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Role of SGLT2 inhibitors in the treatment of visceral obesity

https://doi.org/10.15829/1728-8800-2021-2648

Abstract

The increasing prevalence of obesity limits the prevention of the development and progression of chronic non-communicable diseases. The central methods of risk correction associated with obesity are lifestyle changes and prescribing medications for obesity. Sodium-glucose co-transporter type-2 (SGLT2) inhibitors, also called gliflozins, which are used for type 2 diabetes, have shown additional positive effects on surrogate and hard endpoints in numerous studies. This became the basis for a detailed study of their cardio- and neuroprotective effects and for conducting studies with such drugs in other cohorts of patients. This review presents the results of studies that examined the effect of SGLT2 inhibitors on body weight in overweight and obese individuals, the quantitative characteristics and functional activity of visceral adipose tissue, as well as other components of visceral obesity, and discusses the potential of using these drugs in the management of such patients.

About the Authors

M. A. Druzhilov
Petrozavodsk State University
Russian Federation

Petrozavodsk



T. Yu. Kuznetsova
Petrozavodsk State University
Russian Federation

Petrozavodsk



References

1. World Health Organization. Obesity and overweight fact sheet. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs311/en (15 July 2016).

2. 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. Neeland I, Poirier P, Despres J. Cardiovascular and Metabolic Heterogeneity of Obesity Clinical Challenges and Implications for Management. Circulation. 2018;137:1391-406. doi:10.1161/CIRCULATIONAHA.117.029617.

4. Romantsova TI, Sych YP. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3-17. (In Russ.) doi:10.14341/omet12218.

5. 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.

6. Druzhilov MA, Kuznetsova ТУ, Druzhilova GY. “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. 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.

8. 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.

9. 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.

10. Dedov II, Romantsova TI, Shestakova MV. Rational approach to patients treatment with type 2 diabetes and obesity: results of the all-russian observational program “AURORA”. Obesity and metabolism. 2018;15(4):48-58. (In Russ.) doi:10.14341/OMET10076.

11. Wilding J. Combination therapy for obesity. J Psychopharmacol. 2017;31(11):150-8. doi:10.1177/0269881117737401.

12. Bohula E, Wiviott S, McGuire D, et al. Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med. 2018;379(12):1107-17. doi:10.1056/NEJMoa1808721.

13. 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.

14. Romantsova TI. Glucagon-like peptide-1 analogue liraglutide (SAXENDA®): mechanism of action, efficacy for the treatment of obesity. Obesity and metabolism. 2018;15(1):3-11. (In Russ.) doi:10.14341/OMET201813-11.

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. Zaccardi F, Webb D, Htike Z, et al. Efficacy and safety of sodiumglucose 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.

17. Shestakova MV. DECLARE-TIMI 58 trial in the context of EMPA-REG OUTCOME and CANVAS. Diabetes Mellitus. 2019;22(6):592-601. (In Russ.) doi:10.14341/DM10289.

18. 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 meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31-9. doi:10.1016/S0140-6736(18)32590-X.

19. Ferrannini E. Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology. Cell Metabolism. 2017;26(1):27-38. doi:10.1016/j.cmet.2017.04.011.

20. 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.

21. Kosiborod M, Jhund P, Docherty K, et al. Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF Trial. Circulation. 2019;141:90-9. doi:10.1161/CIRCULATIONAHA.119.044138.

22. 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.

23. Del Prato S, Nauck M, Duran-Garcia S, et al. Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab. 2015;17(6):581-90. doi:10.1111/dom.12459.

24. 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.

25. Frias J, Guja C, Hardy E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomized controlled trial. Lancet Diabetes Endocrinol. 2016;4(12):1004-16. doi:10.1016/S2213-8587(16)30267-4.

26. 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.

27. 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.

28. Pereira M, Lundkvist P, Kamble P, et al. A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: metabolic Effects and Markers Associated with Bodyweight Loss. Diabetes Ther. 2018;9(4):1511-32. doi:10.1007/s13300-018-0449-6.

29. 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.

