COMPARISON BETWEEN THE EFFICACY OF SGLT2 INHIBITORS VERSUS DPP4 INHIBITORS IN INDIAN POPULATION: A SYSTEMATIC REVIEW

Main Article Content

Pushkar Mani
Shipra jain
Ruchi Mathur
Mohammed Shoaib
Aman Mathur

Keywords

Type 2 Diabetes Mellitus, SGL2I, gliflozins, DPP4I, gliptins, Antidiabetic Agents, Indian population, Indians, India, Asians, SGLT2 Inhibitors versus DPP4 inhibitors

Abstract

Introduction: India is among the nations with the largest number of individuals having Diabetes Mellitus. Various elements liable for the increasing magnitude of type 2 diabetes include pathophysiologic and hereditary components as well as the 'Asian Indian phenotype', which makes these patients more prone to acquire T2DM in comparison to Caucasians. In this review efficacy and safety of dipeptidyl peptidase-IV inhibitors and sodium glucose transport inhibitor is going to be reviewed and compared with each other to ascertain effective and safe treatment options across the spectrum of T2DM patients in India.


Material and Methods: ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 guidelines’ were followed to report this systematic review with the inclusion of studies related to the use of oral hypoglycemic agents in Indian patients with type 2 Diabetes Mellitus and comparison between SGL2I and DPP4I in terms of efficacy, adverse effects, and other parameters. The search will be restricted to studies published in the English language on PubMed, Google Scholar, and the Indian Journal of Endocrinology and Metabolism (IJEM) from 2010 to 2021.


Results: The analysis of a number of studies revealed superiority of SGLT2I in several different parameters including reduction in HbA1c levels, improved glycemic control on follow up as well as positive effects on body weight and SBP reduction in comparison to the use of DPP4I. Moreover, use of SGLT2I showed improvement in the levels of TG and HDL-C values with modest worsening of LDL-C values. Reduction in fasting and postprandial glucagon levels was seen with the use of DPP4I in comparison to SGLT-2 inhibition resulting in more rapid insulin secretion and higher levels of intact incretin hormones. DPP4-I show a safe CV profile, however, the use of SGLT2-I resulted in better CV outcome and survival in DM patients as it significantly reduced the risk of all-cause death, CV death, MI and HF without any effect on stroke events. Adverse effects reported with the use of SGLT21 showed an increased risk of developing genital infection and in certain cases increased risk of amputations though not statistically significant. Although, DPP-4 inhibitors (gliptins) showed some positive cardiac and vascular effects in preliminary studies, an unexpected higher risk of hospitalization for heart failure was reported with saxagliptin. Conclusion: Overall, SGLT2I showed more efficacy than DPP4I and revealed superiority in several different parameters making it a more suitable option to improve health outcomes in Indian Diabetic patients

