Assessing Renoprotective Effects of Empagliflozin and Telmisartan Combination Therapy in Non-albuminuric Diabetic Nephropathy: A Retrospective Cohort Study

TL;DR

This study found that combining empagliflozin and telmisartan may slow kidney function decline in people with non-albuminuric diabetic kidney disease.

Contribution

The study is the first to assess the renoprotective effects of empagliflozin plus telmisartan in non-albuminuric diabetic nephropathy.

Findings

Combination therapy slowed eGFR decline by +1.03 mL/min/1.73 m2/year compared to telmisartan alone.

Only 5% of the combination group experienced renal progression versus 10% in the telmisartan-only group.

Incident albuminuria occurred in 8.3% of the combination group versus 13.3% in the telmisartan-only group.

Abstract

Background: Non-albuminuric diabetic kidney disease (DKD) can exhibit “silent” loss of estimated glomerular filtration rate (eGFR) despite normal urine albumin. We examined whether sodium-glucose cotransporter 2 (SGLT2) inhibition added to angiotensin receptor blockade is associated with slower eGFR decline in this phenotype.

Methods: In this retrospective cohort, adults with type 2 diabetes and a non-albuminuric DKD phenotype (urine albumin-to-creatinine ratio (UACR) <30 mg/g on serial testing, with prespecified evidence supporting DKD when baseline eGFR was 60-89 mL/min/1.73 m2) were grouped as concurrent empagliflozin plus telmisartan (n=60) or telmisartan-based care without any SGLT2 inhibitor (n=60). The primary outcome was annualized eGFR slope estimated from repeated measures using weighted linear mixed-effects models.

Results: The analytic cohort included 120 adults with non-albuminuric DKD (empagliflozin + telmisartan, n=60; telmisartan without any SGLT2 inhibitor, n=60). After inverse probability of treatment weighting (IPTW), covariate balance was acceptable (all standardized mean differences <0.10). In weighted linear mixed-effects models, the annualized eGFR slope (negative values indicate decline) was -1.15 mL/min/1.73 m2/year in the empagliflozin + telmisartan group and -2.18 mL/min/1.73 m2/year in the telmisartan-only group, yielding a between-group difference of +1.03 mL/min/1.73 m2/year (slower decline with combination therapy). For event-based outcomes, renal progression occurred in 3/60 (5.0%) with empagliflozin + telmisartan versus 6/60 (10.0%) with telmisartan-only (hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.12-2.06). Incident albuminuria occurred in 5/60 (8.3%) versus 8/60 (13.3%), respectively (odds ratio (OR) 0.59, 95% CI 0.18-1.88).

Conclusions: Combination therapy was associated with slower longitudinal eGFR loss, while event-based outcomes were imprecise, supporting larger prospective validation in normoalbuminuric DKD.