Promising areas of pharmacotherapy for obesity
https://doi.org/10.15829/1560-4071-2021-4279
Abstract
The increasing prevalence of obesity, accompanied by an increase in the frequency of metabolic disorders, hypertension, associated conditions and diseases, dictates the need to optimize preventive and therapeutic strategies of the health care system, including pharmacological approaches to correcting obesity and the related risk. The evolution of this area led both to the disappearance of drugs that increase the risks of cardiovascular events, cancer, mental disorders or having other pronounced adverse effects, and to the emergence of unique drugs that not only lead to a decrease in body mass index, but also allow multifactorial effect on various components of adiposopathy or visceral obesity, among which glucagon-like peptide-1 receptor agonist liraglutide is currently registered with the indication for obesity. In this regard, the study continues in this regard and other representatives of this class, as well as drugs from sodium-glucose cotransporter-2 inhibitors group. Many other promising pharmacological agents are currently being studied, a review of which is presented in this article.
About the Authors
M. A. Druzhilov
Petrozavodsk State University
Russian Federation
Russian Federation
Petrozavodsk
T. Yu. Kuznetsova
Petrozavodsk State University
Russian Federation
Russian Federation
Petrozavodsk
G. A. Chumakova
Altai State Medical University;
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation
Russian Federation
Barnaul,
Kemerovo
References
1. World Health Organization. Obesity and overweight fact sheet. World Health Organization website. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. (1 April 2020).
2. The GBD 2015 Obesity Collaborators. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017;377:13-27. doi:10.1056/NEJMoa1614362.
3. Shlyakhto EV, Nedogoda SV, Konradi АО, et al. The concept of novel national clinical guidelines on obesity. Russ J Cardiol. 2016;4:7-13. (In Russ.) doi:10.15829/1560-4071-2016-4-7-13.
4. Neeland I, Poirier P, Després J. Cardiovascular and Metabolic Heterogeneity of Obesity Clinical Challenges and Implications for Management. Circulation. 2018;137:1391-406. doi:10.1161/CIRCULATIONAHA.117.029617.
5. Chumakova GA, Veselovskaya NG. Clinical significance of visceral obesity. Moscow: GEOTAR-Media, 2016. p. 200. (In Russ.) ISBN: 978-59704-3988-3.
6. Druzhilov MA, Kuznetsova ТY, Druzhilova ОY. “Obesity paradoxes”: main causes of an “inverse” cardiovascular epidemiology. Cardiovascular Therapy and Prevention. 2018;17(5):92-8. (In Russ.) doi:10.15829/1728-8800-2018-5-92-98.
7. Romantsova TI, Sych YP. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3-17. (In Russ.) doi:10.14341/omet12218.
8. Chumakova GA, Kuznetsova TY, Druzhilov MA, et al. Visceral adiposity as a global factor of cardiovascular risk. Russ J Cardiol. 2018;(5):7-14. (In Russ.) doi:10.15829/1560-4071-2018-5-7-14.
9. Kuznetsova TY, Druzhilov MA, Chumakova GA, et al. Strategies and methods for the correction of obesity and associated cardiovascular risk. Russ J Cardiol. 2019;(4):61-67. (In Russ.) doi:10.15829/1560-4071-2019-4-61-67.
10. Apovian C, Aronne L, Bessesen D, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:342-62. doi:10.1210/jc.2014-3415.
11. Dedov II, Melnichenko GA, Shestakova MV, et al. Russian national clinical recommendations for morbid obesity treatment in adults. 3rd revision (Morbid obesity treatment in adults). Obesity and metabolism. 2018;15(1):53-70. (In Russ.). doi:10.14341/OMET2018153-70.
12. Sam A, Salem V, Ghatei M. Rimonabant: From RIO to Ban. J Obes. 2011;2011:432607. doi:10.1155/2011/432607.
13. Sharretts J, Galescu O, Gomatam S, et al. Cancer Risk Associated with Lorcaserin — The FDA’s Review of the CAMELLIA-TIMI 61 Trial. N Engl J Med. 2020;383:1000-2. doi:10.1056/NEJMp2003873.
14. Dedov II, Melnichenko GA, Romantsova TI. The strategy of obesity management: the results of All-Russian observational program “Primavera”. Obesity and Metabolism. 2016;13(1):36-44. (In Russ.) doi:10.14341/OMET2016136-44.
