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29.03.2024 | Cardiometabolic Disease (DM and CV) (CJ Lavie, Section Editor)

Worth Their Weight? An Update on New and Emerging Pharmacologic Agents for Obesity and Their Potential Role for Persons with Cardiac Conditions

verfasst von: Josephine Harrington, G. Michael Felker, James L. Januzzi, Carolyn S. P. Lam, Ildiko Lingvay, Neha J. Pagidipati, Naveed Sattar, Harriette G. C. Van Spall, Subodh Verma, Darren K. McGuire

Erschienen in: Current Cardiology Reports | Ausgabe 3/2024

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Abstract

Purpose of Review

Obesity is associated with cardiovascular (CV) conditions, including but not limited to atherosclerotic disease, heart failure, and atrial fibrillation. Despite this, the impact of intentional weight loss on CV outcomes for persons with obesity and established CV conditions remains poorly studied. New and emerging pharmacologic therapies for weight loss primarily targeting the incretin/nutrient sensing axes induce substantial and sustained weight loss. The glucagon-like-peptide 1 receptor agonists (GLP-1 RA) liraglutide and semaglutide have US FDA approval for the treatment of obesity, and the application for an obesity indication for the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide is presently under FDA review. Extensive phase II and IIIa randomized controlled trials are underway evaluating permutations of combined GLP-1 RA, GIP receptor agonist, GIP receptor antagonist, and glucagon receptor agonists. Clinical outcome trials of these therapies in persons with obesity at high risk of established CV conditions should make it possible to estimate the role of intentional weight loss in managing CV risk via these medications.

Recent Findings

High-dose once weekly injectable semaglutide (2.4 mg/week) use among persons with obesity and heart failure with preserved ejection fraction was effective at both reducing weight and improving health status; exercise capacity was also improved. Ongoing CV outcome trials of oral semaglutide and once weekly injectable tirzepatide will help to establish the role of these therapies among persons with other CV conditions. In addition to these two therapies targeting a CV claim or indication, many other new therapeutics for weight loss, as reviewed, are currently in development.

Summary

The impact of pharmacologic-induced weight loss on CV conditions for persons with obesity and established CV conditions is currently under investigation for multiple agents. These therapies may offer new avenues to manage CV risk in persons with obesity and with established or at high risk for CV disease.
Literatur
1.
3.
Zurück zum Zitat • The GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. New England Journal of Medicine. 2017;377:13–27. In an analysis of data from 68.5 million persons, high BMI was found to account for 4 million deaths globally; more than two-thirds of these deaths were due to cardiovascular disease. • The GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. New England Journal of Medicine. 2017;377:13–27. In an analysis of data from 68.5 million persons, high BMI was found to account for 4 million deaths globally; more than two-thirds of these deaths were due to cardiovascular disease.
4.
Zurück zum Zitat Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341:1097–105. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341:1097–105.
5.
Zurück zum Zitat Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics—2023 update: a report from the American Heart Association. Circulation. 2023;147:e93-621.PubMedCrossRef Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics—2023 update: a report from the American Heart Association. Circulation. 2023;147:e93-621.PubMedCrossRef
6.
Zurück zum Zitat Alexander JK, Amad KH, Cole VW. Observations on some clinical features of extreme obesity, with particular reference to cardiorespiratory effects. Am J Med. 1962;32:512–24.CrossRef Alexander JK, Amad KH, Cole VW. Observations on some clinical features of extreme obesity, with particular reference to cardiorespiratory effects. Am J Med. 1962;32:512–24.CrossRef
7.
Zurück zum Zitat Kasper EK, Hruban RH, Baughman KL. Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure. Am J Cardiol. 1992;70:921–4.PubMedCrossRef Kasper EK, Hruban RH, Baughman KL. Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure. Am J Cardiol. 1992;70:921–4.PubMedCrossRef
8.
