What to Watch for While on GLP-1 Therapy
When initiating or maintaining GLP-1 therapy, prioritize monitoring for gastrointestinal complications (especially nausea and pancreatitis), hypoglycemia risk when combined with insulin or sulfonylureas, diabetic retinopathy progression in high-risk patients, and acute kidney injury from volume depletion.
Gastrointestinal Monitoring
Common GI Side Effects
- Nausea and vomiting are the most frequent adverse effects, occurring in a dose-dependent manner and more commonly with short-acting than long-acting formulations 1, 2.
- Monitor for dyspepsia, gastroesophageal reflux, diarrhea, and abdominal pain, which can significantly impact quality of life 1, 2.
- These symptoms typically occur during initial treatment and gradually diminish with time, usually resolving within a few weeks 3.
- If GI symptoms do not resolve after several weeks, follow up with the healthcare provider 3.
Serious GI Complications
- Watch for signs of acute pancreatitis: persistent severe abdominal pain (sometimes radiating to the back), which may or may not be accompanied by vomiting 4.
- If pancreatitis is suspected, discontinue GLP-1 therapy immediately and do not restart if confirmed 4.
- Use GLP-1 agonists with caution in patients with a history of pancreatitis 3, 1.
- Monitor for gallbladder disease, including cholelithiasis and cholecystitis, as these have been reported with GLP-1 use 1, 5.
Hypoglycemia Risk Management
High-Risk Scenarios
- The risk of hypoglycemia increases significantly when GLP-1 therapy is combined with insulin secretagogues (sulfonylureas, glinides) or insulin 3, 4.
- Instruct patients to monitor glucose more closely at home for the first 4 weeks of therapy, especially if on insulin, sulfonylurea, or glinides 3.
Dose Adjustments
- Consider discontinuing any sulfonylurea or glinide when starting GLP-1 therapy 3.
- For patients taking insulin, reduce total daily insulin dose by up to 20% when initiating GLP-1 therapy 3.
- If HbA1c is well-controlled at baseline or there is a history of frequent hypoglycemic events, wean or stop sulfonylurea before starting 3.
Ophthalmologic Monitoring
- Ensure patients undergo appropriate eye examinations before starting therapy if not done within the last 12 months 3.
- An increased risk of diabetic retinopathy complications has been noted with semaglutide, predominantly in patients with prior history of proliferative retinopathy 3, 4.
- The absolute risk increase is larger among patients with a history of diabetic retinopathy at baseline (8.2% vs 5.2% placebo) compared to those without known history (0.7% vs 0.4% placebo) 4.
- This risk is hypothesized to be due to rapid and sustained reductions in blood glucose 3.
- Monitor patients with a history of diabetic retinopathy for progression 4.
Renal Function Monitoring
Acute Kidney Injury Risk
- Monitor renal function when initiating or escalating doses, particularly in patients reporting severe gastrointestinal reactions 4.
- Acute kidney injury can occur through hemodynamic derangement due to nausea, vomiting, and diarrhea leading to volume depletion 2, 6.
- Most reported events occurred in patients who experienced severe GI losses 4.
Monitoring Strategy
- Check renal function in the first several weeks of therapy, especially in patients with impaired renal function at baseline 3.
- Watch for signs of volume depletion such as orthostatic lightheadedness 3.
- Instruct patients to contact their clinician if symptoms of dehydration occur 3.
Cardiovascular and Hemodynamic Monitoring
- Monitor for increased heart rate: mean increases of 2-3 beats per minute have been observed 5.
- First-time administration or dose escalation increases the risk of transient blood pressure elevation 7.
- Assess for symptoms of hypertensive urgency including severe headache, visual disturbances, and chest pain 7.
Thyroid Monitoring
- GLP-1 receptor agonists carry an FDA Black Box Warning for thyroid C-cell tumors 3.
- They are contraindicated in patients with personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2 3.
- Watch for symptoms of thyroid tumors: lump or swelling in the neck, dysphagia, dyspnea, persistent hoarseness 4.
- Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value but may be considered 4.
Drug Interactions and Contraindications
- Discontinue DPP-4 inhibitors before starting GLP-1 therapy, as they both work through GLP-1 signaling and are not approved for use together 3.
- Avoid in patients with diabetic gastroparesis or active gallbladder disease 3.
- GLP-1 therapy may delay gastric emptying, potentially affecting absorption of other oral medications 1, 8.
Perioperative Considerations
- Consider temporary discontinuation before elective surgery requiring general anesthesia or deep sedation due to risk of pulmonary aspiration 1, 5.
- This is particularly important given the delayed gastric emptying effect of GLP-1 agonists 1.
Mitigation Strategies
Dose Titration
- Start at the lowest dose and up-titrate gradually once every few weeks to minimize nausea and vomiting 3.
- Recommend small portion sizes for meals during titration 3.
- If treatment is suspended, reinitiation should again be at the lowest dose with gradual up-titration 3.
Patient Education
- Educate patients that transient nausea and vomiting are common and usually self-limited with longer-acting formulations 3.
- Advise reducing meal size, limiting alcohol and carbonated drinks, and avoiding high-fat diets to minimize symptoms 1.
- Instruct patients to carry a source of quick-acting carbohydrates if on concomitant insulin or sulfonylureas 3.
Rare but Serious Adverse Events
- Watch for signs of hypersensitivity reactions including anaphylaxis and angioedema; discontinue immediately if these occur 4.
- Monitor for injection site reactions, though these rarely result in discontinuation 6.
- Be aware of potential for diabetic ketoacidosis, which can occur even with blood glucose readings in the 150-250 mg/dL range 3.