What are the pre-treatment requirements before initiating semaglutide (glucagon-like peptide-1 receptor agonist) for weight loss in patients with a history of pancreatitis, thyroid cancer, or severe gastrointestinal disease?

Pre-Treatment Requirements Before Initiating Semaglutide for Weight Loss

Before prescribing semaglutide for weight loss, you must screen for personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), assess for history of pancreatitis, evaluate for severe gastroparesis, confirm the patient is not pregnant or breastfeeding, and review for diabetic retinopathy in patients with diabetes. 1, 2

Absolute Contraindications That Must Be Ruled Out

• Personal or family history of medullary thyroid carcinoma (MTC) is an absolute contraindication based on the FDA Black Box Warning, as semaglutide causes thyroid C-cell tumors in rodents 1, 3, 2
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) is an absolute contraindication 1, 2
• Pregnancy or breastfeeding must be excluded, and women of reproductive potential should discontinue semaglutide at least 2 months before planned pregnancy due to the long washout period 1, 2
• Known hypersensitivity to semaglutide or any product components 1

Critical Medical History Assessment

Pancreatitis History

• History of pancreatitis requires careful consideration, as semaglutide has not been studied in patients with prior pancreatitis and should prompt consideration of alternative therapy 1, 3, 4
• The American Gastroenterological Association recommends using semaglutide with caution in patients with pancreatitis history, though causality between GLP-1 RAs and pancreatitis has not been definitively established 4

Gastrointestinal Disease Assessment

• Clinically meaningful gastroparesis is a contraindication, as semaglutide delays gastric emptying and will worsen symptoms 4, 2
• Prior gastric surgery (including bariatric surgery) requires extreme caution when initiating semaglutide 4
• Severe gastrointestinal disease should be carefully evaluated, as semaglutide causes GI side effects in the majority of patients 3, 5

Thyroid and Endocrine Screening

• Screen for personal history of thyroid cancer beyond MTC, as this requires careful monitoring 4
• Document family history of thyroid cancer specifically, though this was rarely performed in clinical practice according to a 2025 study showing only 1.8% of patients had proper disease history assessment 6

Ophthalmologic History

• History of diabetic retinopathy requires close monitoring, as semaglutide increases the risk of diabetic retinopathy complications, particularly in patients also treated with insulin 1, 4, 2

Pre-Treatment Laboratory and Clinical Assessments

Recommended Laboratory Work

• HbA1c should be measured to establish baseline glycemic status 6
• Serum creatinine and renal function (eGFR) should be assessed, as patients with severe renal impairment require careful monitoring for dehydration-related acute kidney injury 4, 2, 6
• Thyroid function tests (TSH, T3, T4) should be obtained at baseline 6
• Lipid panel (triglycerides, HDL, LDL, total cholesterol) should be measured 6

Laboratory Tests NOT Routinely Required But Consider in High-Risk Patients

• Pancreatic enzymes (lipase, amylase) are not routinely measured pre-treatment according to current practice patterns, though a 2025 study noted none of 715 patients had these checked 6
• Calcitonin levels are not routinely recommended for screening, as they were not measured in any patients in the 2025 practice evaluation 6

Concomitant Medication Review and Adjustment Plan

Diabetes Medications Requiring Dose Reduction

• Reduce insulin dose by 20% when starting semaglutide to minimize hypoglycemia risk 2
• Reduce sulfonylurea dose by 50% when initiating semaglutide 2
• Glinides also increase hypoglycemia risk when combined with semaglutide and may require dose adjustment 4

Oral Contraceptive Considerations

• Patients taking oral hormonal contraceptives should switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and after each dose escalation, as delayed gastric emptying may reduce absorption 4, 2

Medications with Narrow Therapeutic Index

• Review medications like warfarin that may have altered absorption due to delayed gastric emptying 4

Mandatory Patient Counseling Before Initiation

• Counsel patients about the risk of thyroid C-cell tumors and symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness) 1
• Educate on warning signs of pancreatitis (severe abdominal pain radiating to the back, with or without vomiting) and instruct to seek immediate medical attention 4, 2
• Discuss expected gastrointestinal side effects (nausea, vomiting, diarrhea, constipation) that occur in the majority of patients but are typically transient and dose-dependent 3, 5
• Warn about signs of gallbladder disease (right upper quadrant pain, fever, jaundice) given the increased risk of cholelithiasis and cholecystitis 4, 5
• Emphasize the importance of adequate hydration to prevent dehydration-related acute kidney injury, especially during GI side effects 4, 2

Special Population Considerations

Renal Impairment

• Semaglutide can be used in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease without dose adjustment, but requires close monitoring of renal function and hydration status 4, 2

Cardiovascular Disease

• Patients with established cardiovascular disease may derive additional benefit from semaglutide beyond weight loss, as demonstrated in cardiovascular outcome trials 3, 4

Critical Pitfalls to Avoid

• Never start at high doses - always begin at 0.25 mg weekly for 4 weeks to allow adaptation to delayed gastric emptying and minimize GI side effects 4, 2, 1
• Do not prescribe without screening for MTC/MEN 2 family history - this is an absolute contraindication that carries a Black Box Warning 1
• Do not overlook gastroparesis - this condition will be significantly worsened by semaglutide's mechanism of action 4, 2
• Failure to assess disease history is common in clinical practice, with a 2025 study showing 98.6% of patients had at least one relevant condition but only 1.8% had proper pre-treatment disease history assessment 6