Editorial
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Beyond glycemic control: The pleiotropic potential of SGLT-2 inhibitors

Year 2025, Volume: 3 Issue: 3, 99 - 101, 29.10.2025
https://doi.org/10.61845/agrimedical.1811202

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
https://doi.org/10.61845/agrimedical.1811202

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.
There are 29 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Editorial
Authors

Selma Sezen 0000-0001-6575-6149

Publication Date October 29, 2025
Submission Date October 26, 2025
Acceptance Date October 27, 2025
Published in Issue Year 2025 Volume: 3 Issue: 3

Cite

AMA Sezen S. Beyond glycemic control: The pleiotropic potential of SGLT-2 inhibitors. Ağrı Med J. October 2025;3(3):99-101. doi:10.61845/agrimedical.1811202