Sodium-Glucose Cotransporter-2 Inhibitors for People With Chronic Kidney Disease and Diabetes

Are sodium-glucose cotransporter-2 (SGLT-2) inhibitors effective in reducing complications for people with chronic kidney disease (CKD) and type 2 diabetes?

SGLT-2 inhibitors reduce the mortality risk in people with any stage CKD and type 2 diabetes (number needed to treat [NNT] to prevent one death in 1 year = 119).¹ (Strength of Recommendation [SOR]: B, inconsistent or limited-quality patient-oriented evidence.) Although it is unclear whether SGLT-2 inhibitors reduce major adverse cardiac events, they reduce the risk of kidney failure (NNT to prevent one case of kidney failure = 35) and kidney composite outcomes (NNT to prevent one negative outcome = 32). (SOR: B, inconsistent or limited-quality patient-oriented evidence.) SGLT-2 inhibitors also may decrease doubling of serum creatinine and albuminuria progression. (SOR: C, consensus, disease-oriented evidence, usual practice, expert opinion, or case series.) SGLT-2 inhibitors may be effective in reducing the risk of some other complications for patients with CKD and type 2 diabetes; however, more studies are needed to better inform treatment decisions.

More than 38 million adults in the United States have type 2 diabetes.² Diabetes is the leading cause of end-stage kidney disease requiring dialysis or kidney transplantation. Treatment of diabetes with SGLT-2 inhibitors potentially reduces cardiovascular and renal complications.³ However, these drugs may cause adverse effects, such as volume depletion, genital infections, and ketoacidosis. The objective of this Cochrane review was to determine the benefits and harms of SGLT-2 inhibitors for people with CKD and diabetes.¹ Past reviews have concluded that SGLT-2 inhibitors reduce cardiovascular events and adverse kidney outcomes for patients with diabetes; however, those reviews did not include individuals with stage 1 or 2 CKD (estimated glomerular filtration rate [eGFR] of 60 mL/min/1.73 m² or greater) or people with type 1 diabetes.

This Cochrane review included 53 randomized controlled trials (N = 65,241).¹ Studies were conducted between 2012 and 2022 with a median follow-up of 45 weeks. Most studies in this review compared SGLT-2 inhibitors with placebo. No studies included patients receiving dialysis, and only two studies included people with type 1 diabetes. Most studies were multinational, taking place in Austria, China, Denmark, Japan, Thailand, the Netherlands, and the United States. Fifteen studies included people with CKD stages 1 and 2 (eGFR of 60 mL/min/1.73 m² or greater), and 13 studies involved people with CKD stages 3 to 5 (eGFR of less than 60 mL/min/1.73 m²); the remaining studies focused on people with CKD stages 1 to 5.

SGLT-2 inhibitors included bexagliflozin (Brenzavvy), canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and sotagliflozin (Inpefa); however, the authors did not evaluate comparative effectiveness of different treatment dosages.¹ Ipragliflozin, licogliflozin, luseogliflozin, and tofogliflozin were also included, but these drugs are not approved for use in the United States. Drug titration schedules were not uniformly reported. SGLT-2 inhibitors alone or as part of a multidrug regimen were compared with placebo, standard care alone (not otherwise defined), sulfonylureas, dipeptidyl-peptidase-4 inhibitors, or insulin. The main outcomes included all-cause death; 3-point major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke); 4-point major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure); kidney composite outcome (reported as kidney failure, kidney death, with or without 40% or greater decrease in eGFR); kidney failure (eGFR of less than 15 mL/min/1.73 m², dialysis, or kidney transplantation); severe hypoglycemia (defined as hypoglycemia requiring third-party assistance); and diabetic ketoacidosis.