ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13184ometendo-13184Research ArticleОБЗОРЫREVIEWSИнновационные подходы к лечению ожирения: от фармакотерапии к наномедицинеInnovative approaches to the treatment of obesity: from pharmacotherapy to nanomedicinehttps://orcid.org/0000-0003-3870-6394РоманцоваТ. И.RomantsovaT. I.

Романцова Татьяна Ивановна, д.м.н., профессор

125993, Москва, Баррикадная улица, 2/1, стр. 1

Tatiana I. Romantsova, MD, PhD, Professor

2/1, bild.1, Barrikadnaya street, 125993, Moscow

romantsovatatiana@rambler.ruФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МинздраваРоссияRussian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian FederationRussian Federation202408102024214389404Copyright © Романцова Т.И., 20252025Романцова Т.И.Romantsova T.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/13184

В настоящее время 879 миллионов взрослых людей на планете страдают ожирением. Ожирение и сахарный диабет 2 типа (СД2) имеют общие ключевые патофизиологические механизмы. Снижение массы тела является неотъемлемой частью стратегии управления сахарным диабетом (СД). Успехи в изучении патогенеза ожирения способствуют разработке и внедрению в клиническую практику инновационных технологий для борьбы с эпидемией ожирения и СД. Новые лекарственные препараты реализуют свое действие на уровне центральной нервной системы, желудочно-кишечного тракта, жировой ткани, почек, печени, поджелудочной железы, скелетных мышц. Проводится оценка безопасности генной терапии, изучаются возможности особых способов доставки препаратов в ткани-мишени. Рандомизированные клинические исследования свидетельствуют, что эффективность ряда новых фармакологических препаратов в отношении снижения массы тела и нормализации показателей углеводного обмена уже практически сопоставима с результатами бариатрических операций. В данном обзоре обобщены сведения литературных источников о перспективах терапии ожирения и СД2 на основе разработок преимущественно в области пептидных препаратов, моноклональных антител, РНК-терапии

Currently, 879 million adults in the world are obese. Obesity and type 2 diabetes have common key pathophysiological mechanisms. Weight loss is an integral part of diabetes management. Advances in the study of the pathogenesis of obesity contribute to the development and introduction into clinical practice of innovative technologies to combat the epidemic of obesity and diabetes mellitus. New drugs take effect at the level of the central nervous system, gastrointestinal tract, adipose tissue, kidneys, liver, pancreas, and skeletal muscles. The safety of gene therapy is being evaluated, and the potential of special methods of drug delivery to target tissues is being studied. Randomized clinical studies show that the effectiveness of a number of new pharmacological drugs in weight loss and carbohydrate metabolism normalization is already almost comparable to that of bariatric surgery. This review summarizes the literature on the prospects for the treatment of obesity and type 2 diabetes based on developments primarily in the field of peptide drugs, monoclonal antibodies, and RNA therapy.

ожирениеглюкагоноподобный пептид-1гормоны желудочно-кишечного трактамоноклональные антителаРНК-терапияobesityglucagon-like peptide-1gastrointestinal hormonesmonoclonal antibodiesRNA therapyИсследование выполнено при финансовом обеспечении компании ООО «ПРОМОМЕД ДМ». Спонсор не оказывал влияние на выбор исследований, анализ и интерпретацию данных.ReferencesNCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403:1027–1050. doi: 10.1016/S0140-6736(23)02750-2.NCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403:1027–1050. doi: 10.1016/S0140-6736(23)02750-2.GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023 Jul 15;402(10397):203-234. doi: 10.1016/S0140-6736(23)01301-6.GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023 Jul 15;402(10397):203-234. doi: 10.1016/S0140-6736(23)01301-6.Sztanek F, Tóth LI, Pető A, et al. New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes-Beyond and within GLP-1 Receptor Agonists. Biomedicines. 2024 Jun 13;12(6):1320. doi: 10.3390/biomedicines12061320.Sztanek F, Tóth LI, Pető A, et al. New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes-Beyond and within GLP-1 Receptor Agonists. Biomedicines. 2024 Jun 13;12(6):1320. doi: 10.3390/biomedicines12061320.Lingvay I., Sumithran P., Cohen R.V., le Roux C.W. Obesity management as a primary treatment goal for type 2 diabetes: Time to reframe the conversation. Lancet. 2022; 399:394–405. doi: 10.1016/S0140-6736(21)01919-X.Lingvay I., Sumithran P., Cohen R.V., le Roux C.W. Obesity management as a primary treatment goal for type 2 diabetes: Time to reframe the conversation. Lancet. 