What laboratory tests should be obtained before initiating a GLP‑1 receptor agonist in an adult with type 2 diabetes or obesity?

Pre-Treatment Laboratory Testing for GLP-1 Receptor Agonists

Before initiating any GLP-1 receptor agonist (including semaglutide, tirzepatide, liraglutide, or dulaglutide), obtain HbA1c, comprehensive metabolic panel with eGFR, lipid panel, and liver function tests, while screening for absolute contraindications through clinical history. 1

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Essential Baseline Laboratory Tests

Glycemic Assessment

• Measure HbA1c to confirm diabetes diagnosis (≥6.5%) or assess baseline glycemic control if diabetes is already established. 1 Most clinical trials required HbA1c ≥7% for enrollment, establishing this as a practical threshold for initiating therapy. 1
• Obtain fasting plasma glucose (FPG) if HbA1c is borderline (5.7–6.4%) or if hemoglobinopathies are suspected, as diabetes is diagnosed at FPG ≥126 mg/dL. 1

Renal Function Assessment

• Calculate estimated glomerular filtration rate (eGFR) using serum creatinine to assess kidney function. 1, 2 This is critical because while GLP-1 receptor agonists require no dose adjustment across all CKD stages—even when eGFR <30 mL/min/1.73 m²—baseline values are needed to monitor for acute kidney injury secondary to dehydration from gastrointestinal side effects. 2
• Measure urine albumin-to-creatinine ratio (UACR) at baseline, as the National Kidney Foundation recommends annual screening using both eGFR and urine ACR for all patients with type 2 diabetes at diagnosis. 1

Hepatic Assessment

• Obtain liver function tests (ALT, AST, bilirubin, alkaline phosphatase) and calculate the FIB-4 score for risk stratification of liver fibrosis, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). 1 GLP-1 receptor agonists can reduce hepatic steatosis and improve liver function in patients with NAFLD. 2

Cardiovascular Risk Assessment

• Order a complete lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) to assess cardiovascular risk and guide statin therapy. 1 LDL-C goals vary by risk: <100 mg/dL for patients with ASCVD or diabetes, <130 mg/dL for moderately high-risk patients. 1
• Measure blood pressure as hypertension is a major risk factor requiring concurrent management. 1

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Critical Clinical History Screening

Absolute Contraindications (Must Screen Before Prescribing)

• Screen for personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)—these are absolute contraindications to all GLP-1 receptor agonists based on animal studies showing thyroid C-cell tumors. 1, 2, 3
• Document any history of severe hypersensitivity reaction to the specific GLP-1 receptor agonist being considered. 2

Relative Cautions (Document but Not Absolute Contraindications)

• Assess for history of pancreatitis—this is a relative rather than absolute contraindication, as causality between GLP-1 RAs and pancreatitis has not been definitively established. 1, 3 Use with caution and monitor closely. 3
• Document history of diabetic retinopathy, as semaglutide may increase risk of retinopathy complications. 2 Ensure guideline-recommended eye examinations are completed within the last 12 months before starting therapy. 2
• Identify gastroparesis or active gallbladder disease, which are relative contraindications given the delayed gastric emptying effects of GLP-1 receptor agonists. 2
• Note any history of diabetic ketoacidosis, as caution is recommended. 2

Cardiovascular Disease Documentation

• Document history of atherosclerotic cardiovascular disease (ASCVD), heart failure, or prior cardiovascular events, as this influences medication selection—semaglutide has proven cardiovascular benefit with a 26% reduction in major adverse cardiovascular events. 1, 3

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Medication Adjustments Based on Baseline Labs

If HbA1c Is Well-Controlled at Baseline

• Reduce sulfonylurea dose by 50% when starting a GLP-1 receptor agonist to prevent hypoglycemia. 2, 3
• Reduce basal insulin by 20% when initiating GLP-1 therapy to lower hypoglycemia risk. 2, 3

If eGFR <45 mL/min/1.73 m²

• GLP-1 receptor agonists can still be used without dose adjustment, though glycemic efficacy may be reduced. 2 Monitor renal function periodically, particularly when initiating or up-titrating ACE inhibitors or ARBs concurrently. 2

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Post-Initiation Monitoring Schedule

Glycemic Monitoring

• Repeat HbA1c every 3 months until glycemic targets are achieved, then at least twice yearly. 1
• Instruct patients to monitor glucose more closely for the first 4 weeks, especially if on insulin, sulfonylureas, or glinides. 2

Renal Monitoring

• Monitor renal function (eGFR and urine ACR) annually, or more frequently if abnormal. 1 Be particularly vigilant for acute kidney injury secondary to dehydration from gastrointestinal side effects. 2

Hepatic Monitoring

• Repeat thyroid testing (TSH and free T4) before each cycle during the initial treatment period if clinically indicated. 2
• Measure total bilirubin and transaminases periodically, as GLP-1 receptor agonists can reduce hepatic steatosis and improve liver function. 2

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Common Pitfalls to Avoid

• Do not skip screening for MTC or MEN2 family history—this is the only absolute contraindication and must be documented before prescribing. 1, 2, 3
• Do not assume dose adjustment is needed for renal impairment—GLP-1 receptor agonists require no dose modification even when eGFR <30 mL/min/1.73 m², but baseline values are essential for monitoring. 2
• Do not forget to reduce insulin or sulfonylureas when starting GLP-1 therapy in patients with well-controlled HbA1c—this prevents hypoglycemia. 2, 3
• Do not delay eye examination if not completed within the last 12 months, particularly for patients with diabetic retinopathy. 2