Cardiovascular effects of tirzepatide

in Journal of Endocrinology
Authors:
Priya Sumithran Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia
Department of Endocrinology and Diabetes, Alfred Healt, Melbourne, Australia

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Anthony W Russell Department of Endocrinology and Diabetes, Alfred Healt, Melbourne, Australia
School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

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Sophia Zoungas Department of Endocrinology and Diabetes, Alfred Healt, Melbourne, Australia
School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

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https://orcid.org/0000-0003-2672-0949

Correspondence should be addressed to P Sumithran: priya.sumithran@monash.edu

This paper forms part of a special collection on incretins. The guest editors for this collection were Timo Müller and Erin Mulvihill.

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Tirzepatide is a first-in-class dual agonist at receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) for the treatment of T2D and obesity, with unprecedented efficacy for glycaemic control, reductions in body weight and improvements in blood pressure and lipid profile compared with placebo and GLP-1 receptor agonists. To date, clinical trials of tirzepatide have fulfilled the requirement by regulatory authorities of demonstrated cardiovascular safety in high-risk patients. Whether cardiovascular benefits will be found with dual GLP-1/GIP receptor agonists remains uncertain, and the contribution of GIP receptor activation to cardiovascular risk has not been established. Several ongoing large-scale cardiovascular outcome trials for tirzepatide will provide a clearer understanding of where tirzepatide should be positioned in the treatment of established atherosclerotic cardiovascular disease or in people at high risk, in relation to current standard-of-care cardioprotective agents and approaches.

 

