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Osumili B, Sapin H, Yang Z, Ranta K, Paik JS, Blüher M. Efficacy and Safety of Tirzepatide Compared with GLP-1 RAs in Patients with Type 2 Diabetes Treated with Basal Insulin: A Network Meta-analysis. Diabetes Ther 2025; 16:1279-1311. [PMID: 40214900 PMCID: PMC12085526 DOI: 10.1007/s13300-025-01728-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 03/12/2025] [Indexed: 05/18/2025] Open
Abstract
INTRODUCTION The relative efficacy and safety of tirzepatide was compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM) treated with basal insulin using a network meta-analysis (NMA). METHODS A systematic literature review was performed to identify randomized controlled trials of GLP-1 RAs in patients with T2DM treated with insulin and an antihyperglycaemic drug. For the NMA, studies included trials with 100% of patients treated with basal insulin background therapy with a titration scheme comparable to the SURPASS-5 trial. The following data were extracted for efficacy and safety assessment at the primary endpoint of each study: changes from baseline in glycated haemoglobin (HbA1c) and body weight and the incidence of nausea, vomiting or diarrhoea, hypoglycaemia, and patients discontinuing treatment because of adverse events. In this study, a comparative analysis of tirzepatide was performed with the GLP-1 RAs dulaglutide, exenatide, and lixisenatide in addition to placebo. RESULTS A total of six studies were included across the analyses. Tirzepatide 5, 10, and 15 mg showed statistically significant, greater reductions in HbA1c and body weight at the primary endpoint versus all GLP-1 RA comparators and placebo. Tirzepatide 5, 10, and 15 mg showed a statistically significant, higher likelihood of experiencing nausea compared with those who received placebo or exenatide 2 mg; no statistically significant differences were observed when compared with all other GLP-1 RA comparators. No statistically significant differences were observed in the proportions of patients who discontinued treatment because of adverse events when tirzepatide 5, 10, and 15 mg were compared with GLP-1 RA comparators, apart from tirzepatide 10 and 15 mg versus placebo. CONCLUSION Tirzepatide demonstrated statistically significantly greater reductions in HbA1c and body weight when compared with selected GLP-1 RAs and placebo in patients with T2DM treated with basal insulin. Overall, the safety profile of tirzepatide was similar to that of GLP-1RAs.
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Affiliation(s)
- Beatrice Osumili
- Health Economics and Outcomes Research, Eli Lilly and Company Limited, Bracknell, UK
| | - Hélène Sapin
- Research and Development Statistics, Lilly France SAS, Neuilly-Sur-Seine, France
| | | | - Kari Ranta
- Medical Affairs, Eli Lilly Finland, Helsinki, Finland.
| | - Jim S Paik
- Medical Affairs, Eli Lilly and Company, Indianapolis, IN, USA
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany
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Wang H, Guo S, Gu S, Li C, Wang F, Zhao J. The effects of dipeptidyl peptidase-4 inhibitors on cardiac structure and function using cardiac magnetic resonance: a meta-analysis of clinical studies. Front Endocrinol (Lausanne) 2024; 15:1428160. [PMID: 39324124 PMCID: PMC11422118 DOI: 10.3389/fendo.2024.1428160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 08/26/2024] [Indexed: 09/27/2024] Open
Abstract
Objective The aim of the study was to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP4i) on cardiac structure and function by cardiac magnetic resonance (CMR). Research Methods & Procedures: Database including PubMed, Cochrane library, Embase and SinoMed for clinical studies of DPP4i on cardiac structure and function by CMR were searched. Two authors extracted the data and evaluated study quality independently. Mean difference (MD) or standardized MD and 95% confidence intervals (CI) were used for continuous variables. Review Manager 5.3 was used to performed the analysis. Results Ten references (nine studies) were included in this meta-analysis. Most of the studies were assessed as well quality by the assessment of methodological quality. For clinical control studies, the merged MD values of △LVEF by fixed-effect model and the pooled effect size in favor of DPP4i was 1.55 (95% CI 0.35 to 2.74, P=0.01). Compared with positive control drugs, DPP4i can significantly improve the LVEF (MD=4.69, 95%CI=2.70 to 6.69), but no such change compared to placebo (MD=-0.20, 95%CI=-1.69 to 1.29). For single-arm studies and partial clinical control studies that reported LVEF values before and after DPP4i treatment, random-effect model was used to combine effect size due to a large heterogeneity (Chi2 = 11.26, P=0.02, I2 = 64%), and the pooled effect size in favor of DPP4i was 2.31 (95% CI 0.01 to 4.62, P=0.05). DPP4i significantly increased the Peak filling rate (PFR) without heterogeneity when the effect sizes of two single-arm studies were combined (MD=31.98, 95% CI 13.69 to 50.27, P=0.0006; heterogeneity test: Chi2 = 0.56, P=0.46, I2 = 0%). Conclusions In summary, a possible benefit of DPP4i in cardiac function (as measured by CMR) was found, both including ventricular systolic function and diastolic function.
