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The Role of GLP-1 Receptor Agonists in Cardiovascular Health
Semaglutide
Eileen Quinones
•
6 mins
• Jan 20, 2025
Cardiovascular diseases (CVD), such as heart disease, stroke, and heart failure, are among the leading causes of death globally. This is particularly concerning for individuals living with Type 2 diabetes (T2D), who are at a significantly higher risk for developing these conditions. Over the years, diabetes treatments have primarily focused on controlling blood glucose, but the need for therapies that also reduce cardiovascular risk has become more evident. Enter GLP-1 receptor agonists (GLP-1 RAs), a class of medications that not only help manage blood sugar levels but also show substantial cardiovascular benefits.
In this blog, we’ll delve deeper into what GLP-1 RAs are, how they work to reduce cardiovascular risks, and why they are a revolutionary treatment for individuals with T2D at risk for heart-related issues.
What Are GLP-1 Receptor Agonists (GLP-1 RAs)?
GLP-1 receptor agonists (GLP-1 RAs) are a class of drugs that mimic the effects of a naturally occurring hormone called glucagon-like peptide-1 (GLP-1). GLP-1 is an incretin hormone, which means it is released from the gut after eating and helps regulate blood sugar levels. It works by:¹
Increasing Insulin Secretion: GLP-1 stimulates the pancreas to release insulin when blood glucose levels are elevated, which helps lower blood sugar levels.
Decreasing Glucagon: It also inhibits the release of glucagon, a hormone that signals the liver to release glucose into the bloodstream, further helping to lower blood glucose.
Slowing Gastric Emptying: GLP-1 slows down the rate at which food leaves the stomach, which not only helps improve blood sugar control but also promotes feelings of fullness and helps with weight management.
GLP-1 RAs are designed to resist breakdown by the enzyme dipeptidyl peptidase-4 (DPP-4), which normally degrades the natural GLP-1 hormone. This allows GLP-1 RAs to have a longer effect and provide more sustained blood sugar control compared to the body’s natural GLP-1.²
Some well-known GLP-1 RAs include:
Liraglutide (Victoza, Saxenda)
Semaglutide (Ozempic, Wegovy)
Dulaglutide (Trulicity)
Exenatide (Byetta, Bydureon)
These medications have proven to be highly effective in managing blood sugar levels in patients with T2D, but recent cardiovascular outcome trials (CVOTs) have shown that their benefits go far beyond glucose control, making them a critical part of heart disease management as well.
The Link Between Type 2 Diabetes and Cardiovascular Disease²
Type 2 diabetes is a condition characterized by insulin resistance and impaired insulin secretion, leading to chronically elevated blood glucose levels. Over time, high blood glucose can cause damage to blood vessels, nerves, and other organs, contributing to the development of cardiovascular diseases, such as:
Myocardial Infarction (Heart Attack)
Stroke
Heart Failure
Peripheral Artery Disease (PAD)
The increased cardiovascular risk in people with T2D is largely due to the chronic effects of elevated blood glucose. High blood sugar contributes to inflammation, oxidative stress, and the buildup of fatty deposits (atherosclerosis) in the arteries, making them stiff and narrow, which can lead to heart attacks and strokes. In fact, individuals with T2D are two to four times more likely to develop cardiovascular disease than those without diabetes.
Interestingly, the treatment of high blood glucose has traditionally been the primary focus for managing diabetes, but it hasn’t always translated into a significant reduction in cardiovascular events. Older treatments like insulin and sulfonylureas primarily target blood sugar levels but do little to address the underlying cardiovascular risks. This has led researchers to look for new therapies that target both blood glucose and cardiovascular health. GLP-1 RAs have proven to be a breakthrough in this area, providing a dual benefit.
How GLP-1 Receptor Agonists Help Reduce Cardiovascular Risks³
Recent large-scale studies, including multiple cardiovascular outcome trials (CVOTs), have demonstrated that GLP-1 RAs not only help manage blood sugar but also significantly reduce the risk of major adverse cardiovascular events (MACE). MACE refers to serious heart-related events such as heart attack, stroke, cardiovascular death, and hospitalization for heart failure.
Here’s how GLP-1 RAs contribute to reducing cardiovascular risks:
A. Reducing Atherosclerosis and Plaque Buildup
GLP-1 RAs have been shown to have antiatherosclerotic effects, meaning they can help slow or even reverse the development of plaque in the arteries. This is especially important for patients with diabetes, as they tend to develop atherosclerosis at a faster rate due to the damaging effects of high blood glucose. By stabilizing and reducing the size of plaques in the arteries, GLP-1 RAs help prevent blockages that can lead to heart attacks or strokes.
