What follow-up tests are recommended for a patient on Glucagon-like peptide-1 (GLP-1) receptor agonists?

Follow-Up Testing for Patients on GLP-1 Receptor Agonists

Patients on GLP-1 receptor agonists require annual screening for chronic kidney disease (urine albumin-to-creatinine ratio and eGFR), retinopathy assessment (dilated eye exam annually if diabetic retinopathy is present, every 1-2 years if absent with good glycemic control), and monitoring for gastrointestinal symptoms and hypoglycemia at each visit. 1

Kidney Function Monitoring

Annual CKD screening is mandatory for all patients with diabetes on GLP-1 receptor agonists, starting at diagnosis for type 2 diabetes and 5 years after diagnosis for type 1 diabetes. 1

• Measure spot urine albumin-to-creatinine ratio (ACR) annually to detect albuminuria (≥30 mg/g indicates CKD) 1
• Measure eGFR annually; persistent eGFR <60 mL/min/1.73 m² for at least 3 months defines CKD 1
• Consider using cystatin C in addition to creatinine for more precise GFR estimation if initial results are abnormal 1
• Evaluate for temporary causes (dehydration, acute illness) before confirming CKD diagnosis, as persistence for at least 3 months is required 1

Important caveat: GLP-1 receptor agonists themselves are not directly nephrotoxic, but postmarketing reports of acute kidney injury have occurred, primarily in patients experiencing nausea, vomiting, diarrhea, or dehydration 2. Monitor renal function closely when initiating or escalating doses, particularly in patients with pre-existing renal impairment 2.

Retinopathy Screening

Retinopathy status must be assessed when intensifying glucose-lowering therapies with GLP-1 receptor agonists, as rapid A1C reductions can cause initial worsening of diabetic retinopathy. 1

• Type 2 diabetes: Initial dilated comprehensive eye examination at diagnosis, then annually if any level of retinopathy is present 1
• If no retinopathy is present for one or more annual exams and glycemic indicators are at goal, screening every 1-2 years may be considered 1
• If retinopathy is progressing or sight-threatening, examinations must be more frequent than annually 1
• GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide) have been associated with increased risk of rapidly worsening diabetic retinopathy in randomized trials, particularly in patients with established retinopathy 1

Glycemic Monitoring

HbA1c should be measured every 3 months in patients at low risk for complications, with more frequent capillary glucose monitoring in high-risk patients. 1

• Low-risk patients: HbA1c every 3 months with serum glucose at treatment cycles 1
• Moderate-risk patients (on corticosteroids, elevated lipase): Serum glucose 2 hours postprandial or 8 hours after prednisolone dosing at clinic visits; fasting glucose may not capture severity of hyperglycemia 1
• High-risk patients (newly detected hyperglycemia, pre-existing type 2 diabetes): Daily patient self-monitoring with glucometer 1
• Patients using GLP-1 receptor agonists with obesity are at risk of stress hyperglycemia and should have regular capillary glucose measurements with prompt intervention if hyperglycemia occurs 1

Hypoglycemia Assessment

At every visit, assess for hypoglycemia symptoms, particularly in patients taking GLP-1 receptor agonists with insulin secretagogues or insulin. 2

• Adult patients receiving GLP-1 receptor agonists with sulfonylureas or insulin have increased risk of hypoglycemia, including severe hypoglycemia 2
• Pediatric patients (≥10 years) have higher hypoglycemia risk with GLP-1 receptor agonists regardless of insulin or metformin use 2
• Consider dose reduction of sulfonylurea or insulin to lower hypoglycemia risk 2
• Educate patients on signs and symptoms of hypoglycemia at each visit 2

Gastrointestinal Symptom Monitoring

Assess bowel movement frequency, consistency, and upper GI symptoms (nausea, vomiting, abdominal pain) at each follow-up visit. 3, 4

• Most GI adverse events occur within the first month of therapy and may improve with continued use due to tachyphylaxis 3
• Delayed gastric emptying with retained gastric contents has been documented in 24.2-56% of patients despite prolonged fasting 3
• Monitor for signs of bowel obstruction in patients reporting severe constipation 4
• Consider gastric ultrasound if severe symptoms develop, particularly before any procedural sedation 4

Pancreatitis Surveillance

Instruct patients to report persistent severe abdominal pain radiating to the back, with or without vomiting, at every visit. 2

• If pancreatitis is suspected, promptly measure serum lipase or amylase and imaging studies of the pancreas 2
• If pancreatitis is confirmed, discontinue GLP-1 receptor agonist permanently and do not restart 2
• Patients with history of cholelithiasis or alcohol abuse may be at higher risk 2

Gallbladder Disease Monitoring

If cholelithiasis is suspected based on symptoms (right upper quadrant pain, nausea after fatty meals), obtain gallbladder ultrasound and appropriate clinical follow-up. 2

• Acute events of gallbladder disease (cholelithiasis, cholecystitis) have been reported in GLP-1 receptor agonist trials and postmarketing 2

Body Weight and BMI Tracking

Document body weight at each visit to assess treatment response and adjust dosing as needed. 5

• GLP-1 receptor agonists are associated with weight loss compared to placebo or other antidiabetic drugs 5, 6
• Weight reduction is a key therapeutic benefit and should be tracked systematically 5

Duration of Follow-Up

Continue monitoring for at least 12 months after GLP-1 receptor agonist initiation, as checkpoint inhibitor-associated diabetes mellitus has median onset of 12 weeks but cases have been reported years after initiation. 1

• After initial 12-month intensive monitoring period, transition to long-term monitoring as per standard type 2 diabetes screening guidelines 1

Pre-Procedural Considerations

Patients must inform healthcare providers prior to any planned surgeries or procedures requiring general anesthesia or deep sedation that they are taking GLP-1 receptor agonists. 2

• GLP-1 receptor agonists delay gastric emptying, creating risk of pulmonary aspiration during anesthesia 2
• Rare postmarketing reports of pulmonary aspiration have occurred in patients with residual gastric contents despite adherence to preoperative fasting recommendations 2
• Point-of-care gastric ultrasound should be considered before induction of anesthesia to facilitate risk stratification 1