What laboratory tests are required before prescribing semaglutide (glucagon-like peptide-1 receptor agonist)?

Laboratory Testing Before Prescribing Semaglutide

Before prescribing semaglutide, you should order HbA1c, renal function (serum creatinine/eGFR), and lipid panel as baseline metabolic assessments, while ensuring you document personal and family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, pancreatitis, and diabetic retinopathy—though routine calcitonin, lipase, or amylase testing is not required unless clinically indicated.

Essential Baseline Laboratory Tests

Metabolic Parameters

• HbA1c should be measured to establish baseline glycemic control and guide dosing expectations 1
• Serum creatinine and eGFR are essential to assess renal function, particularly since GLP-1 receptor agonists can be used when eGFR is <45 mL/min/1.73 m² (though with reduced glycemic efficacy) 2
• Lipid panel (total cholesterol, LDL, HDL, triglycerides) should be obtained as part of cardiovascular risk assessment 1
• Thyroid function tests (TSH, T3, T4) are commonly obtained in clinical practice 1

What You Do NOT Need to Routinely Order

• Calcitonin levels are not recommended for routine screening before semaglutide initiation 1
• Pancreatic enzymes (lipase, amylase) are not required unless there is clinical suspicion of pancreatitis 1
• Routine glucose monitoring beyond HbA1c is not mandated, though fasting plasma glucose may be helpful in prediabetes populations 3

Critical Clinical History Assessment

Absolute Contraindications to Document

• Personal or family history of medullary thyroid carcinoma (MTC) 4
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 2, 4

These are FDA boxed warnings and represent absolute contraindications to semaglutide use.

Important Clinical Histories to Evaluate

• History of pancreatitis: Semaglutide has not been studied in patients with prior pancreatitis and is not recommended if pancreatitis is suspected or confirmed 4
• Diabetic retinopathy: Document any history, as semaglutide (particularly injectable formulations) may increase risk of retinopathy complications 2, 5
• Gastroparesis or active gallbladder disease: These are relative contraindications given the delayed gastric emptying effects 2
• History of diabetic ketoacidosis: This warrants caution 2

Common Clinical Pitfall

A recent study found that despite 98.6% of patients having at least one relevant disease history, only 1.8% had appropriate pretreatment disease history documentation, and 0% had pancreatic enzyme or calcitonin levels checked 1. This represents a significant gap between ideal practice and reality. While extensive enzyme testing is not required, thorough history-taking is essential and often neglected.

Monitoring Recommendations After Initiation

• Eye examination: Patients should undergo guideline-recommended eye examinations before starting therapy if not done within the last 12 months 2
• Home glucose monitoring: Instruct patients to monitor glucose more closely for the first 4 weeks, especially if on insulin, sulfonylureas, or glinides 2
• Renal function: Monitor kidney function periodically, particularly when initiating or up-titrating ACE inhibitors or ARBs concurrently 2

Medication Adjustments Based on Baseline Labs

• If HbA1c is well-controlled at baseline: Consider reducing sulfonylurea dose by 50% or basal insulin by 20% when starting semaglutide to prevent hypoglycemia 2
• If eGFR <45 mL/min/1.73 m²: Semaglutide can still be used (unlike SGLT2 inhibitors which have more restrictions), though glycemic efficacy may be reduced 2