B. Lowering Blood Pressure
High blood pressure (hypertension) is a major risk factor for heart disease and stroke. GLP-1 RAs have been shown to reduce systolic blood pressure (the upper number in a blood pressure reading), although the reduction is modest. Still, every small decrease in blood pressure can have a significant impact on reducing cardiovascular risk. Lowering blood pressure helps protect the heart and blood vessels from damage over time.
C. Weight Loss Benefits
One of the side effects of GLP-1 RAs is weight loss, which is particularly beneficial for patients with Type 2 diabetes, as obesity is a major risk factor for cardiovascular disease. By promoting satiety and reducing hunger, GLP-1 RAs help patients lose weight. This weight loss can lead to significant improvements in blood pressure, cholesterol levels, and overall heart health. In fact, some GLP-1 RAs, like semaglutide, are now approved specifically for weight management in individuals with or without diabetes.
D. Reducing Inflammation
Inflammation is a key contributor to atherosclerosis and other cardiovascular diseases. GLP-1 RAs have been shown to reduce markers of systemic inflammation, such as C-reactive protein (CRP), which is associated with a higher risk of heart disease. By addressing inflammation, GLP-1 RAs provide an additional layer of protection against cardiovascular events.
These cardiovascular benefits are observed in patients with established cardiovascular disease as well as those at high risk, which is why GLP-1 RAs are increasingly being recommended in diabetes treatment guidelines, even for patients without very high glucose levels.
GLP-1 RAs and Their Role in Kidney Health¹
In addition to cardiovascular benefits, GLP-1 RAs also provide significant protection against kidney damage, which is another common complication of Type 2 diabetes. Chronic kidney disease (CKD) affects a large number of people with diabetes and often leads to kidney failure. The kidneys filter waste from the blood, and when they become damaged, this process becomes less efficient, leading to the buildup of toxins in the body.
GLP-1 RAs can slow the progression of diabetic nephropathy (kidney disease caused by diabetes) by:
Reducing albuminuria (protein in the urine): A key early sign of kidney damage.
Slowing the decline in estimated glomerular filtration rate (eGFR): A measure of kidney function.
In clinical trials, GLP-1 RAs, especially semaglutide and liraglutide, have shown kidney-protective effects, making them an important treatment option for patients with T2D and diabetic kidney disease. Additionally, ongoing trials like the FLOW study are investigating how GLP-1 RAs can impact more severe kidney outcomes, such as end-stage kidney disease (ESKD), and the results so far are promising.⁶
Practical Considerations for Using GLP-1 RAs in Cardiovascular Disease Treatment⁵
While GLP-1 RAs are highly effective, there are several practical considerations to keep in mind:
A. Administration and Convenience
GLP-1 RAs are typically administered by injection, either daily or weekly, depending on the drug. For patients who prefer oral medications, oral semaglutide (brand name Rybelsus) is available. While some patients may find injections less convenient, they are often well-tolerated and offer long-lasting effects. The frequency of injections (once daily, once weekly) also makes them convenient for most patients.
B. Side Effects
The most common side effects of GLP-1 RAs are gastrointestinal in nature, including nausea, vomiting, and diarrhea. These side effects tend to be transient and diminish over time as the body adjusts to the medication. However, for patients who experience severe or persistent symptoms, dose adjustments may be necessary, and symptomatic treatment, such as anti-nausea medications, can be considered.
C. Monitoring and Dosage Adjustments
Patients on GLP-1 RAs should have their kidney function monitored, particularly if they have a history of kidney disease. In most cases, no dose adjustments are required for patients with mild kidney impairment, but GLP-1 RAs should be avoided in patients with severe kidney disease (eGFR <15 mL/min).
D. Patient Selection
GLP-1 RAs are especially beneficial for patients with T2D who have established cardiovascular disease or are at high risk for heart disease. They are also considered for individuals with chronic kidney disease due to their renal protective effects. If you have Type 2 diabetes and are at risk for cardiovascular or kidney disease, it’s worth discussing GLP-1 RAs with your healthcare provider.
Conclusion: GLP-1 RAs—A Dual Solution for Heart and Diabetes Health
GLP-1 receptor agonists have emerged as a groundbreaking treatment for Type 2 diabetes, offering a dual benefit of improving blood glucose control while simultaneously reducing cardiovascular and kidney risks. Their ability to reduce major adverse cardiovascular events, promote weight loss, lower blood pressure, and protect against kidney damage makes them an invaluable tool in managing both diabetes and cardiovascular disease.
