Key result
Initiation of canagliflozin based on a clinical multivariable risk model prevented 16.6 kidney events per 1000 patients treated for 5 years, significantly more than the 9.6 events prevented when guided by HbA1c alone.
Why the study?
SGLT2 inhibitors reduce kidney and heart failure events independent of glycemic effects, but whether initiating canagliflozin guided by multivariable predicted risk is more efficient than strategies guided by HbA1c or UACR alone remained unclear.
Does multivariable risk-guided initiation of canagliflozin prevent more kidney and heart failure outcomes compared to HbA1c or UACR-guided initiation in patients with type 2 diabetes?
Observational (n=3,713)
Double-blind
1:1:1
Yes
Does multivariable risk-guided initiation of canagliflozin prevent more kidney and heart failure outcomes compared to HbA1c or UACR-guided initiation in patients with type 2 diabetes?
Guiding the initiation of SGLT2 inhibitors using a multivariable clinical risk prediction model prevents significantly more kidney and heart failure events than using single markers like HbA1c or albuminuria.
Hypothesis-generating for risk-model guided canagliflozin; leaves open prospective validation before practice change.
Background Sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of kidney and heart failure events independent of glycemic effects. We assessed whether initiation of the SGLT2 inhibitor canagliflozin guided by multivariable predicted risk based on clinical characteristics and novel biomarkers is more efficient to prevent clinical outcomes compared to a strategy guided by HbA1c or urinary-albumin-creatinine ratio (UACR) alone. Methods We performed a post-hoc analysis of the CANVAS trial including 3713 patients with available biomarker measurements. We compared the number of composite kidney (defined as a sustained 40% decline in eGFR, chronic dialysis, kidney transplantation, or kidney death) and composite heart failure outcomes (defined as heart failure hospitalization or cardiovascular (CV) death) prevented per 1000 patients treated for 5 years when canagliflozin was initiated in patients according to HbA1c ≥ 7.5%, UACR, or multivariable risk models consisting of: (1) clinical characteristics, or (2) clinical characteristics and novel biomarkers. Differences in the rates of events prevented between strategies were tested by Chi 2 -statistic. Results After a median follow-up of 6.1 years, 144 kidney events were recorded. The final clinical model included age, previous history of CV disease, systolic blood pressure, UACR, hemoglobin, body weight, albumin, estimated glomerular filtration rate, and randomized treatment assignment. The combined biomarkers model included all clinical characteristics, tumor necrosis factor receptor-1, kidney injury molecule-1, matrix metallopeptidase-7 and interleukin-6. Treating all patients with HbA1c ≥ 7.5% (n = 2809) would prevent 33.0 (95% CI 18.8 to 43.3 ) kidney events at a rate of 9.6 (95% CI 5.5 to 12.6) events prevented per 1000 patients treated for 5 years. The corresponding rates were 5.8 (95% CI 3.4 to 7.9), 16.6 (95% CI 9.5 to 22.0) (P < 0.001 versus HbA1c or UACR approach), and 17.5 (95% CI 10.0 to 23.0) (P < 0.001 versus HbA1c or UACR approach; P = 0.54 versus clinical model). Findings were similar for the heart failure outcome. Conclusion Initiation of canagliflozin based on an estimated risk-based approach prevented more kidney and heart failure outcomes compared to a strategy based on HbA1c or UACR alone. There was no apparent gain from adding novel biomarkers to the clinical risk model. These findings support the use of risk-based assessment using clinical markers to guide initiation of SGLT2 inhibitors in patients with type 2 diabetes.
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Tye et al. (2022) conducted an observational in Type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors (n=3,713). Canagliflozin initiation guided by multivariable predicted risk (clinical model) vs. Canagliflozin initiation guided by HbA1c ≥ 7.5% alone was evaluated on Composite kidney outcome (sustained 40% decline in eGFR, end-stage kidney disease, or kidney death) (NNT 49.0, 95% CI 37.3 to 85.9, p=<0.001). Initiation of canagliflozin based on a clinical multivariable risk model prevented 16.6 kidney events per 1000 patients treated for 5 years, significantly more than the 9.6 events prevented when guided by HbA1c alone.
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