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SGLT2 Inhibitors
Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors are a class of drug that block the kidneys from reabsorbing glucose (sugar). Instead, glucose leaves the body via urine. When blood glucose is controlled, there is less stress for the kidney. SGLT2 inhibitors are an oral medication (taken by mouth) and can help to slow the progression of kidney disease. They also help to lowering the risk of end stage kidney disease (ESKD).You may recognize them as medications that end in “-flozin.” Here are some examples: Farxiga (dapagliflozin), Jardiance (empagliflozin).
How Can they Help Patients with Rare Kidney Disease (RKD)?
There are many ways SGLT2 inhibitors are thought to help in preserving kidney function. One effect of SGLT2 inhibitors is reducing blood pressure in the body and in the glomeruli (kidney filters). Reduced blood pressure in the glomeruli helps to reduce proteinuria. Spilling less protein in the urine is linked to slower progression to ESKD. SGLT2 inhibitors also protect podocytes from damage (or effacement) and loss. Podocyte loss cannot be reversed. Loss of podocytes is associated with worsening kidney function.
Important Note:
When first starting a SGLT2 inhibitor, the estimated glomerular filtration rate (eGFR) may slightly decrease. This reduction is temporary. With continued SGLT2i treatment, the “dip” in eGFR is typically recovered. This means, the eGFR will usually go back to the level it was when you first started taking the medication. Long term use is associated with a slower decline in eGFR (or slower progression to ESKD). (Heerspink, et. al)
*Note: The decision to prescribe a medication is the responsibility of your physician/primary care provider based on his/her evaluation of your condition. The above is meant for informational purposes only. Discuss this information and all information about drugs/medications with your physician before starting or stopping any medication.
Frequently Asked Questions
SGLT2 are pills that you take by mouth. SGLT2 are usually taken once daily, and many people take them in the morning. Try to take your medications at the same time, or times, each day. Do not stop taking your medicines without talking with your doctor first.
SGLT2 inhibitors are FDA approved for kidney disease and considered to be safe. But in some cases, they can cause side effects including:
- Urinary Tract Infections
- Yeast infections
- Hypoglycemia (low blood sugar)
- Hypotension (low blood pressure)
- Increased urinary frequency
For a complete list of potential side effects contact your kidney doctor.
SGLT2 inhibitors are FDA approved for use in adults with eGFR > 20 ml/min per 1.73 m2 with or without diabetes. Talk to your doctor about whether a SGLT2 inhibitor could be right for you in protecting kidney function. (Pradda et. al)
SGLT2 inhibitors are not recommended for:
Adults with eGFR < 20 ml/min per 1.73 m2 or in kidney failure. When eGFR is this low, there is a higher risk side effects, such as low blood pressure, and risk further worsening of kidney function. (Zoungas et. al)
Kidney transplant recipients, though the INFINIT2019 trial is currently investigating the use and safety of SGLT2 inhibitors in this group
Though SGLT2 inhibitors are FDA approved for adults with kidney disease, this is not yet the case for children. In June 2023, the FDA approved SGLT2 inhibitor empagliflozin for diabetes in children (not kidney disease).
Works Cited:
Zanoli L, Granata A, Lentini P, et al. Sodium-glucose linked transporter-2 inhibitors in chronic kidney disease. ScientificWorldJournal. 2015;2015:317507. doi:10.1155/2015/317507
Nespoux J, Vallon V. Renal effects of SGLT2 inhibitors: an update. Curr Opin Nephrol Hypertens. 2020;29(2):190-198. doi:10.1097/MNH.0000000000000584
Wheeler DC, Toto RD, Stefánsson BV, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021;100(1):215-224. doi:10.1016/j.kint.2021.03.033
Kana N. Miyata, Shao-Ling Zhang, John S.D. Chan. The Rationale and Evidence for SGLT2 Inhibitors as a Treatment for Nondiabetic Glomerular Disease. Glomerular Dis 1 April 2021; 1 (1): 21–33. https://doi.org/10.1159/000513659
Eli Lilly and Company Press Release regarding. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. doi:10.1056/NEJMoa2204233
Zoungas, Sophia; Polkinghorne, Kevan R. Are SGLT2 Inhibitors Safe and Effective in Advanced Diabetic Kidney Disease?. CJASN 15(12):p 1694-1695, December 2020. | DOI: 10.2215/CJN.16351020
Padda IS, Mahtani AU, Parmar M. Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. [Updated 2023 May 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576405/
Heerspink HJL, Cherney DZI. Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation. Clin J Am Soc Nephrol. 2021;16(8):1278-1280. doi:10.2215/CJN.02480221
