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No diabetes High atherosclerotic cardiovascular riska Mean eGFR: 80 mL/min/1.73m2 Kidney disease progression Acute kidney injury Cardiovascular death or hospitalization for heart failure Ketoacidosis Lower limb amputationb -2 -1 -5 0.3 0.6 -45 4 4 4 21 0.2 -15 -10 5 -5 0 -20 -25 -30 -35 -40 Events avoided or caused per 1000 patient-years in SGLT2i groups Placebo population mean event rate Events avoided or caused per 1000 patient-years in SGLT2i groups Placebo population mean event rate -6 -4 0.5 1.0 -45 16 23 6 148 0.5 -15 -10 5 -5 0 -20 -25 -30 -35 -40 -34 Stable heart failure Mean eGFR: 61 mL/min/1.73m2 7 17 1.0 104 -2 -5 c 0.0 -23 Mean eGFR: 64 mL/min/1.73m2 Events avoided or caused per 1000 patient-years in SGLT2i groups Placebo population mean event rate -11 -4 1.3 1.1 -45 29 19 7 47 1.2 -15 -10 5 -5 0 -20 -25 -30 -35 -40 -11 Chronic kidney disease Mean eGFR: 45 mL/min/1.73m2 48 16 0.6 11 -15 -5 c 0.0 -2 Mean eGFR: 40 mL/min/1.73m2 Diabetes Figure 19 Absolute benefits and harms of sodium–glucose co-transporter-2 inhibitors in patients with and without diabetes. eGFR, estimated glomerular filtration rate; RR, relative risk; SE, standard error; SGLT2i, sodium–glucose co-transporter-2 inhibitor. Patient group-specific absolute effects estimated by applying the diabetes sub-group-specific RR to the average event rate in the placebo arms (first event only). Negative numbers indicate events avoided by SGLT2 inhibition per 1000 patient-years. Error bars represent SE in the numbers of events avoided or caused, estimated from uncertainty in the RRs. Mean eGFR values are given for combined trial populations by patient group and diabetes status. Placebo population mean event rates are the absolute numbers of events per 1000 patient-years in the placebo groups of all trials in the relevant subpopulation. aAdditionally, two (SE 0.5) fewer myocardial infarctions per 1000 patient-years of SGLT2i treatment were observed in the diabetes and high atherosclerotic cardiovascular risk group. bRRs to determine absolute effects for lower-limb amputation included the CANVAS trial. cToo few ketoacidosis events to estimate absolute effects. Figure adapted from the Nuffield Department of Population Health Renal Studies Group and SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. This is an open access article distributed under the terms of the Creative Commons CC-BY License. https://creativecommons.org/licenses/by/4.0/714 Downloaded from academic.oup.com/eurheartj/article/44/39/4043/7238227 by guest on 07 October 2026