Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes

Clifford J Bailey, Stefano Del Prato, Cheryl Wei, Daniel Reyner, Gabriela Saraiva, Clifford J Bailey, Stefano Del Prato, Cheryl Wei, Daniel Reyner, Gabriela Saraiva

Abstract

Dapagliflozin is associated with greater reductions in HbA1c and weight than saxagliptin in management of type 2 diabetes mellitus (T2DM). The present post hoc analyses compared the durability of these effects over short- and long-term follow-up in patients with T2DM who were inadequately controlled with metformin (≥1500 mg/day) and who were receiving either dapagliflozin (10 mg/day) or saxagliptin (5 mg/day). Failure of glycaemiccontrol was assessed using the slope of the change in HbA1c from baseline-over-time regression line (coefficient of failure [CoF]). CoF was compared directly (dapagliflozin vs saxagliptin) over the short term (NCT01606007, 24 weeks) and indirectly (placebo-adjusted) over the long term (NCT00528879 and NCT00121667, 102 weeks). A low CoF value indicated greater durability. CoF was lower for dapagliflozin versus saxagliptin over 18-24 weeks (-1.38%/year; 95% CI, -2.41 to -0.35; P = .009) and 20-102 weeks (-0.37%/year; 95% CI, -0.73 to -0.02; P = .04). Fewer dapagliflozin-treated patients versus saxagliptin-treated patients required rescue medication or discontinued the study because of failure to achieve glycaemic control at 24 weeks (3.4% vs 9.4%; P = .0191). In patients with T2DM who were inadequately controlled with metformin, dapagliflozin was associated with greater durability of glycaemic control than saxagliptin over 18-24 and 20-102 weeks.

Keywords: CoF; DPP4 inhibitor; SGLT2 inhibitor; T2DM; coefficient of failure; dapagliflozin; durability; glycaemic control; saxagliptin; type 2 diabetes mellitus.

Conflict of interest statement

C. J. B. has been involved in several AstraZeneca‐sponsored studies with dapagliflozin and reports remuneration for participation in research, advisory boards, travel, and educational presentations supported by AstraZeneca. C. W., D. R. and G. S. are current employees of AstraZeneca. S. D. P. has served on advisory panels for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Co., GlaxoSmithKline, Merck & Co., Novartis Pharmaceuticals, Novo Nordisk, Sanofi, Laboratoires Servier, and Takeda Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, Merck & Co., and Novartis Pharmaceuticals.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
A, Time to study discontinuation because of lack of glycaemic control or requirement for rescue medication through Week 24; B, forest plot showing direct comparison of HbA1c CoF for DAPA vs SAXA (Weeks 18–24); C, time to study discontinuation because of lack of glycaemic control or requirement for rescue medication for DAPA + MET vs SAXA + MET through Week 104; D, forest plot showing placebo‐adjusted indirect comparison of 20‐week to 102‐week HbA1c CoF for DAPA + MET vs SAXA + MET. CoF, coefficient of failure; DAPA, dapagliflozin; MET, metformin; PBO, placebo; SAXA, saxagliptin; SD, standard deviation
Figure 2
Figure 2
Forest plots showing placebo‐adjusted indirect comparisons of 20‐week to 102‐week CoF for DAPA + MET vs SAXA + MET with respect to A, FPG, B, SBP and C, body weight. CoF, coefficient of failure; DAPA, dapagliflozin; FPG, fasting plasma glucose; IV: instrumental variable; MET, metformin; PBO: placebo; SAXA, saxagliptin; SBP, systolic blood pressure; SD, standard deviation

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