Exenatide improves β-cell function up to 3 years of treatment in patients with type 2 diabetes: a randomised controlled trial

Eur J Endocrinol. 2016 Oct;175(4):345-52. doi: 10.1530/EJE-16-0286. Epub 2016 Jul 27.

Abstract

Objective: Glucagon-like peptide (GLP)-1 receptor agonist treatment improves β-cell function. In this study, we investigated whether the improvements are sustained during a 3-year treatment period.

Research design and methods: Sixty-nine metformin-treated type 2 diabetes patients were randomised to the GLP1 receptor agonist, exenatide (EXE) twice daily (BID) or to insulin glargine (GLAR). β-cell function parameters were derived using the Mari model from standardised breakfast and lunch meals that were administered before treatment, and after 1 and 3 years of treatment. EXE was administered before breakfast.

Results: Fifty-nine (EXE: n = 30; GLAR: n = 29) and thirty-six (EXE: n = 16; GLAR: n = 20) patients completed the meal at 1- and 3-year treatment respectively. After 3 years, groups had comparable glycaemic control (HbA1c: EXE 6.6 ± 0.2% and GLAR 6.9 ± 0.2%; P = 0.216). Compared with GLAR, at 1 and 3 years, EXE induced a stronger reduction in post-breakfast glucose concentrations (P < 0.001), with lower C-peptide levels (P < 0.001). Compared with GLAR, EXE increased insulin secretion at 8 mmol/L glucose throughout the study period (P < 0.01). Both treatments improved β-cell glucose sensitivity after 1-year treatment. However, only EXE treatment sustained this improvement for 3 years. No consistent changes in other β-cell parameters including rate sensitivity and potentiation were observed.

Conclusions: Compared with GLAR, EXE improved the parameters of β-cell function, especially insulin secretion at 8 mmol/L glucose and β-cell glucose sensitivity, which was sustained during the 3-year treatment period.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Exenatide
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / physiology
  • Male
  • Middle Aged
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Postprandial Period
  • Treatment Outcome
  • Venoms / pharmacology
  • Venoms / therapeutic use*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Exenatide