As more studies explore the broader cardiometabolic benefits of GLP-1 RAs, it’s clear that these medications have the potential to transform the way we treat patients with Type 2 diabetes, particularly those at high risk for heart disease and kidney complications.
If you have Type 2 diabetes and are concerned about your heart health, talk to your healthcare provider about the potential benefits of GLP-1 RAs. With proper management and treatment, it’s possible to reduce the risks of cardiovascular disease and improve overall health.
Sources :
Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials, Badve, Sunil V et al. The Lancet Diabetes & Endocrinology, Volume 13, Issue 1, 15 - 28, 10.1016/S2213-8587(24)00271-7
Ferhatbegović, L., Mršić, D., & Macić-Džanković, A. (2023). The benefits of GLP1 receptors in cardiovascular diseases. Frontiers in Clinical Diabetes and Healthcare, https://doi.org/10.3389/fcdhc.2023.1293926
Frederick Berro Rivera, Linnaeus Louisse A. Cruz, John Vincent Magalong, Jade Monica Marie J. Ruyeras, John Paul Aparece, Nathan Ross B. Bantayan, Kyla Lara-Breitinger, Martha Gulati, Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials, American Journal of Preventive Cardiology, Volume 18, 2024, 100679, ISSN 2666-6677, https://doi.org/10.1016/j.ajpc.2024.100679.
Marx, N., Husain, M., Lehrke, M., Verma, S., & Sattar, N. (2022). GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation, 146(24), 1882- 1894. https://doi.org/10.1161/circulationaha.122.059595
Reed, J., Kanamarlapudi, V., & Bain, S. (2017). Mechanism of cardiovascular disease benefit of glucagon-like peptide 1 agonists. Cardiovascular Endocrinology & Metabolism, 7(1), 18–23. https://doi.org/10.1097/xce.0000000000000147
GLP1RAS in Clinical Practice: Therapeutic Advances and Safety Perspectives - American College of Cardiology. (2024, April 15). American College of Cardiology. https://www.acc.org/Latest-in-Cardiology/Articles/2024/04/15/11/19/GLP1RAs-in-Clinical-Practice
Current version
Jan 20, 2025
Written by
Lose weight effectively
with GLP-1s
Complete our quick questionnaire to identify if you qualify. (approx 3 min)
The Role of GLP-1 Receptor Agonists in Cardiovascular Health
Semaglutide
Eileen Quinones
•
6 mins
• Jan 20, 2025
Cardiovascular diseases (CVD), such as heart disease, stroke, and heart failure, are among the leading causes of death globally. This is particularly concerning for individuals living with Type 2 diabetes (T2D), who are at a significantly higher risk for developing these conditions. Over the years, diabetes treatments have primarily focused on controlling blood glucose, but the need for therapies that also reduce cardiovascular risk has become more evident. Enter GLP-1 receptor agonists (GLP-1 RAs), a class of medications that not only help manage blood sugar levels but also show substantial cardiovascular benefits.
In this blog, we’ll delve deeper into what GLP-1 RAs are, how they work to reduce cardiovascular risks, and why they are a revolutionary treatment for individuals with T2D at risk for heart-related issues.
What Are GLP-1 Receptor Agonists (GLP-1 RAs)?
GLP-1 receptor agonists (GLP-1 RAs) are a class of drugs that mimic the effects of a naturally occurring hormone called glucagon-like peptide-1 (GLP-1). GLP-1 is an incretin hormone, which means it is released from the gut after eating and helps regulate blood sugar levels. It works by:¹
Increasing Insulin Secretion: GLP-1 stimulates the pancreas to release insulin when blood glucose levels are elevated, which helps lower blood sugar levels.
Decreasing Glucagon: It also inhibits the release of glucagon, a hormone that signals the liver to release glucose into the bloodstream, further helping to lower blood glucose.
Slowing Gastric Emptying: GLP-1 slows down the rate at which food leaves the stomach, which not only helps improve blood sugar control but also promotes feelings of fullness and helps with weight management.
GLP-1 RAs are designed to resist breakdown by the enzyme dipeptidyl peptidase-4 (DPP-4), which normally degrades the natural GLP-1 hormone. This allows GLP-1 RAs to have a longer effect and provide more sustained blood sugar control compared to the body’s natural GLP-1.²
Some well-known GLP-1 RAs include:
Liraglutide (Victoza, Saxenda)
Semaglutide (Ozempic, Wegovy)
Dulaglutide (Trulicity)
Exenatide (Byetta, Bydureon)
These medications have proven to be highly effective in managing blood sugar levels in patients with T2D, but recent cardiovascular outcome trials (CVOTs) have shown that their benefits go far beyond glucose control, making them a critical part of heart disease management as well.
The Link Between Type 2 Diabetes and Cardiovascular Disease²
Type 2 diabetes is a condition characterized by insulin resistance and impaired insulin secretion, leading to chronically elevated blood glucose levels. Over time, high blood glucose can cause damage to blood vessels, nerves, and other organs, contributing to the development of cardiovascular diseases, such as:
Myocardial Infarction (Heart Attack)
Stroke
Heart Failure
Peripheral Artery Disease (PAD)
The increased cardiovascular risk in people with T2D is largely due to the chronic effects of elevated blood glucose. High blood sugar contributes to inflammation, oxidative stress, and the buildup of fatty deposits (atherosclerosis) in the arteries, making them stiff and narrow, which can lead to heart attacks and strokes. In fact, individuals with T2D are two to four times more likely to develop cardiovascular disease than those without diabetes.
Interestingly, the treatment of high blood glucose has traditionally been the primary focus for managing diabetes, but it hasn’t always translated into a significant reduction in cardiovascular events. Older treatments like insulin and sulfonylureas primarily target blood sugar levels but do little to address the underlying cardiovascular risks. This has led researchers to look for new therapies that target both blood glucose and cardiovascular health. GLP-1 RAs have proven to be a breakthrough in this area, providing a dual benefit.
How GLP-1 Receptor Agonists Help Reduce Cardiovascular Risks³
Recent large-scale studies, including multiple cardiovascular outcome trials (CVOTs), have demonstrated that GLP-1 RAs not only help manage blood sugar but also significantly reduce the risk of major adverse cardiovascular events (MACE). MACE refers to serious heart-related events such as heart attack, stroke, cardiovascular death, and hospitalization for heart failure.
Here’s how GLP-1 RAs contribute to reducing cardiovascular risks:
A. Reducing Atherosclerosis and Plaque Buildup
GLP-1 RAs have been shown to have antiatherosclerotic effects, meaning they can help slow or even reverse the development of plaque in the arteries. This is especially important for patients with diabetes, as they tend to develop atherosclerosis at a faster rate due to the damaging effects of high blood glucose. By stabilizing and reducing the size of plaques in the arteries, GLP-1 RAs help prevent blockages that can lead to heart attacks or strokes.
B. Lowering Blood Pressure
High blood pressure (hypertension) is a major risk factor for heart disease and stroke. GLP-1 RAs have been shown to reduce systolic blood pressure (the upper number in a blood pressure reading), although the reduction is modest. Still, every small decrease in blood pressure can have a significant impact on reducing cardiovascular risk. Lowering blood pressure helps protect the heart and blood vessels from damage over time.
C. Weight Loss Benefits
One of the side effects of GLP-1 RAs is weight loss, which is particularly beneficial for patients with Type 2 diabetes, as obesity is a major risk factor for cardiovascular disease. By promoting satiety and reducing hunger, GLP-1 RAs help patients lose weight. This weight loss can lead to significant improvements in blood pressure, cholesterol levels, and overall heart health. In fact, some GLP-1 RAs, like semaglutide, are now approved specifically for weight management in individuals with or without diabetes.
D. Reducing Inflammation
Inflammation is a key contributor to atherosclerosis and other cardiovascular diseases. GLP-1 RAs have been shown to reduce markers of systemic inflammation, such as C-reactive protein (CRP), which is associated with a higher risk of heart disease. By addressing inflammation, GLP-1 RAs provide an additional layer of protection against cardiovascular events.
These cardiovascular benefits are observed in patients with established cardiovascular disease as well as those at high risk, which is why GLP-1 RAs are increasingly being recommended in diabetes treatment guidelines, even for patients without very high glucose levels.
GLP-1 RAs and Their Role in Kidney Health¹
In addition to cardiovascular benefits, GLP-1 RAs also provide significant protection against kidney damage, which is another common complication of Type 2 diabetes. Chronic kidney disease (CKD) affects a large number of people with diabetes and often leads to kidney failure. The kidneys filter waste from the blood, and when they become damaged, this process becomes less efficient, leading to the buildup of toxins in the body.
GLP-1 RAs can slow the progression of diabetic nephropathy (kidney disease caused by diabetes) by:
Reducing albuminuria (protein in the urine): A key early sign of kidney damage.
Slowing the decline in estimated glomerular filtration rate (eGFR): A measure of kidney function.