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Affiliation(s)
- Haipeng Wang
- Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Siyi Guo
- The First Clinical Medical College, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Shuo Gu
- Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Jining Medical University, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, Shandong, China
| | - Chunyu Li
- Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, Shandong, China
| | - Fei Wang
- Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, Shandong, China
| | - Junyu Zhao
- Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, Shandong, China
- Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
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Zhang Y, Yang D, Jia Q, Yan J, An F. The effect of glucagon-like peptide-1 receptor agonists on cardiac function and structure in patients with or without type 2 diabetes mellitus: An updated systematic review and meta-analysis. Diabetes Obes Metab 2024; 26:2401-2411. [PMID: 38528818 DOI: 10.1111/dom.15557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 02/07/2024] [Accepted: 02/19/2024] [Indexed: 03/27/2024]
Abstract
AIMS To conduct an updated systematic review and meta-analysis to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with regard to cardiac function and structure in people with or without type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS We conducted a systematic search using the PubMed, Embase and ClinicalTrials.gov online databases. The primary outcome of interest was changes in mitral inflow E-velocity to tissue Doppler e' velocity (E/e') ratio. Secondary outcomes included other indicators of cardiac reverse remodelling and functional capacity comprising changes in left ventricular mass (LVM), left ventricular global longitudinal strain, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction (LVEF), early to atrial mitral inflow velocity ratio, left atrial volume (LAV), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and 6-min walk test (6MWT) results. RESULTS A total of 15 trials involving 898 patients were included in this analysis. GLP-1RAs significantly improved E/e' ratio (mean difference [MD] = -0.73; 95% confidence interval [CI] -1.34, -0.13), LVM (MD = -3.86 g; 95% CI -7.60, -0.12), LAV (MD = -8.20 mL; 95% CI -12.37, -4.04), NT-proBNP level (standardized MD = -0.27; 95% CI -0.47, -0.06), and 6MWT result (MD = +22.31 m; 95% CI 1.64, 42.99). However, GLP-1RAs had no effect on LVEF (MD = +0.31%; 95% CI -1.02, 1.64). CONCLUSIONS In this systematic review and meta-analysis, GLP-1RAs were found to have a positive impact on left ventricle diastolic function, hypertrophy, and exercise capacity, but had no effect on systolic function.
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Affiliation(s)
- Yu Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Danning Yang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Qiufeng Jia
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Jie Yan
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
| | - Fengshuang An
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
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Bohoran TA, Parke KS, Graham-Brown MPM, Meisuria M, Singh A, Wormleighton J, Adlam D, Gopalan D, Davies MJ, Williams B, Brown M, McCann GP, Giannakidis A. Resource efficient aortic distensibility calculation by end to end spatiotemporal learning of aortic lumen from multicentre multivendor multidisease CMR images. Sci Rep 2023; 13:21794. [PMID: 38066222 PMCID: PMC10709583 DOI: 10.1038/s41598-023-48986-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 12/02/2023] [Indexed: 12/18/2023] Open
Abstract
Aortic distensibility (AD) is important for the prognosis of multiple cardiovascular diseases. We propose a novel resource-efficient deep learning (DL) model, inspired by the bi-directional ConvLSTM U-Net with densely connected convolutions, to perform end-to-end hierarchical learning of the aorta from cine cardiovascular MRI towards streamlining AD quantification. Unlike current DL aortic segmentation approaches, our pipeline: (i) performs simultaneous spatio-temporal learning of the video input, (ii) combines the feature maps from the encoder and decoder using non-linear functions, and (iii) takes into account the high class imbalance. By using multi-centre multi-vendor data from a highly heterogeneous patient cohort, we demonstrate that the proposed method outperforms the state-of-the-art method in terms of accuracy and at the same time it consumes [Formula: see text] 3.9 times less fuel and generates [Formula: see text] 2.8 less carbon emissions. Our model could provide a valuable tool for exploring genome-wide associations of the AD with the cognitive performance in large-scale biomedical databases. By making energy usage and carbon emissions explicit, the presented work aligns with efforts to keep DL's energy requirements and carbon cost in check. The improved resource efficiency of our pipeline might open up the more systematic DL-powered evaluation of the MRI-derived aortic stiffness.
