Dapagliflozin Versus Glipizide as Add-on Therapy in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin

Abstract

OBJECTIVEAlthough initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy.RESEARCH DESIGN AND METHODSThis 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA1c, 7.7%), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤10 or ≤20 mg/day, respectively.RESULTSThe primary end point, adjusted mean HbA1c reduction with dapagliflozin (−0.52%) compared with glipizide (−0.52%), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (−3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥5% body weight reduction (33.3%) versus glipizide (2.5%; P < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5%) versus glipizide (40.8%; P < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation.CONCLUSIONSDespite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.

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 …”

Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes

“…These agents reduce HbA 1c by 0.5-1.0% (5.5-11 mmol/mol) versus placebo (7,8). When compared with most standard oral agents in head-to-head trials, they appear to be roughly similarly efficacious with regard to initial HbA 1c lowering (9)(10)(11)(12). Their mechanism of action involves inhibiting the SGLT2 in the proximal nephron, thereby reducing glucose reabsorption and increasing urinary glucose excretion by up to 80 g/day (13,14).…”

Impact of Newer Medications for Type 2 Diabetes on Body Weight

“…In a trial of dapagliflozin vs placebo, dapagliflozin at a dose 10 mg daily resulted in an HbA1C reduction of −0.84 % and a placebosubtracted weight loss of −2.0 kg at six months [61]. In a one year trial comparing dapagliflozin to glipizide, a weight reduction of −3.2 kg was seen in the dapagliflozin group, while the glipizide group gained +1.2 kg, with no significant difference in A1C reduction (0.5 % in both groups), and a significantly lower risk of hypoglycemia in the dapagliflozin group (3.5 % vs 40.8 % in the glipizide group) [62].…”