Semaglutide Side Effects
Tuesday, February 27th, 2024

The ongoing research and development for effective weight loss medications and to treat metabolic disorders has led to the emergence of novel pharmaceutical agents such as semaglutide.

Revered for its potent high blood sugar control and chronic weight management benefits, semaglutide has garnered significant medical attention among individuals striving to manage conditions like type 2 diabetes mellitus and obesity.

Despite the promising benefits that FDA-approved semaglutide has to offer with strong efficacy, it definitely comes with potential side effects just like other medications and which need careful consideration and scrutiny.

From gastrointestinal disturbances to potential risks to cardiometabolic health, our goal with this article will be to delve into the scientific literature and clinical observations to equip the readers with a comprehensive understanding of the physiological mechanisms and clinical manifestations leading to the potential adverse effects that one needs to consider before starting the semaglutide therapy.

While the majority of patients may tolerate semaglutide well, it is essential to be aware of potential adverse reactions that may arise.

Gastrointestinal Disturbances

Gastrointestinal Disturbances

Among the most commonly reported side effects of semaglutide therapy are gastrointestinal symptoms, particularly severe nausea and vomiting. These symptoms typically occur during the initial weeks of treatment and may diminish over time (1,2).

Some individuals may also experience diarrhea as a side effect of semaglutide. This can contribute to fluid and electrolyte imbalances if not managed appropriately

Metabolic Effects

metabolic effects

Being a glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide plays a primary role in lowering blood sugar levels. Semaglutide’s glucose-lowering effects may occasionally lead to hypoglycemia, especially when used concomitantly with other anti-diabetes medications such as metformin, insulin, or sulfonylureas. Therefore, it is crucial that patients should be educated on recognizing and managing low blood sugar/hypoglycemic episodes.

Alternatively, semaglutide therapy can rarely lead to hyperglycemia as well, particularly during periods of illness or stress. Monitoring blood glucose levels is crucial to detect and manage this potential complication.

Significant Appetite Loss

As a potent GLP-1 receptor agonist, it acts on the brain’s appetite centers, specifically the hypothalamus, to increase feelings of fullness (satiety) and decrease hunger.

Additionally, semaglutide slows gastric emptying, prolonging the time it takes for food to leave the stomach. This delayed gastric emptying further contributes to feelings of fullness and reduced appetite.

Severely reduced appetite may lead to significant weight loss which is often unwanted leading to other life-threatening complications.

Acute Pancreatitis

While rare, semaglutide therapy has been associated with acute pancreatitis, one of the potentially life-threatening complications of the pancreas that is characterized by severe stomach pain/abdominal pain radiating to the back, fever, tachycardia, hypotension, jaundice, etc (3).

Patients should be educated on the signs and symptoms of pancreatitis and instructed to discontinue semaglutide and visit the doctor immediately if symptoms occur.

Thyroid Cancer (C-cell) Tumor

Preclinical studies involving rodents show a potential risk of developing medullary thyroid carcinoma, or thyroid cancer (C-cell) tumor associated with the use of semaglutide.

However, it is important to know that there is no relevance proven whether the use of semaglutide is associated with thyroid cancer in humans, and more clinical studies are warranted to establish any association.

Injection-Site Reactions

injection site reactions

While highly unlikely, some individuals may experience unusual or allergic reaction in the form of redness, itching, or nodules at the injection site (3). Don’t use the same body area by administering on multiple injection sites as well as proper injection techniques to avoid these unnecessary allergic reactions.

What To Expect

While semaglutide injections offer significant therapeutic benefits in the management of type 2 diabetes and obesity in patients with high body mass index (BMI), it is imperative for health care professionals and patients to remain vigilant regarding potential adverse effects.

Regular monitoring, patient education, and prompt medical consultation of any concerning severe symptoms are essential components of safe and effective semaglutide therapy in the longer run.


  1. Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., Kushner, R. F., & STEP 1 Study Group (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England journal of medicine, 384(11), 989–1002.
  2. Garvey, W. T., Batterham, R. L., Bhatta, M., Buscemi, S., Christensen, L. N., Frias, J. P., Jódar, E., Kandler, K., Rigas, G., Wadden, T. A., Wharton, S., & STEP 5 Study Group (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature medicine, 28(10), 2083–2091.
  3. Smits, M. M., & Van Raalte, D. H. (2021). Safety of Semaglutide. Frontiers in endocrinology, 12, 645563.

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