15. Andersen А, Lund А, Knop F, et al. Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol. 2018;14(7):390-403. doi:10.1038/s41574-018-0016-2.
16. González N, Moreno-Villegas Z, González-Bris A, et al. Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes. Cardiovasc Diabetol. 2017;16(1):44. doi:10.1186/s12933-017-0528-4.
17. Marsico F, Paolillo S, Gargiulo P, et al. Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. European Heart Journal. 2020;41:3346-58. doi:10.1093/eurheartj/ehaa082.
18. Pi¬Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373:11-22. doi:10.1056/NEJMoa1411892.
19. Pereira М, Eriksson J. Emerging Role of SGLT¬2 Inhibitors for the Treatment of Obesity. Drugs. 2019;79:219-30. doi:10.1007/s40265-019-1057-0.
20. Williams D, Nawaz A, Evans M. Drug Therapy in Obesity: A Review of Current and Emerging Treatments. Diabetes Ther. 2020;11:1199-216. doi:10.1007/s13300-020-00816-y.
21. Guo M, Gu J, Teng F, et al. The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis. Endocrine. 2020;67(2):294-304. doi:10.1007/s12020-01902175-6.
22. Fonseca V, Alvarado-Ruiz R, Raccah D, et al. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012;35:1225-311. doi:10.2337/dc11-1935.
23. Umpierrez G, Povedano S, Manghi F, et al. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care. 2014;37(8):2168-76. doi:10.2337/dc13-2759.
24. O’Neil P, Birkenfeld A, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-49. doi:10.1016/S0140-6736(18)31773-2.
25. Kushner R, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020;28(6):1050-61. doi:10.1002/oby.22794.
26. Marso S, Bain S, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375:1834-44. doi:10.1056/NEJMoa1607141.
27. Ryan D, Lingvay I, Colhoun H, et al. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. American Heart Journal. 2020;229:61-9. doi:10.1016/j.ahj.2020.07.008.
28. Zaccardi F, Webb D, Htike Z, et al. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18(8):783-94. doi:10.1111/dom.12670.
29. Zelniker T, Wiviott S, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and metaanalysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31-9. doi:10.1016/S0140-6736(18)32590-X.
30. Verma S, McMurray J. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61:2108-17. doi:10.1007/s00125-018-4670-7.
31. Cai X, Yang W, Gao X, et al. The Association Between the Dosage of SGLT2 Inhibitor and Weight Reduction in Type 2 Diabetes Patients: a Meta-Analysis. Obesity. 2018;26(1):70-80. doi:10.1002/oby.22066.
32. Reed J. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vascular Health Risk Manag. 2016;12:393-405. doi:10.2147/VHRM.S111991.
33. Davies M, Trujillo A, Vijapurkar U, et al. Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2015;17(4):426-9. doi:10.1111/dom.12439.
34. Bays H, Weinstein R, Law G, et al. Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring). 2014;22(4):1042-9. doi:10.1002/oby.20663.
35. Lundkvist P, Sjostrom C, Amini S, et al. Dapagliflozin once-daily and exenatide once weekly dual therapy: a 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes. Diabetes Obes Metab. 2017;19(1):49-60. doi:10.1111/dom.12779.
36. Hollander P, Bays H, Rosenstock J, et al. Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: a Randomized Clinical Trial. Diabetes Care. 2017;40(5):632-9. doi:10.2337/dc16-2427
37. Ferrannini E, Baldi S, Frascerra S, et al. Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes. 2016;65(5):1190-5. doi:10.2337/db15-1356.
38. Tosaki T, Kamiya H, Himeno T, et al. Sodium-glucose Co-transporter 2 Inhibitors Reduce the Abdominal Visceral Fat Area and May Influence the Renal Function in Patients with Type 2 Diabetes. Intern Med. 2017;56:597-604. doi:10.2169/internalmedicine.56.7196.
39. Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol. 2018;17(1):6. doi:10.1186/s12933-017-0658-8.
40. Iacobellis G, Gra-Menendez S. Effects of Dapagliflozin on Epicardial Fat Thickness in Patients with Type 2 Diabetes and Obesity. Obesity (Silver Spring). 2020;28(6):1068-74. doi:10.1002/oby.22798.
