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SGLT2 INHIBITORS IN DIABETIC KIDNEY DISEASE:
THE TIME TO ACT IS NOW BY MICHAEL LATTANZIO, DO, FASN
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iabetes mellitus is a major cause of diabetic kidney disease (DKD) and end stage kidney disease (ESKD) in the United States. About one-third of patients with diabetes mellitus will ultimately develop DKD and individuals with DKD are at substantial higher risk of cardiovascular disease and death. Renin-angiotensin system (RAS) blockade with ACE inhibitors and ARBs will reduce the risk of DKD by approximately 20% (1). Despite this clear benefit, RAS blockade in DKD remains highly underutilized. Moreover, although DKD is associated with a tremendous cost and healthcare burden, scientific advancement in the field has gone largely unmet. Sodium glucose cotransporter-2 inhibitors (SLGT-2i) have emerged as a powerful treatment option in DKD and has the potential to immediately revolutionize kidney care. Multiple randomized controlled trials analyzing the impact of SGLT-2i on DKD outcomes have recently emerged (2,3,4). These studies involved patients with DKD who were already receiving maximally tolerated doses of RAS blockade, which would be considered the standard of care treatment for DKD. These studies consistently and convincingly demonstrated a substantial reduction in renal outcomes of approximately 30%. SGLT-2 inhibitors are the first drugs for the treatment of DKD that have demonstrated a reduction in all-cause mortality suggesting that the cardiovascular and kidney protection afforded from SGLT2i occur in parallel. The ability of SGLT2i to improve kidney outcomes in individuals with DKD has been an eagerly awaited breakthrough in kidney care community. With any medical intervention, the benefits of such therapies need to be weighed against potential adverse events. With regards to SGLT2 inhibition, these risks include: increased risk of UTI, mycotic genital infections, ketoacidosis, and volume depletion. Additionally, a rise in creatinine (drop in glomerular filtration rateGFR) is expected with the initiation of SGLT2i. The drop in GFR is a reversible, hemodynamic effect and does not represent intrinsic decline in kidney function. The decline in GFR occurs shortly after SGLT2i initiation and is followed by sustained preservation of kidney function over time. Conversely, individuals with DKD that are not treated with SGLT2i will experience a gradual decline in kidney function over time.
The advent of SGLT2i for the treatment of diabetic kidney disease has the potential to transform the future landscape of kidney care. Importantly, the avoidance of ESKD among individuals with progressive DKD is now a realistic and achievable outcome. Now, as a medical community, we must work collaboratively to deploy broad-scale implementation strategies among our patients with type 2 diabetes. A concerted effort for early detection of DKD and prompt identification of candidates for SGLT2i therapy is paramount. If you are part of a medical community caring for individuals with diabetes mellitus, the time to act is now. References 1) Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9. doi: 10.1056/NEJMoa011161. PMID: 11565518. 2) Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):22952306. doi: 10.1056/NEJMoa1811744. Epub 2019 Apr 14. PMID: 30990260. 3) Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. PMID: 32970396. 4) Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPAREG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14. PMID: 27299675.
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