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.
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 per cent 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 per cent – linagliptin; 68.0 per cent – placebo) and non-hepatobiliary patients (56.7 percent – linagliptin; and 62.0 per cent – placebo); rates of serious AEs were 7.9 per cent vs. 9.9 per cent (linagliptin and placebo, respectively) in the hepatobiliary group, and 4.7 percent vs. 6.6 per cent, (linagliptin and placebo, respectively) in the non-hepatobiliary group; fewer patients in the linagliptin group experienced drug related AEs than placebo (12 per cent vs. 15.3 per cent hepatobiliary; 11.6 percent vs. 13.6 per cent non-hepatobiliary); and hypoglycaemia was less frequent with linagliptin versus placebo (12.2 per cent vs. 19.2 per cent hepatobiliary; 11.9 vs. 14.8 non-hepatobiliary).
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 per cent, compared to a 0.08 per cent reduction with placebo, resulting in a treatment difference of 0.82 per cent after 24 weeks; overall incidence of adverse events (AEs) or serious adverse events (SAEs) with linagliptin was similar to placebo (AE 53.6 per cent vs 61.9 per cent, and SAE 4.5 per cent vs. 6.9 per cent respectively); drug-related AEs were lower in the linagliptin arm than with placebo (12.6 per cent vs. 17.5 per cent, respectively); as was the occurrence of investigator defined hypoglycaemia (9.5 per cent vs. 18.1 per cent, respectively). The incidence of symptomatic hypoglycemia events was similar to placebo (1.1 per cent in linagliptin vs 1.5 per cent 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 US 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.
Efficacy and tolerability of linagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, in people with Type 2 Diabetes (T2DM) and liver disease: a pooled analysis of 17 randomised placebo-controlled double-blind studies.
Pooled data were analysed from 7009 subjects (621 with a history of hepatobiliary disorders [among whom the most frequent conditions were hepatic steatosis, cholelithiasis, and cholecystitis]) receiving linagliptin (n=418 with hepatobiliary disorder; n=4207 with no hepatobiliary disorder) or placebo (n=203 with hepatobiliary disorder; n=2181 with no hepatobiliary disorder). Almost 40 percent of subjects in each group (hepatobiliary and non-hepatobiliary) were Asian. All studies had a primary outcome measure of change from baseline HbA1c.
Data from placebo-controlled trials evaluating linagliptin (monotherapy or in combination with common anti-diabetes drugs) were pooled. Efficacy data were pooled from 11 trials, comprising 347 Asian adults with T2D (linagliptin n=239; placebo n=108) that included assessments of more than 24 weeks. Safety data were pooled from 15 trials of varying durations, comprising 518 Asian adults with T2D (linagliptin n=358; placebo n=160).