Affiliation:
1. Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School Boston Massachusetts USA
2. First Department of Propaedeutic Internal Medicine, Laiko General Hospital National and Kapodistrian University of Athens School of Medicine Athens Greece
3. Diabetes and Obesity Unit Athens Medical Center Athens Greece
4. Ansh Labs Webster Texas USA
5. Department of Radiology Athens Medical Center Athens Greece
Abstract
AbstractAimTo investigate the changes of circulating levels of all proglucagon‐derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3 mg) or naltrexone/bupropion (32/360 mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6 months on treatment.Materials and MethodsSeventeen patients with obesity or with overweight and co‐morbidities, but without diabetes, were assigned to receive once‐daily oral naltrexone/bupropion 32/360 mg (n = 8) or once‐daily subcutaneous liraglutide 3 mg (n = 9). Participants were assessed before treatment initiation and after 3 and 6 months on treatment. At the baseline and 3‐month visits, participants underwent a 3‐hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C‐peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance‐assessed liver steatosis and ultrasound‐assessed liver stiffness were measured at each visit.ResultsBoth medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone/bupropion produced a weight‐independent increase in the levels of proglucagon (P < .001) and decreases in glucagon‐like peptide‐2 (GLP‐2), glucagon and the major proglucagon fragment (P ≤ .01), whereas liraglutide markedly upregulated total glucagon‐like peptide‐1 (GLP‐1) levels in a weight‐independent manner (P = .04), and similarly downregulated the major proglucagon fragment, GLP‐2 and glucagon (P < .01). PGDP levels at the 3‐month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat‐free mass, at both the 3‐ and 6‐month visits.ConclusionsPGDP levels in response to liraglutide and naltrexone/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP‐1), and future studies should explore whether the addition of other PGDPs (e.g. GLP‐2) could offer additional benefits.
Funder
Alexander S. Onassis Public Benefit Foundation
National Institute of Diabetes and Digestive and Kidney Diseases
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine