SGLT2 inhibitors show renal benefits vs GLP-1 RAs in T2D patients in the real world

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are superior to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing renal outcomes among patients with type 2 diabetes (T2D) in Hong Kong, a real-world population-based study by the University of Hong Kong has shown.

To date, there has been a lack of head-to-head clinical trials comparing renal effects between SGLT2 inhibitors and GLP-1 RAs. Although network meta-analyses and a large-scale cohort study are available, the results were limited by different definitions of kidney events used in the studies, the absence of patient-level data, or missing values of estimated glomerular filtration rate (eGFR) and albuminuria status. [Diabetes Res Clin Pract 2022;183:109146; BMJ 2021;372:m4573; Diabetes Obes Metab 2021;24:473-485]

“Direct comparison [of SGLT2 inhibitors and GLP-1 RAs] is essential for optimizing the use of antidiabetic agents in reducing kidney outcomes. Hence, we conducted this population-based analysis of T2D patients who were started on SGLT2 inhibitors or GLP-1 RAs,” the researchers stated. [EClinicalMedicine 2022;50:101510]

The researchers retrieved electronic medical records of T2D patients managed in the Hospital Authority between January 2008 and December 2020. The propensity score–matched cohort included 5,102 T2D patients (mean age, 56.2 years; male, 56.0 percent; mean body mass index, 30.0 kg/m²; mean eGFR, 78.0 mL/min/1.73 m²) with a long history of diabetes (mean, 13.9 years) and suboptimal glycaemic control (mean HbA_1c, 8.9 percent) who were started on SGLT2 inhibitors (empagliflozin, 63.2 percent; dapagliflozin, 36.5 percent) or GLP-1 RAs (liraglutide, 47.1 percent; dulaglutide, 29.7 percent; exenatide, 18.9 percent). Most patients also received metformin (82.9 percent) and insulin (69.7 percent).

At a median follow-up of 13 months, SGLT2 inhibitor users had a significantly lower risk of the composite primary kidney outcome (ie, sustained eGFR decline ≥50 percent, incident end-stage kidney disease [ESKD], incident macroalbuminuria and kidney-related mortality) than GLP-1 RA users (hazard ratio [HR], 0.771; 95 percent confidence interval [CI], 0.620–0.959; p=0.020). The renal benefits with SGLT2 inhibitors vs GLP-1 RAs were consistent across subgroups, including age, gender, baseline eGFR, baseline albuminuria status and baseline HbA_1c.

The reduction in risk of the composite kidney outcome with SGLT2 inhibitors was mainly driven by a decreased risk of incident ESKD (HR, 0.532; 95 percent CI, 0.328–0.862; p=0.010). However, there was no significant between-group difference in the risk of sustained eGFR decline ≥50 percent (HR, 0.817; 95 percent CI, 0.592–1.127; p=0.219). The results also showed a trend towards a lower risk of incident macroalbuminuria (HR, 0.743; 95 percent CI, 0.551–1.003; p=0.052) with SGLT2 inhibitors.

The discrepancy in results between incident ESKD and sustained eGFR decline ≥50 percent might be associated with patients’ renal function. The proportion of patients with eGFR <30 mL/min/1.73 m² who reached ESKD without or before sustained eGFR decline ≥50 percent was higher with GLP-1 RAs vs SGLT2 inhibitors (9.77 percent vs 4.13 percent).

Furthermore, SGLT2 inhibitor users had slower eGFR decline vs GLP-1 RA users (-1.186 mL/min/1.73 m²/year vs -1.947 mL/min/1.73 m²/year; p<0.01), despite the acute dip in eGFR during the first month of SGLT2 inhibitor treatment. Among patients with baseline eGFR <60 mL/min/1.73 m², SGLT2 inhibitor users had insignificant decline in eGFR (-0.036 mL/min/1.73 m²; p=0.921) throughout the study period, whereas GLP-1 RA users showed significant eGFR decline (-1.256 mL/min/1.73 m², p<0.001).

“This is the largest real-world, population-based study allowing head-to-head comparison between SGLT2 inhibitors and GLP-1 RAs, … [providing] new evidence which may weigh SGLT2 inhibitors over GLP-1 RAs in clinical practice for T2D patients with the need for kidney protection,” the researchers concluded.