Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial

Ronald Cw Ma; Stefano Del Prato; Baptist Gallwitz; Vyankatesh K Shivane; Diane Lewis-D'Agostino; Zelie Bailes; Sanjay Patel; Jisoo Lee; Maximilian von Eynatten; Maximiliano Di Domenico; Stuart A Ross

doi:10.1111/jdi.12746

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial

J Diabetes Investig. 2017 Sep 16;9(3):579-586. doi: 10.1111/jdi.12746. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
² Section of Diabetes, Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
³ Department of Medicine IV, University Hospital Tübingen, Tübingen, Germany.
⁴ Department of Endocrinology, Seth G. S. Medical College and KEM Hospital, Mumbai, India.
⁵ Boehringer Ingelheim Pharmaceuticals Inc., Connecticut, USA.
⁶ Boehringer Ingelheim Ltd, Bracknell, UK.
⁷ Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
⁸ University of Calgary, LMC Endocrinology Centers, Alberta, Canada.

Abstract

Aims/introduction: Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia.

Materials and methods: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5-12.0% were randomized to double-blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end-point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries.

Results: After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was -2.99 ± 0.18% with linagliptin/metformin and -1.84 ± 0.18% with linagliptin; a treatment difference of -1.15% (95% confidence interval -1.65 to -0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was -0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference -1.78 kg [95% confidence interval -2.99 to -0.57, P = 0.0043]). Drug-related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations.

Conclusions: In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

Keywords: Asia; Diabetes mellitus type 2; Dipeptidyl peptidase-4 inhibitors.