Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes

Diabetes Care. 2017 Nov;40(11):1556-1564. doi: 10.2337/dc17-0589. Epub 2017 Sep 14.

Abstract

Objective: Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes.

Research design and methods: Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/day) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight).

Results: After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ = -0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012).

Conclusions: Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adipocytes / drug effects
  • Blood Glucose / metabolism
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucose Tolerance Test
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Life Style
  • Liraglutide / therapeutic use*
  • Longitudinal Studies
  • Lost to Follow-Up
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Obesity / blood
  • Obesity / complications
  • Obesity / drug therapy*
  • Prediabetic State / blood
  • Prediabetic State / drug therapy*
  • Risk Factors
  • Weight Loss / drug effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • IGF1 protein, human
  • IGF2 protein, human
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Metformin