Intensive insulin therapy combined with metformin is associated with reduction in both glucose variability and nocturnal hypoglycaemia in patients with type 2 diabetes

Diabetes Metab Res Rev. 2017 Oct;33(7). doi: 10.1002/dmrr.2913. Epub 2017 Jul 13.

Abstract

Background: The effect on glucose variability in patients with intensive insulin therapy has not been fully understood. This observational study investigated the different glucose variability and hypoglycaemia patterns in type 2 diabetes patients treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with or without metformin administration.

Methods: During hospitalization, a total of 501 patients with poor glycaemic control and in initial treatment with either CSII alone (n = 187), CSII + Metformin (n = 81), MDI alone (n = 146), or MDI + Metformin (n = 87) were involved in the final analysis. Data obtained from continuous glucose monitoring were used to assess blood glucose fluctuation and nocturnal hypoglycaemia.

Results: Among the 4 groups, no difference was found in mean blood glucose levels. Results in parameters reflecting glucose fluctuation: continuous overlapping net glycaemic action in CSII + Metformin and mean amplitude of glycaemic excursions in MDI + Metformin were significantly lower than those in either CSII alone or MDI alone, respectively, even after adjustment (P = .031 and .006). Frequency of nocturnal hypoglycaemia was significantly decreased in CSII + Metformin as compared with CSII alone (0.6% vs 1.8%) and in MDI + Metformin as compared with MDI alone (1.6% vs 2.3%), with the highest frequency observed in MDI alone and the lowest in CSII + Metformin (all between group P < .001). Consistent results were obtained in between-group comparisons for hypoglycaemia duration. Subgroup analysis matched with baseline body mass index, and glycated haemoglobin and fasting blood glucose further confirmed these findings.

Conclusion: Metformin added to initial CSII or MDI therapy is associated with a reduction in both glucose fluctuation and nocturnal hypoglycaemic risk in patients with type 2 diabetes.

Keywords: continuous subcutaneous insulin infusion; glucose variability; intensive insulin therapy; metformin; multiple daily injections; nocturnal hypoglycaemia.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / therapeutic use*
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Metformin