Zurück zum Zitat Rabbia F, Silke B, Conterno A, Grosso T, De Vito B, Rabbone I, et al. Assessment of cardiac autonomic modulation during adolescent obesity. Obes Res. 2003;11:541–8.PubMedCrossRef Rabbia F, Silke B, Conterno A, Grosso T, De Vito B, Rabbone I, et al. Assessment of cardiac autonomic modulation during adolescent obesity. Obes Res. 2003;11:541–8.PubMedCrossRef
9.
Zurück zum Zitat Abed HS, Samuel CS, Lau DH, Kelly DJ, Royce SG, Alasady M, et al. Obesity results in progressive atrial structural and electrical remodeling: implications for atrial fibrillation. Heart Rhythm. 2013;10:90–100.PubMedCrossRef Abed HS, Samuel CS, Lau DH, Kelly DJ, Royce SG, Alasady M, et al. Obesity results in progressive atrial structural and electrical remodeling: implications for atrial fibrillation. Heart Rhythm. 2013;10:90–100.PubMedCrossRef
10.
Zurück zum Zitat Mahajan R, Lau DH, Brooks AG, Shipp NJ, Manavis J, Wood JPM, et al. Electrophysiological, Electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol. 2015;66:1–11.PubMedCrossRef Mahajan R, Lau DH, Brooks AG, Shipp NJ, Manavis J, Wood JPM, et al. Electrophysiological, Electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol. 2015;66:1–11.PubMedCrossRef
11.
Zurück zum Zitat Munger TM, Dong Y-X, Masaki M, Oh JK, Mankad SV, Borlaug BA, et al. Electrophysiological and hemodynamic characteristics associated with obesity in patients with atrial fibrillation. J Am Coll Cardiol. 2012;60:851–60.PubMedCrossRef Munger TM, Dong Y-X, Masaki M, Oh JK, Mankad SV, Borlaug BA, et al. Electrophysiological and hemodynamic characteristics associated with obesity in patients with atrial fibrillation. J Am Coll Cardiol. 2012;60:851–60.PubMedCrossRef
12.
Zurück zum Zitat McGill HC, McMahan CA, Herderick EE, Zieske AW, Malcom GT, Tracy RE, et al. Obesity accelerates the progression of coronary atherosclerosis in young men. Circulation. 2002;105:2712–8.PubMedCrossRef McGill HC, McMahan CA, Herderick EE, Zieske AW, Malcom GT, Tracy RE, et al. Obesity accelerates the progression of coronary atherosclerosis in young men. Circulation. 2002;105:2712–8.PubMedCrossRef
13.
Zurück zum Zitat Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001;74:579–84.PubMedCrossRef Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001;74:579–84.PubMedCrossRef
14.
Zurück zum Zitat Batsis JA, Sarr MG, Collazo-Clavell ML, Thomas RJ, Romero-Corral A, Somers VK, et al. Cardiovascular risk after bariatric surgery for obesity. Am J Cardiol. 2008;102:930–7.PubMedPubMedCentralCrossRef Batsis JA, Sarr MG, Collazo-Clavell ML, Thomas RJ, Romero-Corral A, Somers VK, et al. Cardiovascular risk after bariatric surgery for obesity. Am J Cardiol. 2008;102:930–7.PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat Doumouras AG, Wong JA, Paterson JM, Lee Y, Sivapathasundaram B, Tarride J-E, et al. Bariatric Surgery and cardiovascular outcomes in patients with obesity and cardiovascular disease: Circulation. 2021;143:1468–80.PubMed Doumouras AG, Wong JA, Paterson JM, Lee Y, Sivapathasundaram B, Tarride J-E, et al. Bariatric Surgery and cardiovascular outcomes in patients with obesity and cardiovascular disease: Circulation. 2021;143:1468–80.PubMed
16.
