Medications Hub

Oral Semaglutide: What You Should Know About the Pill Form of Ozempic

Medications like Ozempic have become widely recognised—not just for their role in type 2 diabetes, but also for their impact on weight and potential cardiovascular benefits. Ozempic, known generically as semaglutide, is a medication that mimics a natural hormone in the body to help regulate blood sugar and appetite. While it’s best known as a weekly injection, a tablet form, called oral semaglutide is now also available.

In this article, we’ll explore what oral semaglutide is, how it works, and what recent research tells us about its role in heart health.

 

What Is Oral Semaglutide?

Oral semaglutide belongs to a class of medications known as GLP-1 receptor agonists. These medications help lower blood sugar by enhancing the body’s natural insulin response and slowing down digestion. They also tend to reduce appetite, which may support weight loss.

The injectable version (Ozempic) has been used for several years and is now complemented by the tablet form (marketed as Rybelsus), which is taken once daily. This provides an option for people who prefer not to use injections, though it must be taken on an empty stomach with water and followed by a short waiting period before eating.

 

The Role of Semaglutide in Managing Type 2 Diabetes

Type 2 diabetes is a complex condition that affects how the body processes blood sugar (glucose). Over time, high blood sugar can lead to damage in various organs including the heart, kidneys, eyes, and nerves. Managing diabetes effectively means not only lowering glucose levels but also reducing the broader risks associated with the condition.

Semaglutide, both in its injectable and oral forms, plays a valuable role in this process.

As a GLP 1 receptor agonist, semaglutide works by mimicking a natural hormone in the gut that helps regulate blood sugar in several ways:

  • It increases insulin release when glucose levels are high
  • It suppresses glucagon, a hormone that raises blood sugar
  • It slows stomach emptying, which helps smooth out spikes in blood sugar after eating
  • It also reduces appetite, which may support weight loss, particularly important since many people with type 2 diabetes also struggle with weight gain

Unlike some older diabetes medications, semaglutide does not typically cause low blood sugar (hypoglycaemia) on its own, making it a safer option when used alone or alongside other medicines like metformin.

What sets semaglutide apart from some other diabetes treatments is its dual effect: improving blood glucose control and offering potential benefits for cardiovascular health, especially in people who already have increased risk.

Oral semaglutide provides this therapeutic benefit in tablet form, offering more choice for people who prefer not to use injections. That said, it still requires careful use, including taking it on an empty stomach and following instructions closely to ensure proper absorption.

While it is not suitable for everyone, and it is not typically used as the first treatment, it can be a useful option for people whose blood sugar remains above target despite lifestyle changes and other medications.

 

Cardiovascular Outcomes: What the Latest Research Shows

While oral semaglutide has primarily been used to manage type 2 diabetes, recent research has focused on its potential cardiovascular effects, especially in patients already at high risk of heart disease.

A landmark study published in The New England Journal of Medicine in April 2025 looked at over 9,600 people with type 2 diabetes and high cardiovascular risk. The study found that those who took oral semaglutide had a 14% lower risk of major adverse cardiovascular events such as heart attack, stroke, or cardiovascular death compared to those on placebo, over a median of four years.

More specifically:

  • Non-fatal heart attacks were reduced by 26%
  • Non-fatal strokes were reduced by 12%

These findings align with earlier studies involving injectable GLP-1 medications and suggest that oral semaglutide may offer similar heart-related benefits, especially in higher-risk individuals.

Reference: McGuire DK, et al. “Oral Semaglutide and Cardiovascular Outcomes in Type 2 Diabetes.” New England Journal of Medicine, April 2025. Link to article

 

What Does This Mean for Patients?

It’s important to view these results in context. Oral semaglutide is not a replacement for lifestyle measures like healthy eating, regular exercise, and smoking cessation. However, for people with type 2 diabetes, particularly those with existing cardiovascular risk, it may offer additional support.

That said, oral semaglutide is not without limitations:

  • It needs to be taken on an empty stomach, which may not be convenient for everyone.
  • Side effects such as nausea or digestive upset can occur, especially when first starting.
  • It’s not yet approved specifically for cardiovascular prevention, though these findings may shape future guidelines.

 

Conclusion

As a cardiologist, I see this research as part of an important shift in how we think about heart health. It reinforces what we have come to understand more clearly over the years that metabolic health and cardiovascular disease are closely linked. Medications like semaglutide offer a valuable tool, not just for controlling blood sugar, but also for supporting overall cardiovascular wellbeing, particularly in people at higher risk.

However, it is important to remember that no single medication can replace the foundations of good heart health. Long term success depends on a combination of strategies: keeping blood pressure and cholesterol under control, staying physically active, making thoughtful food choices, maintaining a healthy weight, and avoiding smoking. These lifestyle factors remain the cornerstone of cardiovascular care. Medications can provide important support, but they work best when combined with a broader and more comprehensive approach to health.

