Predictive factors of efficacy of combination therapy with basal insulin and liraglutide in type 2 diabetes when switched from longstanding basal-bolus insulin: Association between the responses of β- and α-cells to GLP-1 stimulation and the glycaemic control at 6 months after switching therapy

Diabetes Res Clin Pract. 2018 Oct:144:161-170. doi: 10.1016/j.diabres.2018.08.015. Epub 2018 Sep 6.

Abstract

Aims: To evaluate the glycaemic control of combination therapy with basal insulin and liraglutide, and to explore the factors predictive of efficacy in patients with type 2 diabetes when switched from longstanding basal-bolus insulin therapy.

Methods: We studied 41 patients who switched from basal-bolus insulin therapy of more than 3 years to basal insulin/liraglutide combination therapy. Glycaemic control was evaluated at 6 months after switching therapy and used to subdivide the patients into good-responders (HbA1c <7.0% or 1.0% decrease) and poor-responders (the rest of participants). To evaluate the glucose-dependent insulin/glucagon responses without/with liraglutide, a 75-g oral glucose tolerance test (OGTT) was performed twice, before (1st-OGTT) and 2-days after (2nd-OGTT) liraglutide administration.

Results: Twenty-eight patients (68.3%) were identified as good-responders. No differences were found in baseline characteristics including insulin/glucagon responses during 1st-OGTT between the groups. 2nd-OGTT revealed that paradoxical hyperglucagonemia were significantly improved in both groups, but significant increases in insulin secretory response were observed only in good-responders. Logistic regression analyses revealed that the improvement of the insulin-response during 2nd-OGTT compared to that during 1st-OGTT is associated with the good-responder.

Conclusions: Enhancement of glucose-dependent insulin-response under liraglutide administration is a potential predictor of long-term glycaemic control after switching the therapies.

Keywords: Basal; Bolus; GLP-1; Glucagon; Liraglutide; Proinsulin.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Drug Combinations
  • Female
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Secreting Cells / drug effects*
  • Glucagon-Secreting Cells / metabolism
  • Glucagon-Secreting Cells / pathology
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Glycemic Index
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies

Substances

  • Blood Glucose
  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Liraglutide
  • Glucagon-Like Peptide 1