Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin

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Type 2 diabetes mellitus (T2DM) management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2) inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates a 78-week, randomized, double-blind, placebo-controlled trial investigating the impact of empagliflozin, an SGLT2 inhibitor, as add-on to basal insulin in patients with inadequate glycemic control on basal insulin, with or without metformin and/or a sulfonylurea. Empagliflozin added on to basal insulin resulted in significant and sustained reductions in glycated hemoglobin (HbA1c) levels compared with placebo. Empagliflozin has previously been shown to induce weight loss, and was associated with sustained weight loss in this study. This combination therapy was well tolerated, with similar levels of hypoglycemic adverse events in the empagliflozin and placebo groups over the 78-week treatment period. Urinary tract infections and genital infections, side effects associated with SGLT2 inhibitors, were reported more commonly in the empagliflozin group; however, such events led to treatment discontinuation in very few patients. These findings suggest that, with their complementary mechanisms of action, empagliflozin added on to basal insulin may be a useful treatment option in patients on basal insulin who need additional glycemic control without weight gain.

Keywords: type 2 diabetes mellitus, sodium glucose cotransporter 2, empagliflozin, blood glucose, body weight, insulin, combination therapy, hypoglycemic agents.

Abbreviations: ADA, American Diabetes Association; ANCOVA, analysis of covariance; BP, blood pressure; CI, confidence interval; CVD, cardiovascular disease; DKA, diabetic ketoacidosis; DPP-4, dipeptidyl peptidase-4; EASD, European Association for the Study of Diabetes; eGFR, estimated glomerular filtration rate; FAS, full analysis set; FDA, US Food and Drug Administration; FPG, fasting plasma glucose; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated hemoglobin; MDI, multiple daily injection; NPH, neutral protamine Hagedorn; OAD, oral antidiabetes drug; SBP, systolic blood pressure; SE, standard error of mean; SGLT2, sodium glucose cotransporter 2; T2DM, type 2 diabetes mellitus; US, United States.

Citation: Ahmann A. Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin. Drugs in Context 2015; 4: 212288. DOI: 10.7573/dic.212288

Acknowledgments and contributions: The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Writing support was provided by Dhinakaran Sambandan, PhD, of Envision Scientific Solutions, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Potential conflicts of interest: The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests form for the author is available for download at:

The author has received research funding from Novo Nordisk and Sanofi and has served on an advisory board for Sanofi.

Funding declaration: The author received no direct compensation related to the development of the manuscript.

Copyright: Copyright © 2015 Ahmann A. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2015 Ahmann A. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

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Correspondence: Andrew Ahmann, MD, Professor of Medicine, Harold Schnitzer Diabetes Health Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, OP05-DC, Portland, OR 97239, USA.

Submitted: 31 July 2015; Peer review comments to author: 5 August 2015; Published: 11 November 2015

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