2022; 399:394–405. doi: 10.1016/S0140-6736(21)01919-X.Coutinho W, Halpern B. Pharmacotherapy for obesity: moving towards efficacy improvement. Diabetol Metab Syndr. 2024 Jan 3;16(1):6. doi: 10.1186/s13098-023-01233-4.Coutinho W, Halpern B. Pharmacotherapy for obesity: moving towards efficacy improvement. Diabetol Metab Syndr. 2024 Jan 3;16(1):6. doi: 10.1186/s13098-023-01233-4.Angelidi AM, Belanger MJ, Kokkinos A, Koliaki CC, Mantzoros CS. Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy. Endocr Rev. 2022 May 12;43(3):507-557. doi: 10.1210/endrev/bnab034.Angelidi AM, Belanger MJ, Kokkinos A, Koliaki CC, Mantzoros CS. Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy. Endocr Rev. 2022 May 12;43(3):507-557. doi: 10.1210/endrev/bnab034.Barman P, Joshi S, Sharma S, et al. Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics. Int J Pept Res Ther. 2023;29(4):61. doi: 10.1007/s10989-023-10524-3.Barman P, Joshi S, Sharma S, et al. Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics. Int J Pept Res Ther. 2023;29(4):61. doi: 10.1007/s10989-023-10524-3.Kumar MS. Peptides and Peptidomimetics as Potential Antiobesity Agents: Overview of Current Status. Front Nutr. 2019 Feb 18; 6:11. doi: 10.3389/fnut.2019.00011.Kumar MS. Peptides and Peptidomimetics as Potential Antiobesity Agents: Overview of Current Status. Front Nutr. 2019 Feb 18; 6:11. doi: 10.3389/fnut.2019.00011.Bailey CJ, Flatt PR, Conlon JM. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides. 2023 Mar; 161:170939. doi: 10.1016/j.peptides.2023.170939.Bailey CJ, Flatt PR, Conlon JM. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides. 2023 Mar; 161:170939. doi: 10.1016/j.peptides.2023.170939.Andreasen CR, Andersen A, Vilsbøll T. The future of incretins in the treatment of obesity and non-alcoholic fatty liver disease. Diabetologia. 2023 Oct;66(10):1846-1858. doi: 10.1007/s00125-023-05966-9.Andreasen CR, Andersen A, Vilsbøll T. The future of incretins in the treatment of obesity and non-alcoholic fatty liver disease. Diabetologia. 2023 Oct;66(10):1846-1858. doi: 10.1007/s00125-023-05966-9.Aroda VR, Aberle J, Bardtrum L, 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. Lancet Lond Engl. 2023; 402:693–704. doi: 10.1016/S0140-6736(23)01127-3Aroda VR, Aberle J, Bardtrum L, 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. Lancet Lond Engl. 2023; 402:693–704. doi: 10.1016/S0140-6736(23)01127-3Drucker DJ. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. Diabetes Care. 2024 Jun 6:dci240003. doi: 10.2337/dci24-0003.Drucker DJ. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. Diabetes Care. 2024 Jun 6:dci240003. doi: 10.2337/dci24-0003.Kim KM, Gautron L, Godschall E, et al. GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans. Science. 2024 Jul 26;385(6707):438-446. doi: 10.1126/science.adj2537.Kim KM, Gautron L, Godschall E, et al. GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans. Science. 2024 Jul 26;385(6707):438-446. doi: 10.1126/science.adj2537.Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020 Mar 26;5(6):e133429. doi: 10.1172/jci.insight.133429.Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020 Mar 26;5(6):e133429. doi: 10.1172/jci.insight.133429.Drucker DJ. The benefits of GLP-1 drugs beyond obesity. Science. 2024 Jul 19;385(6706):258-260. doi: 10.1126/science.adn4128.Drucker DJ. The benefits of GLP-1 drugs beyond obesity. Science. 2024 Jul 19;385(6706):258-260. doi: 10.1126/science.adn4128.Zhang Q, Delessa CT, Augustin R, et al. The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling. Cell Metab. 2021 Apr 6;33(4):833-844.e5. doi: 10.1016/j.cmet.2021.01.015.Zhang Q, Delessa CT, Augustin R, et al. The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling. Cell Metab. 2021 Apr 6;33(4):833-844.e5. doi: 10.1016/j.cmet.2021.01.015.Le Roux C, Mondoh A. Treatment of obesity with medications binding the glucagon-like peptide 1 receptor: what is the current state of play? Expert Opin Pharmacother. 2024 Feb;25(2):131-138. doi: 10.1080/14656566.2024.2311731.Le Roux C, Mondoh A. Treatment of obesity with medications binding the glucagon-like peptide 1 receptor: what is the current state of play? Expert Opin Pharmacother. 2024 Feb;25(2):131-138. doi: 10.1080/14656566.2024.2311731.Melson E, Ashraf U, Papamargaritis D, Davies MJ. What is the pipeline for future medications for obesity? Int J Obes (Lond). 2024 Feb 1. doi: 10.1038/s41366-024-01473-y.Melson E, Ashraf U, Papamargaritis D, Davies MJ. What is the pipeline for future medications for obesity? Int J Obes (Lond). 