Biomarker panel predicts SGLT2 inhibitor response

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to lower cardiovascular (CV) risk in both patients with and without diabetes. An analysis of the CANVAS trial suggested that a biomarker assay can identify patients that benefit most from therapy.

Circulating biomarkers reflecting different mechanistic pathways may offer insights into how SGLT2 inhibitors reduce CV risk. “We undertook a secondary analysis of the CANVAS trial to understand whether the use of a multimarker panel may not only identify those at highest risk but also identify patients that may benefit from SGLT2 inhibitors,” explained Dr Muthiah Vaduganathan (Brigham and Women´s Hospital, MA, USA) [1].

The CANVAS study (NCT01032629) evaluated the effect of canagliflozin compared with placebo on CV events, including CV death, heart attack, and stroke, in patients with type 2 diabetes whose diabetes was poorly controlled and who had a history of CV events or a high risk of CV events [2]. The biomarker panel used in the current analysis was designed based on 3,040 CANVAS participants. Measured were concentrations of cardiac troponin T by high-sensitivity assay (hs-cTnT), soluble suppression of tumorigenesis-2 (sST2), and insulin-like growth factor-binding protein 7 (IGFBP7). These biomarkers represent myocardial injury (hs-cTNT), vascular congestion (sST2), or acute kidney injury (IGFBP7). Patients were assigned 1 point for every elevated biomarker.

Overall, 36% of the participants had no elevated biomarkers, 35% had 1 elevated biomarker, 27% had 2, and 2% had 3 elevated biomarkers. The higher the biomarker level, the poorer the patients' prognosis. “We found that while the benefit [of SGLT2 inhibitor treatment] with regard to heart failure and kidney events were consistent irrespective of the biomarker score, benefits with regard to major adverse CV events appeared to be greatest in those with multiple abnormal biomarkers,” Dr Vaduganathan said. He concluded that this hypothesis should be tested further in ongoing and completed trials with SGLT2 inhibitors.

1. 
   
   1. Vaduganathan M. Multi-marker biomarker panel, adverse cardiovascular and kidney outcomes, and response to canagliflozin in the CANVAS Program. Heart Failure and World Congress on Acute Heart Failure 2021, 29 June–1 July.
   2. Neal B, et al. New Engl J Med 2017;377:644­–57.

 

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Posted on 19 August, 202122 February, 2024