Author

  • Heart Matters

    Heart Matters, edited by Cardiologist Professor Peter Barlis, is a trusted resource dedicated to providing you with simplified and accurate information about cardiovascular health. It aims to bridge the gap between scientific discoveries and their practical application, empowering you to make informed decisions and promote overall cardiovascular wellness.

Search articles

Newsletter

Subscribe for exclusive heart health resources, valuable tips, and the latest research updates.

Editor's Picks

Empowering heart health

Subscribe to our newsletter and be the first to receive valuable insights, tips, and resources on heart health.

other anti-anginals

When first-line therapies for angina, such as beta blockers, calcium channel blockers, and nitrates, prove inadequate or are not well-tolerated, second-line therapies may be considered.
Perhexiline is a unique medication that enhances the heart's ability to utilize fatty acids for energy, reducing its reliance on oxygen and lowering oxygen demand. This action helps improve blood flow and alleviates chest pain in some patients with refractory angina.
Nicorandil is another second-line option with a dual mechanism of action. It opens potassium channels in smooth muscle cells, causing vasodilation and enhancing coronary blood flow. Additionally, nicorandil also stimulates nitric oxide release, further dilating blood vessels and reducing heart workload.
Trimetazidine is an anti-ischemic agent that improves cardiac efficiency by enhancing glucose metabolism and shifting the heart's energy production to a more oxygen-efficient process. As second-line therapies, these medications offer alternative approaches for managing angina in individuals who do not respond adequately to first-line treatments or those experiencing side effects from other medications.

lipid lowering therapies

Lipid-lowering therapies play a critical role in managing coronary artery disease (CAD), a condition characterized by the narrowing of blood vessels that supply the heart. Among the most commonly discussed and debated classes of medications are statins, which effectively reduce cholesterol levels and are widely prescribed to lower the risk of cardiovascular events. Alongside statins, other medications like ezetimibe, fibrates, and niacin are also utilized to target specific aspects of lipid metabolism, such as cholesterol absorption, triglyceride levels, and raising high-density lipoprotein (HDL) cholesterol. Additionally, the introduction of medications that inhibit PCSK9, an enzyme involved in cholesterol metabolism, has provided a promising new approach to further lower LDL cholesterol levels. These PCSK9 inhibitors, such as Repatha (evolocumab), have shown significant efficacy in reducing LDL cholesterol levels in patients with CAD, especially for those who may not respond well to traditional therapies.

Nitrates

Nitrates are widely used to treat angina and provide quick relief for chest pain. Commonly available in the form of sublingual sprays or tablets, patches, and long-acting tablets, nitrates work by dilating blood vessels, allowing for increased blood flow and reduced resistance. This dilation eases the heart's workload, leading to a decreased demand for oxygen and prompt alleviation of angina symptoms. Sublingual nitrates act rapidly and are often used to provide immediate relief during angina attacks, while patches and long-acting tablets are employed for preventive purposes. However, nitrates may cause side effects such as headaches, dizziness, and flushing, which usually subside over time.

calcium channel blockers

Calcium channel blockers, including amlodipine, felodipine, cardizem (diltiazem), and verapamil, are commonly prescribed for the treatment of angina. These medications work by inhibiting the influx of calcium into the muscle cells of the heart and blood vessels, leading to their relaxation. As a result, blood vessels widen, promoting improved blood flow and reduced blood pressure. In the context of angina, this relaxation decreases the heart's workload, lowering the demand for oxygen and alleviating chest pain. Calcium channel blockers offer a valuable treatment option for individuals with angina, but it is essential to be aware of potential side effects, which may include headaches, dizziness, flushing, and ankle swelling.

Beta blockers

Beta blockers, such as metoprolol, propranolol, atenolol, carvedilol, and bisoprolol, play a crucial role in treating angina. By blocking certain receptors in the heart, they effectively reduce heart rate and the force of contraction, thereby easing the heart's workload. This mechanism of action leads to a decreased demand for oxygen, making beta blockers highly effective in relieving chest pain associated with angina. As with any medication, it's important to consider potential side effects, including tiredness, worsened asthma, erectile dysfunction in some males, and more vivid dreams during sleep. Consult your healthcare provider to determine the suitability of beta blockers for managing your angina and overall heart health.

Anti-platelet Medications

Anti-platelet medications play a crucial role in preventing blood clot formation, reducing the risk of serious cardiovascular events such as heart attacks and strokes. Among the widely used anti-platelet drugs are aspirin, clopidogrel, and ticagrelor.

Aspirin: This well-known medication inhibits platelet activation, making it less likely for platelets to stick together and form clots. Aspirin is commonly used for primary and secondary prevention of heart attacks and strokes.

Clopidogrel: As a potent anti-platelet agent, clopidogrel works by blocking specific receptors on platelets, preventing them from aggregating. It is often prescribed to patients with acute coronary syndrome, those undergoing stent procedures, and for some cases of peripheral arterial disease.

Ticagrelor: Ticagrelor is another effective anti-platelet drug that works by inhibiting platelet activation. It is used in acute coronary syndrome, often given alongside aspirin to reduce the risk of heart-related events.