Dulaglutide Provides CVD Protection with or without Metformin 

Data from the REWIND trial suggest that dulaglutide has cardioprotective properties. 

Cardiovascular events in individuals with type 2 diabetes are approximately twice as prevalent as in individuals without type 2 diabetes. The cause stems from several risk factors such as obesity, hypertension, and irregularity in blood sugar stability. Dulaglutide is a glucagon-like peptide receptor agonist (GLP-1). It aids the pancreas to release an adequate amount of insulin when blood sugar levels are increased. Insulin, in return, guides sugar to be distributed to other parts of the body from the blood, to be used for energy. Dulaglutide can be given in doses 0.75 to 1.5 mg weekly, and is used to decrease the risk of death, heart attack, HbA1c levels, or stroke in patients with type 2 diabetes. Possible side effects from dulaglutide include nausea, diarrhea, a decrease in appetite, and tiredness. Data from the REWIND trial suggest that dulaglutide has cardioprotective properties. 

The study aimed to analyze the cardiovascular benefit of dulaglutide in patients with type 2 diabetes, regardless of whether the patient has been on metformin therapy. The REWIND trial was a multicentered, randomized, double-blinded trial. The Cox regression model was also used. This model is used to show the probability of a particular event to occur at a specific time. The patients received subcutaneous dulaglutide 1.5 mg per week or a placebo. The patients included in the study were patients with type 2 diabetes with a previous cardiovascular incident or increased risk of having a cardiovascular event. The study population consisted of 9,901 participants, 46% of whom were female, and with a median age of 66.2 years. The selection criteria were as follows: patients who were 50 years old or older who had at least one myocardial infarction; were previously or newly diagnosed with type 2 diabetes with HbA1c of 9.5% or lower; were on a stable dose of oral glucose-lowering medication with or without basal insulin of greater than or equal to 3 months, and a BMI of 23 kg/m2 or greater. 1,864 patients were without metformin use at baseline. The measure’s primary outcome was nonfatal myocardial infarction, stroke, or death from a cardiovascular event. The secondary results were microvascular composite endpoints all-cause death, heart failure, and hospitalization due to unstable angina. The safety outcomes included hypersensitivity reactions, gastrointestinal pain, discontinuation of therapy, cancer, and acute pancreatitis. 

The follow-up period lasted approximately 5.4 years. The p-value was 0.05, which was considered significant. The confidence interval was 95%. There was no significant difference shown with dulaglutide regarding the primary outcome in groups with or without metformin being used as therapy. The data showed dulaglutide with metformin having a hazard ratio of 0.93; CI 0.82-1.06 versus without metformin hazard ratio 0.78; CI 0.61-0.99; The p-value for interaction was 0.16. All interaction p-value was more significant than 0.1 for dulaglutide’s effect on the secondary outcome with metformin use.  

The study was designed to gain more knowledge about the effect that dulaglutide has on patients with diabetes who are taking metformin, and to see if there might be a significant difference in improving the threat or occurrence of cardiovascular events in patients using diabetic therapy. Future studies should be directed towards seeing the effects of weight loss or side effect profile demise if metformin were combined with dulaglutide. 

Practice Pearls: 

• Dulaglutide has cardioprotective effects in patients with diabetes. 
• Metformin use does not contribute to the cardioprotective effects exhibited by dulaglutide. 
• Dulaglutide is beneficial in patients with cardiac risk factors. 

CV Benefit of Dulaglutide Present Regardless of Background Metformin Use; Endocrinology 9/2020 

Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide  Diabetes, Obesity and Metabolism 

Shadrielle Robbins, PharmD Candidate, South College School of Pharmacy