Live Longer and Cardiovascular Disease-Free

How many years can the GLP-1RA semaglutide add to your life? 

It is no secret that patients with diabetes have a higher chance of developing cardiovascular disease. Patients who have chronic diabetes can eventually develop impaired blood vessels; notably, blood vessels in the heart. The glucagon-like peptide-1 receptor agonist (GLP-1 RA) class has established a clear benefit for cardiovascular disease. Semaglutide can help decrease cardiovascular events in people with type 2 diabetes who also have a high cardiovascular risk. The researchers wanted to explore deeper into semaglutide and determine how many years can be added to a patient’s life with this drug’s addition. It is imperative to establish how many years a patient with type 2 diabetes can benefit from a drug used to prevent cardiovascular disease. Also, it is believed that even clinicians have a tough time interpreting and relating results from trials to patients. Generally, a patient wants to know how they can benefit from another drug being added to their possibly already complicated drug regimen.  

The researcher’s objective in this pooled cohort was to find the absolute benefit of semaglutide on cardiovascular disease-free years when added to standard care in patients with type 2 diabetes. This study evaluated the objective of patients both with and without cardiovascular disease at baseline. It used data from a Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) and a Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects with Type 2 Diabetes (PIONEER 6). These trials were randomized, placebo-controlled, double-blinded trials that assessed the GLP-1RA semaglutide in patients with type 2 diabetes and a high cardiovascular risk. The baseline characteristics from these trials were used. The majority of the study population had cardiovascular disease, and a minor proportion had chronic kidney at baseline.  

The researchers calculated every patient’s estimated cardiovascular disease-free life years separately and then collectively combined it with the hazard ratio of 0.76 (N=6480;[95% CI: 0.62-0.92]) from the 3-point major adverse cardiovascular events endpoint. The outcomes of this study were to estimate the number of cardiovascular disease-free life years and 10-year cardiovascular disease risk. The method used in this post hoc analysis was a dial model. This model accounts for risk adjustments for lifetime predictions of major adverse cardiovascular events and non-cardiovascular related death in patients with type 2 diabetes. A total of 389,366 patients with type 2 diabetes data from the Swedish National Diabetes Registry was used to construct the dial model.  

The results displayed a wide distribution of cardiovascular disease-free life years that could be gained from adding semaglutide. The mean increase of years gained was 1.7 years (95% CI: 0.5-2.9). The mean absolute ten-year risk reduction was 6.0% (95% CI: 1.9-10.0%), and the number needed to treat was 16.6. The inclusion of semaglutide in a patient’s standard of care was linked with a mean reduction in 10-year cardiovascular risk of 20.0% (95% CI: 6.4- 32.6%).  

The patients who had the highest risk of cardiovascular outcomes were seen to have the ultimate benefit. In patients with type 2 diabetes, cardiovascular disease remains one of the primary causes of both disability and mortality. This study revealed a trend of rising cardiovascular disease-free years with declining age. The younger the patient with type 2 diabetes, the more cardiovascular disease-free life years was gained. Semaglutide shows clinical relevance in patients with established cardiovascular disease. In a 60-year-old male patient with type 2 diabetes and with an average of the baseline characteristics, it is estimated that the addition of semaglutide to the standard of care treatment can reduce his relative risk of a persistent cardiovascular event by about 21%. Also, it is anticipated that semaglutide can add about 2.4 cardiovascular event-free years.  

Practice Pearls: 

• It can be challenging estimating the possible benefits of semaglutide due to patients with type 2 diabetes having different characteristics.   
• It can be concluded that a patient with type 2 diabetes will gain cardiovascular free life years with the add-on of semaglutide to their medication regimen.  
• The dial model was authenticated because the ratio of cardiovascular events at the one-year mark was within 5% of the amount observed.  

Westerink J, Sattar N, Fainberg U, et al. Estimating CVD-free life-years with the addition of semaglutide in people with type 2 diabetes using pooled data from SUSTAIN 6 and PIONEER 6. EASD Virtual Congress. Published in 2020. Accessed October 10, 2020. https://www.easd.org/virtualmeeting2020/#!resources/estimating-cvd-free-life-years-with-the-addition-of-semaglutide-in-people-with-type-2-diabetes-using-pooled-data-from-sustain-6-and-pioneer-6 

Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences 

See more about semaglutide and other GLP-1RA medications in our therapy center.