41. Díaz-Rodríguez E, Agra R, Fernández Á, et al. Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability. Cardiovasc Res. 2018;114:336-46. doi:10.1093/cvr/cvx186.
42. Garvey W, van Gaal L, Leiter L, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018;85:32-7. doi:10.1016/j.metabol.2018.02.002.
43. Sánchez-Garrido M, Brandt S, Clemmensen C, et al. GLP-1/glucagon receptor co-agonism for treatment of obesity. Diabetologia. 2017;60(10):1851-61. doi:10.1007/s00125-017-4354-8.
44. Brandt S, Kleinert M, Tschöp M, et al. Are peptide conjugates the golden therapy against obesity? J Endocrinol. 2018;238(2):109-19. doi:10.1530/JOE-18-0264.
45. Ambery P, Parker V, 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;391(10140):2607-18. doi:10.1016/S0140-6736(18)30726-8.
46. Tillner J, Posch M, Wagner F, et al. A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo controlled first-inhuman and first-in-patient trials. Diabetes Obes Metab. 2019;21(1):120-8. doi:10.1111/dom.13494.
47. Frias J, Bastyr E, Vignati L, et al. The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC0090-2746, in patients with type 2. Diabetes Cell Metab. 2017;26(2):343-52. doi:10.1016/j.cmet.2017.07.011.
48. Frias J, Nauck M, Van J, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392(10160):2180-93. doi:10.1016/S0140-6736(18)32260-8.
49. Usui R, Yabe D, Seino Y. Twincretin as a potential therapeutic for the management of type 2 diabetes with obesity. J Diabetes Investig. 2019;10(4):902-5. doi:10.1111/jdi.13005.
50. Aronne L, Fujioka K, Aroda V, et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebocontrolled, doseescalation study. J Clin Endocrinol Metab. 2007;92(8):2977-83. doi:10.1210/jc.2006-2003.
51. Aronne L, Halseth A, Burns C, et al. Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial. Obesity (Silver Spring). 2010;18(9):1739-46. doi:10.1038/oby.2009.478.
52. Kopelman P, Groot G, Rissanenet A, et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity (Silver Spring). 2010;18(1):108-15. doi:10.1038/oby.2009.155.
53. Abegg K, Bernasconi L, Hutter M, et al. Ghrelin receptor inverse agonists as a novel therapeutic approach against obesity-related metabolic disease. Diabetes Obes Metab. 2017;19(12):1740-50. doi:10.1111/dom.13020.
54. Yadav M, Murumkar P. Advances in patented CB1 receptor antagonists for obesity. Pharm Pat Anal. 2018;7(5):169-73. doi:10.4155/ppa-2018-0020.
55. Kharitonenkov A, DiMarchi R. Fibroblast growth factor 21 night watch: advances and uncertainties in the field. J Intern Med. 2017;281(3):233-46. doi:10.1111/joim.12580.
56. Jimenez V, Jambrina C, Casana E, et al. FGF21 gene therapy as treatment for obesity and insulin resistance. EMBO Mol Med. 2018;10(8):e8791. doi:10.15252/emmm.201708791.
57. May M, Schindler C, Engeli S. Modern pharmacological treatment of obese patients. Ther Adv Endocrinol Metab. 2020;11:1-19. doi:10.1177/2042018819897527.
58. Romantsova TI. Glucagon-like peptide-1 analogue liraglutide (SAXENDA®): mechanism of action, efficacy for the treatment of obesity. Obesity and metabolism. 2018;15(1):311. (In Russ.) doi:10.14341/OMET201813-11.
59. Druzhilov MA, Kuznetsova TY. Internal obesity as a risk factor for arterial hypertension. Russ J Cardiol. 2019;4:7-12. (In Russ.) doi:10.15829/1560-4071-2019-4-7-12.
60. Deol H, Lekkakou L, Viswanath A, et al. Combination therapy with GLP-1 analogues and SGLT-2 inhibitors in the management of diabesity: the real world experience. Endocrine. 2017;55(1):173-8. doi:10.1007/s12020-016-1125-0.
Supplementary files
Review
For citations:
Druzhilov M.A., Kuznetsova T.Yu., Chumakova G.A. Promising areas of pharmacotherapy for obesity. Russian Journal of Cardiology. 2021;26(3):4279. (In Russ.) https://doi.org/10.15829/1560-4071-2021-4279
Views:
818
Email this article 