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

Baseline Testing Before Starting Semaglutide

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

Essential Laboratory Tests

Glycemic Assessment

• Measure HbA1c to establish baseline glycemic control and set individualized targets (generally <7% for most adults with type 2 diabetes). 1
• Obtain fasting plasma glucose to guide titration of concomitant diabetes medications and assess baseline metabolic status. 1

Renal Function Evaluation

• Check serum creatinine and calculate eGFR before starting therapy. 1 This is critical because:
  • Semaglutide requires no dose adjustment at any level of kidney function, including eGFR <30 mL/min/1.73 m². 1, 2
  • Baseline values are needed to monitor for acute kidney injury secondary to dehydration from gastrointestinal adverse effects. 1
  • GLP-1 receptor agonists can be used when eGFR is <45 mL/min/1.73 m², though glycemic efficacy may be somewhat reduced. 1, 2

Hepatic Assessment

• Measure total bilirubin and transaminases (ALT, AST) at baseline. 1 GLP-1 receptor agonists can reduce hepatic steatosis and improve liver function in patients with NAFLD, making baseline values important for monitoring improvement. 1

Lipid Panel

• Obtain a complete lipid panel (total cholesterol, LDL, HDL, triglycerides) to assess baseline cardiovascular risk and monitor improvement during therapy. 3

Critical Clinical History Assessment

Absolute Contraindications (Must Screen)

• Personal or family history of medullary thyroid carcinoma (MTC) – this is an absolute contraindication based on animal studies showing thyroid C-cell tumors. 1, 3
• Multiple endocrine neoplasia syndrome type 2 (MEN 2) – absolute contraindication to all GLP-1 receptor agonists. 1, 3
• Severe hypersensitivity reaction to semaglutide – prior documented severe reaction precludes use. 3

Relative Cautions (Document if Present)

• History of pancreatitis – use with caution; causality has not been definitively established, but vigilance is required. 1, 3
• Active gallbladder disease or symptomatic gallstones – semaglutide increases risk of cholelithiasis and cholecystitis by approximately 38% versus placebo; avoid in patients with active gallbladder symptoms. 3
• History of gastroparesis – delayed gastric emptying effects of semaglutide may worsen symptoms. 1
• Diabetic retinopathy – document if present; semaglutide may increase risk of retinopathy complications, particularly proliferative diabetic retinopathy. 1
• History of diabetic ketoacidosis – use caution when initiating therapy. 1

Cardiovascular Disease Status

• Document established atherosclerotic cardiovascular disease (ASCVD) – including history of myocardial infarction, stroke, peripheral arterial disease, or revascularization. 3 This is important because:
  • Semaglutide reduces major adverse cardiovascular events by 26% (HR 0.74,95% CI 0.58–0.95) in patients with type 2 diabetes and established CVD. 3
  • For patients with CVD and BMI ≥27 kg/m² (even without diabetes), semaglutide 2.4 mg reduces cardiovascular death, nonfatal MI, or stroke by 20% (HR 0.80). 3

Chronic Kidney Disease Assessment

• Identify CKD stage based on eGFR and document albuminuria status (urine albumin-to-creatinine ratio). 2
• For patients with eGFR 25–60 mL/min/1.73 m² and albuminuria, consider whether an SGLT2 inhibitor should be prioritized first for superior renal protection. 2
• For advanced CKD (eGFR <30 mL/min/1.73 m²), GLP-1 receptor agonists become the preferred glucose-lowering class due to lower hypoglycemia risk and maintained efficacy. 2

Ophthalmologic Evaluation

• Ensure guideline-recommended dilated eye examination has been performed within the last 12 months before starting therapy, particularly if diabetic retinopathy is present or suspected. 1

Medication Review and Adjustments

Concomitant Diabetes Medications

• If HbA1c is well-controlled at baseline (<8%):

  • Reduce sulfonylurea dose by 50% or discontinue entirely before starting semaglutide to prevent hypoglycemia. 1, 3
  • Reduce basal insulin by approximately 20% when initiating semaglutide. 1, 3

• Discontinue all DPP-4 inhibitors (e.g., sitagliptin, linagliptin) before starting semaglutide; concurrent use offers no additional benefit. 3

Cardiovascular Medications

• Review antihypertensive regimen – weight loss may necessitate adjustment of blood pressure medications during therapy. 3
• Continue statin therapy without modification; semaglutide can be safely combined with statins, antiplatelet drugs, and antihypertensives. 1

Monitoring Schedule After Initiation

First 4 Weeks

• Instruct patients to monitor glucose more closely, especially if on insulin, sulfonylureas, or glinides, to detect early hypoglycemia. 1
• Assess gastrointestinal tolerance at week 4 before dose escalation. 3

Weeks 12–16

• Re-measure HbA1c, fasting glucose, body weight, and blood pressure to determine treatment efficacy. 3
• Evaluate for treatment response – discontinue if weight loss is <5% after 3 months at therapeutic dose. 3

Every 3–6 Months Thereafter

• Continue monitoring HbA1c, weight, blood pressure, and cardiovascular risk factors until targets are met. 3
• Monitor renal function periodically, particularly when initiating or up-titrating ACE inhibitors or ARBs concurrently. 1

Common Pitfalls to Avoid

• Do not skip screening for MTC or MEN 2 – these are absolute contraindications that must be ruled out before prescribing. 1, 3
• Do not overlook the need to reduce or stop sulfonylureas – their combination with semaglutide markedly increases hypoglycemia risk. 1, 3
• Do not assume renal dose adjustment is necessary – semaglutide dosing remains unchanged across all CKD stages, including eGFR <30 mL/min/1.73 m². 1, 2
• Do not delay ophthalmologic evaluation – ensure dilated eye exam is current before starting therapy if diabetic retinopathy is present. 1
• Do not forget to counsel on gastrointestinal side effects – nausea, vomiting, and diarrhea are common early-treatment events that typically resolve within 4–8 weeks. 3