medwireNews: Real-world data suggest that the sodium-glucose cotransporter (SGLT)2 inhibitor empagliflozin is associated with estimated glomerular ﬁltration rate (eGFR) preservation, weight loss, and a reduced risk for major adverse kidney events when compared with other antihyperglycemics among people with type 2 diabetes.
Using an inverse weighting approach based on propensity scores to adjust for confounding, the investigators analyzed data from 52,535 patients initiating empagliﬂozin in the US Department of Veterans Affairs (VA) healthcare system between 2016 and 2019, and 52,850 new users of other non-SGLT2 inhibitor antihyperglycemics. At baseline, the mean age of patients was 65.63 years, 95.58% were men, and the mean eGFR was 77.41 mL/min per 1.73 m2.
Ziyad Al-Aly (VA St Louis Health Care System, Missouri, USA) and fellow researchers report in Diabetes Care that, on average, the use of empagliﬂozin was associated with an annual eGFR preservation of 0.99 mL/min per 1.73 m2, and a net 2.97 mL/min per 1.73 m2 of eGFR preserved after 3 years of follow-up compared with the use of other agents.
Both groups showed a decline in BMI during follow-up, and the reduction in the empagliﬂozin group was greater than that in the control group, at an average of 1.68 and 0.95 kg/m2, respectively, from corresponding baseline values of 34.06 and 34.17 kg/m2. The annual BMI decrease related to the use of empagliﬂozin was an additional 0.25 and 0.74 kg/m2, after 1 and 3 years, respectively.
Participants given empagliﬂozin were significantly less likely to experience major adverse kidney events (MAKE) – a composite of eGFR decline of more than 50%, end-stage renal disease, or all-cause mortality – than those in the control group group (hazard ratio [HR]= 0.68). In all, MAKE occurred in 4.39% of patients in the empagliflozin group and 6.89% of those in the control group; the adjusted rate difference was 14.99 fewer events per 1000 person–years with empagliflozin.
The study authors say that the protective association between empagliflozin use and renal outcomes “was observed regardless of baseline eGFR, regardless of albuminuria status, in people with and without cardiovascular disease, and in several other prespecified subgroups.”
When patients were categorized by eGFR, the HRs for MAKE associated with empagliflozin use were 0.70, 0.66, 0.78, and 0.71 for eGFR categories of 90 or higher, 60 to less than 90, 45 to less than 60, and 30 to less than 45 mL/min per 1.73 m2, respectively. In participants with no albuminuria, microalbuminuria, and macroalbuminuria the HRs were a corresponding 0.65, 0.72, and 0.74, and they were 0.67 and 0.76, respectively, for people with and without cardiovascular disease.
Al-Aly and co-investigators also note that empagliﬂozin was associated with renoprotective effects when each component of the composite outcome of MAKE was analyzed separately.
“Overall, our results suggest that the salutary kidney effect of SGLT2i observed in randomized clinical trials likely extends to broader populations in real-world settings,” conclude the authors.
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