Laboratory Testing When Starting Semaglutide
Before initiating semaglutide, you must check renal function (serum creatinine and eGFR), HbA1c, thyroid function (TSH, free T4), and a comprehensive metabolic panel including glucose. 1
Essential Baseline Laboratory Tests
Renal Function Assessment
- Measure serum creatinine and calculate eGFR to establish baseline kidney function, as semaglutide causes an initial decline in eGFR that typically plateaus after 12-16 weeks. 1, 2
- Semaglutide can be used when eGFR is <45 mL/min/1.73 m², though glycemic efficacy may be reduced in advanced chronic kidney disease. 1, 3
- Renal function should be monitored periodically after initiation, particularly when starting or up-titrating ACE inhibitors or ARBs concurrently. 1
Glycemic Control Parameters
- Check HbA1c and fasting glucose to establish baseline glycemic control and guide dose adjustments of other diabetes medications. 1
- If HbA1c is well-controlled at baseline, reduce sulfonylurea dose by 50% or basal insulin by 20% when starting semaglutide to prevent hypoglycemia. 1
- Monitor glucose more closely for the first 4 weeks, especially if the patient is on insulin, sulfonylureas, or glinides. 1
Thyroid Function Testing
- Measure TSH and free T4 before initiating therapy, as thyroid function should be monitored routinely. 1
- Repeat thyroid testing (TSH and free T4) before each cycle during the initial treatment period. 4
Lipid Panel
- Check triglycerides, HDL, LDL, and total cholesterol as part of baseline cardiovascular risk assessment. 5
Liver Function
- Measure total bilirubin and transaminases, as GLP-1 receptor agonists can reduce hepatic steatosis and improve liver function in patients with NAFLD. 4, 5
Critical Laboratory Tests NOT Routinely Required
Importantly, pancreatic enzymes (lipase, amylase) and calcitonin are NOT routinely measured before starting semaglutide, despite theoretical concerns about pancreatitis and thyroid C-cell tumors. 5 A 2025 retrospective study found that none of the 715 patients prescribed semaglutide had these tests performed, highlighting a gap between theoretical risk and actual clinical practice. 5
Essential Clinical History Assessment (Not Laboratory-Based)
While not laboratory tests, these critical contraindications must be documented:
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2) is an absolute contraindication. 1, 6, 7
- History of diabetic retinopathy should be documented, as semaglutide may increase risk of retinopathy complications. 1, 8
- History of pancreatitis, gastroparesis, or active gallbladder disease are relative contraindications. 1, 7
Additional Monitoring After Initiation
- Ophthalmologic examination should be performed before starting therapy if not done within the last 12 months, particularly in patients with pre-existing diabetic retinopathy. 1
- Urinary albumin-to-creatinine ratio (UACR) can be monitored in patients with pre-existing albuminuria, as semaglutide significantly reduces UACR in patients with microalbuminuria or macroalbuminuria. 2
Common Pitfall to Avoid
The most significant clinical pitfall is failing to reduce doses of insulin or sulfonylureas when initiating semaglutide, which substantially increases hypoglycemia risk. 1, 6 This medication adjustment should be made proactively based on baseline HbA1c, not reactively after hypoglycemia occurs.