In clinical trials, GLP-1 RAs, especially semaglutide and liraglutide, have shown kidney-protective effects, making them an important treatment option for patients with T2D and diabetic kidney disease. Additionally, ongoing trials like the FLOW study are investigating how GLP-1 RAs can impact more severe kidney outcomes, such as end-stage kidney disease (ESKD), and the results so far are promising.⁶
Practical Considerations for Using GLP-1 RAs in Cardiovascular Disease Treatment⁵
While GLP-1 RAs are highly effective, there are several practical considerations to keep in mind:
A. Administration and Convenience
GLP-1 RAs are typically administered by injection, either daily or weekly, depending on the drug. For patients who prefer oral medications, oral semaglutide (brand name Rybelsus) is available. While some patients may find injections less convenient, they are often well-tolerated and offer long-lasting effects. The frequency of injections (once daily, once weekly) also makes them convenient for most patients.
B. Side Effects
The most common side effects of GLP-1 RAs are gastrointestinal in nature, including nausea, vomiting, and diarrhea. These side effects tend to be transient and diminish over time as the body adjusts to the medication. However, for patients who experience severe or persistent symptoms, dose adjustments may be necessary, and symptomatic treatment, such as anti-nausea medications, can be considered.
C. Monitoring and Dosage Adjustments
Patients on GLP-1 RAs should have their kidney function monitored, particularly if they have a history of kidney disease. In most cases, no dose adjustments are required for patients with mild kidney impairment, but GLP-1 RAs should be avoided in patients with severe kidney disease (eGFR <15 mL/min).
D. Patient Selection
GLP-1 RAs are especially beneficial for patients with T2D who have established cardiovascular disease or are at high risk for heart disease. They are also considered for individuals with chronic kidney disease due to their renal protective effects. If you have Type 2 diabetes and are at risk for cardiovascular or kidney disease, it’s worth discussing GLP-1 RAs with your healthcare provider.
Conclusion: GLP-1 RAs—A Dual Solution for Heart and Diabetes Health
GLP-1 receptor agonists have emerged as a groundbreaking treatment for Type 2 diabetes, offering a dual benefit of improving blood glucose control while simultaneously reducing cardiovascular and kidney risks. Their ability to reduce major adverse cardiovascular events, promote weight loss, lower blood pressure, and protect against kidney damage makes them an invaluable tool in managing both diabetes and cardiovascular disease.
As more studies explore the broader cardiometabolic benefits of GLP-1 RAs, it’s clear that these medications have the potential to transform the way we treat patients with Type 2 diabetes, particularly those at high risk for heart disease and kidney complications.
If you have Type 2 diabetes and are concerned about your heart health, talk to your healthcare provider about the potential benefits of GLP-1 RAs. With proper management and treatment, it’s possible to reduce the risks of cardiovascular disease and improve overall health.
Current version
Jan 20, 2025
Written by
Fact checked by
Eileen Quinones (Certified Family Nurse Practitioner)
Lose weight effectively
with GLP-1s
Complete our quick questionnaire to identify if you qualify. (approx 3 min)
Lose weight effectively
with GLP-1s
Complete our quick questionnaire to identify if you qualify. (approx 3 min)
Sources :
Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials, Badve, Sunil V et al. The Lancet Diabetes & Endocrinology, Volume 13, Issue 1, 15 - 28, 10.1016/S2213-8587(24)00271-7
Ferhatbegović, L., Mršić, D., & Macić-Džanković, A. (2023). The benefits of GLP1 receptors in cardiovascular diseases. Frontiers in Clinical Diabetes and Healthcare, https://doi.org/10.3389/fcdhc.2023.1293926
Frederick Berro Rivera, Linnaeus Louisse A. Cruz, John Vincent Magalong, Jade Monica Marie J. Ruyeras, John Paul Aparece, Nathan Ross B. Bantayan, Kyla Lara-Breitinger, Martha Gulati, Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials, American Journal of Preventive Cardiology, Volume 18, 2024, 100679, ISSN 2666-6677, https://doi.org/10.1016/j.ajpc.2024.100679.
Marx, N., Husain, M., Lehrke, M., Verma, S., & Sattar, N. (2022). GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation, 146(24), 1882- 1894. https://doi.org/10.1161/circulationaha.122.059595
Reed, J., Kanamarlapudi, V., & Bain, S. (2017). Mechanism of cardiovascular disease benefit of glucagon-like peptide 1 agonists. Cardiovascular Endocrinology & Metabolism, 7(1), 18–23. https://doi.org/10.1097/xce.0000000000000147
GLP1RAS in Clinical Practice: Therapeutic Advances and Safety Perspectives - American College of Cardiology. (2024, April 15). American College of Cardiology. https://www.acc.org/Latest-in-Cardiology/Articles/2024/04/15/11/19/GLP1RAs-in-Clinical-Practice