1. [Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin].
- Author
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Nauck M, del Prato S, Meier JJ, Durán-García S, Rohwedder K, Elze M, and Parikh SJ
- Subjects
- Aged, Balanitis chemically induced, Benzhydryl Compounds, Body Weight drug effects, Candidiasis, Vulvovaginal chemically induced, Diabetes Mellitus, Type 2 blood, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Germany, Glipizide adverse effects, Glucosides adverse effects, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents blood, Kaplan-Meier Estimate, Male, Metformin adverse effects, Middle Aged, Sodium-Glucose Transporter 2, Urinary Tract Infections blood, Urinary Tract Infections chemically induced, Blood Glucose metabolism, Diabetes Mellitus, Type 2 drug therapy, Glipizide therapeutic use, Glucosides therapeutic use, Hypoglycemic Agents therapeutic use, Metformin therapeutic use, Sodium-Glucose Transporter 2 Inhibitors
- Abstract
Objective: Although 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 Methods: This 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., Results: The 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., Conclusions: Despite 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., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2013
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