2024 Feb 1. doi: 10.1038/s41366-024-01473-y.Melson E, Miras AD, Papamargaritis D. Future therapies for obesity. Clin Med (Lond). 2023 Jul;23(4):337-346. doi: 10.7861/clinmed.2023-0144.Melson E, Miras AD, Papamargaritis D. Future therapies for obesity. Clin Med (Lond). 2023 Jul;23(4):337-346. doi: 10.7861/clinmed.2023-0144.Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov. 2022 Mar;21(3):201-223. doi: 10.1038/s41573-021-00337-8.Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov. 2022 Mar;21(3):201-223. doi: 10.1038/s41573-021-00337-8.Gogineni P, Melson E, Papamargaritis D, Davies M. Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? Expert Opin Pharmacother. 2024 May;25(7):801-818. doi: 10.1080/14656566.2024.2356254.Gogineni P, Melson E, Papamargaritis D, Davies M. Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? Expert Opin Pharmacother. 2024 May;25(7):801-818. doi: 10.1080/14656566.2024.2356254.Li Y, Cheng Z, Lu W, et al. Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 2 trial. Diabetes Obes Metab. 2024 Mar;26(3):1057-1068. doi: 10.1111/dom.15407.Li Y, Cheng Z, Lu W, et al. Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 2 trial. Diabetes Obes Metab. 2024 Mar;26(3):1057-1068. doi: 10.1111/dom.15407.Guo W, Xu Z, Zou H, et al. Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. Mol Metab. 2023 Sep;75:101762. doi: 10.1016/j.molmet.2023.101762.Guo W, Xu Z, Zou H, et al. Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. Mol Metab. 2023 Sep;75:101762. doi: 10.1016/j.molmet.2023.101762.Saxena AR, Gorman DN, Esquejo RM, et al. Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial. Nat Med 2021; 27:1079–87. doi: 10.1038/s41591-021-01391-w.Saxena AR, Gorman DN, Esquejo RM, et al. Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial. Nat Med 2021; 27:1079–87. doi: 10.1038/s41591-021-01391-w.Fatima H, Rangwala HS, Mustafa MS, et al. Evaluating Glycemic Control Efficacy and Safety of the Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis. Diabetes Metab Syndr Obes. 2023 Nov 7;16:3567-3578. doi: 10.2147/DMSO.S439587.Fatima H, Rangwala HS, Mustafa MS, et al. Evaluating Glycemic Control Efficacy and Safety of the Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis. Diabetes Metab Syndr Obes. 2023 Nov 7;16:3567-3578. doi: 10.2147/DMSO.S439587.Wharton S, Blevins T, Connery L, et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. 2023 Sep 7;389(10):877-888. doi: 10.1056/NEJMoa2302392.Wharton S, Blevins T, Connery L, et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. 2023 Sep 7;389(10):877-888. doi: 10.1056/NEJMoa2302392.Mao T, Meng Q, Zhang H. et al., Discovery of GSBR-1290, a Highly Potent, Orally Available, Novel Small Molecule GLP-1 Receptor Agonist. Diabetes 20 June 2023; 72 (Supplement_1): 760–P. doi.org/10.2337/db23-760-P.Mao T, Meng Q, Zhang H. et al., Discovery of GSBR-1290, a Highly Potent, Orally Available, Novel Small Molecule GLP-1 Receptor Agonist. Diabetes 20 June 2023; 72 (Supplement_1): 760–P. doi.org/10.2337/db23-760-P.Evaluation of the pharmacokinetics, pharmacodynamics, safety, and tolerability of VCT220 tablets in Chinese adult overweight/obese subjects: a 4-week randomized, double-blind, placebo-controlled phase Ib study. https://Clinicaltrial.gov/study/CTR20231482.Evaluation of the pharmacokinetics, pharmacodynamics, safety, and tolerability of VCT220 tablets in Chinese adult overweight/obese subjects: a 4-week randomized, double-blind, placebo-controlled phase Ib study. https://Clinicaltrial.gov/study/CTR20231482.Ansari S, Khoo B, Tan T. Targeting the incretin system in obesity and type 2 diabetes mellitus. Nat Rev Endocrinol. 2024 Aug;20(8):447-459. doi: 10.1038/s41574-024-00979-9.Ansari S, Khoo B, Tan T. Targeting the incretin system in obesity and type 2 diabetes mellitus. Nat Rev Endocrinol. 2024 Aug;20(8):447-459. doi: 10.1038/s41574-024-00979-9.Son JW, Lim S. Glucagon-Like Peptide-1 Based Therapies: A New Horizon in Obesity Management. Endocrinol Metab (Seoul). 2024 Apr;39(2):206-221. doi: 10.3803/EnM.2024.1940.Son JW, Lim S. Glucagon-Like Peptide-1 Based Therapies: A New Horizon in Obesity Management. Endocrinol Metab (Seoul). 2024 Apr;39(2):206-221. doi: 10.3803/EnM.2024.1940.Phase 2 Study of CT-868, a Novel Dual GLP-1/GIP Receptor Modulator, in Overweight/Obese T2D Adults. Obesity Week, 2023, Poster-530: October 17.Phase 2 Study of CT-868, a Novel Dual GLP-1/GIP Receptor Modulator, in Overweight/Obese T2D Adults. Obesity Week, 2023, Poster-530: October 17.Chakravarthy M, Hernandez M, Elliot M. et al. Weight-Independent Effects of CT-868, a Signaling Biased Dual GLP-1/GIP Receptor Modulator, on Glucose Homeostasis in Overweight and Obese Adults with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 774–P. doi.org/10.2337/db23-774-P.Chakravarthy M, Hernandez M, Elliot M. et al. Weight-Independent Effects of CT-868, a Signaling Biased Dual GLP-1/GIP Receptor Modulator, on Glucose Homeostasis in Overweight and Obese Adults with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 774–P. doi.org/10.2337/db23-774-P.Killion EA, Lu SC, Fort M, et al. Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies for the Treatment of Obesity, Do Agonists = Antagonists? Endocr Rev. 2020 Jan 1;41(1): bnz002. doi: 10.1210/endrev/bnz002.Killion EA, Lu SC, Fort M, et al. Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies for the Treatment of Obesity, Do Agonists = Antagonists? Endocr Rev. 2020 Jan 1;41(1): bnz002. doi: 10.1210/endrev/bnz002.Greenhill C. Phase I results for AMG 133. Nat Rev Endocrinol. 20, 193 (2024). doi.org/10.1038/s41574-024-00967-z.Greenhill C. Phase I results for AMG 133. Nat Rev Endocrinol. 20, 193 (2024). doi.org/10.1038/s41574-024-00967-z.Dehestani B, Stratford NR, le Roux CW. Amylin as a Future Obesity Treatment. J Obes Metab Syndr. 2021 Dec 30;30(4):320-325. doi: 10.7570/jomes21071.Dehestani B, Stratford NR, le Roux CW. Amylin as a Future Obesity Treatment. J Obes Metab Syndr. 2021 Dec 30;30(4):320-325. doi: 10.7570/jomes21071.Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021 Dec 11;398(10317):2160-2172. doi: 10.1016/S0140-6736(21)01751-7.Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021 Dec 11;398(10317):2160-2172. doi: 10.1016/S0140-6736(21)01751-7.Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2•4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021 May 8;397(10286):1736-1748. doi: 10.1016/S0140-6736(21)00845-X.Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2•4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021 May 8;397(10286):1736-1748. doi: 10.1016/S0140-6736(21)00845-X.Frias JP, Deenadayalan S, Erichsen L, 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 Lond Engl. 2023; 402:720–730. doi: 10.1016/S0140-6736(23)01163-7Frias JP, Deenadayalan S, Erichsen L, 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 Lond Engl. 2023; 402:720–730. doi: 10.1016/S0140-6736(23)01163-7Mathiesen DS, Lund A, Vilsbøll T, et al. Amylin and Calcitonin: Potential Therapeutic Strategies to Reduce Body Weight and Liver Fat. Front Endocrinol (Lausanne). 2021 Jan 8; 11:617400. doi: 10.3389/fendo.2020.617400.Mathiesen DS, Lund A, Vilsbøll T, et al. Amylin and Calcitonin: Potential Therapeutic Strategies to Reduce Body Weight and Liver Fat. Front Endocrinol (Lausanne). 2021 Jan 8; 11:617400. doi: 10.3389/fendo.2020.617400.Sonne N, Larsen AT, Karsdal MA, Henriksen K. The Impact of Exposure Profile on the Efficacy of Dual Amylin and Calcitonin Receptor Agonist Therapy. Biomedicines. 2022 Sep 22;10(10):2365. doi: 10.3390/biomedicines10102365.Sonne N, Larsen AT, Karsdal MA, Henriksen K. The Impact of Exposure Profile on the Efficacy of Dual Amylin and Calcitonin Receptor Agonist Therapy. Biomedicines. 2022 Sep 22;10(10):2365. doi: 10.3390/biomedicines10102365.Eržen S, Tonin G, Jurišić Eržen D, Klen J. Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity. Int J Mol Sci. 2024 Jan 26;25(3):1517. doi: 10.3390/ijms25031517.Eržen S, Tonin G, Jurišić Eržen D, Klen J. Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity. Int J Mol Sci. 2024 Jan 26;25(3):1517. doi: 10.3390/ijms25031517.Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021 Dec 11;398(10317):2160-2172. doi: 10.1016/S0140-6736(21)01751-7.Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021 Dec 11;398(10317):2160-2172. doi: 10.1016/S0140-6736(21)01751-7.Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2•4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021 May 8;397(10286):1736-1748. doi: 10.1016/S0140-6736(21)00845-X.Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2•4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021 May 8;397(10286):1736-1748. doi: 10.1016/S0140-6736(21)00845-X.Di Prospero NA, Yee J, Frustaci ME, et al. Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose-ranging study. Clin Obes. 2021 Apr;11(2):e12433. doi: 10.1111/cob.12433.Di Prospero NA, Yee J, Frustaci ME, et al. Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose-ranging study. Clin Obes. 2021 Apr;11(2):e12433. doi: 10.1111/cob.12433.Alba M, Yee J, Frustaci ME, Samtani MN, Fleck P. Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study. Clin Obes. 2021 Apr;11(2):e12432. doi: 10.1111/cob.12432.Alba M, Yee J, Frustaci ME, Samtani MN, Fleck P. Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study. Clin Obes. 2021 Apr;11(2):e12432. doi: 10.1111/cob.12432.Nahra R, Wang T, Gadde KM, et al. