Maddaloni E, Cavallari I, La Porta Y, et al. Impact of baseline kidney function on the effects of sodium-glucose co-transporter-2 inhibitors on kidney and heart failure outcomes: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2023 Jan 26. doi: 10.1111/dom.14986.

AIM: To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function.

METHODS: We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality.

RESULTS: Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is' renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.87, 95% CI: 0.56-1.34).

CONCLUSIONS: SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Internal Medicine
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Comments from MORE raters

Cardiology rater

These data confirm the established nephro-protective role of this class of drugs, showing confirmative consistent results with all included trials with no signs of heterogeneity.

Endocrine rater

Excellent meta-analysis of the most significant agents to come along for diabetics since insulin. The earlier they are started the better, but, if not, better late than never. Important information for clinical management that ought to be widely disseminated. Individual pieces of this story have been available in various journals and meetings for awhile, but it's good to have this well-thought-out package.

Internal Medicine rater

These results reflect the beneficial effects of SGLT2i on cardiac and renal function across the eGFR. It is very interesting that the effects on cardiac and renal function are toward the same direction, but the severity of renal dysfunction affects conversely the cardiac or renal outcomes.