Type 2 diabetes (T2D) is a progressive disease requiring add-on antihyperglycemic agents to maintain glycemic goals, although how to escalate therapy remains debatable. The benefits of dapagliflozin (DAPA) over saxagliptin (SAXA) on glycemic control (GC) and weight reduction were demonstrated in a post-hoc analysis (NCT01606007). We now evaluate the failure to sustain GC—the slope of ∆A1c over time regression line (coefficient of failure [CoF])—with DAPA or SAXA add-on to metformin (MET). CoF DAPA vs. SAXA was statistically compared directly over 24 weeks (short term; NCT01606007, patients [pts] with ≥1 ∆A1c value at/post week 18) and indirectly (post-hoc analysis of placebo controlled trials) over 102 weeks (long term; NCT00528879 and NCT00121667, pts with ≥3 ∆A1c values from 3 different visits at/post week 20). A1c CoF was lower for DAPA vs. SAXA both at 24 weeks (1.38%/y greater reduction; p=0.009) and 102 weeks (0.37%/y; p=0.04) (Figure). Fewer DAPA- than SAXA-treated pts required rescue medication or discontinued study for failing to achieve GC over 24 weeks (3.4% vs. 9.4%; p=0.0191). Similarly, the placebo adjusted risk ratio of rescue or study discontinuation for DAPA was numerically lower than SAXA over 102 weeks (0.70 vs. 0.74; p=0.68). These results suggest that in T2D pts inadequately controlled on MET, addition of DAPA is associated with significantly greater durability of GC than SAXA over 102 weeks.
C.J. Bailey: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Servier, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals U.S.A., Inc.. Advisory Panel; Self; Janssen Biotech, Inc., Abbott. C. Wei: Employee; Self; AstraZeneca. G. Luporini Saraiva: Employee; Self; AstraZeneca.