From the Guidelines
Oral compounded semaglutide is associated with common side effects including nausea, vomiting, diarrhea, abdominal pain, and constipation, as well as rare but serious side effects like pancreatitis or gallbladder problems, and should be started at a low dose and gradually increased as tolerated to minimize these effects. The most recent and highest quality study, published in 2023 1, reports that semaglutide is associated with a range of gastrointestinal side effects, including nausea, vomiting, diarrhea, constipation, headache, fatigue, dizziness, and changes in appetite. Other potential side effects may include:
- Abdominal distension
- Eructation
- Gastroenteritis
- Gastroesophageal reflux disease
- Injection site reactions
- Suicidal ideation and behavior To minimize side effects, it is recommended to start with a low dose and gradually increase over several weeks as tolerated, taking the medication with a small amount of food and staying well-hydrated 1. Additionally, a 2024 study published in Anaesthesia 1 provides guidance on managing common adverse effects of GLP-1 receptor agonists, including nausea and vomiting, dyspepsia, diarrhea, gastrointestinal reflux, constipation, and gallbladder disorders. A 2022 study published in Gastroenterology 1 also reports on the harms associated with semaglutide, including a 38% higher risk of serious adverse events compared to placebo. Overall, the evidence suggests that oral compounded semaglutide can be an effective treatment for weight management, but it is essential to carefully monitor patients for potential side effects and adjust the dose accordingly.
From the FDA Drug Label
The risk of hypoglycemia is increased when OZEMPIC is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Documented symptomatic hypoglycemia occurred in 17.3% and 24.4% of patients when OZEMPIC 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea. Severe or blood glucose confirmed symptomatic hypoglycemia occurred in 6.5% and 10.4% of patients when OZEMPIC 0. 5 mg and 1 mg, respectively, was co-administered with a sulfonylurea. Injection Site Reactions In placebo-controlled trials, injection site reactions (e.g., injection-site discomfort, erythema) were reported in 0. 2% of OZEMPIC-treated patients. Increases in Amylase and Lipase In placebo-controlled trials, patients exposed to OZEMPIC had a mean increase from baseline in amylase of 13% and lipase of 22%. Cholelithiasis In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with OZEMPIC 0. 5 mg and 1 mg, respectively. Increases in Heart Rate In placebo-controlled trials, OZEMPIC 0.5 mg and 1 mg resulted in a mean increase in heart rate of 2 to 3 beats per minute. Fatigue, Dysgeusia and Dizziness Other adverse reactions with a frequency of >0.4% were associated with OZEMPIC include fatigue, dysgeusia and dizziness.
The side effects of oral compounded semaglutide (GLP-1 receptor agonist) include:
- Hypoglycemia: increased risk when used with insulin secretagogues or insulin
- Injection site reactions: reported in 0.2% of patients
- Increases in amylase and lipase: mean increase from baseline of 13% and 22%, respectively
- Cholelithiasis: reported in 1.5% and 0.4% of patients treated with 0.5 mg and 1 mg, respectively
- Increases in heart rate: mean increase of 2 to 3 beats per minute
- Fatigue, dysgeusia, and dizziness: reported with a frequency of >0.4% 2
From the Research
Side Effects of Oral Compounded Semaglutide
The side effects of oral compounded semaglutide, a GLP-1 receptor agonist, have been reported in several studies. Some of the common side effects include:
- Nausea and vomiting 3, 4, 5, 6, 7
- Abdominal pain 3, 4, 6, 7
- Diarrhea 6, 7
- Headache 3
- Anorexia 3
- Weakness and fatigue 3
- Gastroparesis 4
Gastrointestinal Disorders
Gastrointestinal disorders are the most commonly reported side effects of semaglutide, with a high prevalence of adverse gastrointestinal events in both oral and injectable dosage forms 6, 7. The most severe reported cases were primarily gastrointestinal disorders, including nausea, vomiting, and abdominal pain 6.
Serious Adverse Events
Serious adverse events, including hemorrhagic diarrhea, hepatic pain, abnormal hormone levels, and pancreatic failure, have been identified in subcutaneous semaglutide, while Dupuytren's contracture has been identified in oral semaglutide 7. The median onset for gastrointestinal side effects was 4 days in both oral and subcutaneous formulations 7.
Administration Errors
Administration errors, including incorrect dosing and lack of pharmacist counseling, have been reported in cases of adverse drug events after incorrect administration of semaglutide for weight loss obtained from compounding pharmacies and an aesthetic spa 3. These errors can lead to large overdoses and patient harm.