Safety and efficacy of initial combination of linagliptin and metformin in patients with type 2 diabetes: A subgroup analysis of Indian patients from a randomized, double-blind, placebo-controlled study.
OBJECTIVE
The number of people with diabetes is increasing exponentially in India. Owing to a unique "Asian Indian Phenotype," Indians develop diabetes a decade earlier and have an earlier onset of complications than Western populations. Therefore, it is essential to evaluate more effective treatment strategies at an earlier stage of disease progression, such as initial combination therapy, in Indian patients. In this study, we evaluated the efficacy and safety of initial combination therapy with linagliptin plus metformin in comparison to linagliptin or metformin monotherapy in Indian patients with type 2 diabetes mellitus.


METHODS
This is a subgroup analysis of Indian patients who participated in a Phase III, 24-week, double-blind, placebo-controlled, trial. Overall, 249 Indian patients were randomized to one of six treatment arms (Two free combination therapy arms: Linagliptin 2.5 mg twice daily [bid] + either low [500 mg, n = 36] or high [1000 mg, n = 44] dose metformin bid and four monotherapy arms: Linagliptin 5 mg once daily [qd, n = 40], metformin 500 mg [n = 49] or 1000 mg bid [n = 45], or placebo [n = 23]).


RESULTS
The placebo-corrected mean change in glycated hemoglobin from baseline (8.9%) to week 24 was -1.83% for linagliptin + metformin 1000 mg bid; -1.46% for linagliptin + metformin 500 mg bid; -1.30% for metformin 1000 mg bid; -1.00% for metformin 500 mg bid; and -0.77% for linagliptin 5 mg qd. None of the patients in the combination therapy arms had hypoglycemia, whereas there was one event in the metformin 1000 mg bid arm. Rates of adverse event were similar across various treatments.


CONCLUSIONS
In this subgroup analysis of Indian patients, initial combination therapy with linagliptin + metformin was more efficacious in improving glycemic control than the monotherapy arms, with a comparable tolerability profile. The results were comparable to the overall population.
Deshmukh Clinic and Research Centre, Pune, Maharashtra, India.
Vaishali
V
Deshmukh
Jnana Sanjeevini Medical Center, Bengaluru, Karnataka, India.
Srikanta
S
Sathyanarayana
Department of Medical Affairs, Boehringer Ingelheim India Pvt. Ltd., Mumbai, Maharashtra, India.
Shalini
S
Menon
Department of Medical Affairs, Boehringer Ingelheim India Pvt. Ltd., Mumbai, Maharashtra, India.
Shiva
S
Patil
Department of Statistics, Boehringer Ingelheim, Bracknell, West Berkshire, UK.
Russel
R
Jones
Department of Medical Affairs, Eli Lilly, Gurgaon, Haryana, India.
Shweta
S
Uppal
Department of Medical Affairs, Boehringer Ingelheim, Singapore.
Kamran
K
Siddiqui
Dipeptidyl peptidase-4 inhibitor; India; initial combination therapy; linagliptin; metformin; type 2 diabetes mellitus