SGLT2 inhibitors tied to kidney benefits, reduced MACE risk

Treatment with sodium-glucose lowering co-transporter 2 inhibitors (SGLT2i) helps arrest the decline in estimated glomerular filtration rate (eGFR) and is associated with a lower risk of adverse kidney events among adults with diabetes, irrespective of baseline albuminuria status, as shown in a study presented at the recent ADA 2023.

A team of researchers led by Kaden K Fujita from the University of Lethbridge in Calgary, Canada, carried out this retrospective cohort study to assess the effectiveness of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i).

Fujita and colleagues used administrative data to identify new users of SGLT2i (2014‒2018) with diabetes and eGFR ≥30 mL/min/1.73 m².

Participants were subsequently matched in a 1:2 ratio to DPP4i users by chronic kidney disease (CKD) stage, albuminuria, and diabetes therapy, and by time-conditional propensity-score (ie, age, sex, A1c, etc). Nonsevere albuminuria was defined as urine albumin to creatinine ratio ≤30 mg/mmol.

Linear and Poisson regression models were used to explore the relationship between SGLT2i use and each of the following outcomes: eGFR decline (acute [≤60 days] and total), adverse kidney events, and all-cause mortality. An adverse kidney event referred to sustained 40-percent loss of eGFR, initiation of kidney replacement therapy, or death from kidney causes.

Kidney events

A total of 19,238 SGLT2i users (mean age 57.9 years, 59.1 percent male) were identified, of whom 94.4 percent had nonsevere albuminuria. Their mean eGFR was 91.7 mL/min/1.73 m². The majority of these participants (62.0 percent) were prescribed an angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker. [ADA 2023, abstract 123-OR]

Over a median follow-up of 1.58 years, the acute change in eGFR was ‒2.79 with SGLT2i compared with ‒1.43 with DPP4i (difference, ‒1.36, 95 percent confidence interval [CI], ‒1.74 to ‒0.98; p<0.001). After 60 days, users of SGLT2i demonstrated lesser annual eGFR loss (0.83, 95 percent CI, 0.66‒1.01; p<0.001) compared with those on DPP4i.

In addition, use of SGLT2i resulted in fewer adverse kidney events (incidence rate ratio [IRR], 0.58, 95 percent CI, 0.47‒0.71; p<0.001), driven primarily by less sustained loss of eGFR, and does not appear to contribute to all-cause mortality (IRR, 0.82, 95 percent CI, 0.66‒1.01; p=0.06).

Notably, these findings were consistent in participants with nonsevere albuminuria.

“SGLT2i may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes, regardless of baseline albuminuria status,” the researchers said.

Cardiovascular events

Apart from these benefits, use of SGLT2i, when combined with a glucagon-like peptide-1 receptor agonist (GLP-1 RA), also contributes to a reduction in the risk of major adverse cardiovascular events (MACE) compared with SGLT2 monotherapy, according to another study presented at ADA 2023. [ADA 2023, abstract 268-OR]

Specifically, SGLT2i plus GLP-1 RA correlated with a 34-percent decrease in MACE risk (hazard ratio, 0.66, 95 percent CI, 0.48‒0.91) relative to SGLT2i alone. Secondary analyses also revealed a reduction in myocardial infarction risk with the combination therapy (HR, 0.64, 95 percent CI, 0.42‒0.98).