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

Diabetes Obes Metab. 2019 Jun;21(6):1305-1310. doi: 10.1111/dom.13653. Epub 2019 Mar 25.


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.

Keywords: HbA1c; basal insulin; glargine; postprandial; type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / drug effects*
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Fasting / physiology
  • Female
  • Humans
  • Insulin Glargine* / administration & dosage
  • Insulin Glargine* / pharmacology
  • Insulin Glargine* / therapeutic use
  • Male
  • Middle Aged
  • Postprandial Period / physiology
  • Randomized Controlled Trials as Topic


  • Blood Glucose
  • Insulin Glargine