Kidney Outcomes with Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk

Dec 27, 2024Clinical journal of the American Society of Nephrology : CJASN

Kidney health in type 2 diabetes with moderate heart risk using four common diabetes medicines

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Abstract

A total of 364,714 adults with type 2 diabetes were analyzed, showing that sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) were superior to dipeptidyl peptidase-4 inhibitors (DPP-4is) and sulfonylureas (SUs) for preventing kidney complications.

SGLT2i therapy showed a hazard ratio of 0.71 for the primary kidney composite outcome compared to DPP-4i.
GLP-1RA therapy had a hazard ratio of 0.87 for the same outcome relative to DPP-4i.
Both SGLT2i and GLP-1RA treatments were associated with risk reductions for kidney complications compared to SU treatment.
When comparing SGLT2i to GLP-1RA, SGLT2i treatment was superior with a hazard ratio of 0.81 for the primary composite outcome.
Similar associations were observed for the secondary composite outcome across all treatment comparisons.

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KEY POINTS: Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists were superior to dipeptidyl peptidase-4 inhibitor and sulfonylurea for preventing kidney complications in patients with type 2 diabetes at moderate cardiovascular disease risk. Sodium-glucose cotransporter 2 inhibitor therapy compared favorably with glucagon-like peptide-1 receptor agonists for kidney disease outcomes.

BACKGROUND: CKD is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear.

METHODS: This retrospective observational study emulated an idealized target trial using claims data from OptumLabs data warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4i), SGLT2i, GLP-1RA, or sulfonylurea (SU) on a primary kidney composite outcome of incident CKD stages 3–5, kidney failure, or need for KRT in patients with type 2 diabetes and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death.

RESULTS: A total of 364,714 adults aged 21 years or older initiating treatment with a DPP-4i (=78,843), GLP-1RA (=42,049), SGLT2i (=45,466), or SU (=198,356) were identified. Relative to DPP-4i, SGLT2i (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.67 to 0.74;< 0.001) and GLP-1RA (HR, 0.87; 95% CI, 0.83 to 0.92;< 0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2i (HR, 0.69; 95% CI, 0.66 to 0.73) and GLP-1RA (HR, 0.86; 95% CI, 0.82 to 0.91) treatment was associated with risk reductions for the primary outcome relative to SU treatment. When comparing SGLT2i with GLP-1RA therapy, SGLT2is were superior for the primary composite outcome (HR, 0.81; 95% CI, 0.75 to 0.86;< 0.001). Similar findings were observed for the secondary composite outcome across all comparisons. N N N N P P P

CONCLUSIONS: SGLT2is and GLP-1RAs were superior to DPP-4is and SUs for preventing kidney complications in a type 2 diabetes population with moderate baseline CVD risk.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:: NCT05214573.

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Kidney Outcomes with Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk

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