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Affiliation(s)
- Tuan Aqeel Bohoran
- School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK
| | - Kelly S Parke
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - Matthew P M Graham-Brown
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - Mitul Meisuria
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - Anvesha Singh
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - Joanne Wormleighton
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - David Adlam
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - Deepa Gopalan
- Imperial College London & Cambridge University Hospitals, Cambridge, CB2 0QQ, UK
| | - Melanie J Davies
- Leicester Diabetes Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, LE5 4PW, UK
| | - Bryan Williams
- Institute of Cardiovascular Science, University College London (UCL), National Institute for Health Research (NIHR), UCL Hospitals Biomedical Research Centre, London, WC1E 6DD, UK
| | - Morris Brown
- Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK
| | - Archontis Giannakidis
- School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.
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Huang YL, Xu XZ, Liu J, Wang PY, Wang XL, Feng HL, Liu CJ, Han X. Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis. BMC Cardiovasc Disord 2023; 23:293. [PMID: 37296380 PMCID: PMC10251583 DOI: 10.1186/s12872-023-03324-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Accepted: 05/27/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND In recent years, the incidence of diabetes mellitus has been increasing annually, and cardiovascular complications secondary to diabetes mellitus have become the leading cause of death in diabetic patients. Considering the high incidence of type 2 diabetes (T2DM) combined with cardiovascular disease (CVD), some new hypoglycemic agents with cardiovascular protective effects have attracted extensive attention. However, the specific role of these regimens in ventricular remodeling remains unknown. The purpose of this network meta-analysis was to compare the effects of sodium glucose cotransporter type 2 inhibitor (SGLT-2i), glucagon-like peptide 1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) on ventricular remodeling in patients with T2DM and/or CVD. METHODS Articles published prior to 24 August 2022 were retrieved in four electronic databases: the Cochrane Library, Embase, PubMed, and Web of Science. This meta-analysis included randomized controlled trials (RCTs) and a small number of cohort studies. The differences in mean changes of left ventricular ultrasonic parameters between the treatment and control groups were compared. RESULTS A total of 31 RCTs and 4 cohort studies involving 4322 patients were analyzed. GLP-1RA was more significantly associated with improvement in left ventricular end-systolic diameter (LVESD) [MD = -0.38 mm, 95% CI (-0.66, -0.10)] and LV mass index (LVMI) [MD = -1.07 g/m2, 95% CI (-1.71, -0.42)], but significantly decreased e' [MD = -0.43 cm/s 95% CI (-0.81, -0.04)]. DPP-4i was more strongly associated with improvement in e' [MD = 3.82 cm/s, 95% CI (2.92,4.7)] and E/e'[MD = -5.97 95% CI (-10.35, -1.59)], but significantly inhibited LV ejection fraction (LVEF) [MD = -0.89% 95% CI (-1.76, -0.03)]. SGLT-2i significantly improved LVMI [MD = -0.28 g/m2, 95% CI (-0.43, -0.12)] and LV end-diastolic diameter (LVEDD) [MD = -0.72 ml, 95% CI (-1.30, -0.14)] in the overall population, as well as E/e' and SBP in T2DM patients combined with CVD, without showing any negative effect on left ventricular function. CONCLUSION The results of the network meta-analysis provided high certainty to suggest that SGLT-2i may be more effective in cardiac remodeling compared to GLP-1RA and DPP-4i. While GLP-1RA and DPP-4i may have a tendency to improve cardiac systolic and diastolic function respectively. SGLT-2i is the most recommended drug for reversing ventricular remodeling in this meta-analysis.
