New Phase III data presented at the American Diabetes Association 73rd Scientific Sessions® (ADA) showed linagliptin improved blood glucose control as monotherapy and in combination with metformin, in Asian people from China, Malaysia and the Philippines with Type 2 Diabetes.
Boehringer Ingelheim and Eli Lilly and Company have presented results from two randomised Phase III clinical trials evaluating the efficacy and safety of linagliptin in Asians from China, Malaysia and the Philippines with Type 2 Diabetes (T2D). The results showed that adults with T2D treated with linagliptin both as monotherapy and in combination with metformin achieved improved blood glucose control compared with placebo.
The rate of Type 2 Diabetes is rapidly increasing in Asia with the present trend indicating that more than 60% of the world’s diabetic population will be in Asia by 2030.1
“People with Type 2 Diabetes in Asia tend to develop diabetes at a younger age when compared to people in other regions,” said Professor Guang Ning, Director and Professor of the Department of Endocrine and Metabolism, Shanghai Ruijin Hospital, China. “Therefore they tend to suffer longer with the complications of Type 2 Diabetes and have a lower life expectancy compared with people with diabetes from other regions. It is becoming increasingly important to find effective, safe and well tolerated treatments for Asian patients with Type 2 Diabetes. The results of these two trials have shown that linagliptin could become an important option for these patients.”
Results of the first Phase III study, evaluating the efficacy and safety of linagliptin monotherapy in Asians from China, Malaysia and the Philippines with T2D showed that linagliptin demonstrated a 0.68% reduction in HbA1c at 24 weeks versus a reduction of 0.18% in the placebo group (baseline HbA1c 8.09%, p<0.0001). Results for the predefined Chinese subgroup were similar to the overall population and the subgroup of patients with baseline HbA1c ≥8.5%, the placebocorrected decrease in HbA1c from baseline at 24 weeks was -0.91% (P<0.0001).1 HbA1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months.2
Results from the second Phase III study evaluating the efficacy and safety of linagliptin added to metformin in Asians from China, Malaysia and The Philippines with T2D found that patients randomised to the linagliptin plus metformin arm achieved a HbA1c reduction of 0.66% versus 0.14% in the placebo group (p<0.0001). In both studies, linagliptin was well tolerated. In the first study, adverse events (AEs) occurred in 28.0% of linagliptin patients and 28.3% of placebo patients, while drugrelated AEs occurred in 3.0% of linagliptin patients and 2.0% of placebo patients. In the second study, AEs occurred in a similar proportion of patients as in the placebo group (27.3% and 28.0%, respectively). Drugrelated AEs were reported for 2.4% and 0.0% of linagliptin and placebo patients, respectively. Investigatordefined hypoglycemia occurred in 0.5% and 0.0% of linagliptin and placebo treated patients respectively, in the first study and 1.0% in both groups in the second study.2,3 The primary endpoint of both studies was change from baseline in mean HbA1c after 24 weeks.2,3
The US Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regulatory authorities worldwide approved linagliptin for the treatment of adult patients with T2D as monotherapy or in combination with metformin/metformin plus sulphonylurea, and as addon therapy to insulin.2 Linagliptin received approval in China in March 2013. With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment.3,4 About the Phase III studies
Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled Type 2 Diabetes mellitus: a 24 week, randomized, Phase III clinical trial: 1218.66
This randomised, Phase III, placebocontrolled, doubleblind 24week study evaluated the efficacy and safety of the DPP4 inhibitor linagliptin as monotherapy in patients with inadequately controlled T2D in three Asian countries. Patients who were treatment naïve or who had been treated with one antihyperglycemic drug were randomised to either linagliptin 5 mg daily or placebo following 4week washout of prior drugs. The primary endpoint was change from baseline in mean HbA1c after 24 weeks. The study included a total of 300 Asian patients (China n=261, Malaysia n=22 and the Philippines n=17) with T2D.
Efficacy and safety of linagliptin in Asian patients with Type 2 Diabetes mellitus inadequately controlled on metformin: a 24 week, randomized, Phase III clinical trial: 1218.65
This randomised, Phase III, placebo controlled, double blind 24 week study evaluated the efficacy and safety of linagliptin added to metformin in Asian people with T2D. Antihyperglycemic drugs other than metformin were washed out for 4 weeks prior to randomization to either linagliptin 5mg daily or placebo added to metformin. The primary endpoint of the study was change from baseline in mean HbA1c after 24 weeks.
The study included a total of 306 Asian patients (China n=265, Malaysia n=17 and the Philippines n=24) with T2D.
Linagliptin (5 mg, once daily) is marketed in Europe as Trajenta® (linagliptin) and in the U.S. as Tradjenta® (linagliptin), as a oncedaily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D. Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine). With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment.4,5 Linagliptin is also approved in combination with metformin in Europe and the US, under the trade name Jentadueto®. Jentadueto® is approved as a twicedaily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D, who are inadequately controlled on their maximal tolerated dose of metformin alone or those already being treated with the combination of linagliptin and metformin.
1 Ramachandran A, et al. Trends in prevalence of diabetes in Asian countries. World J Diabetes. 2012 June 15; 3(6): 110-117.
2 Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled Type 2 Diabetes mellitus: a 24 week, randomized, Phase III clinical trial. Poster No: 1159-P. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions®. June 21-25, Chicago, IL.
3 Efficacy and safety of linagliptin in Asian patients with Type 2 Diabetes mellitus inadequately controlled on metformin: a 24 week, randomized, Phase III clinical trial. Poster No: 1177-P. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions®. June 21-25, Chicago, IL.
4 Jentadueto™ (linagliptin/metformin HCI) tablets. Highlights of Prescribing Information. Initial US Approval: 2012.
5 EMA. Trajenta® (linagliptin) tablets. EMA Summary of Product Characteristics. 2011.
6 International Diabetes Federation. IDF Diabetes Atlas Poster (2012 Update – 5th Edition). 2012.
7 World Health Organization. Fact Sheet No. 312 What is Diabetes? 2009 [cited 2013 January 2013];
8 International Diabetes Federation. What is Diabetes? IDF Diabetes Atlas. 2011; (5th Edition).