medwireNews: People with type 2 diabetes and chronic kidney disease (CKD) are substantially less likely to initiate sodium-glucose cotransporter (SGLT)2 inhibitors than those with normal kidney function, despite their proven renoprotective benefits, research shows.
Specifically, in 2020 SGLT2 inhibitor initiation was three times less common in the first-line setting and six times less common in the second-line setting among people with versus without CKD, despite “evidence from landmark trials demonstrating cardiorenal benefits among patients with CKD, as well as multiple guidelines recommending their use,” write Chintan Dave (Rutgers University, New Brunswick, New Jersey, USA) and co-authors in Diabetes Care.
The temporal analysis of UK clinical practice data showed that metformin is still the most commonly prescribed medication among people with type 2 diabetes, with or without CKD, but its use has declined since 2006, with other drug classes becoming more common.
In particular, initiation of dipeptidyl peptidase (DPP)-4 inhibitors increased by 27.9 percentage points between 2006 and 2020 among people with CKD, while SGLT2 inhibitor use among people without CKD increased by 26.1 percentage points over the same period.
Among 38,622 patients with CKD, metformin initiation as a proportion of overall medication initiation fell significantly from 59.2% in 2006 to 28.4% in 2020, whereas DPP-4 inhibitor use increased significantly from 0.4% to 28.3%. SGLT2 inhibitor use increased from 0.5% to 9.4%, while the use of sulfonylureas increased from a baseline of around 27% to approximately 34% in 2008 then decreased and stabilized at around 20%.
In the 230,963 patients without CKD, metformin use fell significantly from 61.8% in 2007 to 34.1% in 2020, whereas SLGT2 inhibitor initiation increased significantly from 2.4% to 28.5%. DPP-4 inhibitor use also increased, from below 1% in 2006 to around 16% in 2020, while sulfonylurea use fell from around 20% to around 15% after an initial increase that peaked in 2008.
Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was below 5% throughout the study period in people with and without CKD.
The researchers also found that the choice of second-line therapy varied according to CKD status, with DPP-4 inhibitors replacing sulfonylureas as the treatment of choice among people with CKD from around 2015. For those without CKD, SGLT2 inhibitor initiation rates surpassed those for sulfonylurea in 2017 and for DPP-4 inhibitors in 2019.
Dave and co-authors comment: “Compared with DPP-4 [inhibitors], which have a neutral cardiorenal profile, and [sulfonylureas], which have an increased risk of hypoglycemia development in patients with CKD, both SGLT2 [inhibitors] and GLP-1RA confer significant advantages with respect to the prevention of deleterious cardiorenal events.”
They conclude: “As the landscape of diabetes management continues to shift from a glucocentric approach that prioritized reductions in [glycated hemoglobin] to one that considers long-term cardiorenal health, work is needed to identify and eliminate potential barriers associated with the uptake of SGLT2 [inhibitors] and GLP-1RA among patients with CKD.”
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