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  • Adriaenssens A, Biggs E, Darwish T, et al. 2019 Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab 30 987996.e6. (https://doi.org/10.1016/j.cmet.2019.07.013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Aronne L, Sattar N, Horn D, et al. 2024 Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity. JAMA 331 3848. (https://doi.org/10.1001/jama.2023.24945)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Baggio LL, Yusta B, Mulvihill EE, et al. 2018 GLP-1 receptor expression within the human heart. Endocrinology 159 15701584. (https://doi.org/10.1210/en.2018-00004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Balestrieri M, Rizzo M, Barbieri M, et al. 2015 Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment. Diabetes 64 13951406. (https://doi.org/10.2337/db14-1149)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Berglund LM, Lyssenko V, Ladenvall C, et al. 2016 Glucose-dependent insulinotropic polypeptide stimulates osteopontin expression in the vasculature via endothelin-1 and CREB. Diabetes 65 239254. (https://doi.org/10.2337/db15-0122)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bergmann N, Lund A, Gasbjerg L, et al. 2019 Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study. Diabetologia 62 665675. (https://doi.org/10.1007/s00125-018-4810-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bowker N, Hansford R, Burgess S, et al. 2021 Genetically predicted glucose-dependent insulinotropic polypeptide (GIP) levels and cardiovascular disease risk are driven by distinct causal variants in the GIPR region. Diabetes 70 27062719. (https://doi.org/10.2337/db21-0103)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Butler J, Shah S, Petrie M, et al. 2024 Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet 403 16351648. (https://doi.org/10.1016/s0140-6736(24)00469-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cameron-Vendrig A, Reheman A, Siraj MA, et al. 2016 Glucagon-like peptide 1 receptor activation attenuates platelet aggregation and thrombosis. Diabetes 65 17141723. (https://doi.org/10.2337/db15-1141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Campbell JE & Drucker DJ 2013 Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 17 819837. (https://doi.org/10.1016/j.cmet.2013.04.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chan DC, Watts GF, Ooi EM, et al. 2008 Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome. Arterioscler Thromb Vasc Biol 28 18311837. (https://doi.org/10.1161/atvbaha.108.170530)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chaudhuri A, Ghanim H, Vora M, et al. 2012 Exenatide exerts a potent antiinflammatory effect. J Clin Endocrinol Metab 97 198207. (https://doi.org/10.1210/jc.2011-1508)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chuang MH, Chen JY, Wang HY, et al. 2024 Clinical outcomes of tirzepatide or GLP-1 receptor agonists in individuals with type 2 diabetes. JAMA Netw Open 7 e2427258. (https://doi.org/10.1001/jamanetworkopen.2024.27258)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Coskun T, Sloop KW, Loghin C, et al. 2018 LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab 18 314. (https://doi.org/10.1016/j.molmet.2018.09.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dahl D, Onishi Y, Norwood P, et al. 2022 Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA 327 534545. (https://doi.org/10.1001/jama.2022.0078)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • de Lemos JA, Linetzky B, le Roux CW, et al. 2024 Tirzepatide reduces 24-hour ambulatory blood pressure in adults with body mass index ≥27 kg/m(2): SURMOUNT-1 ambulatory blood pressure monitoring substudy. Hypertension 81 e41e43. (https://doi.org/10.1161/hypertensionaha.123.22022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Del Prato S, Kahn SE, Pavo I, et al. 2021 Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet 398 18111824. (https://doi.org/10.1016/s0140-6736(21)02188-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • El K, Douros J, Willard F, et al. 2023 The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets. Nat Metab 5 945954. (https://doi.org/10.1038/s42255-023-00811-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Elrick H, Stimmler L, Hlad CJ Jr, et al. 1964 Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab 24 10761082. (https://doi.org/10.1210/jcem-24-10-1076)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fonseca V, DeVries J, Henry R, et al. 2014 Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: insights from a patient-level pooled analysis of six randomized clinical trials. J Diabetes Complications 28 399405. (https://doi.org/10.1016/j.jdiacomp.2014.01.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Frías J 2020 Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab 15 379394. (https://doi.org/10.1080/17446651.2020.1830759)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Frías JP, Davies MJ, Rosenstock J, et al. 2021 Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 385 503515. (https://doi.org/10.1056/nejmoa2107519)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Garvey WT, Frias JP, Jastreboff AM, et al. 2023 Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 402 613626. (https://doi.org/10.1016/s0140-6736(23)01200-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gasbjerg L, Helsted M, Hartmann B, et al. 2019 Separate and combined glucometabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 in healthy individuals. Diabetes 68 906917. (https://doi.org/10.2337/db18-1123)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gerstein HC, Colhoun HM, Dagenais GR, et al. 2019 Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394 