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Affiliation(s)
- Yi-Lin Huang
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China
| | - Xiao-Zhuo Xu
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China
| | - Jing Liu
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China
| | - Pin-Yao Wang
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China
| | - Xue-Li Wang
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China
| | - Hong-Lin Feng
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China
| | - Cheng-Jiang Liu
- Department of General Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, Anhui, China
| | - Xu Han
- Department of Geriatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhongmen Road, Nanjing, 210001, Jiangsu, China.
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Bai S, Lin C, Jiao R, Cai X, Hu S, Lv F, Yang W, Zhu X, Ji L. Is the steady-state concentration, duration of action, or molecular weight of GLP-1RA associated with cardiovascular and renal outcomes in type 2 diabetes? Eur J Intern Med 2023; 109:79-88. [PMID: 36628824 DOI: 10.1016/j.ejim.2023.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 01/02/2023] [Accepted: 01/05/2023] [Indexed: 01/09/2023]
Abstract
IMPORTANCE Disparities were found in the cardiovascular and renal outcomes among different glucagon-like peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics of GLP-1RA itself are associated with these disparities remains unclear. OBJECTIVE To assess the association between the steady-state concentration, duration of action, or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). DATA SOURCES PubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022. STUDY SELECTION Randomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were included. DATA EXTRACTION AND SYNTHESIS Literature screening and data extraction were performed independently by 2 researchers. The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI). Subgroup analyses were conducted according to steady-state concentration, duration of action and molecular weight of GLP-1RAs. MAIN OUTCOMES AND MEASURES Primary outcomes were major adverse cardiovascular events (MACE), composite renal outcome and all-cause mortality. RESULTS In all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with high steady-state concentration were associated with greater risk reduction in MACE (p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup difference = 0.008) in patients with T2D. Greater risk reductions in MACE between GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared with short acting stratum (p for subgroup difference = 0.04) in patients with T2D. The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular and renal outcomes. CONCLUSIONS AND RELEVANCE GLP-1RAs with high steady-state concentrations might be associated with greater risk reductions in cardiovascular and renal outcomes in patients with T2D. Long acting GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular outcomes. These findings provided new insights for guiding the clinical applications of GLP-1RAs in patients with T2D.
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Affiliation(s)
- Shuzhen Bai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Chu Lin
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Ruoyang Jiao
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xiaoling Cai
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
| | - Suiyuan Hu
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Fang Lv
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Wenjia Yang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Xingyun Zhu
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
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Timmermans M, Topal B, Sanches EE, DE Jongh FW, Cagiltay E, Celik A, Ribeiro R, Parmar C, Ugale S, Proczko M, Stepaniak PS, Buise MP, Severin R, Pouwels S. The effects of glucagon like peptide-1 (GLP-1) on cardiac remodeling: exploring the role of medication and physiological modulation after metabolic surgery. Minerva Endocrinol (Torino) 2022; 47:449-459. [PMID: 33759444 DOI: 10.23736/s2724-6507.21.03296-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Obesity and associated comorbidities reach epidemic proportions nowadays. Several treatment strategies exist, but bariatric surgery has the only longstanding effects. Since a few years, there is increasing interest in the effects of gastro-intestinal hormones, in particular Glucagon-Like Peptide-1 (GLP-1) on the remission of Type 2 Diabetes (T2DM) and its effects on cardiac cardiovascular morbidity, cardiac remodeling, and mortality. In the past years several high quality multicenter randomized controlled trials were developed to assess the effects of GLP-1 receptor agonist therapy on cardiovascular morbidity and mortality. Most of the trials were designed and powered as non-inferiority trials to demonstrate cardiovascular safety. Most of these trials show a reduction in cardiovascular morbidity in patients with T2DM. Some follow-up studies indicate potential beneficial effects of GLP-1 receptor agonists on cardiovascular function in patients with heart failure, however the results are contradictory, and we need long-term studies to make firm conclusions about the pleiotropic properties of incretin-based therapies. However, it seems that GLP-1 receptor agonists have different effects than the increased GLP-1 production after bariatric surgery on cardiovascular remodeling. One of the hypotheses is that the blood concentrations of GLP-1 receptor agonists are three times higher compared to GLP-1 increase after bariatric and metabolic surgery. The purpose of this narrative review is to summarize the effects of GLP-1 on cardiovascular morbidity, mortality and remodeling due to medication but also due to bariatric and metabolic surgery. The second objective is to explain the possible differences in effects of GLP-1 agonists and bariatric and metabolic surgery.
