Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia

ABSTRACT

Objectives: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population.

Methods: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%–12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks.

Results: HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean −2.81% ± 0.12% with linagliptin/metformin (n = 132) and −2.02% ± 0.13% with linagliptin (n = 113); treatment difference −0.79% (95% CI −1.13 to −0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was −3.37% with linagliptin/metformin (n = 76) and −2.53% with linagliptin (n = 61); difference −0.84% (95% CI −1.32 to −0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was −2.08% with linagliptin/metformin (n = 56) and −1.39% with linagliptin (n = 52); difference −0.69% (95% CI −1.23 to −0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred.

Conclusion: Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT01512979

KEYWORDS:

• Diabetes mellitus type 2
• drug therapy combination
• metformin
• dipeptidyl peptidase 4 inhibitors
• linagliptin
• clinical trial

Acknowledgments

Boehringer Ingelheim, the sponsor of this study, is the manufacturer of linagliptin. The authors thank the patients and staff involved in this study. Data from this study have previously been presented at the American Diabetes Association 74th Scientific Sessions, June 13–17, 2014, San Francisco, CA, USA (150-OR) and the 50th Annual Meeting of the European Association for the Study of Diabetes, Vienna, Austria, 15–19 September, 2014 (Poster 894).

Declaration of interest

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Giles Brooke, PhD, CMPP, of Envision Scientific Solutions during the preparation of this manuscript. SA Ross has received honoraria for lectures, received research grants, and served on advisory boards for Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Novo Nordisk, Merck, and Sanofi. AE Caballero has received honoraria for participation in scientific advisory boards organized by Boehringer Ingelheim. S Del Prato has received honoraria for attending meetings, consultancy fees, speaker fees, and/or travel grants from Boehringer Ingelheim. B Gallwitz is a member of advisory boards for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Merck, Roche, Sanofi, and Takeda and has also received honoraria from these companies for giving lectures. D Lewis-D’Agostino, Z Bailes, S Thiemann, H-J. Woerle, and M von Eynatten are employees of Boehringer Ingelheim. S. Patel was an employee of Boehringer Ingelheim at the time of the study, but is now an employee of Daiichi Sankyo Developments Ltd. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This study was funded by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.