GLP-1 drugs and SGLT-2 inhibitors linked to slower kidney decline

The diabetes drugs glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose cotransporter 2 (SGLT-2) inhibitor drugs may also help to slow decline in kidney function in people with type 2 diabetes and albuminuria (high protein levels in the urine), finds a large US study published by The BMJ today.

However, for those without albuminuria, other diabetes drugs (sulfonylureas) led to faster decline in kidney function, highlighting the importance of considering albuminuria when making treatment decisions, say the authors.

Previous studies have shown that GLP-1 receptor agonists and SGLT-2 inhibitors can lower the risk of chronic kidney disease (CKD) progression in people with type 2 diabetes, and suggest that this may be more pronounced among those with greater degrees of albuminuria.

But it's not known whether people without albuminuria taking these drugs experience a similar degree of protection from CKD.

To address this, researchers analyzed health records and insurance claims data for people with type 2 diabetes at moderate risk of cardiovascular disease who started treatment with a GLP-1 receptor agonist or SGLT-2 inhibitor, a sulfonylurea, or a dipeptidyl peptidase-4 (DPP-4) inhibitor after metformin treatment between 2014 and 2022.

A total of 75,455 individuals were included in the analysis (average age 60; 48% women) of whom 61,583 (82%) did not have albuminuria. They were monitored for an average of 32 months, during which time decline in kidney function was assessed using recognized blood tests.

For people with albuminuria, the estimated five year risk of decline in kidney function was 3.2% for GLP-1 receptor agonists or SGLT-2 inhibitors, 4.6% for sulfonylureas, and 5.4% for DPP-4 inhibitors. This represents a 40% lower risk of renal deterioration among people treated with GLP-1 receptor agonists or SGLT-2 inhibitors compared with DPP4 inhibitors.

For people without albuminuria, the estimated five year risk of decline in kidney function was 2.4% for GLP-1 receptor agonists or SGLT-2 inhibitors, 2.8% for sulfonylureas, and 2.1% for DPP-4 inhibitors. This represents a 31% increased risk of renal deterioration among people treated with sulfonylureas compared with DPP4 inhibitors.

The authors acknowledge several study limitations and point out that while target trial emulation is one of the most rigorous approaches for analysing observational data, it is not immune to bias so the findings should still be interpreted with caution.

The authors acknowledge several limitations including a relatively short follow-up period and the possibility that other unmeasured factors may have influenced their results. However, they say the study drew on rich clinical data from a large US population and used an approach that minimizes common sources of bias in observational analyses.

As such, they conclude: "Compared with DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors reduce the risk of deterioration of renal function in people with albuminuria. Little evidence of renal benefit among people without albuminuria was observed over the study follow-up period."