Can SGLT2 Inhibitors Slow Progression of Renal Disease?

A new class of oral diabetes drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors slowed the progression of renal disease over 2 years, according to a new study.

“Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA_1c [glycated hemoglobin], body weight, BP [blood pressure], and albuminuria, implying that canagliflozin confers renoprotection,” the researchers said.

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They sought to determine whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin. Participants were randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg. The study’s end points were annual change in estimated glomerular filtration rate (eGFR) and albuminuria over 2 years of follow-up.

The glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 mL/min per 1.73 m² per year (95% confidence interval [CI], 2.8-3.8), 0.5 mL/min per 1.73 m² per year (95% CI, 0.0-1.0), and 0.9 mL/min per 1.73 m² per year (95% CI, 0.4-1.4), respectively (P<.01 for each canagliflozin group vs glimepiride).

In the subgroup of patients with a baseline urinary albumin-to-creatinine ratio of 30 mg/g or greater, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6%-48.9%; P=.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9%-62.2%; P<.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA_1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years.

“Canagliflozin may offer a novel therapeutic option for patients with type 2 diabetes who are at a high risk of kidney failure,” the researchers concluded, noting a longer follow-up period would be required to completely characterize the effects of the drug on long-term kidney function decline.

—Mike Bederka

Reference:

Heerspink HJL, Desai M, Jardine M, Balis D, Meininger G, Perkovic C. Canagliflozin slows progression of renal function decline independently of glycemic effects [published online August 18, 2016]. J Am Soc Nephrol. doi:10.1681/ASN.2016030278.