1. SGLT2 inhibitors reduced the risk of kidney disease progression by 37% overall, with comparable effects in patients with and without diabetes.
2. SGLT2 inhibitors also reduced the risk of cardiovascular mortality in patients with and without diabetes.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Sodium glucose co-transporter-2 (SGLT2) inhibitors are a class of anti-hyperglycemic drugs which have been shown to have cardiovascular benefitz. Studies have also demonstrated that SGLT2 inhibitors reduce the risk kidney disease progression, but few of these studies evaluated patients without diabetes. This systematic review and meta-analysis analyzed the results from 13 large-scale double-blind trials comparing SGLT2 inhibitors in patients with and without diabetes. Compared to placebo, SGLT2 inhibitors were shown to reduce the risk of kidney disease progression by 37%. This risk reduction was similarly seen in patients with and without diabetes. SGLT2 inhibitors additionally reduced the risk of acute kidney injury and cardiovascular death, irrespective of diabetic status. The risk of adverse effects, such as ketoacidosis and amputation, were shown to be rare and outweighed by the benefits. A limitation of this study includes the lack of participant-level data from some of the included trials. Nevertheless, this study provides strong evidence for the use of SGLT2 inhibitors for reducing the risk of kidney disease progression for both patients with and without diabetes.
In-Depth [systematic review and meta-analysis]: A database search was conducted. Eligible trials included those that assessed SGLT2 inhibitors and were double-blind, placebo-controlled, large-scale (>500 participants in each arm), at least 6 months in duration, and were performed in adults (age ≥ 18 years). The primary outcome was kidney disease progression (defined as a sustained >50% decrease in eGFR, a sustained low eGFR, ESKD, or death from kidney failure). A total of 13 trials (n=90 413) were identified. There were 74 804 (82.7%) participants with diabetes and 15 605 (17.3%) without diabetes. SGLT2 inhibitors reduced the risk of kidney disease progression compared to placebo (RR 0.63, 95% CI 0.58-0.69). This reduction in risk was similar irrespective of diabetes status, primary kidney diagnosis, and baseline eGFR. For secondary outcomes, SGLT2 inhibitors additionally reduced the risk of acute kidney injury by 23%. The risk of cardiovascular death was also reduced (RR 0.86), but not the risk of non-cardiovascular death (RR 0.94). When looking at safety outcomes, the risk of ketoacidosis in patients with diabetes allocated to SGLT2 inhibitors was higher than those allocated to placebo (RR 2.12). Across all trials, SGLT2 inhibitors were associated with an increased risk of lower limb amputation by 15%, mainly driven by the results of one of the 13 trials included.
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