Linagliptin/metformin HCl (fixed combination therapy) for the treatment of Type 2 diabetes mellitus

Abstract

By the year 2030, diabetes mellitus will globally become the seventh leading cause of death. Currently, 382 million individuals worldwide have diabetes mellitus, with 80% residing in low- and middle-income countries. At present, Type 2 diabetes mellitus (T2DM) accounts for 85–95% of the diabetes burden in high-income countries. Alarmingly, this figure may be higher in the low- and middle-income nations. In an effort to combat this silent but deadly disease, pharmaceutical manufacturers have developed a host of different agents, each targeting a specific biochemical pathway. Among the most recent additions to this armament is linagliptin/metformin HCl, a fixed combination therapy compound manufactured by Boehringer Ingelheim. This novel formulation combines metformin, an insulin sensitizer, with linagliptin, a dipeptidyl peptidase-4 enzyme inhibitor. This review will discuss the pharmacokinetic properties of this molecule, assess clinical efficacy and gauge its place in the treatment algorithm for T2DM.

Keywords:

• DPP-4 inhibitor
• Jentadueto
• linagliptin
• metformin
• Type 2 diabetes mellitus

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Key issues

• The fixed dose combination of linagliptin/metformin acts to improve insulin secretion, decrease glucagon levels, suppress hepatic glucose production and increase insulin sensitivity.

• The addition of linagliptin to metformin results in clinically significant reduction in hemoglobin A1c, and may prove to be a valuable second line agent in the treatment of Type 2 diabetes mellitus.

• Splitting the dose of linagliptin to 2.5 mg twice a day is not inferior, in terms of efficacy, to giving linagliptin 5 mg once a day.

• Limited drug–drug interactions exist between linagliptin and metformin, and no meaningful drug–drug interactions were seen between the linagliptin/metformin combination and a host of other agents. The addition of linagliptin does not worsen the gastrointestinal side effects of metformin.

• Linagliptin can be given in any degree of renal dysfunction, and is shown to be efficacious in chronic liver disease. Awaited trials like CAROLINA will further provide cardiovascular outcome data.

• The fixed dose combination of linagliptin/metformin can be used wherever there is no contraindication to the use of metformin.

Notes