(054) Initiation of SGLT2i vs GLP1-RA and the Risk of Acute Kidney Injury in Persons with Type 2 Diabetes Mellitus

Background: Adverse kidney outcomes, including acute kidney injury (AKI), are frequent complications in people with type 2 diabetes mellitus (T2DM). In placebo-controlled randomized trials, both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown efficacy in preventing kidney outcomes; however, no trial has compared the kidney protective effects of these drug classes head-to-head.

Objectives: To conduct an emulated target trial comparing the risk of AKI between SGLT2i and GLP1-RA. Mortality was a secondary endpoint.

Methods: Using data from nationwide Danish population-based registries, we included all adults with T2DM initiating SGLT2i or GLP1-RA in 2015-2020. Patients with prevalent kidney failure, and patients initiating GLP1-RA marketed specifically for treatment of obesity were excluded.
We assessed demographic and diabetes-related baseline characteristics along with comorbidities and comedication. We estimated propensity scores using logistic regression and computed stabilized inverse probability of treatment (sIPT) weights to reduce confounding. We followed patients from treatment initiation until the first of death, emigration, or end of follow-up (31 December 2021), using all creatinine measurements from general practice, in- and outpatient settings to identify AKI during follow-up. Using an intention to treat approach, we estimated the 5-year sIPT weighted risks and risk differences (RDs) of AKI and death using the Aalen-Johansen estimator, comparing SGLT2i to GLP1-RA. We computed confidence intervals (CIs) by bootstrapping.

Results: We included 67,983 individuals (65% initiated SGLT2i), which we followed for a median of 2.8 years. Initiators of SGLT2i were slightly older (median age 63 vs 62 years) and more often male (63% vs 57%) than initiators of GLP1-RA, but with similar median diabetes duration (7 years). Compared to GLP1-RA, fewer initiators of SGLT2i had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at baseline (10% vs 18%), more SGLT2i initiators used metformin (91% vs 84%), and fewer used insulin (11% vs 28%). Initiators of SGLT2i had a lower prevalence of diabetes-related comorbidities than initiators of GLP1-RA. Each variable was well balanced after sIPT weighting.
The 5-year sIPT weighted risk of AKI was 17.0% for initiators of SGLT2i, and 19.1% for initiators of GLP1-RA, corresponding to a reduced risk comparing SGLT2i to GLP1-RA (RD -2.1% (95% CI: - 3.0% to -1.2%)). The sIPT weighted mortality risks were similar in the two groups (SGLT2i: 10.3%, GLP1-RA: 9.7%; RD 0.6% (95% CI: -0.1% to 1.4%)).

Conclusions: People with DMT2 who initiated SGLT2i had a slightly lower 5-year risk of AKI and similar all-cause mortality than those initiating GLP1-RA.