Zurück zum Zitat Fisher DP, Johnson E, Haneuse S, Arterburn D, Coleman KJ, O’Connor PJ, et al. Association between bariatric surgery and macrovascular disease outcomes in patients with type 2 diabetes and severe obesity. JAMA. 2018;320:1570–82.PubMedPubMedCentralCrossRef Fisher DP, Johnson E, Haneuse S, Arterburn D, Coleman KJ, O’Connor PJ, et al. Association between bariatric surgery and macrovascular disease outcomes in patients with type 2 diabetes and severe obesity. JAMA. 2018;320:1570–82.PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, et al. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022;28:591–8.PubMedPubMedCentralCrossRef Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, et al. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022;28:591–8.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.PubMedPubMedCentralCrossRef Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.PubMedPubMedCentralCrossRef
19.
Zurück zum Zitat Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–44.PubMedCrossRef Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–44.PubMedCrossRef
20.
Zurück zum Zitat Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002.PubMedCrossRef Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002.PubMedCrossRef
22.
Zurück zum Zitat Nissen SE, Wolski KE, Prcela L, Wadden T, Buse JB, Bakris G, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial. JAMA. 2016;315:990–1004.PubMedCrossRef Nissen SE, Wolski KE, Prcela L, Wadden T, Buse JB, Bakris G, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial. JAMA. 2016;315:990–1004.PubMedCrossRef
23.
Zurück zum Zitat Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im K, et al. Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med. 2018;379:1107–17.PubMedCrossRef Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im K, et al. Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med. 2018;379:1107–17.PubMedCrossRef
25.
Zurück zum Zitat James WPT, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363:905–17.PubMedCrossRef James WPT, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363:905–17.PubMedCrossRef
26.
Zurück zum Zitat Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. 2012;367:1577–9.PubMedCrossRef Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. 2012;367:1577–9.PubMedCrossRef
27.
Zurück zum Zitat Blüher M, Aras M, Aronne LJ, Batterham RL, Giorgino F, Ji L, et al. New insights into the treatment of obesity. Diabetes Obes Metab. 2023;25:2058–72.PubMedCrossRef Blüher M, Aras M, Aronne LJ, Batterham RL, Giorgino F, Ji L, et al. New insights into the treatment of obesity. Diabetes Obes Metab. 2023;25:2058–72.PubMedCrossRef
29.
Zurück zum Zitat Topol EJ, Bousser M-G, Fox KA, Creager MA, Despres J-P, Easton JD, et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. The Lancet. 2010;376:517–23.CrossRef Topol EJ, Bousser M-G, Fox KA, Creager MA, Despres J-P, Easton JD, et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. The Lancet. 2010;376:517–23.CrossRef
30.
Zurück zum Zitat Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019;394:121–30.CrossRef Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet. 2019;394:121–30.CrossRef
31.
Zurück zum Zitat Hernandez AF, Green JB, Janmohamed S, D’Agostino RB, Granger CB, Jones NP, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. The Lancet. 2018;392:1519–29.CrossRef Hernandez AF, Green JB, Janmohamed S, D’Agostino RB, Granger CB, Jones NP, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. The Lancet. 2018;392:1519–29.CrossRef
32.
Zurück zum Zitat Sattar N, Lee MMY, Kristensen SL, Branch KRH, Del Prato S, Khurmi NS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9:653–62.PubMedCrossRef Sattar N, Lee MMY, Kristensen SL, Branch KRH, Del Prato S, Khurmi NS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9:653–62.PubMedCrossRef
34.
Zurück zum Zitat • Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389:1069–84. The STEP-HFpEF found that among persons with HF and preserved ejection fraction, 2.4 mg SC once weekly semaglutide versus placebo led to significant improvements in the co-primary outcomes of weight loss and health status as measured by the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score. • Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389:1069–84. The STEP-HFpEF found that among persons with HF and preserved ejection fraction, 2.4 mg SC once weekly semaglutide versus placebo led to significant improvements in the co-primary outcomes of weight loss and health status as measured by the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score.
37.
Zurück zum Zitat Eli Lilly and Company. A Phase 3, Randomized, double-blind study to investigate the efficacy and safety of once-daily oral ly3502970 compared with placebo in adult participants with obesity or overweight with weight-related comorbidities (ATTAIN-1). clinicaltrials.gov; 2023 Jul. Report No.: NCT05869903. Available from: https://clinicaltrials.gov/study/NCT05869903 Eli Lilly and Company. A Phase 3, Randomized, double-blind study to investigate the efficacy and safety of once-daily oral ly3502970 compared with placebo in adult participants with obesity or overweight with weight-related comorbidities (ATTAIN-1). clinicaltrials.gov; 2023 Jul. Report No.: NCT05869903. Available from: https://​clinicaltrials.​gov/​study/​NCT05869903
38.
