Content area
Full Text
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 HbA^sub 1c^, 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 HbA^sub 1c^ 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.
Diabetes Care 34:2015-2022, 2011
Metformin is recommended as the initial oral antidiabetic drug (OAD) therapy for patients with type 2 diabetes (1-5), but the progressive nature of type 2 diabetes often requires treatment intensification to maintain glycémie control (6). A sulfonylurea or insulin is commonly added to metformin as a second step (1-5). Although initially effective, sulfonylurea treatment is associated with poor glycémie durability (6), weight gain, and hypoglycemia (7,8).
Dapagliflozin is the first in a novel class of glucose-lowering medications, the selective sodium-glucose cotransporter 2 (SGLT2) inhibitors (9). These agents reduce glucose reabsorption from the proximal tubule of the kidney, leading to increased urinary glucose excretion with resulting net caloric loss...