“Strongly consider an SGLT2-inhibitor in most T2DM patients”

 

Data from 2 large clinical trials showed new benefits of the dual sodium-glucose cotransporter 1 and 2 (SGLT1/SGLT2) inhibitor sotagliflozin for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease as well as those with T2DM and recently worsening heart failure (HF). Both trials were terminated early due to COVID-19-related loss of funding.

Prof. Deepak Bhatt (Brigham and Women’s Hospital, USA) presented results of the SOLOIST-WHF trial (NCT03521934) as well as the SCORED trial (NCT03315143), both of which tested sotagliflozin [1,2]. Results were simultaneously published in the New England Journal of Medicine [3,4]. SOLOIST-WHF only randomised about a third of the planned number of participants; SCORED was fully enrolled but with an abbreviated follow-up period.

SOLOIST-WHF was a multicentre, randomised, double-blinded, placebo-controlled phase 3 study evaluating the cardiovascular (CV) efficacy of 200 mg sotagliflozin once daily versus placebo added to standard of care in 1,222 patients with T2DM recently hospitalised for worsening HF [1,3]. The primary composite endpoint was the total number of deaths from cardiovascular causes, hospitalisations for HF, and urgent visits for HF in patients starting treatment within 3 days of hospital discharge. There were 51.0 and 76.3 primary endpoint events per 100 patient-years in the sotagliflozin and placebo groups, respectively (HR 0.67; 95% CI 0.52–0.85; P<0.001). The number of CV deaths per 100 patient-years was 10.6 and 12.5, respectively (HR 0.84; 95% CI 0.58–1.22; P=0.36). Because enrolment ended earlier, the researchers revied the primary endpoint to total number of CV death and hospitalisations for HF to increase the power of the power of the trial. The results for first occurrence of CV death or hospitalisation for HF (i.e. the original primary endpoint) were consistent with those of the modified primary endpoint (HR 0.71; 95% CI 0.57–0.89; P=0.003).

SCORED was a multicentre, randomised, double-blinded, phase 3 study evaluating the CV efficacy of sotagliflozin versus placebo when added to standard of care in 10,584 patients with T2DM, chronic kidney disease (CKD) with an eGFR of 25–60 ml/minute/1.73 m², and risks for CV disease [2,4]. The primary composite endpoint was death from CV causes, hospitalisations for HF, and urgent visits for HF. The initial dose of 200 mg once daily of sotagliflozin was increased to 400 mg once daily if side effects were manageable.

Again, the primary endpoint was met: the number of primary endpoint events per 100 patient-years in the sotagliflozin and placebo group was 5.6 and 7.5, respectively (HR 0.74; 95% CI 0.63–0.88; P<0.001). The number of CV deaths per 100 patient-years was 2.2 versus 2.4 events (HR 0.90; 95% CI 0.73–1.12; P=0.35). There was an average reduction in haemoglobin A1c of 0.56% and 0.25% in the sotagliflozin and placebo group in patients with eGFR <30 ml/minute/1.73 m² (P<0.001). In patients with eGFR ≥30 ml/minute/1.73 m², haemoglobin A1c was 0.60% lower in the sotagliflozin group and 0.17% lower in the placebo group (P<0.001).

Prof. Bhatt concluded that with careful patient selection and monitoring, an SGLT2 inhibitor should be strongly considered in the majority of T2DM patients, including those admitted with acute decompensated HF, with HF with either reduced or preserved ejection fraction, and with CKD across the full range of proteinuria.

1. 
   
   1. Bhatt D, et al. Sotagliflozin in Diabetes Patients with Recent Worsening Heart Failure – SOLOIST-WHF. LBS.07, AHA Scientific Sessions 2020, 13-17 Nov.
   2. Bhatt D, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease – SCORED. LBS.07, AHA Scientific Sessions 2020, 13–17 Nov.
   3. Bhatt D, et al. New Engl J Med 2021; 384:117–128.
   4. Bhatt D, et al. New Engl J Med 2021; 384:129–139.

 



Posted on 18 February 202117 May 2024