Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists Versus Other Glucose-Lowering Agents in People With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Data.
Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents.
We searched PubMed and Embase for observational cohort studies (April 2005-January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.
Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49-78 years, 5%-64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05-1.20]), kidney-related hospitalizations (1.66 [1.01-2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27-1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76-0.92]), kidney-related hospitalizations (0.73 [0.65-0.83]), and ESKD (0.70 [0.63-0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80-0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.
In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.
We searched PubMed and Embase for observational cohort studies (April 2005-January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.
Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49-78 years, 5%-64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05-1.20]), kidney-related hospitalizations (1.66 [1.01-2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27-1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76-0.92]), kidney-related hospitalizations (0.73 [0.65-0.83]), and ESKD (0.70 [0.63-0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80-0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.
In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.
Authors
Fishkin Fishkin, Rozenberg Rozenberg, Schechter Schechter, Sehtman-Shachar Sehtman-Shachar, Aharon-Hananel Aharon-Hananel, Leibowitz Leibowitz, Yanuv Yanuv, Mosenzon Mosenzon
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