Boehringer Ingelheim and Eli Lilly and Company announce new data that reinforce the efficacy and tolerability of linagliptin in people with Type 2 Diabetes (T2D) and liver disease, as well as Asian people with T2D aged 65 years or older. The data add to a growing body of clinical evidence supporting the use of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor from Boehringer Ingelheim (BI) and Eli Lilly and Company, in a broad range of adults with T2D. The data will be announced on Saturday 9th November during the 2013 International Conference on Diabetes and Metabolism & 5th Asian Association for the Study of Diabetes (AASD) Annual Scientific meeting.
Adults with T2D aged 65 years or older and those with pre-existing liver and biliary disease are characterised by limited treatment options. With the rate of T2D rapidly growing in Asia, and the prevalence of T2D and hepatobiliary diseases being high, especially in Asian countries, effective and safe treatment options are increasingly becoming a priority. Moreover, given the major elimination of linagliptin via the entero-hepatic system, it is particularly important to further characterise the efficacy and safety of linagliptin in T2D patients with liver and biliary complications.
Efficacy and tolerability in people with T2D and previous/current liver and biliary disease
In a pooled analysis of 17 double-blind placebo controlled randomised clinical trials investigating the efficacy and tolerability of linagliptin in people with T2D and self-reported previous/current liver and biliary disease, results showed:
Linagliptin demonstrated a statistically significant placebo-adjusted reduction in HbA1c of 0.52 and 0.62 percent in patients with- and without hepatobiliary disorders, respectively, from baseline to 24 weeks.
Overall incidence of adverse events (AEs) was similar for hepatobiliary (65.1 percent – linagliptin; 68.0 percent – placebo) and non-hepatobiliary patients (56.7 percent – linagliptin; and 62.0 percent - placebo).
Rates of serious AEs were 7.9 percent vs. 9.9 percent (linagliptin and placebo, respectively) in the hepatobiliary group, and 4.7 percent vs. 6.6 percent, (linagliptin and placebo, respectively) in the non-hepatobiliary group.
Fewer patients in the linagliptin group experienced drug related AEs than placebo (12 percent vs. 15.3 percent hepatobiliary; 11.6 percent vs. 13.6 percent non-hepatobiliary); and hypoglycaemia was less frequent with linagliptin versus placebo (12.2 percent vs. 19.2 percent hepatobiliary; 11.9 vs. 14.8 non-hepatobiliary).
Efficacy and safety in Asian elderly people with T2D
In a second pooled analysis investigating the efficacy and safety of linagliptin (as monotherapy or in combination with common anti-hyperglycaemic drugs) in Asian people aged 65 years or older with uncontrolled T2D, results showed:
Linagliptin demonstrated a statistically significant reduction in HbA1c of 0.90 percent, compared to a 0.08 percent reduction with placebo, resulting in a treatment difference of 0.82 percent after 24 weeks.
Overall incidence of adverse events (AEs) or serious adverse events (SAEs) with linagliptin was similar to placebo (AE 53.6 percent vs 61.9 percent, and SAE 4.5 percent vs. 6.9 percent respectively).
Drug-related AEs were lower in the linagliptin arm than with placebo (12.6 percent vs. 17.5 percent, respectively); as was the occurrence of investigator defined hypoglycaemia (9.5 percent vs. 18.1 percent, respectively).
The incidence of symptomatic hypoglycemia events was similar to placebo (1.1 percent in linagliptin vs 1.5 percent in placebo) when patients were not on insulin or sulphonylurea background therapy.
Commenting on the studies, Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, said: “The effects of treatment on health and safety in specific groups of people with Type 2 Diabetes, such as the elderly and those with liver disease, must be considered when selecting the most appropriate therapy. However, those patients present complications that limit their choice of treatment. The findings that will be presented at AASD support linagliptin’s safety and efficacy in these populations with Type 2 Diabetes, and confirm that linagliptin is an important treatment option.”
The U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), Japan Pharmaceuticals and Medical Devices Agency (PMDA) and several other regulatory authorities worldwide have approved linagliptin for the treatment of adults with T2D as monotherapy or in combination with metformin, metformin + sulphonylurea, and as add-on therapy to insulin. With linagliptin, no dose adjustment is required regardless of renal function or hepatic impairment.