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Affiliation(s)
- Marieke Timmermans
- Department of Surgery, Haaglanden Medical Center, The Hague, the Netherlands
| | - Besir Topal
- Department of Cardiothoracic Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
| | - Elijah E Sanches
- Department of Surgery, Haaglanden Medical Center, The Hague, the Netherlands
| | - Frank W DE Jongh
- Department of Plastic Surgery, Haaglanden Medical Center, The Hague, the Netherlands
| | - Eylem Cagiltay
- School of Medicine, Department of Physiology, Istanbul Bilim University, Istanbul, Turkey
| | | | - Rui Ribeiro
- Multidisciplinary Center for Metabolic Disease, Santo António Clinic, Amadora, Portugal
| | - Chetan Parmar
- Department of Surgery, Whittington Hospital, London, UK
| | - Surendra Ugale
- Bariatric and Metabolic Surgery Clinic, Virinchi Hospitals, Hyderabad, India
| | - Monika Proczko
- Department of General, Endocrine and Transplant Surgery, University Medical Center, Gdansk University, Gdansk, Poland
| | - Pieter S Stepaniak
- Department of Health Operations Management, Noordwest Hospital Group, Alkmaar, the Netherlands
| | - Marc P Buise
- Department of Anesthesiology, Intensive Care and Pain Medicine, Catharina Hospital, Eindhoven, the Netherlands
| | - Rich Severin
- Department of Physical Therapy, College of Applied Health Sciences, University of Illinois, Chicago, IL, USA.,Doctor of Physical Therapy Program, Robbins College of Health and Human Sciences, Baylor University, Waco, TX, USA
| | - Sjaak Pouwels
- Department of Intensive Care Medicine, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands -
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Yates T, Sargeant JA, King JA, Henson J, Edwardson CL, Redman E, Gulsin GS, Brady EM, Ahmad E, Stensel DJ, Webb DR, McCann GP, Khunti K, Davies MJ. Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials. Diabetes Care 2022; 45:2749-2752. [PMID: 35984425 DOI: 10.2337/dc22-0888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/26/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS Liraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.
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Affiliation(s)
- Thomas Yates
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, U.K
| | - James A King
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, U.K
| | - Joe Henson
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
| | - Charlotte L Edwardson
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
| | - Emma Redman
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, U.K
| | - Gaurav S Gulsin
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- Department of Cardiovascular Sciences, University of Leicester, Leicester, U.K
| | - Emer M Brady
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- Department of Cardiovascular Sciences, University of Leicester, Leicester, U.K
| | - Ehtasham Ahmad
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
| | - David J Stensel
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, U.K
- Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan
| | - David R Webb
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
| | - Gerry P McCann
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
- Department of Cardiovascular Sciences, University of Leicester, Leicester, U.K
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- NIHR Applied Research Collaboration East Midlands, Leicester, U.K
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, U.K
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester, U.K
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9
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Barker MM, Zaccardi F, Brady EM, Gulsin GS, Hall AP, Henson J, Htike ZZ, Khunti K, McCann GP, Redman EL, Webb DR, Wilmot EG, Yates T, Yeo J, Davies MJ, Sargeant JA. Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile: A pooled analysis. World J Diabetes 2022; 13:260-271. [PMID: 35432761 PMCID: PMC8984563 DOI: 10.4239/wjd.v13.i3.260] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/08/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The diagnosis of type 2 diabetes (T2D) in younger adults, an increasingly common public health issue, is associated with a higher risk of cardiovascular complications and mortality, which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.
AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.
METHODS A pooled dataset was used, comprised of data from five previous studies of adults with T2D, including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years. Anthropometric and blood biomarker measurements included body weight, body mass index (BMI), waist circumference, body fat percentage, glycaemic control (HbA1c), lipid profile and blood pressure. Univariable and multivariable linear regression models, adjusted for diabetes duration, sex, ethnicity and smoking status, were used to investigate the association between age at diagnosis and each cardiovascular risk factor.
RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female, current smokers and treated with glucose-lowering medications, compared to participants diagnosed later in life. Participants diagnosed with T2D under the age of 40 also had higher body weight, BMI, waist circumference and body fat percentage, in addition to a more adverse lipid profile, compared to participants diagnosed at an older age. Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight [95% confidence interval (CI): 0.52-0.82 kg], 0.18 kg/m2 higher BMI (95%CI: 0.10-0.25) and 0.32 cm higher waist circumference (95%CI: 0.14-0.49), after adjustment for duration of diabetes and other confounders. Younger age at diagnosis was also significantly associated with higher HbA1c, total cholesterol, low-density lipoprotein cholesterol and triglycerides.
CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile, compared to those diagnosed later in life.
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Affiliation(s)
- Mary M Barker
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Francesco Zaccardi
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Emer M Brady
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Gaurav S Gulsin
- Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, United Kingdom
| | - Andrew P Hall
- The Hanning Sleep Laboratory, University Hospitals of Leicester NHS Trust, University of Leicester, Leicester LE5 4PW, United Kingdom
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
| | - Zin Zin Htike
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester LE5 4PW, United Kingdom
- National Institute for Health Research, Applied Research Collaboration East Midlands, Leicester LE5 4PW, United Kingdom
| | - Gerald P McCann
- Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, United Kingdom
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
| | - Emma L Redman
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester LE5 4PW, United Kingdom
| | - David R Webb
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
| | - Emma G Wilmot
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- Department of Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, United Kingdom
| | - Tom Yates
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
| | - Jian Yeo
- Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, United Kingdom
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester LE5 4PW, United Kingdom
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
- National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
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10
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Janani L, Bamehr H, Tanha K, Mirzabeigi P, Montazeri H, Tarighi P. Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Drug Res (Stuttg) 2021; 71:477-488. [PMID: 34388848 DOI: 10.1055/a-1555-2797] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes. METHODS We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction. RESULTS In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD -0.99; 95% CI; (-1.87, -0.12); p=0.026)) and sitagliptin+metformin treated groups (MD -1.09; 95% CI; (-1.69, -0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD -0.23; 95% CI; (-0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD -0.52; 95% CI; (-0.96, 0.08); p=0.020)) comparing to placebo. CONCLUSION Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.
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Affiliation(s)
- Leila Janani
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hadi Bamehr
- Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Kiarash Tanha
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Parastoo Mirzabeigi
- Department of Clinical Pharmacy, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Montazeri
- Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
| | - Parastoo Tarighi
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
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11
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Ahmad E, Waller HL, Sargeant JA, Webb MA, Htike ZZ, McCann GP, Gulsin G, Khunti K, Yates T, Henson J, Davies MJ, Webb DR. Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial. Diabetes Obes Metab 2021; 23:1409-1414. [PMID: 33565691 DOI: 10.1111/dom.14343] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/23/2021] [Accepted: 02/04/2021] [Indexed: 12/30/2022]
Abstract
The mechanisms behind the beneficial cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with dipeptidyl peptidase-4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP-1RA liraglutide (1.8 mg once-daily) and the DPP4i sitagliptin (100 mg once-daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26-week, randomized, active-comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m2 , HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1-alpha (SDF-1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between-group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between-group differences in CPCs, nitric oxide, C-reactive protein, interleukin-6, tumour necrosis factor alpha and advanced glycation end-products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF-1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis-generating. Purposive trials are required to examine these findings further.
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Affiliation(s)
- Ehtasham Ahmad
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Helen L Waller
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - M'Balu A Webb
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Zin Zin Htike
- Diabetes Research Centre, University of Leicester, Leicester, UK
- Nottingham University Hospitals, Nottingham, UK
| | - Gerry P McCann
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Gaurav Gulsin
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Applied Research Collaborations (ARC) East Midlands, Leicester, UK
| | - Tom Yates
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - David R Webb
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
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12
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Gopal K, Chahade JJ, Kim R, Ussher JR. The Impact of Antidiabetic Therapies on Diastolic Dysfunction and Diabetic Cardiomyopathy. Front Physiol 2020; 11:603247. [PMID: 33364978 PMCID: PMC7750477 DOI: 10.3389/fphys.2020.603247] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 11/16/2020] [Indexed: 12/11/2022] Open
Abstract
Diabetic cardiomyopathy is more prevalent in people with type 2 diabetes mellitus (T2DM) than previously recognized, while often being characterized by diastolic dysfunction in the absence of systolic dysfunction. This likely contributes to why heart failure with preserved ejection fraction is enriched in people with T2DM vs. heart failure with reduced ejection fraction. Due to revised mandates from major health regulatory agencies, all therapies being developed for the treatment of T2DM must now undergo rigorous assessment of their cardiovascular risk profiles prior to approval. As such, we now have data from tens of thousands of subjects with T2DM demonstrating the impact of major therapies including the sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors on cardiovascular outcomes. Evidence to date suggests that both SGLT2 inhibitors and GLP-1R agonists improve cardiovascular outcomes, whereas DPP-4 inhibitors appear to be cardiovascular neutral, though evidence is lacking to determine the overall utility of these therapies on diastolic dysfunction or diabetic cardiomyopathy in subjects with T2DM. We herein will review the overall impact SLGT2 inhibitors, GLP-1R agonists, and DPP-4 inhibitors have on major parameters of diastolic function, while also highlighting the potential mechanisms of action responsible. A more complete understanding of how these therapies influence diastolic dysfunction will undoubtedly play a major role in how we manage cardiovascular disease in subjects with T2DM.
