Dapagliflozin plus Saxagliptin Add-On vs. Glimepiride Add-On to Metformin in Patients with Poorly Controlled Type 2 Diabetes

Abstract

Add-on therapy with a single oral antihyperglycemic agent is often insufficient to provide glycemic control in patients with type 2 diabetes (T2D) uncontrolled on metformin (MET) monotherapy. This randomized, parallel-group, double-blind, 52-week trial (NCT02419612) evaluated the efficacy and safety of dual add-on therapy with dapagliflozin (DAPA) 10 mg/d + saxagliptin (SAXA) 5 mg/d vs. single add-on of titrated glimepiride (GLIM) 1-6 mg/d in patients with T2D (A1C, 7.5-10.5%) receiving stable MET ≥1500 mg/d. The primary end point was change in A1C from baseline to week 52; secondary end points were changes in body weight and systolic blood pressure (SBP) and the proportions of patients achieving A1C <7% or requiring treatment intensification by week 52. Mean±SD baseline data (N=443) were similar in both arms: age, 56.1±9.7 years; A1C, 8.5±0.8%; weight, 89.7±18.5 kg; duration of T2D, 7.8±6.4 years. DAPA + SAXA + MET resulted in significant reductions in A1C, body weight and SBP, a greater proportion of patients achieving A1C <7% and a lower proportion of patients requiring treatment intensification vs. GLIM + MET (Table). All treatments were well tolerated. Hypoglycemia incidence was lower for DAPA + SAXA + MET (18.5%) than GLIM + MET (44.0%). Add-on of DAPA + SAXA provided greater improvement in glycemic control and reduced body weight vs. GLIM in patients with T2D poorly controlled by MET. Disclosure J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson & Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc.. G. Gonzalez-Galvez: None. E.K. Johnsson: Employee; Self; AstraZeneca. J. Maaske: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. Stock/Shareholder; Spouse/Partner; AstraZeneca. A. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC..