medwireNews: Data from primary care suggest that use of sodium-glucose cotransporter (SGLT)2 inhibitors, and possibly glucagon-like peptide (GLP)-1 receptor agonists, may reduce the risk for cardiovascular disease (CVD) events in people with type 2 diabetes without previous events.
“These data call for trials to evaluate the efficacy and cost-effectiveness of these interventions and their combination in the primary prevention setting,” say the researchers, adding that “pragmatic trials embedded within health care systems” could be the optimal approach.
They concede that these medications are expensive, but stress that “80% of diabetes care costs cover managing complications, mostly CVD.”
As reported in Diabetes Care, Alison Wright (University of Manchester, UK) and study co-authors used data from 440,089 UK primary care patients with type 2 diabetes in nested case–control analyses. The cases were matched with up to 20 controls by age, sex, healthcare practice, date of cohort entry, and diabetes duration.
Among the 336,334 people initially free of major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), use of an SGLT2 inhibitor was associated with a significant 18% reduction in the likelihood of having a first event.
Combining SGLT2 inhibitors with GLP-1 receptor agonists was associated with an even larger 30% reduction, despite use of the latter medications alone being associated with only a nonsignificant 7% reduced likelihood. These associations were independent of factors including ethnicity, deprivation, microvascular complications, comorbidities, glycated hemoglobin, BMI, and other medications.
Among the 411,206 study participants without heart failure at baseline, the likelihood of having a first event was a significant 51% lower with use of an SGLT2 inhibitor, a smaller but still significant 18% lower with use of a GLP-1 receptor agonist, and 57% lower with the combination.
The data contrast somewhat with clinical trial findings for secondary prevention, which support GLP-1 receptor agonists for prevention of atherosclerotic events, and SGLT2 inhibitors for heart failure prevention.
But Wright and team note the “growing evidence” that myocardial metabolic abnormalities can contribute to heart failure risk, and that the GLP-1 protein boosts insulin secretion, insulin sensitivity, and glucose uptake. This means that GLP-1 receptor agonist treatment “could be a potential modulator to enhance myocardial glucose metabolism” and therefore reduce heart failure risk, they believe.
Finally, the researchers observe that SGLT2 inhibitors and GLP-1 receptor agonists have “overlapping and distinct mechanisms of action,” which could account for the positive effects observed in this study, although they caution that only a limited number of people received both medication classes.
“The combined use of these agents is of significant interest because we are not aware of any trials investigating their effectiveness,” they write.
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