What are the potential side effects and management strategies for a patient with type 2 diabetes or obesity starting Ozempic (semaglutide)?

Ozempic (Semaglutide) Side Effects

Most Common Side Effects

Gastrointestinal symptoms are the predominant side effects of Ozempic, occurring in the majority of patients but typically being transient and dose-dependent. 1, 2

Gastrointestinal Effects

• Nausea occurs in 18-40% of patients, typically mild-to-moderate and decreases over time 1
• Diarrhea affects 12-16% of patients 1
• Vomiting occurs in 8-16% of patients 1, 2
• Constipation is common and can be managed by avoiding high-fat diets 1, 2
• Abdominal pain and dyspepsia are frequently reported 1, 2
• Esophageal reflux results from delayed gastric emptying and can be reduced by limiting alcohol and carbonated drinks 2

Slow dose titration starting at 0.25 mg weekly for 4 weeks, then 0.5 mg, then 1 mg if needed, is essential to minimize these gastrointestinal side effects. 1, 2

Serious Adverse Events

Pancreatitis Risk

• Stop Ozempic immediately and seek medical attention if you develop severe, persistent abdominal pain that radiates to your back, with or without vomiting 1, 3
• Pancreatitis has been reported in clinical trials, though causality has not been definitively established 1
• Use with caution in patients with a history of pancreatitis 1, 2

Gallbladder Disease

• Increased risk of cholelithiasis (gallstones) and cholecystitis requiring monitoring 1, 2
• The mechanism relates to rapid weight loss and altered bile composition 2
• Monitor for right upper quadrant pain, fever, or jaundice 2

Kidney Problems

• Acute kidney injury can occur from dehydration secondary to severe gastrointestinal effects, particularly in patients with pre-existing kidney disease 1, 2, 3
• Monitor renal function closely when initiating or escalating doses, especially with severe GI symptoms 2
• Ensure adequate fluid intake to prevent dehydration-related kidney injury 2
• Unlike some other GLP-1 receptor agonists, semaglutide requires no dose adjustment for renal impairment but warrants careful monitoring 2

Hypoglycemia Risk

• Your risk for low blood sugar is higher if you use Ozempic with insulin or sulfonylureas 1, 3
• Reduce insulin dose by approximately 20% or sulfonylurea doses by 50% when starting Ozempic 1
• Signs of hypoglycemia include: shakiness, sweating, confusion, dizziness, blurred vision, fast heartbeat, slurred speech, and headache 3
• Semaglutide alone carries very low intrinsic hypoglycemia risk due to its glucose-dependent mechanism 2

Cardiovascular Effects

• Elevated heart rate is a common side effect requiring monitoring 2
• Cardiac arrhythmia/tachycardia may occur; if symptomatic, monitoring and consideration of beta blockers may be necessary 2
• Acute myocardial infarction has been reported in clinical trials 2

Vision Changes

• Tell your healthcare provider if you have changes in vision during treatment 3
• Patients with diabetic retinopathy should be monitored closely for progression 2

Thyroid Concerns

• Ozempic carries an FDA Black Box Warning regarding the risk of thyroid C-cell tumors based on rodent studies 2
• Absolutely contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2, 3

Other Notable Side Effects

• Injection site reactions occur with subcutaneous administration 2
• Insomnia has been reported 1
• Suicidal ideation has been reported in clinical trials 1, 2
• Dysaesthesia (abnormal sensations) can occur, particularly at higher doses 4

Management Strategies

For Nausea and Vomiting

• Reduce meal size 2
• Eat smaller, more frequent meals 1
• Avoid high-fat foods 2
• Limit alcohol and carbonated beverages 2
• If symptoms persist beyond the first few weeks at a given dose, consider remaining at that dose longer before escalating 2

For Constipation

• Avoid high-fat diets 2
• Increase fluid intake 2
• Consider fiber supplementation 1

For Reflux Symptoms

• Limit alcohol and carbonated drinks 2
• Avoid lying down immediately after eating 1

Missed Dose Protocol

• If you miss a dose, take it as soon as possible within 5 days after the missed dose 3
• If more than 5 days have passed, skip the missed dose and take your next dose on the regularly scheduled day 3
• If 2 consecutive doses are missed and you previously tolerated the medication well, resume at the same dose 2
• If 3 or more consecutive doses are missed, restart the titration schedule 2

Critical Contraindications

• Pregnancy and breastfeeding 2
• Personal or family history of medullary thyroid cancer or MEN2 1, 2, 3
• Severe hypersensitivity reaction to semaglutide 2
• Not recommended in patients with clinically meaningful gastroparesis 2

Monitoring Requirements

• Check blood sugar as your healthcare provider tells you to 3
• Monitor renal function, especially with severe GI symptoms 2
• Check for signs of gallbladder disease periodically 2
• Monitor for elevated heart rate 2
• Regular blood tests including blood sugar levels and hemoglobin A1C 3
• Assess efficacy and safety at least monthly for the first 3 months, then at least quarterly thereafter 2

Drug Interactions

• Ozempic delays gastric emptying and may affect absorption of oral medications, particularly those with narrow therapeutic index like warfarin 2
• For oral hormonal contraceptive users, add or switch to non-oral contraception for 4 weeks after initiation and each dose escalation 2
• Do not mix insulin and Ozempic together in the same injection 3
• Increased hypoglycemia risk when combined with insulin or insulin secretagogues 1, 2

When to Seek Immediate Medical Attention

• Severe, persistent abdominal pain that radiates to your back (possible pancreatitis) 1, 3
• Symptoms of serious allergic reaction: itching, rash, or difficulty breathing 3
• Signs of severe dehydration: decreased urination, extreme thirst, confusion 2
• Symptoms of gallbladder disease: right upper quadrant pain, fever, jaundice 2
• Severe hypoglycemia: confusion, loss of consciousness, seizures 3