable dose of pioglitazone of 45 mg/day (or 30 mg/day, if 45 mg/day was not tolerated) for 12 weeks were randomized after a 2 weeks lead-in period to 5 or 10 mg of dapagliflozin or placebo in addition to their current dose of pioglitazone. Dose titration of dapagliflozin or pioglitazone was not permitted during the study.…”

“…[4][5][6][7] SGLT2, located in the renal proximal tubule, reabsorbs most of the filtered glucose 8 and its inhibition represents a new pharmacotherapy for the treatment of Type 2 diabetes. Dapagliflozin, a potent and selective SGLT2 inhibitor, has been shown to improve glycemic control in patients with Type 2 diabetes when used as monotherapy 9 or in combination with metformin, 10 sulfonylureas, 11 thiazolidinedione (TZD), 12 or insulin. 7,13 This article attempt to highlight the pharmacology, clinical studies and current regulatory status of dapagliflozin (Farxiga ™ ) in the treatment of Type 2 DM.…”