Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes

AIMS: To investigate the effects of exercise in combination with a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), liraglutide, or placebo for the treatment of type 2 diabetes. METHODS: Thirty‐three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of either exercise and liraglutide or exercise and placebo. Both groups had three supervised 60‐minute training sessions per week including spinning and resistance training. RESULTS: Glycated haemoglobin (HbA1c) levels dropped by a mean ± standard deviation of 2.0% ± 1.2% (from 8.2% ± 1.4%) in the exercise plus liraglutide group vs 0.3% ± 0.9% (from 8.0% ± 1.2%) in the exercise plus placebo group ( P < .001), and body weight was reduced more with liraglutide (−3.4 ± 2.9 kg vs −1.6 ± 2.3 kg; P < .001). Compared with baseline, similar reductions were seen in body fat (exercise plus liraglutide: −2.5% ± 1.4% [ P < .001]; exercise plus placebo: −2.2% ± 1.9% [ P < .001]) and similar increases were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 ± 0.5 L O(2)/min [ P < .001]; exercise plus placebo: 0.4 ± 0.4 L O(2)/min [ P = .002]). Greater reductions in fasting plasma glucose (−3.4 ± 2.3 mM vs −0.3 ± 2.6 mM, P < .001) and systolic blood pressure (−5.4 ± 7.4 mm Hg vs −0.6 ± 11.1 mm Hg, P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The two groups experienced similar increases in quality of life during the intervention. CONCLUSIONS: In obese patients with type 2 diabetes, exercise combined with GLP‐1RA treatment near‐normalized HbA1c levels and caused a robust weight loss when compared with placebo. These results suggest that a combination of exercise and GLP‐1RA treatment is effective in type 2 diabetes

Dissecting the physiology and pathophysiology of glucagon-like peptide-1

Copyright © 2018 Paternoster and Falasca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. An aging world population exposed to a sedentary life style is currently plagued by chronic metabolic diseases, such as type-2 diabetes, that are spreading worldwide at an unprecedented rate. One of the most promising pharmacological approaches for the management of type 2 diabetes takes advantage of the peptide hormone glucagon-like peptide-1 (GLP-1) under the form of protease resistant mimetics, and DPP-IV inhibitors. Despite the improved quality of life, long-term treatments with these new classes of drugs are riddled with serious and life-threatening side-effects, with no overall cure of the disease. New evidence is shedding more light over the complex physiology of GLP-1 in health and metabolic diseases. Herein, we discuss the most recent advancements in the biology of gut receptors known to induce the secretion of GLP-1, to bridge the multiple gaps into our understanding of its physiology and pathology