Cardiovascular Risk Reduction in Patients with Type 2 Diabetes

Semaglutide

Most recently, the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) was completed, assessing cardiovascular safety of a once-weekly injectable glucagon-like peptide-1 (GLP-1) analogue. This noninferiority trial studied 3297 patients with type 2 diabetes over the age of 50 years with established macrovascular disease, chronic heart failure, or chronic kidney disease (stage III or higher), or over the age of 60 years with at least 1 other cardiovascular risk factor. The patients were randomized to 1 of 2 doses of once-weekly semaglutide or placebo injection. A composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was decreased by 26% in the pooled semaglutide group. This was driven primarily by a reduction in nonfatal stroke, with no statistically significant reduction in nonfatal myocardial infarction or cardiovascular mortality. Significant secondary outcomes showed a reduction in new or worsening nephropathy (HR 0.64), and an unexpected increase in retinopathy (HR 1.76) [65].

All of these trials utilized their respective agents as add-on to existing antihyperglycemic therapy. Therefore, first-line antihyperglycemic therapy in a patient with T2DM remains metformin. For the patient with established vascular disease or who is at high risk for developing vascular disease, add-on therapy using an antihyperglycemic agent with proven cardiovascular benefits, such as empagliflozin or liraglutide, is suggested [9,11]. Semaglutide is not yet available for clinical use. The choice between these agents should be based on patient preference, cost, side effect profile, and absence of contraindications.

Currently, there are more studies underway with similar designs with different agents. As these studies are reported in the upcoming years, it is hoped that the options for reduction of cardiovascular risk will increase, and that we will have multiple antihyperglycemic agents that will provide not only glycemic benefit but also cardiovascular risk reduction.

Case Conclusion

The patient continues to abstain from smoking. He follows up with a dietitian and is enrolled in an exercise program. He remains on his cardiac medications. For glycemic control, he continues on his previous antihyperglycemic therapy and an antihyperglycemic agent with proven cardiovascular benefit is added. With these interventions, he understands that his risk is mitigated, but given his history and previous event, he remains at high risk for future vascular disease.

Conclusion

The care of a patient with diabetes requires a multifactorial approach. All patients are at risk for developing the vascular complications of diabetes, and it is these complications that ultimately result in the nearly doubled risk of mortality in patients with diabetes. Various trials have shown that targeted interventions can and do reduce the risk for cardiovascular disease in a measurable way. Above and beyond targeted interventions, we now know that strict multifactorial interventions can result in a clinically significant reduction in both mortality and cardiovascular disease. This multifactorial approach is supported by guidelines around the world [12,44,45]. A standardized approach to the assessment of risk and the application of interventions is critical. More recent data show that specific antihyperglycemic therapies can also reduce cardiovascular events above and beyond their glycemic effects. The rates of cardiovascular events in patients with diabetes have declined over time, and hopefully this trend will continue as further research supports additional interventions.