Zurück zum Zitat Eli Lilly and Company. A phase 3, open-label study of once daily LY3502970 compared with insulin glargine in adult participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. clinicaltrials.gov; 2023 Apr. Report No.: NCT05803421. Available from: https://clinicaltrials.gov/ct2/show/NCT05803421 Eli Lilly and Company. A phase 3, open-label study of once daily LY3502970 compared with insulin glargine in adult participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. clinicaltrials.gov; 2023 Apr. Report No.: NCT05803421. Available from: https://​clinicaltrials.​gov/​ct2/​show/​NCT05803421
40.
Zurück zum Zitat Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Christensen L, Davies M, et al. Design and baseline characteristics of STEP-HFpEF program evaluating semaglutide in patients with obesity HFpEF phenotype. JACC Heart Fail. 2023;11:1000–10.PubMedCrossRef Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Christensen L, Davies M, et al. Design and baseline characteristics of STEP-HFpEF program evaluating semaglutide in patients with obesity HFpEF phenotype. JACC Heart Fail. 2023;11:1000–10.PubMedCrossRef
42.
Zurück zum Zitat Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. cell metabolism. 2018;27:740–56. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. cell metabolism. 2018;27:740–56.
43.
Zurück zum Zitat Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet. 2021;397:971–84.CrossRef Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet. 2021;397:971–84.CrossRef
44.
Zurück zum Zitat Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021;325:1403–13.PubMedCrossRef Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021;325:1403–13.PubMedCrossRef
45.
Zurück zum Zitat Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414–25.PubMedCrossRef Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414–25.PubMedCrossRef
46.
Zurück zum Zitat Kadowaki T, Isendahl J, Khalid U, Lee SY, Nishida T, Ogawa W, et al. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2022;10:193–206.PubMedCrossRef Kadowaki T, Isendahl J, Khalid U, Lee SY, Nishida T, Ogawa W, et al. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2022;10:193–206.PubMedCrossRef
47.
Zurück zum Zitat Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28:2083–91.PubMedPubMedCentralCrossRef Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28:2083–91.PubMedPubMedCentralCrossRef
48.
Zurück zum Zitat Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24:1553–64.PubMedPubMedCentralCrossRef Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24:1553–64.PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Borlaug BA, Kitzman DW, Davies MJ, Rasmussen S, Barros E, Butler J, et al. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023;1–8. Borlaug BA, Kitzman DW, Davies MJ, Rasmussen S, Barros E, Butler J, et al. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023;1–8.
50.
Zurück zum Zitat Novo Nordisk A/S. Effect of semaglutide 2.4 mg once-weekly on function and symptoms in subjects with obesity-related heart failure with preserved ejection fraction, and type 2 diabetes. clinicaltrials.gov; 2023 Mar. Report No.: NCT04916470. Available from: https://clinicaltrials.gov/ct2/show/NCT04916470 Novo Nordisk A/S. Effect of semaglutide 2.4 mg once-weekly on function and symptoms in subjects with obesity-related heart failure with preserved ejection fraction, and type 2 diabetes. clinicaltrials.gov; 2023 Mar. Report No.: NCT04916470. Available from: https://​clinicaltrials.​gov/​ct2/​show/​NCT04916470
51.
Zurück zum Zitat • Lingvay I, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. Obesity (Silver Spring). 2023;31:111–22. In this study of 17,604 persons with BI ≥ 27 kg/m2 and established ASCVD, randomization to weight loss drug semaglutide resulted in a 20% reduction in the primary composite outcome of CV death, myocardial infarction, and stroke. • Lingvay I, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. Obesity (Silver Spring). 2023;31:111–22. In this study of 17,604 persons with BI ≥ 27 kg/m2 and established ASCVD, randomization to weight loss drug semaglutide resulted in a 20% reduction in the primary composite outcome of CV death, myocardial infarction, and stroke.
