What laboratory tests are recommended prior to initiating tirzepatide (a dual GIP (Glucose-dependent Insulinotropic Polypeptide) and GLP-1 (Glucagon-like Peptide-1) receptor agonist) therapy?

Laboratory Tests Prior to Initiating Tirzepatide

Before starting tirzepatide, obtain baseline fasting plasma glucose (or HbA1c if diabetes diagnosis needs confirmation), comprehensive metabolic panel including renal function tests, lipid panel, and complete blood count. 1

Essential Baseline Laboratory Testing

Glucose Assessment

• Fasting plasma glucose (FPG) is the preferred initial test for diabetes screening and baseline glycemic assessment 1
• HbA1c testing provides valuable baseline glycemic control data for monitoring treatment response, though it is not required for diagnosis if diabetes is already established 1
• If FPG is <126 mg/dL but diabetes is suspected, consider 75-g oral glucose tolerance test (OGTT) 1

Renal Function Testing

• Serum creatinine and estimated glomerular filtration rate (eGFR) are critical before initiating tirzepatide 1
• Tirzepatide can be used in chronic kidney disease, but caution is warranted when initiating or escalating doses due to potential acute kidney injury risk 2, 3
• While no dedicated kidney outcomes trials exist specifically for tirzepatide, monitoring renal function is essential given the drug class effects 1
• A modest eGFR decline (3-10%) may occur with GLP-1 receptor agonists and should not prompt discontinuation unless acute kidney injury is suspected 1

Hepatic Function

• Liver function tests (AST, ALT, bilirubin, alkaline phosphatase) should be obtained at baseline 1
• This is particularly important as tirzepatide has favorable effects on metabolic dysfunction-associated steatotic liver disease 1

Lipid Panel

• Fasting lipid profile including LDL cholesterol, HDL cholesterol, and triglycerides should be measured 1
• Tirzepatide has been shown to reduce LDL cholesterol and triglycerides 4
• Baseline lipid values help assess cardiovascular risk and monitor treatment effects 1

Complete Blood Count

• Full blood count with differential is recommended as part of routine baseline assessment 1

Special Considerations and Additional Testing

Calcium Monitoring in High-Risk Patients

• Serum calcium should be checked in patients on chronic thiazide diuretics (especially hydrochlorothiazide) or those with chronic kidney disease 5
• A potential drug interaction between tirzepatide and thiazides may cause severe hypercalcemia, particularly in patients with impaired renal clearance 5
• Follow-up calcium monitoring within 1-2 weeks of initiating tirzepatide is strongly recommended in these high-risk populations 5

Cardiovascular Risk Assessment

• Evaluate for established atherosclerotic cardiovascular disease (ASCVD), heart failure, or high cardiovascular risk factors 1
• Blood pressure measurement is essential, as tirzepatide improves blood pressure control 4
• While tirzepatide cardiovascular outcomes data are still emerging, the SURPASS trials showed no increased cardiovascular risk and potential benefit 6, 7

Contraindication Screening

• Personal or family history of medullary thyroid carcinoma is an absolute contraindication 3
• Multiple Endocrine Neoplasia syndrome type 2 is an absolute contraindication 3
• Screen for history of pancreatitis, though this is not an absolute contraindication 3

Medication Interaction Considerations

Concurrent Medications Requiring Monitoring

• Review use of medications with narrow therapeutic index (e.g., warfarin) due to potential delayed absorption from gastric emptying effects 2
• Assess for oral hormonal contraceptive use—advise adding non-oral contraception for 4 weeks after dose escalations 2
• Evaluate concurrent use of medications that increase diabetes risk (glucocorticoids, statins, thiazide diuretics, certain HIV medications) 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for extensive additional testing beyond the essential baseline labs listed above 1
• Do not routinely check CPK unless symptoms of myalgia develop, as asymptomatic CPK elevations may occur but are not clinically significant 1
• Do not discontinue tirzepatide for modest eGFR declines (3-10%) as this is an expected hemodynamic effect, not true kidney injury 1
• Do not overlook calcium monitoring in patients on chronic thiazide therapy, as this represents a newly recognized serious drug interaction 5

Ongoing Monitoring After Initiation

• Repeat comprehensive metabolic panel, lipid panel, and complete blood count periodically during treatment 1
• Monitor HbA1c at least quarterly after dose stabilization to assess glycemic response 3
• Reassess at least monthly during dose escalation phases 3
• In patients with CKD or on thiazides, check serum calcium within 1-2 weeks of starting therapy 5