121130. (https://doi.org/10.1016/s0140-6736(19)31149-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ginsberg HN, Elam MB, Lovato LC, et al. 2010 Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 362 15631574. (https://doi.org/10.1056/NEJMoa1001282)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gögebakan Ö, Osterhoff MA, Schüler R, et al. 2015 GIP increases adipose tissue expression and blood levels of MCP-1 in humans and links high energy diets to inflammation: a randomised trial. Diabetologia 58 17591768. (https://doi.org/10.1007/s00125-015-3618-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hankosky ER, Wang H, Neff LM, et al. 2024 Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis. Diabetes Obes Metab 26 319328. (https://doi.org/10.1111/dom.15318)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Heimbürger S, Hoe B, Nielsen C, et al. 2021 The effect of 6-day subcutaneous glucose-dependent insulinotropic polypeptide infusion on time in glycaemic range in patients with type 1 diabetes: a randomised, double-blind, placebo-controlled crossover trial. Diabetologia 64 24252431. (https://doi.org/10.1007/s00125-021-05547-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hermansen K, Bækdal TA, Düring M, et al. 2013 Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial. Diabetes Obes Metab 15 10401048. (https://doi.org/10.1111/dom.12133)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hojberg P, Vilsboll T, Rabol R, et al. 2009 Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52 199207. (https://doi.org/10.1007/s00125-008-1195-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Holst JJ, Orskov C, Vagn Nielsen O, et al. 1987 Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett 211 169174. (https://doi.org/10.1016/0014-5793(87)81430-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jastreboff AM, Aronne LJ, Ahmad NN, et al. 2022 Tirzepatide once weekly for the treatment of obesity. N Engl J Med 387 205216. (https://doi.org/10.1056/nejmoa2206038)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jastreboff AM, le Roux CW, Stefanski A, et al. 2024 Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med [epub]. (https://doi.org/10.1056/nejmoa2410819)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jujić A, Atabaki-Pasdar N, Nilsson PM, et al. 2020 Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality: a prospective study. Diabetologia 63 10431054. (https://doi.org/10.1007/s00125-020-05093-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jujić A, Nilsson PM, Atabaki-Pasdar N, et al. 2021 Glucose-dependent insulinotropic peptide in the high-normal range is associated with increased carotid intima-media thickness. Diabetes Care 44 224230. (https://doi.org/10.2337/dc20-1318)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kahles F, Liberman A, Halim C, et al. 2018 The incretin hormone GIP is upregulated in patients with atherosclerosis and stabilizes plaques in ApoE(-/-) mice by blocking monocyte/macrophage activation. Mol Metab 14 150157. (https://doi.org/10.1016/j.molmet.2018.05.014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Killion EA, Lu SC, Fort M, et al. 2020 Glucose-dependent insulinotropic polypeptide receptor therapies for the treatment of obesity, do agonists = antagonists? Endocr Rev 41 121. (https://doi.org/10.1210/endrev/bnz002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim M, Platt M, Shibasaki T, et al. 2013 GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat Med 19 567575. (https://doi.org/10.1038/nm.3128)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. 2023 Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 389 22212232. (https://doi.org/10.1056/nejmoa2307563)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lovshin JA, Barnie A, DeAlmeida A, et al. 2015 Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes. Diabetes Care 38 132139. (https://doi.org/10.2337/dc14-1958)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ludvik B, Giorgino F, Jódar E, et al. 2021 Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet 398 583598. (https://doi.org/10.1016/s0140-6736(21)01443-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lv X, Wang H, Chen C, et al. 2024 The effect of tirzepatide on weight, lipid metabolism and blood pressure in overweight/obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Syndr Obes 17 701714. (https://doi.org/10.2147/dmso.s443396)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lønborg J, Vejlstrup N, Kelbæk H, et al. 2012 Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J 33 14911499. (https://doi.org/10.1093/eurheartj/ehr309)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Marso SP, Bain SC, Consoli A, et al. 2016 Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375 18341844. (https://doi.org/10.1056/nejmoa1607141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nagashima M, Watanabe T, Terasaki M, et al. 2011 Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice. Diabetologia 54 26492659. (https://doi.org/10.1007/s00125-011-2241-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nauck MA & D'Alessio DA 2022 Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Cardiovasc Diabetol 21 169. (https://doi.org/10.1186/s12933-022-01604-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nauck M, Stöckmann F, Ebert R, et al. 1986 Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29 4652. (https://doi.org/10.1007/bf02427280)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nauck M, Heimesaat M, Orskov C, et al. 1993 Preserved incretin activity of glucagon-like peptide-1 [7-36 amide] but not of synthetic human gastric-inhibitory polypeptide in patients with type-2 diabetes-mellitus. J Clin Invest 91 301307. (https://doi.org/10.1172/jci116186)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nauck MA, Niedereichholz U, Ettler R, et al. 1997 Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 273 E981E988. (https://doi.org/10.1152/ajpendo.1997.273.5.e981)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nauck M, Meier J, Cavender M, et al. 2017 Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation 136 849870. (https://doi.org/10.1161/circulationaha.117.028136)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nicholls SJ, Bhatt DL, Buse JB, et al. 2024 Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. Am Heart J 267 111. (https://doi.org/10.1016/j.ahj.2023.09.