Abstract 188 | pdf Downloads 111

References

1. Anjana RM, Pradeepa R, Unnikrishnan R, Tiwaskar M, Aravind SR, Saboo B, Joshi SR, Mohan V. New and Unique Clusters of Type 2 Diabetes Identified in Indians. J Assoc Physicians India. 2021 Feb;69(2):58-61. PMID: 33527813.
2. Demla C, Thomas A, Jose J, Joshy AL, Hrishikesh MA, Rajendran A, Parsekar SS. Instruments measuring the quality of life among people living with type 2 diabetes mellitus in India: a systematic review protocol. BMJ Open. 2021 Apr 2;11(4):e043831. doi: 10.1136/bmjopen-2020-043831. PMID: 33811053; PMCID: PMC8023725.
3. Cho NH, Shaw JE, Karuranga S, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res ClinPract. 2018;138:271–281. doi:10.1016/j.diabres.2018.02.023
4. Diabetes Foundation India, 2013. http://www.diabetesfoundationindia.org/about.htm
5. World Health Organization . Diabetes, 2018. Available: https://www.who.int/news-room/fact-sheets/detail/diabetes
6. Sahoo SK, Zaidi G, Vipin VP, Chapla A, Thomas N, Yu L, Asthana P, Bhatia E. Heterogeneity in the aetiology of diabetes mellitus in young adults: A prospective study from north India. Indian J Med Res. 2019 Apr;149(4):479-488. doi: 10.4103/ijmr.IJMR_1004_17. PMID: 31411171; PMCID: PMC6676834.
7. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4–14.
8. India state-level disease burden initiative diabetes collaborators. The increasing burden of diabetes and variations among states of India: the Global Burden of Disease Study 1990-2016. Lancet Glob Health. 2018;6:e1352–62.
9. Jevalikar G, Kohli C, Bansal B, Mishra SK, Wasir JS, Singh S, et al. Childhood and youth onset diabetes: A single centre experience. Indian J Pediatr. 2016;83:792–8.
10. Shariff AI, Kumar N, Yancy WS Jr, Corsino L. Type 2 Diabetes and Atherosclerotic Cardiovascular Disease in South Asians: a Unique Population with a Growing Challenge. Curr Diab Rep. 2020 Jan 30;20(1):4. doi: 10.1007/s11892-020-1291-6. PMID: 32002674.
11. Joshi SR. Diabetes care in India. Ann Glob Health 2015;81:830–8. 10.1016/j.aogh.2016.01.002]
12. Erande S, Sarwardekar S, Desai B. QT/QTc safety and efficacy evaluation of teneligliptin in Indian type 2 diabetes mellitus patients: the "thorough QT/QTc" study (Q-SET study). Diabetes Metab Syndr Obes. 2019 Jun 21;12:961-967. doi: 10.2147/DMSO.S202458. PMID: 31417296; PMCID: PMC6593689.
13. Emerging Risk Factors Collaboration , Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta‐analysis of 102 prospective studies. Lancet. 2010;375(9733):2215‐2222.
14. Deerochanawong C, Chan SP, Matawaran BJ, Sheu WH, Chan J, Man NH, Suastika K, Khoo CM, Yoon KH, Luk A, Mithal A, Linong J. Use of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations. Diabetes Obes Metab. 2019 Nov;21(11):2354-2367. doi: 10.1111/dom.13819. Epub 2019 Jul 17. PMID: 31264765; PMCID: PMC6852284.
15. Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, Kawaguchi M, Canovatchel W, Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013 Sep;36(9):2508-15. doi: 10.2337/dc12-2491. Epub 2013 Apr 5. Erratum in: Diabetes Care. 2013 Dec;36(12):4172. PMID: 23564919; PMCID: PMC3747923.
16. Rosenstock J, Mathieu C, Chen H, Garcia-Sanchez R, Saraiva GL. Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. Arch Endocrinol Metab. 2018 Aug;62(4):424-430. doi: 10.20945/2359-3997000000056. PMID: 30304106.
17. Wang Z, Sun J, Han R, Fan D, Dong X, Luan Z, Xiang R, Zhao M, Yang J. Efficacy and safety of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as monotherapy or add-on to metformin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes Obes Metab. 2018 Jan;20(1):113-120. doi: 10.1111/dom.13047. Epub 2017 Aug 10. PMID: 28656707.
18. Zilli RW, Rached CDA, Silva FPD, Baena RC. Long-term efficacy of gliflozins versus gliptins for Type 2 Diabetes after metformin failure: a systematic review and network meta-analysis. Rev Assoc Med Bras (1992). 2020 Apr;66(4):458-465. doi: 10.1590/1806-9282.66.4.458. PMID: 32578779.
19. Thayer S, Aguilar R, Korrer S, Chow W. HbA1c Outcomes in Patients Treated With Canagliflozin Versus Sitagliptin in US Health Plans. Clin Ther. 2017 Oct;39(10):2061-2072. doi: 10.1016/j.clinthera.2017.08.019. Epub 2017 Sep 22. PMID: 28943114.
