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Brief review

Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin

Pages 901-911 | Accepted 05 Mar 2015, Published online: 16 Mar 2015
 

Abstract

Background:

Treatment of type 2 diabetes mellitus invariably requires the use of multiple daily medications which can impact negatively on patient adherence. As a result, there is growing interest in the use of single-pill combinations that can reduce the pill burden. Many such formulations incorporate metformin, although this agent is not suitable for all patients. The single-pill combination of the dipeptidyl peptidase-4 inhibitor linagliptin with the sodium glucose co-transporter 2 inhibitor empagliflozin offers a new and attractive option, given their complementary mechanisms of action.

Scope:

Publications with titles containing the keywords ‘linagliptin’ or ‘empagliflozin’ were identified from a non-systematic search of PubMed without date restrictions, together with abstracts presented at the annual meetings of the American Diabetes Association and the European Association for the Study of Diabetes 2012–2014. ClinicalTrials.gov was searched for entries containing these two keywords. Additional references known to the author were included.

Findings:

The efficacy and safety of linagliptin and empagliflozin as monotherapy or in combination with other oral antidiabetic drugs has been established through extensive clinical trial programs. Studies specifically evaluating the efficacy/safety of a dipeptidyl peptidase-4 inhibitor/sodium glucose co-transporter 2 inhibitor in combination are limited, but do include two studies of linagliptin/empagliflozin of up to 52 weeks in duration. These studies show that the single-pill combination of linagliptin and empagliflozin produced clinical improvements in glycemic control that were generally superior to the improvements seen with linagliptin and empagliflozin alone, but with a safety profile comparable to that of the individual constituents.

Conclusions:

The single-pill combination of linagliptin and empagliflozin, with their complementary mechanisms of action, is a promising treatment option for patients with type 2 diabetes mellitus. It would reduce the daily pill burden in this population, potentially improving adherence to, and optimizing the benefits of, treatment of diabetes mellitus.

Transparency

Declaration of funding

This review was sponsored by Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.

Declaration of financial/other relationships

R.A. has disclosed that he has received grants and personal fees from Sanofi and Takeda; grants from Becton Dickinson and GlaxoSmithKline; and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Medtronic and Novo Nordisk.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, and are all three are members of CMRO’s Editorial and International Advisory board. Disclosures are published on CMRO’s website.

Acknowledgments

The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The author received no direct compensation related to the development of the manuscript. Writing assistance was provided by Charlie Bellinger BSc 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.

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