When basal insulin is not enough: A dose–response relationship between insulin glargine 100 units/mL and glycaemic control

Abstract

Aims A post‐hoc analysis to assess the impact in people with type 2 diabetes, of increasing doses of basal insulin on glycaemic measures, body weight and hypoglycaemia. Research Design and Methods We included data from prospective, randomized controlled treat‐to‐target trials of ≥24 weeks' duration in people with type 2 diabetes, uncontrolled on metformin and sulphonylureas, and treated with insulin glargine 100 units/mL (U100), who had at least six fasting plasma glucose (FPG) measurements. The impact of insulin dose on glycated haemoglobin (HbA1c) values, FPG, hypoglycaemia incidence (<3.9 mmol/L [70 mg/dL]), and body weight was analysed. A total of 458 participants from three eligible trials were included. Results The observed relationship between higher basal insulin doses and glycaemic control was non‐linear, with increasing insulin dose leading to smaller reductions in FPG and HbA1c for doses >0.3 IU/kg/d, with a plateauing effect at 0.5 IU/kg/d. Total daily dose of insulin >0.5 IU/kg/d resulted in greater weight gain, but without higher rates of hypoglycaemia, compared with insulin doses ≤0.5 IU/kg/d. Conclusions This analysis indicates that basal insulin doses >0.5 IU/kg/d have diminishing additional impact on improving glycaemic measures, with the disadvantage of additional weight gain. Clinicians should consider anti‐hyperglycaemic treatment intensification at doses approaching 0.5 IU/kg/d.

Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial

“…Clinical experience as well as recent analyses of insulin glargine U100 have indicated that when a basal insulin dose of 0.5 units/kg/day is approached or exceeded, there is little incremental glycemic benefit with the disadvantage of weight gain [15]. The percentages of participants in this analysis who reached an A1C goal of \ 7.0% (\ 53 mmol/mol) were comparable, regardless of whether participants received a dose of B 0.5 units/kg/day or [ 0.5 units/ kg/day insulin in both the iGlarLixi and iGlar arms (iGlarLixi: 56.8% vs. 56.3%, respectively, p = 0.9235; iGlar: 32.7% vs. 29.5%, respectively, p = 0.5203) ( Table S2 in the electronic supplementary material).…”

Higher versus standard starting dose of insulin glargine 100 U/mL in overweight or obese Chinese patients with type 2 diabetes: Results of a multicentre, open‐label, randomized controlled trial (BEYOND VII)

“…Initiating Gla‐100 at a starting dose of 0.3 U/kg is not only safe but also contributes to improving glycaemic control. A recent study reported a non‐linear relationship between basal insulin doses and glycaemic control, with the efficacy inflection point at 0.3 U/kg, and a plateauing effect at 0.5 U/kg . A starting dose of 0.3 U/kg of insulin glargine may therefore reduce the gap between the initial and final dose required, thus reducing the titration period.…”

When basal insulin is not enough: response to M Davidson

“…We thank Dr Davidson for his interest in our paper, which observed the non‐linear relationship between insulin doses resulting in smaller reductions in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) concentration in patients whose maximum doses were <0.3 IU/kg and >0.5 IU/kg, and we have included the data requested.…”