Improved glucose control with reduced hypoglycaemic risk when linagliptin is added to basal insulin in elderly patients with type 2 diabetes

AimTo assess the efficacy, hypoglycaemia risk and other safety markers of linagliptin as an additional therapy in older patients (aged 70years) inadequately controlled with basal insulin. MethodsA prespecified safety analysis from the linagliptin trials programme was carried out to explore the hypoglycaemia risk when linagliptin was added to background basal insulin therapy in elderly patients (70years). To do this, two eligible, randomized, placebo-controlled, clinical trials (NCT00954447 and NCT01084005) of 24 and 52weeks, respectively, were analysed. ResultsA total of 247 elderly individuals [meanstandard deviation (s.d.) age 74 +/- 4years, glycated haemoglobin (HbA1c) 8.2 +/- 0.8%] on basal insulin (mean +/- s.d. baseline dose 36 +/- 25IU/day) were identified. Alongside placebo-adjusted change in HbA1c with linagliptin of -0.77% [95% confidence interval (CI) -0.95 to 0.59; p<0.0001] after 24weeks, the hazard ratios (HRs) of both overall and confirmed hypoglycaemia [blood glucose 3.9mmol/l (70mg/dl)], were significantly lower with linagliptin than with placebo: HR 0.61 (95% CI 0.39-0.97) versus 0.59 (95% CI 0.37-0.94), respectively (both p<0.05). Moreover, significantly less confirmed hypoglycaemia was present in linagliptin-treated patients with renal impairment [HR 0.45 (95% CI 0.27-0.76)], moderate hyperglycaemia [HbA1c 7.5 to <9.0%; HR 0.51 (95% CI 0.27-0.99)], lower fasting plasma glucose levels [<152mg/dl; HR 0.49 (95% CI 0.28-0.86)] and those treated with higher insulin doses [insulin 35.6IU/day; HR 0.46 (95% CI 0.23-0.91); p<0.05 for all]. Severe hypoglycaemia was rare and the incidence was lower with linagliptin (0.8%) versus placebo (2.5%): HR 0.21 (95% CI 0.02-2.30). Conclusions<p id="dom12490-para-0004">Despite improvements in hyperglycaemia and no relevant on-trial insulin dose reductions, adding linagliptin to basal insulin appears to decrease hypoglycaemia risk. The biological basis of this phenomenon warrants further research but may involve counter-regulatory effects of incretin hormones.