What baseline lab tests are recommended for a patient with a suspected metabolic disorder, such as diabetes, prior to initiating treatment with Glucagon-Like Peptide-1 (GLP-1) receptor agonists or therapies targeting GLP-1 and Glucose-Dependent Insulinotropic Polypeptide (GIP)?

Baseline Laboratory Testing for GLP-1 and GLP-1/GIP Receptor Agonists

Obtain baseline HbA1c, fasting plasma glucose, comprehensive metabolic panel (including eGFR and electrolytes), lipid panel, and liver function tests before initiating GLP-1 or GLP-1/GIP receptor agonist therapy.

Essential Baseline Laboratory Tests

Glycemic Assessment

• HbA1c measurement is required to confirm diabetes diagnosis (≥6.5%) or assess baseline glycemic control 1
• Fasting plasma glucose (FPG) provides additional diagnostic confirmation if HbA1c is borderline or if hemoglobinopathies are present (diabetes diagnosed at FPG ≥126 mg/dL) 1
• Most clinical trials of GLP-1 RAs required baseline HbA1c ≥7% for enrollment, though lower thresholds may be appropriate for cardiovascular indications 1

Renal Function Assessment

• Estimated glomerular filtration rate (eGFR) must be measured using serum creatinine to assess kidney function and guide dosing 1
• Urine albumin-to-creatinine ratio (ACR) should be obtained to screen for chronic kidney disease, as GLP-1 RAs have proven kidney benefits in patients with albuminuria 1
• Annual screening with both eGFR and urine ACR is recommended for all patients with type 2 diabetes at diagnosis 1
• Consider cystatin C-based eGFR if creatinine-based estimates are unreliable 1

Hepatic Assessment

• Liver function tests (ALT, AST, bilirubin, alkaline phosphatase) should be obtained, particularly in patients with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) 2
• FIB-4 score calculation (using age, AST, ALT, and platelet count) is recommended for risk stratification of liver fibrosis in patients with MASLD 2
• If FIB-4 indicates indeterminate or high risk, proceed to liver stiffness measurement or Enhanced Liver Fibrosis (ELF) testing 2

Lipid Profile

• Complete lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) is necessary to assess cardiovascular risk and guide statin therapy 1, 3
• LDL-C goals vary by risk: <100 mg/dL for patients with ASCVD or diabetes, <130 mg/dL for moderately high-risk patients 3
• Statins remain first-line therapy for dyslipidemia; GLP-1 RAs should never be prescribed as primary lipid-lowering therapy 3

Electrolytes and Metabolic Panel

• Serum potassium is particularly important if considering combination therapy with SGLT2 inhibitors or RAS inhibitors, which may affect potassium levels 1
• Comprehensive metabolic panel provides baseline assessment of electrolytes, glucose, and renal function 1

Additional Screening Considerations

Cardiovascular Risk Assessment

• Document history of atherosclerotic cardiovascular disease (ASCVD), heart failure, or prior cardiovascular events, as this influences medication selection 1
• Blood pressure measurement is essential, as hypertension is a major risk factor requiring concurrent management 1

Contraindications to Assess

• Screen for personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (contraindications to GLP-1 RA therapy) 4
• Assess for history of pancreatitis, though this is a relative rather than absolute contraindication 4
• GLP-1 RAs are contraindicated in Child-Pugh C cirrhosis and require caution in Child-Pugh B cirrhosis 2

Common Pitfalls to Avoid

• Do not delay treatment waiting for liver biopsy confirmation in patients with high-risk noninvasive test results who require diabetes treatment 2
• Do not discontinue metformin unnecessarily; it can be continued with eGFR ≥30 mL/min/1.73 m² (reduce dose to 1000 mg daily if eGFR 30-44 mL/min/1.73 m²) 1
• Do not combine different incretin classes (GLP-1 RA, GIP/GLP-1 RA, DPP-4 inhibitors) due to risk of adverse effects without additional benefit 4
• Do not use HbA1c alone in patients with hemoglobinopathies, recent blood loss, pregnancy, or conditions with increased red cell turnover; use glucose-based criteria instead 1
• Do not stop SGLT2 inhibitors or RAS inhibitors for modest eGFR declines (<30% within a week); hemodynamic eGFR decline is expected and not associated with renal safety concerns 1

Monitoring After Initiation

• Repeat HbA1c every 3 months until glycemic targets are achieved, then at least twice yearly 1
• Monitor renal function (eGFR and urine ACR) annually, or more frequently if abnormal 1
• Assess for gastrointestinal symptoms during dose escalation, as nausea, diarrhea, and vomiting are common but usually transient 1, 5
• Consider SIBO breath testing if persistent gastrointestinal symptoms develop, as GLP-1 RAs may increase short-term SIBO risk 5