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study. Diabetes Care. 2021 Jun;44(6):1433-1442. doi: 10.2337/dc20-2151.Nahra R, Wang T, Gadde KM, et al. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study. Diabetes Care. 2021 Jun;44(6):1433-1442. doi: 10.2337/dc20-2151.Ambery P, Parker VE, Stumvoll M, et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018 Jun 30;391(10140):2607-2618. doi: 10.1016/S0140-6736(18)30726-8.Ambery P, Parker VE, Stumvoll M, et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018 Jun 30;391(10140):2607-2618. doi: 10.1016/S0140-6736(18)30726-8.Harrison SA, Browne SK, Suschak JJ, et al. Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study. J Hepatol. 2024 Jul 11:S0168-8278(24)02362-6. doi: 10.1016/j.jhep.2024.07.006.Harrison SA, Browne SK, Suschak JJ, et al. Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study. J Hepatol. 2024 Jul 11:S0168-8278(24)02362-6. doi: 10.1016/j.jhep.2024.07.006.Blüher M, Rosenstock J, Hoefler J, et al. Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia. 2024 Apr;67(4):758. doi: 10.1007/s00125-024-06095-7.Blüher M, Rosenstock J, Hoefler J, et al. Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia. 2024 Apr;67(4):758. doi: 10.1007/s00125-024-06095-7.Zhihong Y, Chen W, Qianqian Z, et al. Emerging roles of oxyntomodulin-based glucagon-like peptide-1/glucagon co-agonist analogs in diabetes and obesity. Peptides. 2023 Apr;162:170955. doi: 10.1016/j.peptides.2023.170955.Zhihong Y, Chen W, Qianqian Z, et al. Emerging roles of oxyntomodulin-based glucagon-like peptide-1/glucagon co-agonist analogs in diabetes and obesity. Peptides. 2023 Apr;162:170955. doi: 10.1016/j.peptides.2023.170955.Ji L, Jiang H, Cheng Z,et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun. 2023 Dec 14;14(1):8289. doi: 10.1038/s41467-023-44067-4.Ji L, Jiang H, Cheng Z,et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun. 2023 Dec 14;14(1):8289. doi: 10.1038/s41467-023-44067-4.Blüher M, Aras M, Aronne LJ, et al. New insights into the treatment of obesity. Diabetes Obes Metab. 2023 Aug;25(8):2058-2072. doi: 10.1111/dom.15077.Blüher M, Aras M, Aronne LJ, et al. New insights into the treatment of obesity. Diabetes Obes Metab. 2023 Aug;25(8):2058-2072. doi: 10.1111/dom.15077.Nalisa DL, Cuboia N, Dyab E, Jackson IL, Felix HJ, Shoki P, Mubiana M, Oyedeji-Amusa M, Azevedo L, Jiang H. Efficacy and safety of Mazdutide on weight loss among diabetic and non-diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2024 Feb 14;15:1309118. doi: 10.3389/fendo.2024.1309118.Nalisa DL, Cuboia N, Dyab E, Jackson IL, Felix HJ, Shoki P, Mubiana M, Oyedeji-Amusa M, Azevedo L, Jiang H. Efficacy and safety of Mazdutide on weight loss among diabetic and non-diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2024 Feb 14;15:1309118. doi: 10.3389/fendo.2024.1309118.Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022 Sep 6;34(9):1234-1247.e9. doi: 10.1016/j.cmet.2022.07.013.Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022 Sep 6;34(9):1234-1247.e9. doi: 10.1016/j.cmet.2022.07.013.Jakubowska A, Roux CWL, Viljoen A. The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update. Endocrinol Metab (Seoul). 2024 Feb;39(1):12-22. doi: 10.3803/EnM.2024.1942.Jakubowska A, Roux CWL, Viljoen A. The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update. Endocrinol Metab (Seoul). 2024 Feb;39(1):12-22. doi: 10.3803/EnM.2024.1942.Knerr PJ, Mowery SA, Douros JD, et al. Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice. Mol Metab. 2022 Sep;63:101533. doi: 10.1016/j.molmet.2022.101533.Knerr PJ, Mowery SA, Douros JD, et al. Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice. Mol Metab. 2022 Sep;63:101533. doi: 10.1016/j.molmet.2022.101533.Li, W., Zhou, Q., Cong, Z. et al. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discov 10, 77 (2024). doi.org/10.1038/s41421-024-00700-0.Li, W., Zhou, Q., Cong, Z. et al. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discov 10, 77 (2024). doi.org/10.1038/s41421-024-00700-0.Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022 Nov 26;400(10366):1869-1881. doi: 10.1016/S0140-6736(22)02033-5.Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022 Nov 26;400(10366):1869-1881. doi: 10.1016/S0140-6736(22)02033-5.Jastreboff AM, Kaplan LM, Frías JP, et al. Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023 Aug 10;389(6):514-526. doi: 10.1056/NEJMoa2301972.Jastreboff AM, Kaplan LM, Frías JP, et al. Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023 Aug 10;389(6):514-526. doi: 10.1056/NEJMoa2301972.Hale C, Véniant MM. Growth differentiation factor 15 as a potential therapeutic for treating obesity. Mol Metab. 