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      Dipeptidyl peptidase-4 inhibitors versus sulfonylureas on the top of metformin in patients with diabetes and acute myocardial infarction

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          Abstract

          Background

          Recent trials have shown that both the extent of glycated hemoglobin reduction and the duration of enhanced glycemic control are major factors that may affect cardiovascular outcome results. We aimed to investigate the impact of metformin (MET) combined with dipeptidyl peptidase-4 (DPP4) inhibitors or sulfonylureas (SU) on long-term clinical outcomes in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM).

          Methods

          This study was a prospective cohort trial. From November 2011 to December 2015, a total of 13,104 AMI patients were consecutively enrolled from the Korea AMI registry-National Institutes of Health. The patients were divided into the MET + DPP4 inhibitors group and the MET + SU group. The primary endpoint, major adverse cardiac events (MACE), was defined as the composite of all-cause death, recurrent myocardial infarction (MI), and any repeat revascularization up to 3-year follow-up. To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed.

          Results

          Baseline well-matched two groups were generated (the MET + DPP4 inhibitors group, n=468 and the MET + SU group, n=468). During 3-year clinical follow-up, the cumulative incidence of MACE between the two groups was not significantly different after adjustment (16.8% for MET + DPP4 inhibitors group vs. 19.4% for MET + SU group, P=0.302). However, the MET + DPP4 inhibitors group was associated with reduced risk of MI [1.3% vs. 4.9%; hazard ratio (HR): 0.228, 95% confidence interval (CI): 0.090–0.580, P=0.001] than the MET + SU group.

          Conclusions

          In patients with AMI and type 2 DM, the use of MET combined with DPP4 inhibitors was associated with reduced incidence of recurrent MI than MET combined with SU during 3-year follow-up.

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          Most cited references52

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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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            Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes.

            Jennifer B Green, M Angelyn Bethel, Paul W Armstrong … (2015)
            Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease.
            Article 0 comments Cited 339 times – based on 0 reviews     Review now
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              The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes.

              Daniel Drucker, Michael A. Nauck (2006)
              Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.
              Article 0 comments Cited 315 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cardiovasc Diagn Ther
                Journal ID (iso-abbrev): Cardiovasc Diagn Ther
                Journal ID (publisher-id): CDT
                Title: Cardiovascular Diagnosis and Therapy
                Publisher: AME Publishing Company
                ISSN (Print): 2223-3652
                ISSN (Electronic): 2223-3660
                Publication date (Electronic): 01 February 2024
                Publication date (Print): 15 February 2024
                Volume: 14
                Issue: 1
                Pages: 38-50
                Affiliations
                [1 ]Division of Cardiology, Department of Internal Medicine, Kangwon National University College of Medicine, Kangwon National University School of Medicine, Chuncheon , South Korea;
                [2 ]deptCardiovascular Research Institute , Korea University , Seoul, South Korea;
                [3 ]deptCardiovascular Center , Korea University Guro Hospital , Seoul, South Korea;
                [4 ]The Heart Center of Chonnam National University Hospital , Gwangju, South Korea
                Author notes

                Contributions: (I) Conception and design: AY Her, BG Choi, SW Rha, YH Kim; (II) Administrative support: SW Rha, YH Kim, MH Jeong; (III) Provision of study materials or patients: AY Her, SW Rha, YH Kim, MH Jeong; (IV) Collection and assembly of data: AY Her, BG Choi; (V) Data analysis and interpretation: AY Her, BG Choi, SW Rha, YH Kim; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work as co-first authors.

                Correspondence to: Seung-Woon Rha, MD, PhD. Cardiovascular Center, Korea University Guro Hospital, 148, Gurodong-ro, Guro-gu, 08308, Seoul, South Korea. Email: swrha617@ 123456yahoo.co.kr ; Yong Hoon Kim, MD, PhD. Division of Cardiology, Department of Internal Medicine, Kangwon National University College of Medicine, Kangwon National University School of Medicine, 24289, 156 Baengnyeong Road, Chuncheon City, Gangwon Province, South Korea. Email: yhkim02@ 123456kangwon.ac.kr .
                [^]

                ORCID: Ae-Young Her, 0000-0002-9990-6843; Byoung Geol Choi, 0000-0002-6090-869X; Seung-Woon Rha, 0000-0001-9456-9852; Yong Hoon Kim, 0000-0002-9669-3598; Myung Ho Jeong, 0000-0003-2424-810X.

                Article
                Publisher ID: cdt-14-01-38
                DOI: 10.21037/cdt-23-349
                PMC ID: 10904300
                PubMed ID: 38434553
                SO-VID: fdd5adab-ae21-45d9-b42a-e2e41784aa58
                Copyright © 2024 Cardiovascular Diagnosis and Therapy. All rights reserved.
                License:

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                Date received : 19 August 2023
                Date accepted : 08 December 2023
                Categories
                Subject: Original Article

                Keywords: metformin (met),dipeptidyl peptidase-4 inhibitors (dpp4i),sulfonylureas (su),acute myocardial infarction (ami),type 2 diabetes mellitus (type 2 dm)
                Data availability:
                Keywords: metformin (met), dipeptidyl peptidase-4 inhibitors (dpp4i), sulfonylureas (su), acute myocardial infarction (ami), type 2 diabetes mellitus (type 2 dm)

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