30. Tosaki T, Kamiya H, Himeno T, et al. Sodium-glucose Cotransporter 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.

31. 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.

32. Fukuda T, Bouchi R, Terashima M, et al. Ipragliflozin Reduces Epicardial Fat Accumulation in Non-Obese Type 2 Diabetic Patients with Visceral Obesity: A Pilot Study. Diabetes Ther. 2017;8:851-61. doi:10.1007/s13300-017-0279-y.

33. 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.

34. Yagi S, Hirata Y, Ise T, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2017;9:78. doi:10.1186/s13098-017-0275-4.

35. 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.

36. van Woerden G, Gorter T, Westenbrink B, et al. Epicardial fat in heart failure patients with mid-range and preserved ejection fraction. Eur J Heart Fail. 2018;20(11):1559-66. doi:10.1002/ejhf.1283.

37. Xu L, Nagata N, Nagashimada M, et al. SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice. EBioMedicine. 2017;20:137-49. doi:10.1016/j.ebiom.2017.05.028.

38. 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.

39. 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.

40. Oliva R, Bakris G. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors. J Am Soc Hypertens. 2014;8(5):330-9. doi:10.1016/j.jash.2014.02.003.

41. Sakai S, Kaku K, Seino Y, et al. Efficacy and safety of the SGLT2 inhibitor luseogliflozin in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index: pooled analysis of data from 52-week phase III trials. Clin Ther. 2016;38(4):843-62. doi:10.1016/j.clinthera.2016.01.017.

42. Mori H, Okada Y, Kawaguchi M, et al. A case of type 2 diabetes with a change from a non-dipper to a dipper blood pressure pattern by dapagliflozin. J UOEH. 2016;38(2):149-53. doi:10.7888/juoeh.38.149.

43. Chilton R, Tikkanen I, Hehnke U, et al. Impact of empagliflozin on blood pressure in dipper and non-dipperpatients with type 2 diabetes mellitus and hypertension. Diabetes Obesity Metab. 2017;19(11):1620-4. doi:10.1111/dom.12962.

44. Sano M. Hemodynamic effects of sodium-glucose cotransporter 2 inhibitors. J Clin Med Res. 2017;9(6):457-60. doi:10.14740/jocmr3011w.

45. 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.

46. Bosch А, Ott C, Jung S, et al. How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. Cardiovasc Diabetol. 2019;18(1):44. doi:10.1186/s12933-019-0839-8.

47. Solini A, Giannini L, Seghieri M, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol. 2017;16(1):138. doi:10.1186/s12933-017-0621-8.

48. Briand F, Mayoux E, Brousseau E, et al. Empagliflozin, via switching metabolism toward lipid utilization, moderately increases LDL cholesterol levels through reduced LDL catabolism. Diabetes. 2016;65(7):2032-8. doi:10.2337/db16-0049.

49. 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.

50. Shyangdan D, Uthman O, Waugh N. SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. BMJ Open. 2016;6(2):e009417. doi:10.1136/bmjopen-2015-009417.

51. Gonzalez N, Moreno-Villegas Z, Gonzalez-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.

52. Prattichizzo F, La Sala L, Ryden L, et al. Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases. Eur J Prev Cardiol. 2019;26(2S):73-80. doi:10.1177/2047487319880040.

53. Ferrannini G, Hach T, Crowe S, et al. Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015;38(9):1730-5. doi:10.2337/dc15-0355.

54. Verma S. Potential Mechanisms of Sodium-Glucose Co-Transporter 2 Inhibitor-Related Cardiovascular Benefits. Am J Cardiol. 2019;124(1S):36-44. doi:10.1016/j.amjcard.2019.10.028.

55. 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.

56. 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/s12020-019-02175-6.


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Druzhilov M.A., Kuznetsova T.Yu. Role of SGLT2 inhibitors in the treatment of visceral obesity. Cardiovascular Therapy and Prevention. 2021;20(1):2648. (In Russ.) https://doi.org/10.15829/1728-8800-2021-2648

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ISSN 1728-8800 (Print)
ISSN 2619-0125 (Online)