Beyond glycemic control: The pleiotropic potential of SGLT-2 inhibitors
Year 2025,
Volume: 3 Issue: 3, 99 - 101, 29.10.2025
Selma Sezen
Abstract
According to the journal rules, an abstract is not required for the Editorial article type.
Ethical Statement
Ethics committee approval is not required for this article.
References
-
Sano R, Shinozaki Y, Ohta T. Sodium-glucose cotransporters: functional properties and pharmaceutical potential. J Diabetes Investig. 2020;11(4):770–82.
-
Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet. 2021;398(10296):262–76.
-
Bendotti G, Montefusco L, Pastore I, Lazzaroni E, Lunati ME, Fiorina P. The anti-inflammatory and immunological properties of SGLT-2 inhibitors. J Endocrinol Invest. 2023;46(12):2445–52.
-
White JR. Apple trees to sodium glucose co-transporter inhibitors: a review of SGLT2 inhibition. Clin Diabetes. 2010;28(1):5–10.
-
Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest. 1987;79(5):1510–5.
-
Blondel O, Bailbe D, Portha B. Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. Metabolism. 1990;39(8):787–93.
-
Brichard SM, Henquin JC, Girard J. Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. Diabetologia. 1993;36:292–8.
-
Helvacı Ö, Helvacı B. A story of serendipities: from phlorizin to gliflozins. Exp Clin Transplant. 2023;21(Suppl 2):105–8.
-
Balakumar P, Sundram K, Dhanaraj SA. Dapagliflozin: glucuretic action and beyond. Pharmacol Res. 2014;82:34–9.
-
Moradi-Marjaneh R, Paseban M, Sahebkar A. Natural products with SGLT2 inhibitory activity: possibilities of application for the treatment of diabetes. Phytother Res. 2019;33(10):2518–30.
-
Chen X, Wang J, Lin Y, Liu Y, Zhou T. Signaling pathways of podocyte injury in diabetic kidney disease and the effect of sodium-glucose cotransporter 2 inhibitors. Cells. 2022;11(23):3913.
-
Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease. Front Immunol. 2023;14:1213473.
-
Wanner C, Nangaku M, Kraus BJ, Zinman B, Mattheus M, Hantel S, et al. How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial. Nephrol Dial Transplant. 2024;39(9):1504–13.
-
Upadhyay A. SGLT2 inhibitors and kidney protection: mechanisms beyond tubuloglomerular feedback. Kidney360. 2024;5(5):771–82.
-
Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46.
-
Antlanger M, Domenig O, Kaltenecker CC, et al. Combined sodium glucose co-transporter-2 inhibitor and angiotensin-converting enzyme inhibition upregulates the renin-angiotensin system in chronic kidney disease with type 2 diabetes: results of a randomized, double-blind, placebo-controlled exploratory trial. Diabetes Obes Metab. 2022;24(5):816–26.
-
Tavares CAM, Azevedo LCP, Rea-Neto Á, et al. Dapagliflozin for critically ill patients with acute organ dysfunction: the DEFENDER randomized clinical trial. JAMA. 2024;332(5):401–11.
-
U.S. Food and Drug Administration. Guidance for industry on diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes; availability. Fed Regist. 2008;73.
-
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.
-
Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL Study. Circulation. 2017;136(3):249–59.
-
Rådholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program. Circulation. 2018;138(5):458–68.
-
Ramírez-Rodríguez AM, González-Ortiz M, Martínez-Abundis E. Effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. Exp Clin Endocrinol Diabetes. 2020;128(8):506–11.
-
Zhang J, Xing C, Cheng X, He B. Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: a randomized controlled trial. Front Endocrinol (Lausanne). 2022;13:1003238.
-
Benedetti R, Benincasa G, Glass K, et al. Effects of novel SGLT2 inhibitors on cancer incidence in hyperglycemic patients: a meta-analysis of randomized clinical trials. Pharmacol Res. 2022;175:106039.
-
Ren D, Sun Y, Zhang D, et al. SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis. Cancer Lett. 2021;519:277–88.
-
Mohsin S, Hasan M, Sheikh ZM, et al. Efficacy of SGLT2 inhibitors for anthracycline-induced cardiotoxicity: a meta-analysis in cancer patients. Future Cardiol. 2024;20(7–8):395–407.
-
Fan G, Zuo H, Lin L, Xu C, Yan R. The efficacy and safety of sodium glucose cotransporter 2 inhibitors for patients with anticancer therapy: a meta-analysis of cohort studies. Glob Heart. 2025;20(1):53.
-
Copur S, Yildiz AB, Covic A, Kanbay M. Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer? Eur J Clin Invest. 2024;54(2):e14131.
-
Tseng PT, Zeng BY, Hsu CW, et al. The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis. BMC Med. 2025;23(1):197.
