Saxagliptin and metformin XR combination therapy provides glycemic control over 24 hours in patients with T2DM inadequately controlled with metformin

Abstract

Objective:

To assess 24-hour glycemic control with saxagliptin compared with placebo as add-on treatment to metformin in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control.

Research design and methods:

This was a 4-week, multicenter, randomized, double-blind, placebo-controlled Phase IIIb trial comparing the antihyperglycemic activity of saxagliptin 5 mg once daily in combination with a stable dose of metformin extended release (XR) vs. placebo in combination with metformin XR in patients with T2DM inadequately controlled (screening glycated hemoglobin [HbA_1c] 7–10%) with stable doses of metformin immediate release or metformin XR ≥ 1500 mg/day. Ninety-three adult patients were randomized and received treatment. The primary outcome measure was change from baseline to week 4 in 24-hour mean weighted glucose (MWG).

Results:

The reduction from baseline in 24-hour MWG was significantly greater for saxagliptin 5 mg + metformin XR (−13.8 mg/dL; −0.77 mmol/L) compared with placebo + metformin XR (3.0 mg/dL; 0.17 mmol/L) (p = 0.0001). At week 4, the mean decrease in plasma glucose was sustained through a 24-hour period in saxagliptin-treated patients. Treatment with saxagliptin 5 mg + metformin XR resulted in significant mean reductions from baseline in 4-hour mean weighted postprandial glucose (PPG), 2-hour PPG, 3-day average mean daily glucose, and fasting plasma glucose levels compared with placebo + metformin XR (p ≤ 0.001). The proportion of adverse events (AEs) was similar in the two treatment groups, with no reported hypoglycemic AEs in saxagliptin-treated patients. The 4-week evaluation period may have been insufficient to evaluate longer term effects on hyperglycemia or to identify additional AEs.

Conclusions:

In patients with T2DM treated with metformin XR, saxagliptin 5 mg orally administered once daily in the evening for 4 weeks effectively lowered plasma glucose concentrations through the 24-hour dosing interval and was well tolerated.

Key words:

• Combination therapy
• DPP-4 inhibitor
• Metformin XR
• Saxagliptin
• Type 2 diabetes mellitus

Transparency

Declaration of funding

Funding for this study was provided by Bristol-Myers Squibb and AstraZeneca.

Declaration of financial/other relationships

K.S. has disclosed that he has received funding from Bristol-Myers Squibb for this study and has received research funding from AstraZeneca, sanofi-aventis, GlaxoSmithKline, Novartis, Hoffman-La Roche, Janssen-Cilag EMEA and Merck & Co., Inc. I.R. has disclosed that he is on the speakers bureaus for Eli Lilly, Novo Nordisk and MSD Pharmaceuticals; has participated on advisory boards for Hoffman-La Roche, Novo Nordisk, AstraZeneca, Bristol-Myers Squibb, MSD Pharmaceuticals and Daiichi Sankyo Co., Ltd; and has consulted for AstraZeneca, Bristol-Myers Squibb, Andromeda Biotech and HealOr. J.N. has disclosed that he is on the speakers bureaus for Novartis, Pfizer Inc., Daiichi Sankyo Co., Ltd, Bristol-Myers Squibb, sanofi-aventis and Boehringer Ingelheim. S.R., N.B. and R.C. have disclosed that they are employees of Bristol-Myers Squibb.

Acknowledgements

Editorial support was provided by Gina Coviello, MS, and Paul Ruest, PhD, of Quintiles Medical Communications, Parsippany, NJ, USA. The authors also acknowledge Susan Mullin and Joretta Wong for their help with study conduct and protocol management.