August 23, 2016
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Canagliflozin may slow renal disease progression

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Canagliflozin, an SGLT2 inhibitor, may be more effective for slowing the progression of renal disease compared with glimepiride, a sulfonylurea, over 2 years in patients with type 2 diabetes, study data show.

Hiddo J.L. Heerspink , PhD, of the University Medical Center Groningen in the Netherlands, and colleagues conducted a secondary analysis of clinical trial data on 1,450 people with type 2 diabetes randomly assigned to canagliflozin (Invokana, Janssen) 100 mg (n = 483), canagliflozin 300 mg (n = 485) or glimepiride (n = 482) from Aug. 28, 2009, to Jan. 30, 2013. Researchers also evaluated a subgroup of participants with a urinary albumin-to-creatinine ratio of 30 mg/g or more (glimepiride, n = 76; cangliflozin 100 mg, n = 76; canagliflozin 300 mg, n = 78).

Compared with an annual slope of an estimated glomerular filtration rate (eGFR) decline of 3.3 mL/min per 1.73 m2 per year in the glimepiride group, the canagliflozin groups had declines of 0.5 mL/min per 1.73 m2 per year (100 mg group; P < .001 vs. the glimepiride group) and 0.9 mL/min per 1.73 m2 per year (300 mg group; P = .002 vs. the glimepiride group). In the subgroup of participants with urinary albumin-to-creatinine ratio of 30 mg/g or more, declines in eGFR were also lower in the canagliflozin groups compared with the glimepiride groups.

In the full cohort, 46 participants in the glimepiride group reached the endpoint of the 30% eGFR decline compared with 32 in the canagliflozin 100 mg group (HR = 0.66; 95% CI, 0.42-1.05) and 43 in the 300 mg group (HR = 0.93; 95% CI, 0.62-1.42). In the subgroup of participants with urinary albumin-to-creatinine ratio of 30 mg/g or more, the HRs were 0.37 (95% CI, 0.15-0.9) for the canagliflozin 100 mg group and 0.69 (95% CI, 0.33-1.45) for the 300 mg group compared with glimepiride for the endpoint of 30% eGFR decline.

The canagliflozin groups had greater reductions in HbA1c and changes in systolic blood pressure compared with the glimepiride group.

“Since glycemic control was only modestly different between cangliflozin and glimepiride, our results suggest that potential kidney protective effects of canagliflozin may be unrelated to glycemic control,” Heerspink said in a press release. “Our results are especially important since many patients with diabetes are at risk of progressive kidney function loss, and canagliflozin may offer a new and improved therapeutic opportunity for these patients.”

In an accompanying editorial, Ian de Boer, MD, and Steven Kahn, MD, ChB, both of the University of Washington in Seattle, wrote that SGLT2 inhibitors may also reduce cardiovascular events.

“The apparent renal and CV benefits of SGLT2 inhibitors will encourage primary care physicians and endocrinologists to use these agents more frequently in the care of patients with type 2 diabetes,” they wrote. “Of course, adverse effects, costs, alternative agents and individual patient characteristics must also be taken into account.” – by Amber Cox

Disclosure: Heerspink reports various financial ties with AbbVie, Astellas, AstraZeneca, Boehringer Ingeheim, Janssen and ZS Pharma. de Boer reports various financial ties with Abbvie, Amgen, Bayer, Boehringer Ingelheim, Ironwood, Janssen and Medtronic. Kahn reports various financial time with AstraZeneca, Boehringer Ingelheim, Elcelyx, Eli Lilly, GlaxoSmithKline, Janssen, Intarcia, Merck, Novo Nordisk and Receptos. Please see the full study for a list of all other authors’ relevant financial disclosures.