Screening Patients for Tirzepatide Therapy
Before initiating tirzepatide, obtain baseline fasting plasma glucose (or HbA1c), comprehensive metabolic panel including renal function, lipid panel, and complete blood count, and assess for absolute contraindications including personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2. 1
Essential Baseline Laboratory Testing
Core metabolic and glycemic assessment:
- Fasting plasma glucose is the preferred initial test for diabetes screening and baseline glycemic assessment 1
- HbA1c provides valuable baseline data for monitoring treatment response (not required if diabetes already established) 1
- Comprehensive metabolic panel including serum creatinine and estimated glomerular filtration rate (eGFR) 1
- Complete blood count 1
- Lipid panel (total cholesterol, LDL, HDL, triglycerides) to assess baseline cardiovascular risk 1, 2
A modest eGFR decline of 3-10% may occur with GLP-1 receptor agonists and should not prompt discontinuation unless acute kidney injury is suspected. 1 This represents an expected hemodynamic effect rather than true kidney injury 1.
Cardiovascular and Metabolic Risk Assessment
Evaluate for established atherosclerotic cardiovascular disease (ASCVD), heart failure, or high cardiovascular risk factors including history of myocardial infarction, stroke, peripheral arterial disease, or coronary revascularization 3, 1. Measure blood pressure at baseline as tirzepatide produces blood pressure reduction and may require antihypertensive medication adjustment 3, 2.
Absolute Contraindications to Screen For
Do not prescribe tirzepatide if the patient has:
- Personal or family history of medullary thyroid cancer 3, 1, 2
- Multiple endocrine neoplasia syndrome type 2 3, 1, 2
These represent absolute contraindications based on animal studies showing thyroid C-cell tumors 2, 4.
Gastrointestinal and Gallbladder Assessment
Before initiating tirzepatide, assess for existing gallbladder disease or risk factors for cholelithiasis including history of gallstones, cholecystitis, or biliary colic 5. Consider avoiding use in patients at high risk for biliary disease when possible 5.
Screen for severe gastrointestinal motility disorders:
- History of gastroparesis 3, 5
- Severe gastric outlet obstruction 6
- History of recurrent intestinal obstruction 6
Tirzepatide delays gastric emptying and may worsen these conditions 5, 7.
Medication Review and Hypoglycemia Risk Assessment
Review all current medications to identify:
- Insulin use (requires 20% dose reduction at tirzepatide initiation) 3, 2
- Sulfonylureas or glinides (consider discontinuation or dose reduction) 3
- Other GLP-1 receptor agonists or DPP-4 inhibitors (must discontinue—do not combine) 3, 2
- Weight-promoting medications that could be switched to alternatives 2
If HbA1c is well-controlled at baseline (<8%) or patient has history of frequent hypoglycemic events, plan to wean or stop sulfonylurea and reduce total daily insulin dose by approximately 20% when starting tirzepatide. 3
Special Population Considerations
For patients with chronic kidney disease: Tirzepatide can be initiated if eGFR is above 20 mL/min/1.73 m² 3. No dedicated kidney outcomes trials for tirzepatide have been published, though the dual GIP/GLP-1 mechanism suggests potential renal benefits 3.
For patients with cardiovascular disease: While tirzepatide demonstrates superior weight loss and metabolic benefits, semaglutide has proven cardiovascular outcome benefits with 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke 2. Consider this when selecting between agents 2.
Patient Eligibility Criteria
Confirm the patient meets indication criteria:
- BMI ≥30 kg/m² (obesity), OR 2
- BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) 2
- For Asian American individuals, use BMI ≥23 kg/m² threshold 3
Document failed lifestyle modifications including diet and exercise attempts, as this is essential for both clinical appropriateness and insurance authorization 2.
Patient Education Before Initiation
Educate patients regarding:
- Gastrointestinal side effects (nausea, vomiting, diarrhea) are common, dose-dependent, and typically mild-to-moderate 4, 6
- Symptoms of gallbladder disease (right upper quadrant pain) that warrant immediate medical attention 5
- Symptoms of pancreatitis (persistent severe abdominal pain, nausea, vomiting) requiring urgent evaluation 3, 4
- Need for home glucose monitoring if on insulin or sulfonylureas, especially first 4 weeks 3
- Dietary modifications to minimize side effects: reduce meal size, limit alcohol and carbonated drinks, avoid high-fat foods 3, 5
Monitoring Schedule After Initiation
Repeat comprehensive metabolic panel, lipid panel, and complete blood count periodically during treatment as recommended by the American Diabetes Association and Endocrine Society 1. Assess patients at least every 3 months for continued weight loss progress, cardiovascular risk factors, and medication adherence 2. Evaluate efficacy at 12-16 weeks on the maximum tolerated therapeutic dose 2.
Do not delay treatment waiting for extensive additional testing beyond the essential baseline labs listed above. 1 The priority is to initiate therapy promptly once contraindications are ruled out and baseline labs are obtained 1.
Common Pitfalls to Avoid
- Do not combine tirzepatide with other GLP-1 receptor agonists (including semaglutide) or DPP-4 inhibitors—this provides no added benefit and increases adverse effects 3, 2
- Do not discontinue tirzepatide for modest eGFR declines (3-10%) as this is an expected hemodynamic effect 1
- Do not forget to reduce insulin doses at initiation—failure to do so significantly increases hypoglycemia risk 3, 2
- Do not overlook women of childbearing potential—those using oral contraceptives should switch to non-oral methods or add barrier contraception for 4 weeks after initiation and each dose escalation 2