Christa D Bowes1, Lillian F Lien1, Javed Butler2. 1. Division of Endocrinology, University of Mississippi, Jackson, MS, USA. 2. Department of Medicine, (L650), University of Mississippi, 2500 North State Street, Jackson, MS, 39216, USA. jbutler4@umc.edu.
Abstract
PURPOSE OF REVIEW: This review aims to summarize and discuss heart failure outcomes for current glucose-lowering agents in patients with type 2 diabetes mellitus. RECENT FINDINGS: Current regulations require cardiovascular outcomes trials for new glucose-lowering therapies to establish that there is no unacceptable increase in cardiovascular risk prior to approval. These cardiovascular outcomes trials include glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Overall, 87,162 patients have been studied in 10 published cardiovascular outcomes trials. There was no significant increase in major adverse cardiovascular events including cardiovascular mortality, myocardial infarction, and stroke in any of these trials. Heart failure was a component of the secondary endpoint of all of these trials, but only two of these studies show a significant improvement in rates of hospitalization for heart failure. Expanded regulatory labeling for reduction in cardiovascular mortality (empagliflozin) and reduction in major adverse cardiovascular events (liraglutide) has recently been established. Saxagliptin and to a lesser part alogliptin have been associated with an increased rate of hospitalization for heart failure. Canagliflozin and empagliflozin are the only two medications that have shown a clear benefit in rates of heart failure hospitalization in treatment of patients with type 2 diabetes mellitus.
PURPOSE OF REVIEW: This review aims to summarize and discuss heart failure outcomes for current glucose-lowering agents in patients with type 2 diabetes mellitus. RECENT FINDINGS: Current regulations require cardiovascular outcomes trials for new glucose-lowering therapies to establish that there is no unacceptable increase in cardiovascular risk prior to approval. These cardiovascular outcomes trials include glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Overall, 87,162 patients have been studied in 10 published cardiovascular outcomes trials. There was no significant increase in major adverse cardiovascular events including cardiovascular mortality, myocardial infarction, and stroke in any of these trials. Heart failure was a component of the secondary endpoint of all of these trials, but only two of these studies show a significant improvement in rates of hospitalization for heart failure. Expanded regulatory labeling for reduction in cardiovascular mortality (empagliflozin) and reduction in major adverse cardiovascular events (liraglutide) has recently been established. Saxagliptin and to a lesser part alogliptin have been associated with an increased rate of hospitalization for heart failure. Canagliflozin and empagliflozin are the only two medications that have shown a clear benefit in rates of heart failure hospitalization in treatment of patients with type 2 diabetes mellitus.
Authors: Benjamin M Scirica; Deepak L Bhatt; Eugene Braunwald; P Gabriel Steg; Jaime Davidson; Boaz Hirshberg; Peter Ohman; Robert Frederich; Stephen D Wiviott; Elaine B Hoffman; Matthew A Cavender; Jacob A Udell; Nihar R Desai; Ofri Mosenzon; Darren K McGuire; Kausik K Ray; Lawrence A Leiter; Itamar Raz Journal: N Engl J Med Date: 2013-09-02 Impact factor: 91.245
Authors: Rury R Holman; M Angelyn Bethel; Robert J Mentz; Vivian P Thompson; Yuliya Lokhnygina; John B Buse; Juliana C Chan; Jasmine Choi; Stephanie M Gustavson; Nayyar Iqbal; Aldo P Maggioni; Steven P Marso; Peter Öhman; Neha J Pagidipati; Neil Poulter; Ambady Ramachandran; Bernard Zinman; Adrian F Hernandez Journal: N Engl J Med Date: 2017-09-14 Impact factor: 91.245
Authors: William C Cushman; Gregory W Evans; Robert P Byington; David C Goff; Richard H Grimm; Jeffrey A Cutler; Denise G Simons-Morton; Jan N Basile; Marshall A Corson; Jeffrey L Probstfield; Lois Katz; Kevin A Peterson; William T Friedewald; John B Buse; J Thomas Bigger; Hertzel C Gerstein; Faramarz Ismail-Beigi Journal: N Engl J Med Date: 2010-03-14 Impact factor: 91.245
Authors: Philip D Home; Stuart J Pocock; Henning Beck-Nielsen; Paula S Curtis; Ramon Gomis; Markolf Hanefeld; Nigel P Jones; Michel Komajda; John J V McMurray Journal: Lancet Date: 2009-06-06 Impact factor: 79.321
Authors: Kenneth W Mahaffey; Bruce Neal; Vlado Perkovic; Dick de Zeeuw; Greg Fulcher; Ngozi Erondu; Wayne Shaw; Elisa Fabbrini; Tao Sun; Qiang Li; Mehul Desai; David R Matthews Journal: Circulation Date: 2017-11-13 Impact factor: 29.690
Authors: Christianne L Roumie; Jea Young Min; Lucy D'Agostino McGowan; Caroline Presley; Carlos G Grijalva; Amber J Hackstadt; Adriana M Hung; Robert A Greevy; Tom Elasy; Marie R Griffin Journal: J Am Heart Assoc Date: 2017-04-19 Impact factor: 5.501
Authors: Mikhail Kosiborod; Matthew A Cavender; Alex Z Fu; John P Wilding; Kamlesh Khunti; Reinhard W Holl; Anna Norhammar; Kåre I Birkeland; Marit Eika Jørgensen; Marcus Thuresson; Niki Arya; Johan Bodegård; Niklas Hammar; Peter Fenici Journal: Circulation Date: 2017-05-18 Impact factor: 29.690
Authors: Steven P Marso; Gilbert H Daniels; Kirstine Brown-Frandsen; Peter Kristensen; Johannes F E Mann; Michael A Nauck; Steven E Nissen; Stuart Pocock; Neil R Poulter; Lasse S Ravn; William M Steinberg; Mette Stockner; Bernard Zinman; Richard M Bergenstal; John B Buse Journal: N Engl J Med Date: 2016-06-13 Impact factor: 176.079