52.
Zurück zum Zitat Margulies KB, Hernandez AF, Redfield MM, Givertz MM, Oliveira GH, Cole R, et al. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016;316:500–8.PubMedPubMedCentralCrossRef Margulies KB, Hernandez AF, Redfield MM, Givertz MM, Oliveira GH, Cole R, et al. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016;316:500–8.PubMedPubMedCentralCrossRef
53.
Zurück zum Zitat Khan MS, Fonarow GC, McGuire DK, Hernandez AF, Vaduganathan M, Rosenstock J, et al. Glucagon-like peptide 1 receptor agonists and heart failure. Circulation. 2020;142:1205–18.PubMedCrossRef Khan MS, Fonarow GC, McGuire DK, Hernandez AF, Vaduganathan M, Rosenstock J, et al. Glucagon-like peptide 1 receptor agonists and heart failure. Circulation. 2020;142:1205–18.PubMedCrossRef
54.
Zurück zum Zitat Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hänselmann A, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19:69–77.PubMedCrossRef Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hänselmann A, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19:69–77.PubMedCrossRef
55.
Zurück zum Zitat Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381:841–51.PubMedCrossRef Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381:841–51.PubMedCrossRef
56.
Zurück zum Zitat McGuire DK, Busui RP, Deanfield J, Inzucchi SE, Mann JFE, Marx N, et al. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial. Diabetes Obes Metab. 2023;25:1932–41.PubMedCrossRef McGuire DK, Busui RP, Deanfield J, Inzucchi SE, Mann JFE, Marx N, et al. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial. Diabetes Obes Metab. 2023;25:1932–41.PubMedCrossRef
57.
Zurück zum Zitat Knop FK, Aroda VR, Vale RD do, Holst-Hansen T, Laursen PN, Rosenstock J, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2023;402:705–19. Knop FK, Aroda VR, Vale RD do, Holst-Hansen T, Laursen PN, Rosenstock J, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2023;402:705–19.
58.
Zurück zum Zitat Aroda VR, Aberle J, Bardtrum L, Christiansen E, Knop FK, Gabery S, et al. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. The Lancet. 2023;402:693–704.CrossRef Aroda VR, Aberle J, Bardtrum L, Christiansen E, Knop FK, Gabery S, et al. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. The Lancet. 2023;402:693–704.CrossRef
59.
Zurück zum Zitat Fisman EZ, Tenenbaum A. The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect. Cardiovasc Diabetol. 2021;20:225.PubMedPubMedCentralCrossRef Fisman EZ, Tenenbaum A. The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect. Cardiovasc Diabetol. 2021;20:225.PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31:410–21.PubMedCrossRef Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31:410–21.PubMedCrossRef
61.
Zurück zum Zitat Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205–16.PubMedCrossRef Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205–16.PubMedCrossRef
62.
Zurück zum Zitat Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al. 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. The Lancet. 2023;402:613–26.CrossRef Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al. 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. The Lancet. 2023;402:613–26.CrossRef
64.
Zurück zum Zitat McGuire DK, D’Alessio D, Nicholls SJ, Nissen SE, Riesmeyer JS, Pavo I, et al. Transitioning to active-controlled trials to evaluate cardiovascular safety and efficacy of medications for type 2 diabetes. Cardiovasc Diabetol. 2022;21:163.PubMedPubMedCentralCrossRef McGuire DK, D’Alessio D, Nicholls SJ, Nissen SE, Riesmeyer JS, Pavo I, et al. Transitioning to active-controlled trials to evaluate cardiovascular safety and efficacy of medications for type 2 diabetes. Cardiovasc Diabetol. 2022;21:163.PubMedPubMedCentralCrossRef
65.
Zurück zum Zitat Nicholls SJ, Bhatt DL, Buse JB, Prato SD, Kahn SE, Lincoff AM, et al. 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. 2023;S0002–8703(23):00280–6. Nicholls SJ, Bhatt DL, Buse JB, Prato SD, Kahn SE, Lincoff AM, et al. 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. 2023;S0002–8703(23):00280–6.
