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

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.

• Authors: Francesca Santilli, Paola G Simeone, Maria T Guagnano, Marika Leo, Marica T Maccarone, Augusto Di Castelnuovo, Cristina Sborgia, Riccardo C Bonadonna, Ermanno Angelucci, Virginia Federico, Stefano Cianfarani, Lamberto Manzoli, Giovanni Davì, Armando Tartaro, Agostino Consoli
• Journal: Diabetes care (Diabetes Care) Vol. 40 Issue 11 Pg. 1556-1564 (11 2017) ISSN: 1935-5548 [Electronic] United States
• PMID: 28912305 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 by the American Diabetes Association.

Chemical References

• 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

Topics

• Adipocytes (drug effects)
• Blood Glucose (metabolism)
• Body Mass Index
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
• Female
• Glucagon-Like Peptide 1 (analogs & derivatives, 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, metabolism)
• Life Style
• Liraglutide (therapeutic use)
• Longitudinal Studies
• Lost to Follow-Up
• Male
• Metformin (therapeutic use)
• Middle Aged
• Obesity (blood, complications, drug therapy)
• Prediabetic State (blood, drug therapy)
• Risk Factors
• Weight Loss (drug effects)