Triple therapy with dapagliflozin (DAPA) 10 mg/d + saxagliptin (SAXA) 5 mg/d added to metformin (MET) has greater efficacy than dual therapy in type 2 diabetes (T2D) inadequately controlled by MET alone. We tested triple therapy with the lower starting dose of DAPA in a randomized, parallel-group, double-blind, 24-week trial (NCT02681094) to evaluate the efficacy and safety of DAPA 5 mg/d + SAXA 5 mg/d add-on therapy vs. add-on of either agent in patients with T2D (A1C 7.5-10%) uncontrolled with stable MET ≥1500 mg/d monotherapy. The primary end point was change in A1C from baseline to week 24; secondary end points were the proportion of participants achieving A1C <7% at week 24 and changes in FPG and body weight from baseline to week 24. At baseline, mean±SD patient characteristics were similar in all arms: age, 56.7±10.5 years; A1C, 8.2±0.9%; BMI, 31.9±5.4 kg/m2; T2D duration, 7.6±6.1 years. Triple therapy resulted in significant decreases in A1C and FPG vs. both dual therapies, and reduced body weight vs. SAXA + MET (Table). Incidences of genital infections were 3.4%, 1.7% and 0%; urinary tract infections 3.1%, 2.0% and 2.4%; hypoglycemia 5.8%, 2.7% and 3.4% for DAPA + SAXA + MET, DAPA + MET and SAXA + MET, respectively.
In conclusion, DAPA 5 mg/d + SAXA 5 mg/d added to MET led to greater improvement in glycemic control vs. either agent added to MET in T2D uncontrolled with MET monotherapy.
J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. S. Perl: Employee; Self; AstraZeneca. E.K. Johnsson: Employee; Self; AstraZeneca. S. Jacob: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, AstraZeneca, Eli Lilly and Company. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk Foundation. Advisory Panel; Self; MSD K.K.. Speaker's Bureau; Self; MSD K.K., Menarini Group, Roche Diabetes Care Health and Digital Solutions.
