Addition of insulin lispro protamine suspension or insulin glargine to oral type 2 diabetes regimens: a randomized trial

Abstract

The addition of basal insulin to existing oral therapy can help patients with type 2 diabetes (T2D) achieve glycaemic targets. This study compares the efficacy and safety of insulin lispro protamine suspension (ILPS) and insulin glargine in insulin-naive patients with T2D and inadequate control on oral antihyperglycaemic medication (OAM). An open-label, randomized, multicentre, multinational 24-week study of 471 patients receiving ≥2 OAMs for ≥3 months with a body mass index between 25 and 45 kg/m(2) and HbA1c 7.5-10.0% was conducted. ILPS was injected once or twice daily vs. glargine injected once daily plus prestudy OAMs. Primary objective compared the HbA1c change from baseline. HbA1c change from baseline to endpoint was similar in both groups [-1.46% (ILPS) and -1.41% (glargine)]. Least-squares mean difference (95% CI) for HbA1c (-0.05 [-0.21, 0.11]%), glycaemic variability (0.06 [-0.06, 0.19] mmol/l) and weight change (-0.01 [-0.61, 0.59] kg) showed non-inferiority (margins of 0.4%, 0.8 mmol/l and 1.5 kg, respectively). Percentages of patients achieving HbA1c <7.0% were 43.8% ILPS and 41.2% glargine. Mean daily insulin dose was 0.39 vs. 0.35 U/kg (p = 0.02) and weight gain was 1.04 vs. 1.07 kg for ILPS vs. glargine (p = 0.98). Overall hypoglycaemia (episodes/patient/year) was similar for ILPS and glargine (24.2 ± 28.8 vs. 23.0 ± 30.9); nocturnal (6.1 ± 10.6 vs. 4.1 ± 9.4, p < 0.001) rates were higher for ILPS. Severe hypoglycaemia was higher for ILPS vs. glargine (n = 9 vs. n = 2; p = 0.04). At endpoint, ILPS was non-inferior to glargine in HbA1c change from baseline, but associated with increased risk of hypoglycaemia.