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Clinical Trial
. 2018 Nov;20(11):2598-2607.
doi: 10.1111/dom.13437. Epub 2018 Jul 16.

Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus glimepiride as add-on to metformin in patients with type 2 diabetes

Dirk Müller-Wieland  1 , Monika Kellerer  2 , Katarzyna Cypryk  3 , Dasa Skripova  4 , Katja Rohwedder  5 , Eva Johnsson  6 , Ricardo Garcia-Sanchez  7 , Raisa Kurlyandskaya  6 , C David Sjöström  6 , Stephan Jacob  8 , Jochen Seufert  9 , Nalina Dronamraju  7 , Katalin Csomós  10
Affiliations
Clinical Trial

Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus glimepiride as add-on to metformin in patients with type 2 diabetes

Dirk Müller-Wieland et al. Diabetes Obes Metab. 2018 Nov.

Abstract

Objective: To compare the efficacy and safety of dapagliflozin and dapagliflozin plus saxagliptin vs glimepiride as add-on to metformin in patients with type 2 diabetes.

Research design and methods: This 52-week, multicentre, double-blind, active-controlled study (NCT02471404) randomized (1:1:1) patients (n = 939; HbA1c 7.5%-10.5%) on metformin monotherapy (≥1500 mg/day) to add-on dapagliflozin 10 mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1 to 6 mg (titrated). The primary efficacy end point was change in HbA1c from baseline to Week 52.

Results: Baseline mean age, diabetes duration and HbA1c were 58.4 years, 7.0 years and 8.3%, respectively. Adjusted mean HbA1c change from baseline was -1.20% with dapagliflozin plus saxagliptin and -0.82% with dapagliflozin, vs -0.99% with glimepiride (mean dose at Week 52, 4.6 mg). Changes in body weight (-3.2 kg and -3.5 kg vs +1.8 kg) and systolic blood pressure (SBP; -6.4 mm Hg and -5.6 mm Hg vs -1.6 mm Hg) were significantly greater with dapagliflozin plus saxagliptin and dapagliflozin than with glimepiride. FPG decreased significantly with dapagliflozin plus saxagliptin compared with glimepiride (-2.1 mmol/L vs -1.5 mmol/L) and was similar with dapagliflozin (-1.6 mmol/L) compared with glimepiride. Confirmed incidence of hypoglycaemia was lower with dapagliflozin regimens than with glimepiride (0 and 1 vs 13 patients) and fewer patients required rescue. Genital infections were more frequent with dapagliflozin; other AE profiles were similar.

Conclusions: Dapagliflozin, saxagliptin and metformin improved glycaemic control compared with glimepiride plus metformin; add-on of dapagliflozin alone showed efficacy similar to that of glimepiride. Both dapagliflozin regimens decreased body weight and SBP, with a lower incidence of hypoglycaemia compared with glimepiride.

Keywords: DPP-IV inhibitor; SGLT2 inhibitor; dapagliflozin; phase III study; sulphonylureas; type 2 diabetes.

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Conflict of interest statement

D. M.‐W. is a member of speakers' bureaux and advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Novo Nordisk and Sanofi. M. K. is a member of speakers' bureaux and advisory boards for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi. K. C. has received honoraria and consulting fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Novo Nordisk, Medtronic and Roche. D. S. has no conflicts of interest to disclose. K. R. is an employee of AstraZeneca. E. J., R. G.‐S., R. K. and C. D. S. are employees of and stockholders in AstraZeneca. S. J. has received honoraria, research support and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol‐Myers Squibb, Daiichi Sankyo Inc., Janssen, Johnson & Johnson, Lilly, Merck, Merck Sharp & Dohme, Novartis, Novo Nordisk, Orexigen, Pfizer, Roche, Sanofi‐Aventis and Servier. J. S. has served on advisory boards and/or speakers' bureaux for Amgen, AstraZeneca, Bayer, Berlin‐Chemie, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Ipsen, Janssen, LifeScan, Merck, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi‐Aventis and Takeda; and has received research support from Amgen, Eli Lilly, GlaxoSmithKline, Intarcia, Ipsen, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, Servier and Takeda. N. Dronamraju is an employee of AstraZeneca. K. Csomós has no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Study design and patient disposition. aDrug regimens were administered once daily and matching placebos were included. bGLIM treatment began at 1 mg/day and was titrated (up or down) in 1 mg increments at subsequent visits, as needed. Abbreviations: DAPA, dapagliflozin; GLIM, glimepiride; MET, metformin; SAXA, saxagliptin
Figure 2
Figure 2
A, HbA1c, adjusted mean change (±SE) from baseline at week 52 and B, adjusted mean change (±SE) from baseline over time (FAS). aAll values are given as least‐squares mean ±standard error. bSuperiority P value vs GLIM + MET (two‐sided). cDAPA + MET was non‐inferior to GLIM + MET, based on a prespecified non‐inferiority margin of 0.3%. Abbreviations: DAPA, dapagliflozin; FAS, full analysis set; GLIM, glimepiride; HbA1c, glycated haemoglobin; MET, metformin; SAXA, saxagliptin; SE, standard error
See this image and copyright information in PMC

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