Generic semaglutide side effects: what the Canadian product monograph says

Most common side effects

This page follows the product monograph of Semaglutide Injection (Dr. Reddy's Laboratories Ltd.), a generic semaglutide injection. It does not describe the generic products of other companies.

In clinical trials, the most frequently reported adverse reactions were gastrointestinal disorders, including nausea, diarrhea and vomiting. In general, these reactions were mild or moderate in severity.

The majority of the nausea, vomiting and diarrhea events occurred during dose escalation.

The patient information in the product monograph lists the side effects by frequency:

• Very common (may affect more than 1 in 10 people): nausea and diarrhea. These usually go away over time.
• Very common: low blood sugar (hypoglycemia) when Semaglutide Injection is used with a sulfonylurea or insulin.
• Common (may affect up to 1 in 10 people): vomiting, headache, indigestion, inflamed stomach (gastritis), reflux or heartburn, stomach pain, bloating, constipation, burping and gas.
• Also common: gall stones, feeling dizzy, feeling tired, weight loss, less appetite, an increase of pancreatic enzymes and complications of diabetic eye disease.
• Also common: low blood sugar when Semaglutide Injection is used with an oral antidiabetic other than a sulfonylurea.
• Uncommon (may affect up to 1 in 100 people): a change in the way food or drink tastes, and fast pulse.
• Also uncommon: injection site reactions, and allergic reactions like rash, itching or hives.
• Rare (may affect up to 1 in 1,000 people): severe allergic reactions (anaphylactic reactions, angioedema).
• Unknown frequency: intestinal obstruction including ileus, and a delay in emptying of the stomach.

Numbers from the clinical trials

Table 2 of the product monograph gives the adverse reactions in seven phase 3a trials of 30 or 52 weeks duration. The trials tested semaglutide 0.5 mg and 1 mg.

Gastrointestinal adverse reactions led 3.9% of patients on 0.5 mg and 5.9% of patients on 1 mg to discontinue treatment.

In a 40-week trial, gastrointestinal disorders were reported in 34.0% of patients on 2 mg and in 30.8% of patients on 1 mg.

Table 2 gives these percentages of patients on semaglutide 0.5 mg and on semaglutide 1 mg:

• Nausea: 17.0% and 19.9%.
• Diarrhea: 12.2% and 13.3%.
• Abdominal pain: 8.7% and 8.1%.
• Vomiting: 6.4% and 8.4%.
• Constipation: 6.9% and 6.2%.
• Decreased appetite: 6.3% and 7.2%.

Serious warnings

The product monograph has a Serious Warnings and Precautions Box about the risk of thyroid C-cell tumours.

Semaglutide causes thyroid C-cell tumours in rats and mice at clinically relevant exposures. It is unknown whether semaglutide causes these tumours, including medullary thyroid carcinoma (MTC), in humans.

The patient information says to tell your doctor if you get a lump or swelling in your neck, hoarseness, trouble swallowing or shortness of breath. These may be symptoms of thyroid cancer.

The product monograph also gives these warnings:

• Pancreatitis: acute pancreatitis has been observed with the use of GLP-1 receptor agonists. If pancreatitis is suspected, Semaglutide Injection should be discontinued.
• Low blood sugar: a sulfonylurea medicine or insulin with Semaglutide Injection might increase the risk of low blood sugar levels (hypoglycemia).
• Diabetic eye disease: fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disease.
• Sudden loss of vision: this may be caused by a very rare side effect called non-arteritic anterior ischaemic optic neuropathy (NAION).
• Heart: Semaglutide Injection may increase heart rate and could cause changes known as PR prolongation.
• Dehydration: nausea, vomiting and diarrhea can cause dehydration. The patient information says that it is important to drink plenty of fluids.
• Kidneys: in patients with impaired renal function, dehydration could cause a deterioration of renal function.
• Gallbladder: acute events of gallbladder disease, such as cholelithiasis or cholecystitis, have been reported in GLP-1 receptor agonist trials and post-market.
• Stomach and bowel: use of GLP-1 receptor agonists may be associated with severe gastrointestinal disease (ileus).
• Gastroparesis (delayed stomach emptying): Semaglutide Injection may lead to serious or severe gastrointestinal adverse events. Talk to your doctor before you use it.
• Anaesthesia or sedation: tell your healthcare professional that you take Semaglutide Injection before a procedure that requires general anaesthesia or sedation.

Who must not use it

The product monograph says that Semaglutide Injection should not be used during pregnancy, and for at least two months before a planned pregnancy.

Semaglutide Injection should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Semaglutide Injection is not indicated for use in pediatric patients (under 18 years of age).

The patient information says: do not use Semaglutide Injection if:

• You are allergic to semaglutide or to any of the other ingredients of this medicine.
• You or a member of your family has ever had medullary thyroid cancer (MTC).
• You have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• You are pregnant or breastfeeding.

When to stop and get medical help

The patient information has a rule for an overdose. If you think that you took too much Semaglutide Injection, contact a healthcare professional, a hospital emergency department or a regional poison control centre immediately. You can also call the toll-free number of Health Canada, 1-844 POISON-X (1-844-764-7669). Do this even if there are no signs or symptoms.

For complications of diabetic eye disease (common), the product monograph says to talk to your healthcare professional in all cases.

If you notice a sudden loss of vision or rapidly worsening eyesight, the patient information says to contact your doctor urgently.

The product monograph has a table of serious side effects. For the four below, it says to talk to your healthcare professional, stop the drug and get immediate medical help.

• Pancreatitis (uncommon): severe and ongoing pain in the stomach area, which could be a sign of inflamed pancreas.
• Severe hypoglycemia, or low blood sugar (uncommon): feeling confused, fits and passing out.
• Severe allergic reaction (rare): breathing problems, swelling of face, lips, tongue and/or throat with difficulty swallowing and a fast heartbeat.
• Non-arteritic anterior ischemic optic neuropathy (very rare): sudden vision loss that may be painless, blurring or cloudiness of vision, headaches.

Ask a health professional

This page repeats what the Canadian product monograph says. It is not medical advice. Ask your pharmacist or your prescriber what applies to you.