66.
Zurück zum Zitat Eli Lilly and Company. Efficacy and safety of tirzepatide once weekly versus placebo after an intensive lifestyle program in participants without type 2 diabetes who have obesity or are overweight with weight-related comorbidities: a randomized, double blind, placebo-controlled Trial (SURMOUNT-3). clinicaltrials.gov; 2023 May. Report No.: NCT04657016. Available from: https://clinicaltrials.gov/study/NCT04657016 Eli Lilly and Company. Efficacy and safety of tirzepatide once weekly versus placebo after an intensive lifestyle program in participants without type 2 diabetes who have obesity or are overweight with weight-related comorbidities: a randomized, double blind, placebo-controlled Trial (SURMOUNT-3). clinicaltrials.gov; 2023 May. Report No.: NCT04657016. Available from: https://​clinicaltrials.​gov/​study/​NCT04657016
67.
Zurück zum Zitat Eli Lilly and Company. Efficacy and safety of tirzepatide once weekly versus placebo for maintenance of weight loss in participants without type 2 diabetes who have obesity or are overweight with weight-related comorbidities: a randomized, double-blind, placebo-controlled trial (SURMOUNT-4). clinicaltrials.gov; 2023 May. Report No.: NCT04660643. Available from: https://clinicaltrials.gov/study/NCT04660643 Eli Lilly and Company. Efficacy and safety of tirzepatide once weekly versus placebo for maintenance of weight loss in participants without type 2 diabetes who have obesity or are overweight with weight-related comorbidities: a randomized, double-blind, placebo-controlled trial (SURMOUNT-4). clinicaltrials.gov; 2023 May. Report No.: NCT04660643. Available from: https://​clinicaltrials.​gov/​study/​NCT04660643
68.
Zurück zum Zitat Frias JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Macura S, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402:720–30.PubMedCrossRef Frias JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Macura S, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402:720–30.PubMedCrossRef
69.
Zurück zum Zitat Novo Nordisk A/S. The cardiovascular safety of cagrilintide 2.4 mg s.c. in combination with semaglutide 2.4 mg s.c. (CagriSema 2.4 mg/2.4 mg s.c.) once-weekly in participants with obesity and established cardiovascular disease. clinicaltrials.gov; 2023 Apr. Report No.: NCT05669755. Available from: https://clinicaltrials.gov/ct2/show/NCT05669755 Novo Nordisk A/S. The cardiovascular safety of cagrilintide 2.4 mg s.c. in combination with semaglutide 2.4 mg s.c. (CagriSema 2.4 mg/2.4 mg s.c.) once-weekly in participants with obesity and established cardiovascular disease. clinicaltrials.gov; 2023 Apr. Report No.: NCT05669755. Available from: https://​clinicaltrials.​gov/​ct2/​show/​NCT05669755
70.
Zurück zum Zitat Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389:877–88.PubMedCrossRef Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389:877–88.PubMedCrossRef
72.
Zurück zum Zitat Le Roux CW. A phase 2, randomized, double-blind, placebo-controlled, dose-finding study of BI 456906 in people with overweight/obesity. Presented at the American Diabetes Association's 83rd Scientific Sessions 2023. Le Roux CW. A phase 2, randomized, double-blind, placebo-controlled, dose-finding study of BI 456906 in people with overweight/obesity. Presented at the American Diabetes Association's 83rd Scientific Sessions 2023.
73.
Zurück zum Zitat LE Roux CA, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. 51-OR: a phase 2, randomized, double-blind, placebo-controlled, dose-finding study of bi 456906 in people with overweight/obesity. Diabetes. 2023;72:51-OR. LE Roux CA, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. 51-OR: a phase 2, randomized, double-blind, placebo-controlled, dose-finding study of bi 456906 in people with overweight/obesity. Diabetes. 2023;72:51-OR.
76.