2021 Apr;46:101117. doi: 10.1016/j.molmet.2020.101117.Hale C, Véniant MM. Growth differentiation factor 15 as a potential therapeutic for treating obesity. Mol Metab. 2021 Apr;46:101117. doi: 10.1016/j.molmet.2020.101117.Borner T, Wald HS, Ghidewon MY, et al. GDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss. Cell Rep. 2020 Apr 21;31(3):107543. doi: 10.1016/j.celrep.2020.107543.Borner T, Wald HS, Ghidewon MY, et al. GDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss. Cell Rep. 2020 Apr 21;31(3):107543. doi: 10.1016/j.celrep.2020.107543.Guida C, Ramracheya R. PYY, a Therapeutic Option for Type 2 Diabetes? Clin Med Insights Endocrinol Diabetes. 2020 Jan 22;13:1179551419892985. doi: 10.1177/1179551419892985.Guida C, Ramracheya R. PYY, a Therapeutic Option for Type 2 Diabetes? Clin Med Insights Endocrinol Diabetes. 2020 Jan 22;13:1179551419892985. doi: 10.1177/1179551419892985.Gaich G, Chien JY, Fu H, Glass LC, Deeg MA, Holland WL, Kharitonenkov A, Bumol T, Schilske HK, Moller DE. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 2013 Sep 3;18(3):333-40. doi: 10.1016/j.cmet.2013.08.005.Gaich G, Chien JY, Fu H, Glass LC, Deeg MA, Holland WL, Kharitonenkov A, Bumol T, Schilske HK, Moller DE. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 2013 Sep 3;18(3):333-40. doi: 10.1016/j.cmet.2013.08.005.Zhang C, Gao G, Li Y, Ying J, Li J, Hu S. Design of a Dual Agonist of Exendin-4 and FGF21 as a Potential Treatment for Type 2 Diabetes Mellitus and Obesity. Iran J Pharm Res. 2023 Aug 9;22(1):e131015. doi: 10.5812/ijpr-131015.Zhang C, Gao G, Li Y, Ying J, Li J, Hu S. Design of a Dual Agonist of Exendin-4 and FGF21 as a Potential Treatment for Type 2 Diabetes Mellitus and Obesity. Iran J Pharm Res. 2023 Aug 9;22(1):e131015. doi: 10.5812/ijpr-131015.Carbonetti MP, Almeida-Oliveira F, Majerowicz D. Use of FGF21 analogs for the treatment of metabolic disorders: a systematic review and meta-analysis. Arch Endocrinol Metab. 2023 Nov 10;68:e220493. doi: 10.20945/2359-4292-2022-0493.Carbonetti MP, Almeida-Oliveira F, Majerowicz D. Use of FGF21 analogs for the treatment of metabolic disorders: a systematic review and meta-analysis. Arch Endocrinol Metab. 2023 Nov 10;68:e220493. doi: 10.20945/2359-4292-2022-0493.Castelli MS, McGonigle P, Hornby PJ. The pharmacology and therapeutic applications of monoclonal antibodies. Pharmacol Res Perspect. 2019 Dec;7(6):e00535. doi: 10.1002/prp2.535.Castelli MS, McGonigle P, Hornby PJ. The pharmacology and therapeutic applications of monoclonal antibodies. Pharmacol Res Perspect. 2019 Dec;7(6):e00535. doi: 10.1002/prp2.535.Makowski EK, Schardt JS, Tessier PM. Improving antibody drug development using bionanotechnology. Curr Opin Biotechnol. 2022 Apr;74:137-145. doi: 10.1016/j.copbio.2021.10.027.Makowski EK, Schardt JS, Tessier PM. Improving antibody drug development using bionanotechnology. Curr Opin Biotechnol. 2022 Apr;74:137-145. doi: 10.1016/j.copbio.2021.10.027.Авдеева, Ж. И., Алпатова, Н. А., Солдатов, А. А., и соавт. Безопасность лекарственных препаратов моноклональных антител, связанная с проявлением их иммуногенности. Иммунология, 2015; 36(4), 247-256.Avdeeva ZhI, Alpatova NA, Soldatov AA,i soavt. Bezopasnost’ lekarstvennyh preparatov monoklonal’nyh antitel, svyazannaya s proyavleniem ih immunogennosti. Immunologiya. 2015;36(4):247-256Афанасьева О.И., Ежов М.В., Покровский С.Н. Антисмысловые олигонуклеотиды и терапевтические моноклональные антитела как основа для создания новых поколений биологических липидснижающих препаратов. Российский кардиологический журнал. 2018;(8):99-109. doi.org/10.15829/1560-4071-2018-8-99-109.[Afanas’eva OI, Ezhov MV, Pokrovskij SN. Antismyslovye oligonukleotidy i terapevticheskie monoklonal’nye antitela kak osnova dlya sozdaniya novyhAkpan I, Goncalves MD, Dhir R, Yin X, Pistilli EE, Bogdanovich S, Khurana TS, Ucran J, Lachey J, Ahima RS. The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity. Int J Obes (Lond). 2009 Nov;33(11):1265-73. doi: 10.1038/ijo.2009.162.pokolenij biologicheskih lipidsnizhayushchih preparatov.Rossijskij kardiologicheskij zhurnal. 2018;(8):99-109. doi.org/10.15829/1560-4071-2018-8-99-109.Garito T, Roubenoff R, Hompesch M, Morrow L, Gomez K, Rooks D, Meyers C, Buchsbaum MS, Neelakantham S, Swan T, Filosa LA, Laurent D, Petricoul O, Zakaria M. Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals. Diabetes Obes Metab. 2018 Jan;20(1):94-102. doi: 10.1111/dom.13042.Akpan I, Goncalves MD, Dhir R, Yin X, Pistilli EE, Bogdanovich S, Khurana TS, Ucran J, Lachey J, Ahima RS. The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity. Int J Obes (Lond). 