What baseline laboratory tests and monitoring schedule are recommended for a patient starting a glucagon‑like peptide‑1 (GLP‑1) receptor agonist or dual GLP‑1/glucose‑dependent insulinotropic polypeptide (GIP) therapy?

Baseline Laboratory Testing and Monitoring for GLP-1/GIP Therapy

Before initiating any GLP-1 receptor agonist or dual GLP-1/GIP therapy, obtain HbA1c, comprehensive metabolic panel with eGFR, lipid panel, and liver function tests; then reassess HbA1c every 3 months until target is achieved and renal function annually.

Essential Baseline Laboratory Tests

Glycemic Assessment

• Measure HbA1c to confirm diabetes diagnosis (≥6.5%) and establish baseline glycemic control; most clinical trials require HbA1c ≥7% for GLP-1 RA enrollment. 1
• Obtain fasting plasma glucose if HbA1c is borderline or hemoglobinopathies are suspected, with diabetes diagnosed at FPG ≥126 mg/dL. 1

Renal Function Evaluation

• Calculate eGFR using serum creatinine to assess kidney function and guide dosing decisions; the National Kidney Foundation mandates annual screening with both eGFR and urine albumin-to-creatinine ratio (UACR) for all patients with type 2 diabetes at diagnosis. 1
• This baseline is critical because GLP-1 RAs undergo minimal renal excretion due to structural modifications (amino acid substitutions, fatty acid conjugation, albumin fusion), but renal function still influences overall drug clearance. 2

Hepatic Assessment

• Order liver function tests (ALT, AST, bilirubin, alkaline phosphatase) and calculate FIB-4 score for risk stratification of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), as recommended by the American Association for the Study of Liver Diseases. 1

Cardiovascular Risk Stratification

• Obtain complete lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) to assess cardiovascular risk and guide statin therapy; the American College of Cardiology sets LDL-C goals at <100 mg/dL for patients with ASCVD or diabetes, and <130 mg/dL for moderately high-risk patients. 1
• Document history of atherosclerotic cardiovascular disease (ASCVD), heart failure, or prior cardiovascular events, as this directly influences medication selection between GLP-1 RAs (which reduce MACE by 26–29%) and other agents. 1
• Measure blood pressure because hypertension is a major risk factor requiring concurrent management. 1

Critical Safety Screening

Thyroid Cancer Risk

• Screen for personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2); these are absolute contraindications to GLP-1 RA therapy per the Endocrine Society. 1

Pancreatitis History

• Assess for history of pancreatitis, though this represents a relative rather than absolute contraindication. 1

Post-Initiation Monitoring Schedule

Glycemic Monitoring

• Repeat HbA1c every 3 months until glycemic targets are achieved (typically <7% for most adults), then at least twice yearly thereafter. 1
• This 3-month interval is the longest acceptable period before assessing effectiveness and avoiding therapeutic inertia. 3

Renal Surveillance

• Monitor eGFR and urine ACR annually, or more frequently if abnormal at baseline. 1
• Increased monitoring frequency (every 3–6 months) is warranted when eGFR declines toward 45 mL/min/1.73 m². 3

Vitamin B12 Assessment

• Check vitamin B12 levels periodically in patients on long-term metformin (which is often combined with GLP-1 RAs), especially if anemia or peripheral neuropathy develop. 3

Drug-Drug Interaction Considerations

Gastric Emptying Effects

• GLP-1 RAs and dual GIP/GLP-1 agonists delay gastric emptying, which can affect absorption of concomitantly administered oral medications. 4
• Significant exposure changes have been observed for oral contraceptives following tirzepatide administration and for levothyroxine following oral semaglutide, indicating the need for close monitoring in these instances. 2
• Most mechanism-of-action-mediated drug interactions involving delayed gastric emptying have been found clinically insignificant, but these two exceptions require vigilance. 2

Combination Therapy Warnings

• Never combine different incretin classes (GLP-1 RA, GIP/GLP-1 RA, DPP-4 inhibitor) due to risk of adverse effects without additional glucose-lowering benefit. 4
• Use caution when combining these medications with insulin or sulfonylureas due to increased hypoglycemia risk. 4

Common Pitfalls to Avoid

• Do not skip baseline renal function testing; although GLP-1 RAs undergo minimal renal excretion, eGFR influences drug clearance and is essential for assessing concomitant metformin safety. 2
• Do not delay HbA1c reassessment beyond 3 months after initiation; prolonged therapeutic inertia increases complication risk. 1
• Do not overlook thyroid cancer screening; this is an absolute contraindication that must be documented before prescribing. 1
• Do not assume all drug interactions are insignificant; specifically monitor oral contraceptive efficacy with tirzepatide and thyroid function with oral semaglutide. 2