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nogi Y, Nagashima M, Terasaki M, et al. 2012 Glucose-dependent insulinotropic polypeptide prevents the progression of macrophage-driven atherosclerosis in diabetic apolipoprotein E-null mice. PLoS One 7 e35683. (https://doi.org/10.1371/journal.pone.0035683)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Packer M, Zile M, Kramer C, et al. 2024 Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med [epub]. (https://doi.org/10.1056/nejmoa2410027)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pederson R, Satkunarajah M, McIntosh C, et al. 1998 Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor (-/-) mice. Diabetes 47 10461052. (https://doi.org/10.2337/diabetes.47.7.1046)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pyke C, Heller RS, Kirk RK, et al. 2014 GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 155 12801290. (https://doi.org/10.1210/en.2013-1934)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rosenstock J, Wysham C, Frías JP, et al. 2021 Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet 398 143155. (https://doi.org/10.1016/s0140-6736(21)01324-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sattar N, McGuire DK, Pavo I, et al. 2022 Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med 28 591598. (https://doi.org/10.1038/s41591-022-01707-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schirra J, Leicht P, Hildebrand P, et al. 1998 Mechanisms of the antidiabetic action of subcutaneous glucagon-like peptide-1(7-36)amide in non-insulin dependent diabetes mellitus. J Endocrinol 156 177186. (https://doi.org/10.1677/joe.0.1560177)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schwartz EA, Koska J, Mullin MP, et al. 2010 Exenatide suppresses postprandial elevations in lipids and lipoproteins in individuals with impaired glucose tolerance and recent onset type 2 diabetes mellitus. Atherosclerosis 212 217222. (https://doi.org/10.1016/j.atherosclerosis.2010.05.028)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Smits MM, Muskiet MH, Tonneijck L, et al. 2016 Exenatide acutely increases heart rate in parallel with augmented sympathetic nervous system activation in healthy overweight males. Br J Clin Pharmacol 81 613620. (https://doi.org/10.1111/bcp.12843)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Thondam S, Cuthbertson D & Wilding J 2020 The influence of glucose-dependent insulinotropic polypeptide (GIP) on human adipose tissue and fat metabolism: implications for obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Peptides 125 170208. (https://doi.org/10.1016/j.peptides.2019.170208)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Turton MD, O'Shea D, Gunn I, et al. 1996 A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379 6972. (https://doi.org/10.1038/379069a0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ussher JR, Campbell JE, Mulvihill EE, et al. 2018 Inactivation of the glucose-dependent insulinotropic polypeptide receptor improves outcomes following experimental myocardial infarction. Cell Metab 27 450460.e6. (https://doi.org/10.1016/j.cmet.2017.11.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wadden T, Chao A, Machineni S, et al. 2023 Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med 29 29092918. (https://doi.org/10.1038/s41591-023-02597-w)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Walldius G & Jungner I 2004 Apolipoprotein B and apolipoprotein A-I: risk indicators of coronary heart disease and targets for lipid-modifying therapy. J Intern Med 255 188205. (https://doi.org/10.1046/j.1365-2796.2003.01276.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wilson JM, Nikooienejad A, Robins DA, et al. 2020 The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diabetes Obes Metab 22 24512459. (https://doi.org/10.1111/dom.14174)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wilson JM, Lin Y, Luo MJ, et al. 2022 The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: a post hoc analysis. Diabetes Obes Metab 24 148153. (https://doi.org/10.1111/dom.14553)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xie D, Li Y, Xu M, et al. 2022 Effects of dulaglutide on endothelial progenitor cells and arterial elasticity in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 21 200. (https://doi.org/10.1186/s12933-022-01634-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang Y, He L, Liu P, et al. 2024 Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: a systematic review and pairwise and network meta-analysis. Diabetes Obes Metab 26 548556. (https://doi.org/10.1111/dom.15342)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang Q, Delessa C, Augustin R, et al. 2021 The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling. Cell Metab 33 833844.e5. (https://doi.org/10.1016/j.cmet.2021.01.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zheng C, Khoo C, Furtado J, et al. 2010 Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. Circulation 121 17221734. (https://doi.org/10.1161/circulationaha.109.875807)

    • PubMed
    • Search Google Scholar
    • Export Citation