In type 2 diabetes with CKD and additional CV risk factors, sotagliflozin reduced total MACE vs. placebo at a median 14 mo
A manufacturer trial found cardiovascular (CV) benefits to sotagliflozin for patients with diabetes and chronic kidney disease (CKD), but the study did not prove it should be used in place of just a sodium-glucose cotransporter-2 inhibitor, an ACP Journal Club commentary said.
The rate of major adverse cardiovascular events (MACE) was lower in patients randomized to sotagliflozin, a combination sodium-glucose cotransporter-1 and -2 inhibitor, according to a prespecified secondary analysis of the SCORED trial. The industry-funded trial included more than 10,000 patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular (CV) risk factors, recruited at 750 sites in 44 countries. Patients in the sotagliflozin group had 4.8 MACEs per 100 person-years, compared to 6.3 per 100 person-years in the placebo group.
The study was published in the April issue of The Lancet Diabetes & Endocrinology. The following commentary by Aarti Thakkar, MD, MPH, and L. Kristin Newby, MD, MHS, was published in the ACP Journal Club section of Annals of Internal Medicine on June 3.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors, including dapagliflozin, empagliflozin, and canagliflozin, have consistently improved heart failure and kidney-related outcomes but have not clearly improved ischemic outcomes.
In a secondary analysis of the SCORED trial, Aggarwal and colleagues found that, compared with placebo, sotagliflozin reduced total MACE, as well as the post hoc secondary outcomes of total myocardial infarction (MI) events and total stroke events. The results suggest that sotagliflozin, a combination SGLT1 and SGLT2 inhibitor, may have different effects than SGLT2-specific inhibitors, specifically in patients with type 2 diabetes.
The analysis also showed that the effect of sotagliflozin on total MACE did not differ across subgroups of sex, age, geographical region, heart failure–related criteria, estimated glomerular filtration rate, urinary albumin–creatinine ratio, and CV disease history. However, several caveats should be noted when considering these subgroup results. The original SCORED trial was designed to assess the noninferiority of sotagliflozin vs. placebo for MACE, but the trial was prematurely closed and did not achieve the number of events required to adequately power analyses of secondary outcomes. In addition, investigator-reported outcomes were not independently adjudicated due to loss of funding. This, in conjunction with the lack of correction for multiple comparisons, may increase the risk for a type 1 error and potentially overstate the effects of sotagliflozin, both for MACE and the secondary outcomes of MI and stroke.
The analysis by Aggarwal and colleagues provides valuable insights that should inform future research on the effect of combined SGLT1 and SGLT2 inhibitors on disease progression, especially ischemic CV disease; however, the findings are insufficient to support preferential use of sotagliflozin over selective SGLT2 inhibitors. Because SGLT2 inhibitors have been shown to reduce MACE and heart failure hospitalization, they should be used in patients with type 2 diabetes who have, or are at high risk for, ischemic heart disease or who have heart failure and an ejection fraction <40%.