What baseline laboratory and clinical assessments are required before starting semaglutide (GLP‑1 receptor agonist)?

Pre-Treatment Testing Before Starting Semaglutide

Before initiating semaglutide, you must obtain baseline HbA1c, renal function (serum creatinine and eGFR), and a comprehensive metabolic panel, while screening for absolute contraindications including personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN 2). 1

Mandatory Baseline Laboratory Tests

Essential Metabolic Parameters

• HbA1c – Required to establish baseline glycemic control and set individualized targets (generally <7% for most adults with diabetes). 1
• Serum creatinine and eGFR – Critical because semaglutide requires no dose adjustment across all CKD stages, including eGFR <30 mL/min/1.73 m², but you need baseline values to monitor for acute kidney injury from dehydration. 2, 1
• Fasting plasma glucose – Helps guide titration of concomitant diabetes medications. 1

Lipid and Hepatic Assessment

• Lipid panel (total cholesterol, LDL, HDL, triglycerides) – Establishes baseline cardiovascular risk and allows monitoring of improvement with treatment. 3, 1
• Total bilirubin and transaminases (ALT, AST) – GLP-1 receptor agonists can reduce hepatic steatosis and improve liver function in patients with NAFLD, so baseline values are needed. 1

Thyroid Function

• TSH, free T4, and free T3 – Should be measured at baseline, particularly because semaglutide carries an FDA black box warning regarding thyroid C-cell tumors based on animal studies. 1, 4

Critical Clinical History Screening

Absolute Contraindications (Must Screen)

• Personal or family history of medullary thyroid carcinoma (MTC) – This is an absolute contraindication; semaglutide must not be prescribed if present. 3, 1, 4
• Multiple endocrine neoplasia syndrome type 2 (MEN 2) – Another absolute contraindication that must be ruled out before initiation. 3, 1, 4
• Pregnancy or breastfeeding status – Semaglutide is contraindicated in pregnancy and breastfeeding. 4

Relative Contraindications and High-Risk Conditions

• History of pancreatitis – Document this carefully; semaglutide should be used with caution, though causality has not been definitively established. 3, 1, 4
• History of diabetic retinopathy – Patients with proliferative diabetic retinopathy require documentation and close monitoring, as semaglutide may increase risk of retinopathy complications. 1, 4
• Active gallbladder disease or symptomatic gallstones – This is a relative contraindication given the 38% increased risk of cholelithiasis and cholecystitis with semaglutide. 4
• History of gastroparesis or severe GI motility disorders – Semaglutide delays gastric emptying and is not recommended in patients with clinically meaningful gastroparesis. 1, 4
• Prior gastric surgery (including bariatric surgery) – Requires extreme caution due to altered gastric anatomy and emptying. 4

Baseline Assessments for Monitoring

Cardiovascular and Metabolic

• Blood pressure – Baseline measurement is essential because semaglutide modestly lowers blood pressure, which may necessitate adjustment of antihypertensive medications. 3, 4
• Body weight and BMI – Document baseline to track weight loss efficacy (target ≥5% weight loss after 3 months). 3
• Waist circumference – Useful for tracking visceral adiposity reduction. 3

Ophthalmologic

• Guideline-recommended eye examination – Should be completed within the last 12 months before starting therapy if the patient has diabetes. 1

Tests That Are NOT Routinely Required

Pancreatic Enzymes

• Pancreatic lipase and amylase – Despite theoretical concerns, these are not routinely measured before starting semaglutide, though a 2025 retrospective study found that none of 715 patients had these checked pre-treatment. 5
• Calcitonin – Not routinely measured before semaglutide initiation, despite thyroid cancer concerns. 5

Medication Review and Adjustments

Concomitant Diabetes Medications

• If on sulfonylureas – Reduce dose by approximately 50% or discontinue entirely before starting semaglutide to prevent hypoglycemia. 1
• If on basal insulin – Reduce dose by approximately 20% when initiating semaglutide, especially if HbA1c is well-controlled at baseline. 1
• If on DPP-4 inhibitors – Discontinue all DPP-4 inhibitors (e.g., sitagliptin, linagliptin) before starting semaglutide; concurrent use offers no additional benefit. 1

Special Population Considerations

Renal Impairment

• eGFR <45 mL/min/1.73 m² – Semaglutide can still be used without dose adjustment, though glycemic efficacy may be reduced; monitor renal function closely for acute kidney injury from dehydration. 2, 1
• eGFR <30 mL/min/1.73 m² – No dose adjustment required, but careful monitoring for gastrointestinal side effects that could lead to dehydration is essential. 2, 1

Cardiovascular Disease

• Established ASCVD – Document this carefully, as semaglutide provides a 26% reduction in major adverse cardiovascular events (HR 0.74) in patients with type 2 diabetes and established CVD. 3

Common Pitfalls to Avoid

• Do not skip screening for MTC or MEN 2 family history – This is the most critical safety screen and is an absolute contraindication. 3, 1, 4
• Do not forget to assess for symptomatic gallstones – Semaglutide is strongly contraindicated in patients with symptomatic gallbladder disease. 4
• Do not initiate semaglutide without baseline renal function – You need this to monitor for acute kidney injury from dehydration, which is a serious risk. 1, 4
• Do not overlook diabetic retinopathy history – Patients with proliferative retinopathy require close monitoring during treatment. 1, 4
• Do not forget to reduce insulin or sulfonylurea doses – Failure to do so significantly increases hypoglycemia risk. 1