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      Cardiovascular and Renal Outcomes of Incretin-based Therapies: A Review of Recent Clinical Trials

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          To report the cardiovascular and renal effects of incretin-based therapies.

          Methods

          The studies of clinical trials on incretin-based therapy published in medical journals from the years 2010 to 2017 were comprehensively searched using MEDLINE and EMBASE with no language restriction. The studies were reviewed and the cardiovascular and renal risks reported were recorded.

          Results

          Incretin-based therapeutics represent novel and promising anti-diabetes drugs, the direct cardiovascular actions which may translate into demonstrable clinical benefits on cardiovascular outcomes. Furthermore, incretin-based therapies do not adversely affect renal function.

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          Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

          Steven P Marso, Gilbert H Daniels, Kirstine Brown-Frandsen … (2016)
          The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.
          Article 0 comments Cited 1237 times – based on 0 reviews     Review now
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            Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.

            Benjamin Scirica, Deepak Bhatt, Eugene Braunwald … (2013)
            The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).
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              Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes

              William B. White, Christopher P. Cannon, Simon R. Heller … (2013)
              To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Curr Cardiol Rev
                Journal ID (iso-abbrev): Curr Cardiol Rev
                Journal ID (publisher-id): CCR
                Title: Current Cardiology Reviews
                Publisher: Bentham Science Publishers
                ISSN (Print): 1573-403X
                ISSN (Electronic): 1875-6557
                Publication date (Electronic): November 2020
                Publication date (Print): November 2020
                Volume: 16
                Issue: 4
                Pages: 253-257
                Affiliations
                Seccion de Endocrinologia y Nutrition, Hospital General Universitario Santa Lucia , Cartagena, , Spain; Centro de Salud Jesús Marín, Murcia, , Spain; Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athen , Athens, , Greece; 1 st Department of Pediatrics, “Aghia Sophia Children’s Hospital” Medical School, National and Kapodistrian University of Athens , Athens, , Greece; Department of Internal Medicine, KAT General Hospital , Athens, , Greece; Department of Surgery, Health Center of Peristeri , Athens, , Greece; Department of Internal Medicine, General Hospital of Athens “Elpis” , Athens, , Greece; Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School of Athens, Ethnikon and Kapodistrian University of Athens , Athens, , Greece
                Author notes
                [* ]Address correspondence to this author at the 1 st Department of Pediatrics, “Aghia Sophia Children’s Hospital” Medical School, National and Kapodistrian University of Athens, Athens, Greece; Tel: 0030 097 8541719;, E-mail: evi_farmaki@ 123456hotmail.com
                Article
                Publisher ID: CCR-16-253
                DOI: 10.2174/1573403X15666190603111056
                PMC ID: 7903512
                PubMed ID: 31161994
                SO-VID: 27f64a02-2010-4640-9ef9-0665b85bca6e
                Copyright © © 2020 Bentham Science Publishers
                License:

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                Date received : 14 October 2018
                Date revision received : 11 March 2019
                Date accepted : 22 March 2019
                Categories
                Subject: Article

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: incretin-based therapies,hormones,diabetes,cardiovascular,renal,clinical trials
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: incretin-based therapies, hormones, diabetes, cardiovascular, renal, clinical trials

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