2009 Nov;33(11):1265-73. doi: 10.1038/ijo.2009.162.Heymsfield SB, Coleman LA, Miller R, et al. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2033457. doi: 10.1001/jamanetworkopen.2020.33457.Garito T, Roubenoff R, Hompesch M, Morrow L, Gomez K, Rooks D, Meyers C, Buchsbaum MS, Neelakantham S, Swan T, Filosa LA, Laurent D, Petricoul O, Zakaria M. Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals. Diabetes Obes Metab. 2018 Jan;20(1):94-102. doi: 10.1111/dom.13042.Bays HE, Fitch A, Christensen S, Burridge K, Tondt J. Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. Obes Pillars. 2022 Apr 15;2:100018. doi: 10.1016/j.obpill.2022.100018.Heymsfield SB, Coleman LA, Miller R, et al. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2033457. doi: 10.1001/jamanetworkopen.2020.33457.Petricoul O, Nazarian A, Schuehly U, Schramm U, David OJ, Laurent D, Praestgaard J, Roubenoff R, Papanicolaou DA, Rooks D. Pharmacokinetics and Pharmacodynamics of Bimagrumab (BYM338). Clin Pharmacokinet. 2023 Jan;62(1):141-155. doi: 10.1007/s40262-022-01189-0.Bays HE, Fitch A, Christensen S, Burridge K, Tondt J. Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. Obes Pillars. 2022 Apr 15;2:100018. doi: 10.1016/j.obpill.2022.100018.Bechtold C, Ansarullah, Brynczka C, Volkan g. et al. Taldefgrobep Alfa Improves Body Composition as Monotherapy and in Combination with Semaglutide in a DIO Mouse Model. Diabetes 14 June 2024; 73 (Supplement_1): 2053–LB. doi.org/10.2337/db24-2053-LBPetricoul O, Nazarian A, Schuehly U, Schramm U, David OJ, Laurent D, Praestgaard J, Roubenoff R, Papanicolaou DA, Rooks D. Pharmacokinetics and Pharmacodynamics of Bimagrumab (BYM338). Clin Pharmacokinet. 2023 Jan;62(1):141-155. doi: 10.1007/s40262-022-01189-0.Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese (EMBRAZE). Clinicaltrial.gov/study/NCT06445075Bechtold C, Ansarullah, Brynczka C, Volkan g. et al. Taldefgrobep Alfa Improves Body Composition as Monotherapy and in Combination with Semaglutide in a DIO Mouse Model. Diabetes 14 June 2024; 73 (Supplement_1): 2053–LB. doi.org/10.2337/db24-2053-LBGewitz A, Mendell J, Wang Y, Harris C, Olenchock BA, Podgrabinska S, Zheng W, Zhao A, Pan H, Vanhoutte F, Davis JD. Pharmacokinetics and pharmacodynamics of mibavademab (a leptin receptor agonist): Results from a first-in-human phase I study. Clin Transl Sci. 2024 Apr;17(4):e13762. doi: 10.1111/cts.13762.Efficacy and Safety of Apitegromab for the Treatment of Adults Who Are Overweight or Obese (EMBRAZE). Clinicaltrial.gov/study/NCT06445075Osborn O, Brownell SE, Sanchez-Alavez M, Salomon D, Gram H, Bartfai T. Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity. Cytokine. 2008 Oct;44(1):141-8. doi: 10.1016/j.cyto.2008.07.004.Gewitz A, Mendell J, Wang Y, Harris C, Olenchock BA, Podgrabinska S, Zheng W, Zhao A, Pan H, Vanhoutte F, Davis JD. Pharmacokinetics and pharmacodynamics of mibavademab (a leptin receptor agonist): Results from a first-in-human phase I study. Clin Transl Sci. 2024 Apr;17(4):e13762. doi: 10.1111/cts.13762.Baruch A, Wong C, Chinn LW, et al. Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28992-29000. doi: 10.1073/pnas.2012073117.Osborn O, Brownell SE, Sanchez-Alavez M, Salomon D, Gram H, Bartfai T. Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity. Cytokine. 2008 Oct;44(1):141-8. doi: 10.1016/j.cyto.2008.07.004.Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002 Jul;8(7):738-42. doi: 10.1038/nm727.Baruch A, Wong C, Chinn LW, et al. Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28992-29000. doi: 10.1073/pnas.2012073117.Boer GA, Keenan SN, Miotto PM, et al GIP receptor deletion in mice confers resistance to high-fat diet-induced obesity via alterations in energy expenditure and adipose tissue lipid metabolism. Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E835-E845. doi: 10.1152/ajpendo.00646.2020.Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002 Jul;8(7):738-42. doi: 10.1038/nm727.Wolfe MM, Apovian CM, Boylan MO. Glucose-dependent insulinotropic polypeptide monoclonal antibodies prevent and treat obesity in wild-type and hyperphagic mice. Obesity (Silver Spring). 2023 Jun;31(6):1499-1504. doi: 10.1002/oby.23758.Boer GA, Keenan SN, Miotto PM, et al GIP receptor deletion in mice confers resistance to high-fat diet-induced obesity via alterations in energy expenditure and adipose tissue lipid metabolism. Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E835-E845. doi: 10.1152/ajpendo.00646.2020.Lu SC, Chen M, Atangan L, et al. GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys. Cell Rep Med. 2021 Apr 30;2(5):100263. doi: 10.1016/j.xcrm.2021.100263.Wolfe MM, Apovian CM, Boylan MO. Glucose-dependent insulinotropic polypeptide monoclonal antibodies prevent and treat obesity in wild-type and hyperphagic mice. Obesity (Silver Spring). 