Can GLP-1 RAs Mitigate the Risks of Cardiovascular Disease?
Can GLP-1 RAs Mitigate the Risks of Cardiovascular Disease?
— By Dawn Sweet, Ph.D.
GLP-1 RAs are now known to have cardiovascular benefits in addition to glycemic control and weight loss.
Glucagon-like peptide-1 receptor agents (GLP-1 RAs) are now demonstrating efficacy for mitigating the risks of cardiovascular disease.1 While the positive effects of GLP-1s for glycemic control and weight loss are increasingly supported, their role in mitigating major cardiovascular adverse events are also becoming clearer. For example, GLP-1 cardiovascular benefits include the reduction of fatal and non-fatal stroke and coronary revascularization. However, while the news is promising, it should be noted that in some cardiovascular outcome trials GLP-1s did not yield cardiovascular benefits.1,6
Cardiovascular Outcome Trials
Antihyperglycemic agents like GLP-1s are now shown to decrease the risk of cardiovascular disease in patients with and without type 2 diabetes as reported across several randomized controlled trials.
LEADER
The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial (LEADER; N = 9340 RCT)2 found that CVD-related mortality occurred in fewer patients in the Liraglutide group (n = 218) compared to the control group (n = 278) and all-cause mortality rate was also lower in the liraglutide group. Also important to note, the number of non-fatal myocardial infarction and non-fatal stroke were also lower in the Liraglutide group, though the authors note that the differences were not statistically significant.
SUSTAIN-6
The Trial to Evaluate Cardiovascular and Other Long-Term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6; N = 3297 RCT).3 In the SUSTAIN-6 study, 2,735 patients with type 2 diabetes were randomly assigned to once-weekly Semaglutide (0.5 mg or 1.0 mg) or a placebo for 104 weeks. The first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were the primary composite outcomes. The rate of CVD-related death was lower in patients in the Semaglutide group compared to the control group.
HARMONY
The HARMONY trial4 was a double-blind, randomized, placebo control trial across 28 countries and 610 sites. Patients with type 2 diabetes and CVD who were 40 or older were randomly assigned to an Albiglutide group (N = 4,731 / Albiglutide dosed at 30 – 50mg determined by glycemic tolerance) or a control group (N = 4,732). The primary composite outcome was death from CVD causes, non-fatal myocardial infarction, or non-fatal stroke. The risk of the primary outcomes was 22 percent less in the Albiglutide group compared to the control group. The authors note that only myocardial infarction showed a significant point-estimate indicating a beneficial effect. The authors also note that their results are consistent with the benefits of Liraglutide and Semaglutide, however they appear to be greater than the results achieved with Lixisenatide and Exenatide. The significant reduction in death, which was observed in the LEADER trial, was not observed in the HARMONY trial.
REWIND
The REWIND trial5 was a multicenter, randomized, double-blind, placebo-controlled trial across 24 countries at 371 sites. Patients with type 2 diabetes with a history of a cardiovascular event or cardiovascular risk factors were randomly assigned to the Dulagutide (N – 4,929; 1.5 mg) group or a control group (N = 4,952). There were six month follow ups for the incident of CVD. The primary outcomes were the initial occurrence of non-fatal myocardial infarction, non-fatal stroke, or death from other CVD causes. The incident rate of primary outcomes was 2.4 per 100 in the Duaglutide group. Results suggest that Duaglutide is effective for use in middle-aged adults with type 2 diabetes and a history of CVD or to mitigate the risks of CVD.
ELIXA
The Evaluation of Lixisenatide in Acute Coronary Syndrome trial (ELIXA)6 was the first clinical trial to explore the efficacy of GLP-1s for mitigating CVD risks. The ELIXA trial was a multicenter, randomized, double-blind, placebo-controlled trial that included patients with type 2 diabetes, 30 or older, with a recent, acute coronary event. Lixisenatide was not associated with a significant difference in rates of cardiovascular events.
Which GLP-1 is best for Cardiovascular Benefit?
As noted in the HARMONY trial,4 it is difficult to determine which GLP-1 is the best for achieving cardiovascular benefits. Whether the differences between and among these GLP-1s is real is currently an empirical uncertainty. To answer this question, a direct comparison between and among GLP-1s is neeed.4
Implications for Clinical Practice
Across several randomized control trials, GLP-1 RAs have been found to mitigate the risks of CVD in patients with type 2 diabetes and/or with risk factors for cardiovascular disease. While there is currently no empirical evidence to suggest one GLP-1 is superior to others, health care professionals now have treatment options that are backed by empirical evidence to guide which GLP-1 may be right for their patients. Antihyperglycemic agents like GLP-1 can do double or triple duty — help patients with glycemic control, help patients lose weight, and mitigate CVD risk factors.
Working collaboratively with patients to implement sustainable lifestyle changes can help them achieve long-term weight loss and glycemic control. Supporting a nutrient-dense diet with a scientifically formulated meal replacements can shore up positive outcomes and can help patients not only meet their RDAs for micro- and macronutrients but also support healthy food choices. Health care professionals should talk with patients about strategies for selecting nutrient-dense foods and supplementing these choices with scientifically formulated meal replacements.
Source(s):
2 Liraglutide and cardiovascular outcomes in type 2 diabetes
3 Semaglutide and cardiovascular outcomes in patients with type 2 diabetes
6 Lixisenatide in patients with type 2 diabetes and acute coronary syndrome
About the Author: Dr. Dawn M. Sweet has over 20 years of experience in the field of communication. Dr. Sweet has given several invited talks to and workshops for academic and private sector audiences on the role of nonverbal and verbal communication in achieving positive outcomes and mitigating bias. Her research has been published in several top ranked peer-review journals, and it has been featured on NPR’s River to River / All Things Considered, Buzzfeed, and Science Daily. Her research has also been used to inform expert testimony.
About Robard: For 45 years, Robard Corporation’s medical obesity treatment programs and nutrition products have been utilized by physicians, surgeons and hospitals across the United States to successfully treat patients living with obesity. To learn more about us and how we can help your practice and patients, visit us online at www.Robard.com, email us at info@robard.com, or call (800) 222-9201.
