The results from two phase III clinical studies that showed Linagliptin ( Tradjenta ) in Asian adults, as monotherapy and in combination with Metformin, improved blood glucose control in people with type 2 diabetes ( T2D ) from China, Malaysia and the Philippines, were presented at the American Diabetes Association ( ADA ) 73rd Scientific Sessions.
In Asia, the rate of type 2 diabetes is rapidly increasing. If the current trend continues, it is estimated that more than 60% of the world's diabetes population will be in Asia by 2030. Similarly, in the United States, the rate of T2D in Chinese Americans is much higher than the rate in the Chinese population living in rural China. A combination of both genetic and environmental influences is attributed to the higher rate of type 2 diabetes mellitus in people of Asian descent.
In the first study, Linagliptin monotherapy demonstrated a 0.68% reduction in HbA1c ( from a mean baseline HbA1c of 7.95% ) at 24 weeks among Asian patients from China, Malaysia, and the Philippines, compared with a reduction of 0.18% ( from a mean baseline HbA1c of 8.09% ) in the placebo group ( placebo-corrected difference of -0.50%; p less than 0.0001 ). In a pre-defined subgroup of patients with a baseline HbA1c of at least 8.5%, treatment with Linagliptin resulted in a placebo-adjusted reduction in HbA1c of 0.91% ( p less than 0.0001 ) at 24 weeks. HbA1c is measured in people with diabetes mellitus to provide an index of blood glucose control for the previous two to three months.
Results from the second study showed an HbA1c reduction of 0.66% ( from a mean baseline HbA1c of 7.99% ) at 24 weeks among Asian patients from China, Malaysia, and the Philippines who received Linagliptin added to Metformin at 24 weeks, versus a reduction of 0.14% ( from a mean baseline HbA1c of 8% ) among patients receiving placebo added to Metformin ( placebo-corrected difference in HbA1c was -0.52%; p less than 0.0001 ).
In both studies, the incidence of adverse events was similar in each treatment group compared with placebo. The incidence of adverse reactions for Linagliptin were 28.0% in the monotherapy study and 27.3% in the add-on therapy study, and comparable to the placebo arm ( 28.3% and 28.0%, respectively ).
In the monotherapy study, drug-related adverse reactions were reported in 3.0% of Linagliptin patients and 2.0% of placebo patients; in the add-on trial, drug-related adverse effects were reported in 2.4% of Linagliptin patients and 0.0% of placebo patients. In addition, investigator-defined hypoglycemia occurred in 0.5% of Linagliptin patients and 0.0% of placebo patients in the monotherapy study, and in 1.0% of patients in both groups of the add-on study.
The first study was a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Linagliptin monotherapy for 24 weeks in Asian patients with inadequately controlled type 2 diabetes mellitus. The study included a total of 300 patients with T2D from China ( n=261 ), Malaysia ( n=22 ) and the Philippines ( n=17 ). Patients who were treatment naïve or who had been treated with one antihyperglycemic drug were randomized to either Linagliptin 5 mg daily or placebo following a 4-week washout period of prior drugs. The primary endpoint was change from baseline in mean HbA1c after 24 weeks. Mean HbA1c levels at baseline were 7.95% for patients in the Linagliptin group and 8.09% for patients in the placebo group.
The second study, also a randomized, double-blind, placebo-controlled trial, evaluated the efficacy and safety of Linagliptin as add-on therapy to Metformin in Asian patients with inadequately controlled type 2 diabetes mellitus. The study included a total of 306 patients with T2D from China ( n=265 ), Malaysia ( n=17 ) and the Philippines ( n=24 ). 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.4 Mean HbA1c levels at baseline were 7.99% for patients in the Linagliptin group and 8.00% for patients in the placebo group.
Linagliptin is a DPP-4 inhibitor that does not require dose adjustments, regardless of declining renal function or hepatic impairment. ( Xagena )
Source: Lilly, 2013