20. Thayer S, Chow W, Korrer S, Aguilar R. Real-world evaluation of glycemic control among patients with type 2 diabetes mellitus treated with canagliflozin versus dipeptidyl peptidase-4 inhibitors. Curr Med Res Opin. 2016 Jun;32(6):1087-96. doi: 10.1185/03007995.2016.1159954. Epub 2016 Mar 16. PMID: 26938635.
21. Bailey CJ, Del Prato S, Wei C, Reyner D, Saraiva G. Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes. Diabetes Obes Metab. 2019 Nov;21(11):2564-2569. doi: 10.1111/dom.13841. Epub 2019 Aug 26. PMID: 31364269; PMCID: PMC6851837.
22. Wysham CH, Lefebvre P, Pilon D, Lafeuille MH, Emond B, Kamstra R, Pfeifer M, Duh MS, Ingham M. An investigation into the durability of glycemic control in patients with type II diabetes initiated on canagliflozin or sitagliptin: A real-world analysis of electronic medical records. J Diabetes Complications. 2019 Feb;33(2):140-147.
doi: 10.1016/j.jdiacomp.2018.10.016. Epub 2018 Oct 31. PMID: 30554838.
23. Bailey RA, Damaraju CV, Martin SC, Meininger GE, Rupnow MF, Blonde L. Attainment of diabetes-related quality measures with canagliflozin versus sitagliptin. Am J Manag Care. 2014 Jan;20(1 Suppl):s16-24. PMID: 24512193.
24. Bailey RA, Vijapurkar U, Meininger GE, Rupnow MF, Blonde L. Diabetes-related quality measure attainment: canagliflozin versus sitagliptin based on a pooled analysis of 2 clinical trials. Am J Manag Care. 2014 Dec;20(13 Suppl):s296-305. PMID: 25734218.
25. Bailey RA, Vijapurkar U, Meininger G, Rupnow MF, Blonde L. Diabetes-Related Composite Quality End Point Attainment: Canagliflozin Versus Sitagliptin Based on a Pooled Analysis of 2 Clinical Trials. Clin Ther. 2015 May 1;37(5):1045-54. doi: 10.1016/j.clinthera.2015.02.020. Epub 2015 Mar 18. PMID: 25795432.
26. Cha SA, Park YM, Yun JS, Lim TS, Song KH, Yoo KD, Ahn YB, Ko SH. A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes. Lipids Health Dis. 2017 Apr 13;16(1):58. doi: 10.1186/s12944-017-0443-4. PMID: 28403877; PMCID: PMC5390350.
27. Imre E, Gunhan HG, Erel P, Ustay O. SGLT2 inhibitors improve plasma atherogenic biomarkers in patients with type 2 diabetes: a real world retrospective observational study. Minerva Endocrinol (Torino). 2021 May 12. doi: 10.23736/S2724-6507.21.03465-5. Epub ahead of print. PMID: 33979071.
28. Liu Y, Xu J, Wu M, Xu B, Kang L. Empagliflozin protects against atherosclerosis progression by modulating lipid profiles and sympathetic activity. Lipids Health Dis. 2021 Jan 12;20(1):5. doi: 10.1186/s12944-021-01430-y. PMID: 33436015; PMCID: PMC7802233.
29. Muzurović E, Mikhailidis DP. Impact of glucagon-like peptide 1 receptor agonists and sodium-glucose transport protein 2 inhibitors on blood pressure and lipid profile. Expert Opin Pharmacother. 2020 Dec;21(17):2125-2135. doi: 10.1080/14656566.2020.1795132. Epub 2020 Jul 22. PMID: 32697112.
30. Mukai J, Yoshiyama A, Kubota R. Clinical relevance between sodium-glucose co-transporter 2 inhibitors and lipid profiles in Asian patients with type 2 diabetes mellitus: a systematic review with a meta-analysis of randomized controlled trials. J Pharm Health Care Sci. 2020 Mar 14;6:4. doi: 10.1186/s40780-020-00160-0. PMID: 32190340; PMCID: PMC7071682.
31. Alsalim W, Persson M, Ahrén B. Different glucagon effects during DPP-4 inhibition versus SGLT-2 inhibition in metformin-treated type 2 diabetes patients. Diabetes Obes Metab. 2018 Jul;20(7):1652-1658. doi: 10.1111/dom.13276. Epub 2018 Mar 24. PMID: 29498469.
32. Zhu X, Lin C, Li L, Hu S, Cai X, Ji L. SGLT2i increased the plasma fasting glucagon level in patients with diabetes: A meta-analysis. Eur J Pharmacol. 2021 Jul 15;903:174145. doi: 10.1016/j.ejphar.2021.174145. Epub 2021 May 3. PMID: 33957085.
33. Savarese G, D'Amore C, Federici M, De Martino F, Dellegrottaglie S, Marciano C, Ferrazzano F, Losco T, Lund LH, Trimarco B, Rosano GM, Perrone-Filardi P. Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis. Int J Cardiol. 2016 Oct 1;220:595-601. doi: 10.1016/j.ijcard.2016.06.208. Epub 2016 Jun 27. PMID: 27390996.
34. Scheen AJ. Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors. Circ Res. 2018 May 11;122(10):1439-1459.
doi: 10.1161/CIRCRESAHA.117.311588. PMID: 29748368; PMCID: PMC5959222.
35. Lee SJ, Lee KH, Oh HG, Seo HJ, Jeong SJ, Kim CH. Effect of Sodium-Glucose Cotransporter-2 Inhibitors versus Dipeptidyl Peptidase 4 Inhibitors on Cardiovascular Function in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease. J Obes Metab Syndr. 2019 Dec;28(4):254-261. doi: 10.7570/jomes.2019.28.4.254. Epub 2019 Dec 30. PMID: 31909368; PMCID: PMC6939702.
