What laboratory tests should be ordered prior to initiating tirzepatide (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) therapy?

Laboratory Tests Prior to Initiating Tirzepatide

Before starting tirzepatide, obtain baseline HbA1c, comprehensive metabolic panel (including renal function and liver function tests), lipid panel, and body weight/BMI measurements. 1

Essential Baseline Laboratory Tests

Metabolic and Glycemic Assessment

• HbA1c should be measured at baseline to establish glycemic control and guide treatment goals 1
• Fasting glucose or random glucose can be obtained if HbA1c is unavailable, though fasting samples are preferred for accurate assessment 1

Renal Function Monitoring

• Comprehensive metabolic panel (CMP) including creatinine, blood urea nitrogen (BUN), and electrolytes must be obtained before initiation 1
• Estimated glomerular filtration rate (eGFR) should be calculated, as tirzepatide is partially renally excreted and may cause early transient eGFR changes 2, 3
• Consider obtaining both creatinine-based and cystatin C-based eGFR in patients with obesity, as body composition changes can affect creatinine measurements and lead to discordant results 2
• Serum calcium should be monitored, particularly in patients on chronic thiazide diuretics or with chronic kidney disease, as tirzepatide may interact with calcium metabolism 4

Hepatic Function

• Liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) should be obtained at baseline 1

Cardiovascular Risk Assessment

• Lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) should be measured before starting therapy 1
• Blood pressure measurement is essential as part of cardiometabolic risk stratification 1

Additional Baseline Measurements

• Body weight, BMI, and waist circumference should be documented to track treatment response 1
• Urine albumin-to-creatinine ratio (UACR) should be obtained if not recently measured, as tirzepatide reduces albuminuria 1, 3

Special Considerations and Monitoring Caveats

Patients on Thiazide Diuretics

• Close calcium monitoring is critical in patients taking hydrochlorothiazide or other thiazides, as the combination with tirzepatide may precipitate severe hypercalcemia 4
• Obtain baseline calcium and recheck within 1-2 weeks of initiating tirzepatide in these patients 4

Patients with Chronic Kidney Disease

• Baseline renal function is particularly important as CKD patients may experience greater absolute benefit from tirzepatide but require careful monitoring 2, 3
• Consider both creatinine and cystatin C-based eGFR measurements due to potential confounding from obesity-related changes in muscle mass 2

Pregnancy Testing

• While not specifically mentioned for tirzepatide in the provided guidelines, pregnancy testing should be considered in females of reproductive potential given the general approach to diabetes medications 5

Follow-Up Laboratory Monitoring

Early Follow-Up (4-12 Weeks)

• Fasting glucose or HbA1c should be rechecked at 4 weeks to assess early glycemic response 1
• Renal function (CMP) should be repeated at 12 weeks, as tirzepatide may cause an early transient dip in eGFR (particularly with creatinine-based measurements) 2, 3
• Calcium levels should be rechecked within 1-2 weeks in patients on thiazide diuretics 4

Long-Term Monitoring (3-12 Months)

• HbA1c should be reassessed at 3 months and then every 3-6 months thereafter 1
• Lipid panel should be repeated at 3-6 months and annually 1
• Renal function and liver function tests should be monitored every 3-6 months 1
• Body weight and blood pressure should be checked at each visit 1

Important Clinical Pitfalls

• Do not rely solely on creatinine-based eGFR in obese patients receiving tirzepatide, as weight loss and changes in muscle mass can artificially alter creatinine levels and lead to misleading eGFR trends 2
• Avoid combining tirzepatide with other incretin-based therapies (GLP-1 receptor agonists or DPP-4 inhibitors) due to increased risk of adverse effects without additional benefit 1, 6
• Exercise caution when combining with insulin or sulfonylureas, as this increases hypoglycemia risk despite tirzepatide's glucose-dependent mechanism 1, 6
• Monitor for gastrointestinal symptoms including diarrhea, which may be more common with tirzepatide compared to GLP-1 receptor agonists alone 7