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.