title: Glucagon and heart in type 2 diabetes: new perspectives.
abstract: Increased levels of glucagon in type 2 diabetes are well known and, until now, have been considered deleterious. However, glucagon has an important role in the maintenance of both heart and kidney function. Moreover, in the past, glucagon has been therapeutically used for heart failure treatment. The new antidiabetic drugs, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors, are able to decrease and to increase glucagon levels, respectively, while contrasting data have been reported regarding the glucagon like peptide 1 receptors agonists. The cardiovascular outcome trials, requested by the FDA, raised some concerns about the possibility that the dipeptidyl peptidase-4 inhibitors can precipitate the heart failure, while, at least for empagliflozin, a positive effect has been shown in decreasing both cardiovascular death and heart failure. The recent LEADER Trial, showed a significant reduction of cardiovascular death with liraglutide, but a neutral effect on heart failure. A possible explanation of the results with the DPPIV inhibitors and empagliflozin might be related to their divergent effect on glucagon levels. Due to unclear effects of glucagon like peptide 1 receptor agonists on glucagon, the possible role of this hormone in the Leader trial remains unclear.
authors: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), C/Rosselló, 149-153, 08036, Barcelona, Spain. aceriell@clinic.ub.es.|Department of Cardiovascular and Metabolic Diseases, IRCCS Multimedica, Sesto San Giovanni, MI, Italy. aceriell@clinic.ub.es.
authors: Antonio
authors: A
authors: Ceriello
authors: Department of Cardiovascular and Metabolic Diseases, IRCCS Multimedica, Sesto San Giovanni, MI, Italy.
authors: Stefano
authors: S
authors: Genovese
authors: Diabetology, Careggi Hospital, University of Florence, Florence, Italy.
authors: Edoardo
authors: E
authors: Mannucci
authors: Department of Cardiovascular and Metabolic Diseases, IRCCS Multimedica, Sesto San Giovanni, MI, Italy.
authors: Edoardo
authors: E
authors: Gronda
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005960:Glucosides / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism; D012307:Risk Factors; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000069450:Liraglutide; D005934:Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; C570240:empagliflozin
keywords: Glucagon; Heart failure; T2D