Glisemik kontrolün ötesinde: SGLT-2 inhibitörlerinin pleiotropik potansiyeli
Year 2025,
Volume: 3 Issue: 3, 99 - 101, 29.10.2025
Selma Sezen
Abstract
Dergi kurallarına göre Editöryal makale türü için özet zorunluluğu yoktur.
Ethical Statement
Ethics committee approval is not required for this article.
References
-
Sano R, Shinozaki Y, Ohta T. Sodium-glucose cotransporters: functional properties and pharmaceutical potential. J Diabetes Investig. 2020;11(4):770–82.
-
Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet. 2021;398(10296):262–76.
-
Bendotti G, Montefusco L, Pastore I, Lazzaroni E, Lunati ME, Fiorina P. The anti-inflammatory and immunological properties of SGLT-2 inhibitors. J Endocrinol Invest. 2023;46(12):2445–52.
-
White JR. Apple trees to sodium glucose co-transporter inhibitors: a review of SGLT2 inhibition. Clin Diabetes. 2010;28(1):5–10.
-
Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest. 1987;79(5):1510–5.
-
Blondel O, Bailbe D, Portha B. Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. Metabolism. 1990;39(8):787–93.
-
Brichard SM, Henquin JC, Girard J. Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. Diabetologia. 1993;36:292–8.
-
Helvacı Ö, Helvacı B. A story of serendipities: from phlorizin to gliflozins. Exp Clin Transplant. 2023;21(Suppl 2):105–8.
-
Balakumar P, Sundram K, Dhanaraj SA. Dapagliflozin: glucuretic action and beyond. Pharmacol Res. 2014;82:34–9.
-
Moradi-Marjaneh R, Paseban M, Sahebkar A. Natural products with SGLT2 inhibitory activity: possibilities of application for the treatment of diabetes. Phytother Res. 2019;33(10):2518–30.
-
Chen X, Wang J, Lin Y, Liu Y, Zhou T. Signaling pathways of podocyte injury in diabetic kidney disease and the effect of sodium-glucose cotransporter 2 inhibitors. Cells. 2022;11(23):3913.
-
Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease. Front Immunol. 2023;14:1213473.
-
Wanner C, Nangaku M, Kraus BJ, Zinman B, Mattheus M, Hantel S, et al. How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial. Nephrol Dial Transplant. 2024;39(9):1504–13.
-
Upadhyay A. SGLT2 inhibitors and kidney protection: mechanisms beyond tubuloglomerular feedback. Kidney360. 2024;5(5):771–82.
-
Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46.
-
Antlanger M, Domenig O, Kaltenecker CC, et al. Combined sodium glucose co-transporter-2 inhibitor and angiotensin-converting enzyme inhibition upregulates the renin-angiotensin system in chronic kidney disease with type 2 diabetes: results of a randomized, double-blind, placebo-controlled exploratory trial. Diabetes Obes Metab. 2022;24(5):816–26.
-
Tavares CAM, Azevedo LCP, Rea-Neto Á, et al. Dapagliflozin for critically ill patients with acute organ dysfunction: the DEFENDER randomized clinical trial. JAMA. 2024;332(5):401–11.
-
U.S. Food and Drug Administration. Guidance for industry on diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes; availability. Fed Regist. 2008;73.
-
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.
-
Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL Study. Circulation. 2017;136(3):249–59.
-
Rådholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program. Circulation. 2018;138(5):458–68.
-
Ramírez-Rodríguez AM, González-Ortiz M, Martínez-Abundis E. Effect of dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. Exp Clin Endocrinol Diabetes. 2020;128(8):506–11.
-
Zhang J, Xing C, Cheng X, He B. Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: a randomized controlled trial. Front Endocrinol (Lausanne). 2022;13:1003238.
-
Benedetti R, Benincasa G, Glass K, et al. Effects of novel SGLT2 inhibitors on cancer incidence in hyperglycemic patients: a meta-analysis of randomized clinical trials. Pharmacol Res. 2022;175:106039.
-
Ren D, Sun Y, Zhang D, et al. SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis. Cancer Lett. 2021;519:277–88.
-
Mohsin S, Hasan M, Sheikh ZM, et al. Efficacy of SGLT2 inhibitors for anthracycline-induced cardiotoxicity: a meta-analysis in cancer patients. Future Cardiol. 2024;20(7–8):395–407.
-
Fan G, Zuo H, Lin L, Xu C, Yan R. The efficacy and safety of sodium glucose cotransporter 2 inhibitors for patients with anticancer therapy: a meta-analysis of cohort studies. Glob Heart. 2025;20(1):53.
-
Copur S, Yildiz AB, Covic A, Kanbay M. Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer? Eur J Clin Invest. 2024;54(2):e14131.
-
Tseng PT, Zeng BY, Hsu CW, et al. The pharmacodynamics-based prophylactic benefits of GLP-1 receptor agonists and SGLT2 inhibitors on neurodegenerative diseases: evidence from a network meta-analysis. BMC Med. 2025;23(1):197.