Real-world data show kidney benefit of initiating SGLT2i vs. other glucose-lowering drugs in T2DM
Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study
Introduction and methods
Large clinical trials on the new class of glucose-lowering drugs SGLT2 inhibitors (SGLT2i) have demonstrated a substantial reduction of risk of hospital admission for HF and a slowed progression of kidney function decline in patients with type 2 diabetes (T2DM) with or without chronic kidney disease [1-4]. The CVD-REAL study showed that the benefits of SGLT2i were also seen in a large, broad patient population with T2DM treated in daily clinical practice [5-7]. To date, it was unknown whether the kidney benefits of treatment with SGLT2i seen in clinical trials would also translate to clinical practice.
Nowadays, large clinical practice data sources are available with records of a broad range of clinical data. This allows assessment of the association between SGLT2i use and kidney function in a real-world practice setting. The CVD-REAL 3 study compared the associations between initiation of SGLT2i and other glucose-lowering treatment and the rate of eGFR decline and kidney outcomes in patients with T2DM in Israel, Italy, Japan, Taiwan and the United Kingdom (UK). All available SGLT2i were considered, meaning dapagliflozin and empagliflozin in all countries, plus canagliflozin in Italy, Japan and the UK, and ipragliflozin, tofogliflozin and luseogliflozin in Japan.
Included patients had at least two eGFR measurements before the index date of treatment initiation, with at least one eGFR measurement within the 180 days of the index date. The time span between the first and last eGFR measurement before the index data should be at least 180 days. 43,429 individuals who started SGLT2i treatment and 237,605 who initiated other glucose-lowering drugs, were included in this study. Individuals in the two treatment groups were propensity-matched. Mean follow-up time was 14.9 months for both treatment types. The main outcome was the rate of change in eGFR from initiation of SGLT2i or other glucose-lowering drug treatment.
- Before treatment, the SGLT2i group showed a mean annual rate of eGFR change of -0.73 mL/min/1.73m² and those in the other treatment group of -0.75 mL/min/1.73m².
- After initiation of therapy, the mean annual eGFR change was 0.46 mL/min/1.73m² in those starting SGLT2i and 01.21 in those starting other therapies. The between-group difference in the rate of eGFR decline was 1.53 mL/min/1.73m² per year (95%CI: 1.34-1.72, P<0.0001), favoring SGLT2i.
- The between-group difference in the rate of eGFR decline was similar across HbA1c and eGFR subgroups, and did not depend on presence or absence of CV disease or concomitant treatment with diuretics or ACEi or ARBs.
- A composite endpoint of a sustained reduction in eGFR of 50% or more or end-stage kidney disease (ESKD) occurred at rates of 3.0 and 6.3 per 10.000 patients-years for SGTL2i or other drugs, respectively. This resulted in a 51% lower risk with SGLT2i (HR: 0.49, 95%CI: 0.35-0.67, P<0.0001).
- SGLT2i use relative to treatment with other drugs was associated with a lower risk of a confirmed 57%, 50% and 40% eGFR decline, as well as a lower risk of hospital admission for HF and all-cause mortality.
This study in real-world clinical practice data sources of over 65,000 patients showed that initiation of SGLT2i, compared with other glucose-lowering drugs, was associated with a significantly lower rate of eGFR decline. The risk of a clinically relevant composite renal endpoint was also reduced. Results were consistent across the five countries in different geographic regions, and across subgroups based on baseline eGFR or HbA1c, or presence of CVD. Thus, these results suggest that SGLT2i are able to slow progression of chronic kidney disease in patients with T2DM, also in real-world daily clinical practice.