Efficacy and safety of linagliptin to improve glucose control in older people with type 2 diabetes on stable insulin therapy: A randomized trial

Abstract

Aim To assess the addition of linagliptin as an alternative to insulin uptitration in older people with type 2 diabetes on stable insulin therapy. Materials and Methods This phase 4, randomized, multicentre, double‐blinded, placebo‐controlled, 24‐week study recruited individuals on stable insulin, with baseline HbA1c 7.0%‐10.0%, aged ≥60 years and body mass index ≤45 kg/m2. HbA1c and fasting plasma glucose were measured at study visits, and participants assessed glycaemic control with a self‐monitoring blood glucose device. Adverse events (AEs) were reported during the study. Results Three hundred and two participants were randomized 1:1 to linagliptin 5 mg qd and placebo, with one third of patients from Japan. Study population age and HbA1c (baseline mean ± SD) were 72.4 ± 5.4 years and 8.2 ± 0.8%, respectively; ~80% of participants were aged ≥70 years; 80% had macrovascular complications, one third had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2; and half had been diagnosed with diabetes for >15 years. Linagliptin significantly improved glucose control at 24 weeks (HbA1c‐adjusted mean change vs. placebo: –0.63%; P <0.0001) and the probability of achieving predefined HbA1c targets without hypoglycaemia (HbA1c <8.0%: OR 2.02; P <0.05 and HbA1c <7.0%: OR 2.44; P <0.01). Linagliptin versus placebo was well tolerated, with similar incidences of AEs, including clinically important hypoglycaemia (blood glucose <54 mg/dL) or severe hypoglycaemia. Conclusions Addition of linagliptin improves glucose control without an excess of hypoglycaemia in older patients with type 2 diabetes on stable insulin therapy.

Long-Term Efficacy and Safety of Linagliptin in a Japanese Population with Type 2 Diabetes Aged ≥ 60 Years Treated with Basal Insulin: A Randomised Trial

“…Conversely, more patients receiving linagliptin vs. placebo had their insulin dose reduced during the study. These trends were consistent at 24 and 52 weeks (Supplementary Table 3) and mirror the results from the global study [25].…”

“…In terms of glycaemic control and risk of hypoglycaemia, the results from the Japanese study at 24 and 52 weeks were consistent with the results from the global study, which was only conducted for 24 weeks [25]. In line with the results from the global study, linagliptin vs. placebo was effective in helping participants in the Japanese study population to achieve significantly lower levels of HbA1c; this finding was confirmed at both 24 and 52 weeks.…”

“…This local study conducted in Japan was part of a global study (ClinicalTrials.gov: NCT02240680) investigating the efficacy and safety of linagliptin in older patients on stable treatment with insulin [25]. The global study was conducted over a 24-week period, while the study in Japanese participants was extended to 52 weeks.…”

“…Following screening and a 1-week placebo run-in, participants were randomised to receive either linagliptin 5 mg qd or placebo for 52 weeks. For the global study, a sample size of 300 patients (150 per study arm) was calculated to provide at least 99% power at the two-sided significance level of 5% to show superiority for HbA1c reduction from baseline [25]. In Japan, the randomisation of at least 100 patients was planned; a proportion of 33% (Japanese population vs. total population of the global study) was considered sufficient to assess consistency of the results of the primary end point between the Japanese sub-population and total population according to the MHLW guidance ‘Basic principles on Global Clinical Trials’ [26].…”

“…The randomisation, study procedures and statistical analysis have previously been reported for the global study [25]. Briefly, patients were randomly assigned to one of the two treatment arms; linagliptin 5 mg qd or placebo, in a 1:1 ratio.…”