What labs should be obtained before starting tirzepatide in an 18‑year‑old female who is gaining weight despite diet and exercise?

Pre-Treatment Laboratory Evaluation for Tirzepatide in an 18-Year-Old Female

Before starting tirzepatide in this 18-year-old woman with unexplained weight gain, you must obtain baseline labs to rule out secondary causes of obesity, screen for contraindications, and establish metabolic parameters for monitoring.

Essential Baseline Laboratory Tests

Metabolic and Diabetes Screening

• Fasting glucose and HbA1c – Screen for prediabetes or undiagnosed type 2 diabetes, as tirzepatide's efficacy varies by glycemic status 1
• Fasting lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) – Establish baseline cardiovascular risk and monitor treatment response 1
• Comprehensive metabolic panel – Assess baseline renal function (creatinine, eGFR) and electrolytes, as GLP-1 receptor agonists can cause dehydration through gastrointestinal side effects 1

Thyroid and Hormonal Evaluation

• TSH (thyroid-stimulating hormone) – Rule out hypothyroidism as a reversible cause of weight gain in a young woman
• Consider screening for Cushing's syndrome if clinical features suggest hypercortisolism (striae, proximal muscle weakness, easy bruising)
• Consider polycystic ovary syndrome (PCOS) evaluation if menstrual irregularities or hyperandrogenism are present

Safety Screening

• Lipase and amylase – Establish baseline pancreatic enzyme levels, as tirzepatide increases risk of gallbladder/biliary disease and has uncertain relationship with pancreatitis 2
• Liver function tests (ALT, AST) – Baseline hepatic function, particularly relevant as tirzepatide improves metabolic dysfunction-associated steatotic liver disease 2
• Pregnancy test (β-hCG) – Mandatory in any woman of childbearing age before initiating tirzepatide

Critical Contraindication Screening

• Personal or family history of medullary thyroid carcinoma (MTC) – Absolute contraindication; thyroid C-cells express GLP-1 receptors 2
• Personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) – Absolute contraindication
• History of pancreatitis – Relative contraindication; requires careful risk-benefit assessment 2

Clinical Reasoning

The 2025 AACE guidelines emphasize that tirzepatide is highly effective for obesity management, achieving 22.5% weight reduction at 72 weeks with the 15 mg dose 1. However, in an 18-year-old with weight gain "despite diet and exercise," you must first exclude secondary causes of obesity before attributing this to primary obesity requiring pharmacotherapy.

Key consideration for this young patient: The most common adverse events are gastrointestinal (nausea in 25% of patients, vomiting and diarrhea in up to 10%), occurring primarily during dose escalation 2. These can lead to dehydration and electrolyte disturbances, making baseline renal function assessment critical 1.

Common Pitfalls to Avoid

1. Starting tirzepatide without ruling out secondary obesity causes – Hypothyroidism, Cushing's syndrome, and PCOS are treatable conditions that may explain weight gain in a young woman
2. Failing to obtain pregnancy test – Tirzepatide safety in pregnancy is not established
3. Missing MTC/MEN 2 family history – This is an absolute contraindication that must be screened through careful history-taking 2
4. Not establishing baseline pancreatic enzymes – While causality between GLP-1 receptor agonists and pancreatitis remains uncertain, tirzepatide increases gallbladder/biliary disease risk 2

Monitoring Strategy

After initiating tirzepatide at the starting dose of 2.5 mg weekly with monthly titration to maximum 15 mg weekly 1, monitor for:

• Gastrointestinal symptoms during dose escalation (most common side effect)
• Dehydration and renal function if vomiting/diarrhea occurs 1
• Severe abdominal pain (stop immediately if pancreatitis suspected) 2
• Weight loss response and metabolic improvements (lipids, glucose parameters)

The evidence strongly supports tirzepatide's efficacy for obesity management 1, but appropriate patient selection through comprehensive laboratory screening is essential to maximize safety and identify treatable secondary causes of weight gain in this young patient.