ACP Journal Club: SGLT-2 inhibitors reduce adverse renal and CV outcomes in patients with or without diabetes

The results of this meta-analysis of sodium-glucose cotransporter-2 (SGLT-2) inhibitors highlight the opportunity for internists, nephrologists, endocrinologists, and cardiologists to collaborate to expand use of the drug class, an ACP Journal Club commentary said.

A large meta-analysis looked at the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on chronic kidney disease (CKD) progression, as well as cardiovascular (CV) outcomes. It included participants from 13 randomized controlled trials (RCTs), 82.7% with diabetes, and found that SGLT-2 inhibitors reduced the risk of CKD progression to a similar extent whether or not patients had diabetes. Risk of acute kidney injury or CV death was also lower in patients taking SGLT-2 inhibitors versus those on placebo.

The study was published online by The Lancet on Nov. 6, 2022, and summarized in the November ACP Diabetes Monthly. The following commentary by Tejas Patel, MD, was published in the ACP Journal Club section of Annals of Internal Medicine on March 7.

In addition to reducing hyperglycemia, SGLT-2 inhibitors or gliflozins have unexpectedly delayed progression of diabetic nephropathy. Whereas this drug class has revolutionized the care of patients with both CKD and type 2 diabetes, it is important to establish if it confers benefit in patients with CKD who do not have diabetes. A collaborative meta-analysis, which included >90,000 patients from >12 RCTs, assessed effects in patients with CKD but without diabetes.

Most patients in the studies in the meta-analysis also used renin–angiotensin system (RAS) inhibitors. It is unclear how patients would fare if they did not take RAS inhibitors (e.g., due to intolerance or allergy). In addition, some patient subgroups with kidney disease were excluded from the largest renal trials, specifically renal transplant recipients and those with autosomal dominant polycystic kidney disease. Further, safety of SGLT-2 inhibitors in patients with CKD and type 1 diabetes remains to be determined. Despite these caveats, the meta-analysis confirmed that SGLT-2 inhibitors reduce CKD progression, acute kidney injury, and CV death, regardless of diabetes status. There were no new safety signals.

SGLT-2 inhibitors are the first class of agents added to treatment options for CKD since the benefits of RAS inhibitors were identified about 25 years ago. Where do we go from here given these consistent, robust data? The nephrology community sees this as an opportunity to collaborate with internists, endocrinologists, and cardiologists to expand SGLT-2 inhibitor use, even in patients with low glomerular filtration rates, and to continue use at least until patients start dialysis. Barriers to prescribing SGLT-2 inhibitors include clinical inertia, variable coverage by payers, and patient hesitancy due to the asymptomatic nature of CKD. Identifying clinician-level barriers, negotiating value-based care with payers, and educating patients about improving target organ damage would help SGLT-2 inhibitors gain widespread acceptance.