Japan: Proteinuria regression with canagliflozin treatment in patients with T2DM (type 2 diabetes mellitus) and chronic heart failure (CHF) is associated with the pretreatment insulin level, says a new study published in Diabetes, Obesity and Metabolism.
"These results may provide clinicians with novel mechanistic insights into canagliflozin's beneficial effects on renal outcomes," the researchers wrote. "They may warrant discussion for selecting preferred patients profiles, including pretreatment insulin levels."

In patients with type 2 diabetes and concomitant chronic disease, there is an increased prevalence of heart failure linked with significant morbidity and mortality. Canagliflozin is an SGLT2 (sodium-glucose cotransporter 2) inhibitor that reduces the risk of cardiovascular events.
The non-glycemic effects of SGLT2 inhibitors, such as reduction in body weight, blood pressure, risk of CV and renal events, and excess plasma fluid, have been shown in many studies have been demonstrated in many trials. Those cardiovascular outcomes trials, however, included few participants with concomitant heart failure, and their HF types were not phenotypes.
Satoshi Yamaguchi, Fukushima Medical University School of Medicine, Fukushima, Japan, and colleagues aimed to investigate factors associated with proteinuria regression in patients with type 2 diabetes treated with canagliflozin.
For this purpose, they performed a post hoc analysis of the CANDLE trial. The CANDLE trial compared the effect of 24 weeks of canagliflozin or glimepiride treatment for changes in N-terminal pro-brain natriuretic peptide in patients with T2DM and chronic heart failure. Factors linked with proteinuria regression at 24 weeks were evaluated.
The authors reported the following findings:
The proteinuria regression rate was higher (27.5% versus 10.7%), and that of progression was lower (8.8% versus 23.2%) in the canagliflozin versus the glimepiride group.
The researchers found no differences in the change in the estimated glomerular filtration rate category between groups.
At 24 weeks, homeostatic model assessment of β-cell function, insulin level, homeostatic model assessment for insulin resistance and estimated plasma volume were decreased in the regression subclass but not in the progression subclass, suggesting proteinuria regression is associated with the declines in these values in the canagliflozin group.
Higher insulin level at baseline was solely associated with proteinuria regression in the multivariate logistic regression model (baseline insulin, as per a 1-mlU/L increase, odds ratio 1.24).
Among patients with type 2 diabetes accompanying chronic heart failure, proteinuria regression with canagliflozin treatment was linked with pretreatment insulin level.
Reference:
Yamaguchi S, Shimabukuro M, Tanaka A, Imai T, Hiramitsu S, Takahashi N, Kadokami T, Ajioka M, Suzuki M, Node K; CANDLE Trial Investigators. Canagliflozin reduces proteinuria by targeting hyperinsulinaemia in diabetes patients with heart failure: A post hoc analysis of the CANDLE trial. Diabetes Obes Metab. 2023 Feb;25(2):354-364. doi: 10.1111/dom.14876. Epub 2022 Oct 23. PMID: 36193841.