What baseline assessments and laboratory tests (including medical history, physical exam, fasting plasma glucose, hemoglobin A1c, comprehensive metabolic panel with serum creatinine and estimated glomerular filtration rate, liver enzymes, fasting lipid profile, complete blood count, pregnancy test, thyroid‑stimulating hormone and free thyroxine, calcitonin or neck ultrasound if indicated, retinal examination for diabetes, electrocardiogram for cardiovascular disease, and medication review) should be performed before initiating semaglutide?

Baseline Assessments Before Initiating Semaglutide

Before starting semaglutide, you must screen for absolute contraindications (personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2), obtain baseline HbA1c and fasting glucose, check comprehensive metabolic panel with renal function, and assess cardiovascular disease status—but routine measurement of calcitonin, thyroid ultrasound, or retinal examination is not required unless specific risk factors are present. 1

Mandatory Screening for Absolute Contraindications

Screen every patient for personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) before prescribing semaglutide, as these are absolute contraindications based on animal studies showing thyroid C-cell tumors. 2, 1, 3

• Do not measure baseline calcitonin or perform thyroid ultrasound routinely, as these are not recommended by current guidelines unless the patient has a thyroid nodule or other specific thyroid concerns 4
• The contraindication is based on family/personal history alone, not on screening tests 1, 3

Required Laboratory Tests

Metabolic Parameters

• Obtain baseline HbA1c to establish glycemic control and set individualized targets (generally <7% for most adults with diabetes) 1
• Measure fasting plasma glucose to guide titration of concomitant diabetes medications 1
• Check comprehensive metabolic panel including serum creatinine and estimated glomerular filtration rate (eGFR)—no dose adjustment is required for semaglutide across all stages of chronic kidney disease, including eGFR <30 mL/min/1.73 m² 1, 5

Lipid Profile

• Obtain fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) to assess baseline cardiovascular risk and monitor improvement, particularly in patients with dyslipidemia 1

Liver Function

• Check liver enzymes (ALT, AST) at baseline, especially in patients with suspected metabolic dysfunction-associated steatotic liver disease (MASLD), as semaglutide may provide therapeutic benefits for underlying liver disease 1

Clinical History and Physical Examination

Cardiovascular Assessment

• Document established atherosclerotic cardiovascular disease (prior MI, stroke, peripheral arterial disease, or revascularization), as semaglutide reduces major adverse cardiovascular events by 26% in patients with type 2 diabetes and established CVD (HR 0.74,95% CI 0.58-0.95) 1, 6
• For patients with cardiovascular disease and obesity/overweight without diabetes, semaglutide 2.4 mg weekly reduces cardiovascular death, nonfatal MI, or stroke by 20% (HR 0.80) 6

Pancreatitis History

• Assess for history of pancreatitis—semaglutide may be used with caution as causality has not been definitively established, but patients should be monitored for signs of pancreatitis 1, 7, 3

Gallbladder Disease

• Screen for symptomatic gallbladder disease or active gallstones, as semaglutide increases the risk of cholelithiasis and cholecystitis by approximately 38% versus placebo and should be avoided in patients with symptomatic gallstones 1

Diabetic Retinopathy

• For patients with type 2 diabetes and existing diabetic retinopathy, particularly those on insulin, perform baseline retinal examination and monitor carefully during treatment, as rapid glucose lowering may worsen retinopathy 7
• Routine retinal examination is not required for all patients starting semaglutide, only those with pre-existing retinopathy or high risk 7

Tests That Are NOT Routinely Required

Thyroid Function Tests

• Routine measurement of TSH, free T4, or calcitonin is not recommended before starting semaglutide unless the patient has symptoms or history of thyroid disease 4
• The contraindication for MTC/MEN 2 is based on personal/family history, not laboratory screening 1, 3

Pancreatic Enzymes

• Baseline measurement of pancreatic lipase or amylase is not recommended, as these tests have poor predictive value for pancreatitis risk 4

Electrocardiogram

• Routine ECG is not required before starting semaglutide unless clinically indicated by cardiovascular symptoms or known cardiac disease 1

Complete Blood Count

• Routine CBC is not required before initiating semaglutide 1

Pregnancy Testing

• Perform pregnancy test in women of childbearing potential, as semaglutide is contraindicated in pregnancy and breastfeeding 1

Medication Review and Adjustments

Concomitant Diabetes Medications

• When initiating semaglutide in patients on basal insulin, reduce insulin dose by approximately 20% to prevent hypoglycemia 1, 8
• Discontinue or reduce sulfonylurea dose by 50% before starting semaglutide to minimize hypoglycemia risk 1
• Stop all DPP-4 inhibitors (e.g., sitagliptin, linagliptin) before starting semaglutide, as concurrent use provides no additional glycemic benefit 1, 3

Oral Medications with Narrow Therapeutic Index

• Review medications with narrow therapeutic indices, as semaglutide delays gastric emptying and may affect absorption of oral medications, though clinical studies have not demonstrated clinically significant impacts when the 30-minute interval is observed 1, 8

Eligibility Criteria Verification

For Obesity Management (Wegovy 2.4 mg)

• Verify BMI ≥30 kg/m² (obesity) or BMI ≥27 kg/m² with at least one weight-related comorbidity (type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) 1

For Type 2 Diabetes (Ozempic)

• Confirm diagnosis of type 2 diabetes with inadequate glycemic control (HbA1c >7% on current therapy) and/or obesity (BMI ≥30 kg/m²) 1

Common Pitfalls to Avoid

• Do not order routine calcitonin levels or thyroid ultrasound—these are not recommended and create unnecessary cost and patient anxiety 4
• Do not delay treatment waiting for extensive baseline testing beyond the essential labs listed above 1
• Do not overlook the need to reduce or discontinue sulfonylureas and insulin, as this significantly increases hypoglycemia risk 1
• Do not assume renal dose adjustment is necessary—semaglutide requires no dose modification across all CKD stages 1, 5
• Do not prescribe semaglutide to patients with personal or family history of MTC or MEN 2, as this is an absolute contraindication 1, 3