Table 1.

Recommendations for prescribing SGLT2i therapy in CKD

Indications

•Congestive heart failure (eGFR >20 ml/min per 1.73 m2) •Established ASCVD or high risk for ASCVD in patients with T2DM (eGFR ≥30 ml/min per 1.73 m2) •CKD with or without T2DMa, with eGFR ≥20 ml/min per 1.73 m2 and UACR ≥200 mg/g •As an additional therapy with ACEi/ARBs at maximum tolerated dose of SGLT2i •To be prescribed in the earlier CKD stages to improve clinical outcomes.

Uncertain indications

•T1DM •eGFR <20 ml/min per 1.73 m2 (maybe continued till patient requires dialysis) •Insufficient evidence of use in polycystic kidney disease, lupus nephritis, vasculitides, and type 1 DKD •No clear evidence for discontinuation during AKI unless contraindicated based on concerns about efficacy or the pill count. In that case, treatment should be resumed at the earliest.b

Key practice points:

•Because there is no evidence of a graded dose response, titrating to a higher dose is not necessary for maximizing the cardiorenal benefits. Notably, though a higher dose of SGLT2i may improve glycemic control, the glucose-lowering effect of SGLT2i decreases at lower eGFR levels. •SGLT2i should be initiated at the lowest recommended daily dose: canagliflozin 100 mg, dapagliflozin 10 mg, empagliflozin 10 mg, or ertugliflozin 5 mg. •SGLT2is can be safely used in patients with CKD stages 1 to 4. •Initiation of SGLT2i therapy may lead to reversible decline in the eGFR and is generally not an indication to discontinue treatment. •No need for monitoring of renal function parameters and electrolytes at 1 month after initiating SGLT2i beyond what is performed in general clinical practice for patients with eGFR ≥20 to <45 ml/min per 1.73 m2, UACR <200 mg/g, heart failure, and risk of volume depletion with concomitant use of RAAS blockers and loop diuretics. •Consult diabetologist if there is confusion on the etiology of diabetes (T1DM, LADA, secondary diabetes due to pancreatitis) or if patient is taking multiple insulin injections or presenting significant glycemic imbalance (HbA1c >9%) •No consultation needed if the patient is only treated with drugs that do not induce hypoglycemia (metformin, DPP-4i, GLP-1 RA) or no significant alteration of glycemic control is required. •If the patient is already being treated with drugs inducing hypoglycemia (SU, glinides, insulin), it is necessary to consult diabetologist for adjustment of doses of these drugs. •SGLT2i reduce HbA1c levels by a mean of 0.7% in patients with eGFR >60 ml/min per 1.73 m2. • Physicians must check HbA1c levels before prescribing SGLT2i: ○ If HbA1c >8%, dose reduction of hypoglycemic drugs usually not necessary ○ If HbA1c is 7% to 8%, reduce the dose of SU or glinide by 50% and insulin dose by 10%; self-monitoring of blood glucose. •If HbA1c <7%, SU or glinide can be discontinued and insulin dose reduction by 20%, self-monitoring of blood glucose. Initiation of SGLT2is is associated with a reduced risk of AKI in comparison to initiation of other anti-glycemic agents.c •In case of nondiabetic patients detecting glucosuria is a simple parameter to assess therapy adherence when urine dipstick is available, due to resource constraints in many African countries, this may not be sustainable in the long term. Furthermore, a reduced renal threshold for glycosuria in some patients may negate this.

ACEi, angiotensin-converting enzyme inhibitors; ASCVD, atherosclerotic cardiovascular disease; ARB, angiotensin receptor blockers; CKD, chronic kidney disease; DKD, diabetic kidney disease; DPP-4i, dipeptidyl peptidase-4 inhibitors; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycosylated hemoglobin; LADA, late onset diabetes of adulthood; RAAS, renin-angiotensin aldosterone system; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SU, sulfonylureas; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; UACR, urine albumin-to-creatinine ratio.

^aNondiabetic kidney disease includes ischemic nephropathy, IgA nephropathy, FSGS, chronic pyelonephritis, chronic interstitial nephritis.

^bCarriazo S, Ortiz A. Stopping kidney protection in the elderly following acute kidney injury: think mortality. Clinical Kidney Journal. 2022 Jun;15(6):1037; Meraz-Muñoz AY, Weinstein J, Wald R. eGFR Decline after SGLT2 Inhibitor Initiation: The Tortoise and the Hare Reimagined. Kidney360. 2021 Jun 24;2(6):1042–7.

^cZhuo M, Paik JM, Wexler DJ, Bonventre JV, Kim SC, Patorno E. SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults with Type 2 Diabetes. Am J Kidney Dis. 2022 Jun;79(6):858-867.e1. doi:10.1053/j.ajkd.2021.09.015.