Can semaglutide cause heart palpitations?
No, according to the available evidence-based studies, semaglutide does not cause heart palpitations.
Safety studies of that drug showed no electrical cycle changes, which are normally the primary cause of heart palpitations. No ECG changes were found at normal and high dosages of semaglutide [1].
In fact, a recent study suggests that semaglutide may decrease the risk of heart palpitations. A study by Dao-Gen Yin et al. has found that this diabetes medication can reduce the risk of atrial fibrillation by nearly a third [2]. Atrial fibrillation is one of the conditions that causes symptoms of heart palpitations.
However, semaglutide is a very recent drug (it came out in 2017), and due to this, little is known about its long term use. The studies and statements do not exclude the possibility of heart palpitations occurring with long-term use.
What is Semaglutide?
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. This is a type of medication that mimics the action of GLP-1, a naturally occurring hormone in the body. Semaglutide is used in the treatment of type 2 diabetes mellitus (DM2). However, recently, it has started to be used in the treatment of obesity [3, 4, 5, 6].
Semaglutide is an active substance in the drugs Ozempic, Wegovy, and Rybelsus. While Rybelsus comes in the form of a tablet, Ozempic and Wegovy are subcutaneous injections administered once a week. The oral form of semaglutide offers a convenient alternative to injectable diabetes medications [3, 4, 5, 7].
Although Semaglutide was developed to treat DM2, it shows promising potential in other treatments. The list of suggested diseases that could be managed with semaglutide includes type 1 diabetes, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, kidney disease, Alzheimer's disease, and pulmonary diseases [6].
How does semaglutide work?
Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue [6]. It works by mimicking the functions of the natural hormone GLP-1 in the body.
One of the primary effects of semaglutide is the induction of weight loss. It regulates lipid metabolism and decreases fat accumulation as well as lipids found in the blood [8]. The regulation is supported by the decreases in appetite and lower fat absorption, as well as decreased lipogeneses in the liver and the increase in insulin sensitivity of the cells.
Another property of semaglutide is its anti-inflammatory effect. In a study of acute lung injury in rats, Zeyu Jiang et al. showed that cases of pretreated semaglutide were found to have smaller inflammatory reactions. It was measured by a reduced production of the inflammatory markers TNF-α and IL-6 [9].
The anti-inflammatory factor also has a positive effect on the kidneys. It protects against acute kidney injury [10].
Additionally, semaglutide has been shown to protect against Alzheimer's disease. Protection from this neurodegenerative disease is achieved by enhancing autophagy and inhibiting apoptosis [11]. It also has potential benefits for chronic liver disease-induced skeletal muscle atrophy by stimulating GLP-1R in myocytes [12].
Furthermore, in mouse models that are prone to atherosclerosis, semaglutide has been found to reduce vessel remodeling following vascular injury [13]. This can be an effect of the reduction in lipid levels as well as lower inflammatory levels. Both of those factors contribute to the endothelial imbalance, which is a main contributor to atherosclerosis.
Semaglutide allows for modulating the calory intake. It has been shown to reduce food intake and slow gastric emptying [14]. The cause of this reduced food intake is the feeling of fullness and lower hunger levels this drug evokes in the brain.
How does semaglutide influence the heart?
Semaglutide has been found to have several beneficial effects on the heart. The primary impact on the heart is caused directly by weight loss. With a smaller mass, the workload of the myocardium declines, stressing the heart to a lesser extent. Additionally, lower blood pressure as well as lipid and sugar levels in the blood follow the loss in weight, lowering the cardiovascular risk factors. This GLP-1 analogue reduces the risk of heart attack, stroke, or death in type 2 diabetes and heart disease [15]
A direct impact on the heart Semaglutide is achieved by decreasing oxidative stress and inflammation. In conditions like excessive exercise-induced myocardial injury, it helps to contain the damage and thus any complications [16]. Similarly, it protects the heart against cisplatin-induced cardiotoxicity. It normalizes the targeted mitochondrial functions and oxidation pathways [17].
Furthermore, due to the reduced expression of certain proteins in neutrophils, semaglutide ameliorates obesity-induced cardiac inflammation and oxidative stress [18].
In patients with heart failure and obesity, semaglutide has been shown to improve heart-related symptoms. Regardless of the starting health status, it improves exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide levels [19]. The last one is a marker of a failing heart and is increased in cases where the heart is overloaded with volume.
In sepsis, semaglutide has been found to protect against sepsis-triggered myocardial inflammation and injury. A potential pathway for this cardioprotective mechanism is the reactivation of myocardial autophagy [20].
Is semaglutide safe to use in cardiovascular disease?
Semaglutide is safe to use in cardiovascular disease. It has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes and obesity. Even patients with no diabetes can benefit from this GLP-1 agonist. It was demonstrated that patients with cardiovascular diseases without diabetes had 20% less frequent cardiovascular events when receiving semaglutide [21, 22].
In another study, Mansoor Husain et al. focused on the outcomes of oral semaglutide treatment. It was found that, in terms of cardiovascular safety, the outcome of the semaglutide was not worse than that of the placebo group. This indicates that cardiovascular risk is not high when taking this drug [23].