Zurück zum Zitat Altimmune, Inc. A phase 2, multicenter, randomized, double-blind, placebo-controlled and parallel group 48-week study to evaluate the efficacy and safety of ALT-801 in the treatment of obesity (MOMENTUM Trial). clinicaltrials.gov; 2022 Sep. Report No.: NCT05295875. Available from: https://clinicaltrials.gov/study/NCT05295875 Altimmune, Inc. A phase 2, multicenter, randomized, double-blind, placebo-controlled and parallel group 48-week study to evaluate the efficacy and safety of ALT-801 in the treatment of obesity (MOMENTUM Trial). clinicaltrials.gov; 2022 Sep. Report No.: NCT05295875. Available from: https://​clinicaltrials.​gov/​study/​NCT05295875
78.
Zurück zum Zitat Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, et al. Triple–hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389:514–26.PubMedCrossRef Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, et al. Triple–hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389:514–26.PubMedCrossRef
79.
Zurück zum Zitat Eli Lilly and Company. A randomized, double-blind, phase 3 study to investigate the efficacy and safety of LY3437943 once weekly compared to placebo in participants with severe obesity and established cardiovascular disease. clinicaltrials.gov; 2023 Jul. Report No.: NCT05882045. Available from: https://clinicaltrials.gov/study/NCT05882045 Eli Lilly and Company. A randomized, double-blind, phase 3 study to investigate the efficacy and safety of LY3437943 once weekly compared to placebo in participants with severe obesity and established cardiovascular disease. clinicaltrials.gov; 2023 Jul. Report No.: NCT05882045. Available from: https://​clinicaltrials.​gov/​study/​NCT05882045
81.
Zurück zum Zitat Amgen. A phase 2 randomized, placebo-controlled, double-blind, dose-ranging study to evaluate the efficacy, safety, and tolerability of AMG 133 in adult subjects with overweight or obesity, with or without type 2 diabetes mellitus. clinicaltrials.gov; 2023 Aug. Report No.: NCT05669599. Available from: https://clinicaltrials.gov/study/NCT05669599 Amgen. A phase 2 randomized, placebo-controlled, double-blind, dose-ranging study to evaluate the efficacy, safety, and tolerability of AMG 133 in adult subjects with overweight or obesity, with or without type 2 diabetes mellitus. clinicaltrials.gov; 2023 Aug. Report No.: NCT05669599. Available from: https://​clinicaltrials.​gov/​study/​NCT05669599
82.
Zurück zum Zitat Rivus Pharmaceuticals, Inc. Exploratory Phase 2a, double-blind, placebo-controlled, dose escalation study to determine the safety, tolerability, PD, and PK of HU6 for the treatment of subjects with obese Heart Failure With Preserved Ejection Fraction (HFpEF). clinicaltrials.gov; 2023 Jun. Report No.: NCT05284617. Available from: https://clinicaltrials.gov/study/NCT05284617 Rivus Pharmaceuticals, Inc. Exploratory Phase 2a, double-blind, placebo-controlled, dose escalation study to determine the safety, tolerability, PD, and PK of HU6 for the treatment of subjects with obese Heart Failure With Preserved Ejection Fraction (HFpEF). clinicaltrials.gov; 2023 Jun. Report No.: NCT05284617. Available from: https://​clinicaltrials.​gov/​study/​NCT05284617
Metadaten
Titel
Worth Their Weight? An Update on New and Emerging Pharmacologic Agents for Obesity and Their Potential Role for Persons with Cardiac Conditions
verfasst von
Josephine Harrington
G. Michael Felker
James L. Januzzi
Carolyn S. P. Lam
Ildiko Lingvay
Neha J. Pagidipati
Naveed Sattar
Harriette G. C. Van Spall
Subodh Verma
Darren K. McGuire
Publikationsdatum
29.03.2024
Verlag
Springer US
Erschienen in
Current Cardiology Reports / Ausgabe 3/2024
Print ISSN: 1523-3782
Elektronische ISSN: 1534-3170
DOI
https://doi.org/10.1007/s11886-023-02016-z

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