36. Fuchigami A, Shigiyama F, Kitazawa T, Okada Y, Ichijo T, Higa M, Hiyoshi T, Inoue I, Iso K, Yoshii H, Hirose T, Kumashiro N. Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR). Cardiovasc Diabetol. 2020 Jan 7;19(1):1. doi: 10.1186/s12933-019-0977-z. PMID: 31910850; PMCID: PMC6945792.
37. Birkeland KI, Bodegard J, Banerjee A, Kim DJ, Norhammar A, Eriksson JW, Thuresson M, Okami S, Ha KH, Kossack N, Mamza JB, Zhang R, Yajima T, Komuro I, Kadowaki T. Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study. Diabetes Obes Metab. 2021 Jan;23(1):75-85. doi: 10.1111/dom.14189. Epub 2020 Sep 28. PMID: 32893440; PMCID: PMC7756303.
38. Fralick M, Colacci M, Thiruchelvam D, Gomes T, Redelmeier DA. Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors and the risk of heart failure: A nationwide cohort study of older adults with diabetes mellitus. Diabetes Obes Metab. 2021 Apr;23(4):950-960. doi: 10.1111/dom.14300. Epub 2021 Jan 13. PMID: 33336894.
39. Adimadhyam S, Lee TA, Calip GS, Smith Marsh DE, Layden BT, Schumock GT. Risk of amputations associated with SGLT2 inhibitors compared to DPP-4 inhibitors: A propensity-matched cohort study. Diabetes Obes Metab. 2018 Dec;20(12):2792-2799. doi: 10.1111/dom.13459. Epub 2018 Aug 5. PMID: 29971914.
40. Potier L, Mohammedi K, Velho G, Roussel R. SGLT2 inhibitors and lower limb complications: the diuretic-induced hypovolemia hypothesis. Cardiovasc Diabetol. 2021 May 13;20(1):107. doi: 10.1186/s12933-021-01301-x. PMID: 33985506; PMCID: PMC8120812.
41. Lin C, Zhu X, Cai X, Yang W, Lv F, Nie L, Ji L. SGLT2 inhibitors and lower limb complications: an updated meta-analysis. Cardiovasc Diabetol. 2021 Apr 28;20(1):91. doi: 10.1186/s12933-021-01276-9. Erratum in: Cardiovasc Diabetol. 2021 Jun 9;20(1):119. PMID: 33910574; PMCID: PMC8082772.
42. Lin DS, Lee JK, Chen WJ. Clinical Adverse Events Associated with Sodium-Glucose Cotransporter 2 Inhibitors: A Meta-Analysis Involving 10 Randomized Clinical Trials and 71 553 Individuals. J Clin Endocrinol Metab. 2021 Jun 16;106(7):2133-2145. doi: 10.1210/clinem/dgab274. PMID: 33895840.
43. Qiu M, Ding LL, Zhang M, Zhou HR. Comparison of the risk of SGLT2is and NonSGLT2is in leading to amputation: A network meta-analysis. J Diabetes Complications. 2021 Feb;35(2):107803. doi: 10.1016/j.jdiacomp.2020.107803. Epub 2020 Nov 26. PMID: 33293207.
44. Varshney N, Billups SJ, Saseen JJ, Fixen CW. Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes. Ther Adv Drug Saf. 2021 Mar 29;12:2042098621997703. doi: 10.1177/2042098621997703. PMID: 33854754; PMCID: PMC8010840.
45. Ko S, Kim H, Shinn J, Byeon SJ, Choi JH, Kim HS. Estimation of sodium-glucose cotransporter 2 inhibitor-related genital and urinary tract infections via electronic medical record-based common data model. J Clin Pharm Ther. 2021 Aug;46(4):975-983. doi: 10.1111/jcpt.13381. Epub 2021 Feb 10. PMID: 33565150.
46. Nakhleh A, Zloczower M, Gabay L, Shehadeh N. Effects of sodium glucose co-transporter 2 inhibitors on genital infections in female patients with type 2 diabetes mellitus- Real world data analysis. J Diabetes Complications. 2020 Jul;34(7):107587.
doi: 10.1016/j.jdiacomp.2020.107587. Epub 2020 Apr 18. PMID: 32354622.
47. Sandhu P, Ong JP, Garg V, Altaha M, Bello O, Singal SR, Verma S, Yan AT, Connelly KA. The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF). Acta Diabetol. 2021 May;58(5):633-641. doi: 10.1007/s00592-020-01661-y. Epub 2021 Jan 23. PMID: 33483855.
48. Orime K, Terauchi Y. Efficacy and safety of saxagliptin for the treatment of type 2 diabetes mellitus. Expert Opin Pharmacother. 2020 Dec;21(17):2101-2114.
doi: 10.1080/14656566.2020.1803280. Epub 2020 Sep 29. PMID: 32990096.
49. Singh AK, Singh R. Heart Failure Hospitalization with DPP-4 Inhibitors: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Endocrinol Metab. 2019 Jan-Feb;23(1):128-133.
doi: 10.4103/ijem.IJEM_613_18. PMID: 31016167; PMCID: PMC 6446681.
50. Ling AW, Chan CC, Chen SW, Kao YW, Huang CY, Chan YH, Chu PH. The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cardiovasc Diabetol. 2020 Nov 6;19(1):188.
doi: 10.1186/s12933-020-01162-w. PMID: 33158436; PMCID: PMC7 648323