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Affiliation(s)
- Keshav Gopal
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.,Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.,Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada
| | - Jadin J Chahade
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.,Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.,Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada
| | - Ryekjang Kim
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.,Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.,Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada
| | - John R Ussher
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.,Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.,Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada
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13
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Randhawa VK, Dhanvantari S, Connelly KA. How Diabetes and Heart Failure Modulate Each Other and Condition Management. Can J Cardiol 2020; 37:595-608. [PMID: 33276047 DOI: 10.1016/j.cjca.2020.11.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 11/25/2020] [Accepted: 11/26/2020] [Indexed: 12/21/2022] Open
Abstract
Heart failure (HF) and diabetes mellitus (DM) confer considerable burden on the health care system. Although these often occur together, DM can increase risk of HF, whereas HF can accelerate complications of DM. HF is a clinical syndrome resulting from systolic or diastolic impairment caused by ischemic, nonischemic (eg, DM), or other etiologies. HF exists along a spectrum from stage A (ie, persons at risk of DM) to stage D (ie, refractory HF from end-stage DM cardiomyopathy [DMCM]). HF is further categorized by reduced, midrange, and preserved ejection fraction (EF). In type 2 DM, the most prevalent form of DM, several pathophysiological mechanisms (eg, insulin resistance and hyperglycemia) can contribute to myocardial damage, leading to DMCM. Management of HF and DM and patient outcomes are guided by EF and drug efficacy. In this review, we focus on the interplay between HF and DM on disease pathophysiology, management, and patient outcomes. Specifically, we highlight the role of novel antihyperglycemic (eg, sodium glucose cotransporter 2 inhibitors) and HF therapies (eg, renin-angiotensin-aldosterone system inhibitors) on HF outcomes in patients with DM and HF.
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Affiliation(s)
- Varinder Kaur Randhawa
- Cardiovascular Medicine, Kaufman Center for Heart Failure, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Savita Dhanvantari
- Metabolism and Diabetes, Imaging Program, Lawson Health Research Institute and Medical Biophysics, Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
| | - Kim A Connelly
- Division of Cardiology, Department of Medicine, St Michael's Hospital, Keenan Research Centre for Biomedical Research, Toronto, Ontario, Canada.
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14
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Gulsin GS, Henson J, Brady EM, Sargeant JA, Wilmot EG, Athithan L, Htike ZZ, Marsh AM, Biglands JD, Kellman P, Khunti K, Webb D, Davies MJ, Yates T, McCann GP. Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes. Diabetes Care 2020; 43:2248-2256. [PMID: 32680830 PMCID: PMC7440912 DOI: 10.2337/dc20-0706] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 06/09/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2. RESULTS A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO2 18.0 ± 6.6 vs. 27.8 ± 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (β = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e') (β = -0.388; P = 0.001) were independently associated with peak VO2 in subjects with T2D. CONCLUSIONS In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure.
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Affiliation(s)
- Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K.
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Emer M Brady
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Emma G Wilmot
- Diabetes Department, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, U.K
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Zin Z Htike
- Diabetes Department, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, U.K
| | - Anna-Marie Marsh
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | | | - Peter Kellman
- National Heart, Lung, and Blood Institute, Bethesda, MD
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - David Webb
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K.
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