2023 Jun;31(6):1499-1504. doi: 10.1002/oby.23758.Véniant MM, Lu SC, Atangan L, et al. GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab. 2024 Feb;6(2):290-303. doi: 10.1038/s42255-023-00966-w.Lu SC, Chen M, Atangan L, et al. GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys. Cell Rep Med. 2021 Apr 30;2(5):100263. doi: 10.1016/j.xcrm.2021.100263.Su L-J, Ji Z-H, Xu M-X, et al. RNA-based nanomedicines and their clinical applications. Nano Research, 2023, 16(12): 13182-13204. https://doi.org/10.1007/s12274-023-6238-5.Véniant MM, Lu SC, Atangan L, et al. GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab. 2024 Feb;6(2):290-303. doi: 10.1038/s42255-023-00966-w.Huang X, Kong N, Zhang X, Cao Y, Langer R, Tao W. The landscape of mRNA nanomedicine. Nat Med. 2022 Nov;28(11):2273-2287. doi: 10.1038/s41591-022-02061-1.Su L-J, Ji Z-H, Xu M-X, et al. RNA-based nanomedicines and their clinical applications. Nano Research, 2023, 16(12): 13182-13204. https://doi.org/10.1007/s12274-023-6238-5.Guo, Y., Wan, Z., Zhao, P. et al. Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes. J Nanobiotechnol 19, 402 (2021). https://doi.org/10.1186/s12951-021-01145-3.Huang X, Kong N, Zhang X, Cao Y, Langer R, Tao W. The landscape of mRNA nanomedicine. Nat Med. 2022 Nov;28(11):2273-2287. doi: 10.1038/s41591-022-02061-1.Huang X, Xia Z, Huang Y, et al. Combined therapy with pioglitazone and FGF21 mRNA synergistically ameliorates metabolic disorders in NAFLD rats. Heliyon. 2023 Apr 1;9(4):e15146. doi: 10.1016/j.heliyon.2023.e15146.Guo, Y., Wan, Z., Zhao, P. et al. Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes. J Nanobiotechnol 19, 402 (2021). https://doi.org/10.1186/s12951-021-01145-3.Bartesaghi S, Wallenius K, Hovdal D, et al. Subcutaneous delivery of FGF21 mRNA therapy reverses obesity, insulin resistance, and hepatic steatosis in diet-induced obese mice. Mol Ther Nucleic Acids. 2022 Apr 18;28:500-513. doi: 10.1016/j.omtn.2022.04.010. PMID: 35592498; PMCID: PMC9079007.Huang X, Xia Z, Huang Y, et al. Combined therapy with pioglitazone and FGF21 mRNA synergistically ameliorates metabolic disorders in NAFLD rats. Heliyon. 2023 Apr 1;9(4):e15146. doi: 10.1016/j.heliyon.2023.e15146.Katsumura S, Siddiqui N, Goldsmith MR et al. Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure. Cell Metab. 2022 Apr 5;34(4):564-580.e8. doi: 10.1016/j.cmet.2022.03.005.Bartesaghi S, Wallenius K, Hovdal D, et al. Subcutaneous delivery of FGF21 mRNA therapy reverses obesity, insulin resistance, and hepatic steatosis in diet-induced obese mice. Mol Ther Nucleic Acids. 2022 Apr 18;28:500-513. doi: 10.1016/j.omtn.2022.04.010. PMID: 35592498; PMCID: PMC9079007.Tsai VWW, Husaini Y, Sainsbury A, et al. The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases. Cell Metab. 2018 Sep 4;28(3):353-368. doi: 10.1016/j.cmet.2018.07.018. PMID: 30184485.Katsumura S, Siddiqui N, Goldsmith MR et al. Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure. Cell Metab. 2022 Apr 5;34(4):564-580.e8. doi: 10.1016/j.cmet.2022.03.005.Gan LM, Lagerström-Fermér M, Carlsson LG, et al. Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes. Nat Commun. 2019 Feb 20;10(1):871. doi: 10.1038/s41467-019-08852-4.Tsai VWW, Husaini Y, Sainsbury A, et al. The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity, Cachexia, and Other Associated Diseases. Cell Metab. 2018 Sep 4;28(3):353-368. doi: 10.1016/j.cmet.2018.07.018. PMID: 30184485.Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34. doi: 10.1001/jama.2016.7602.Gan LM, Lagerström-Fermér M, Carlsson LG, et al. Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes. Nat Commun. 2019 Feb 20;10(1):871. doi: 10.1038/s41467-019-08852-4.Roomy MA, Hussain K, Behbehani HM, et al. Therapeutic advances in obesity management: an overview of the therapeutic interventions. Front Endocrinol (Lausanne). 2024 Apr 23;15:1364503. doi: 10.3389/fendo.2024.1364503.Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34. doi: 10.1001/jama.2016.7602.Roomy MA, Hussain K, Behbehani HM, et al. Therapeutic advances in obesity management: an overview of the therapeutic interventions. Front Endocrinol (Lausanne). 2024 Apr 23;15:1364503. doi: 10.3389/fendo.2024.1364503.Roomy MA, Hussain K, Behbehani HM, et al. Therapeutic advances in obesity management: an overview of the therapeutic interventions. Front Endocrinol (Lausanne). 2024 Apr 23;15:1364503. doi: 10.3389/fendo.2024.1364503.

The authors declare that there are no conflicts of interest present.