Is a patient with hypertension, symptomatic migraines, proteinuria, obesity, erythrocytosis, leukocytosis, mildly elevated alanine transaminase (ALT) levels, and a family history of hyperthyroidism a good candidate for a Glucagon-like peptide-1 (GLP-1) receptor agonist, such as liraglutide (Victoza) or semaglutide (Ozempic)?

GLP-1 Receptor Agonist Candidacy in This Patient

Yes, this patient is an excellent candidate for GLP-1 receptor agonist therapy, particularly given the combination of obesity, hypertension, proteinuria (suggesting possible diabetic kidney disease), and symptomatic migraines that may actually improve with treatment. 1, 2

Primary Indication: Obesity with Cardiovascular Risk

Your patient meets clear criteria for GLP-1 therapy based on obesity alone, with additional cardiovascular risk factors (hypertension, proteinuria) that strengthen the indication. 1 The AGA guidelines recommend GLP-1 receptor agonists for adults with obesity or overweight with weight-related comorbidities, which this patient clearly has. 1

• The presence of hypertension and proteinuria suggests early cardiovascular and renal disease, making this patient potentially "very high risk" for atherosclerotic cardiovascular disease. 1
• GLP-1 receptor agonists (specifically liraglutide, semaglutide, or dulaglutide) are recommended in patients at very high/high cardiovascular risk to reduce cardiovascular events. 1

Unexpected Benefit: Migraine Improvement

The patient's symptomatic migraines may actually improve with liraglutide therapy, independent of weight loss. 2 A 2025 prospective study demonstrated that liraglutide reduced monthly headache days from 19.8 to 10.7 days (mean reduction of 9.1 days, p<0.001) in patients with high-frequency or chronic migraine and obesity. 2 This effect was independent of BMI reduction, potentially related to GLP-1's effects on intracranial pressure control. 2

Addressing the Mildly Elevated ALT

• An ALT of 31 U/L is within normal limits or only minimally elevated (normal range typically <40 U/L for most labs). 1
• This should not preclude GLP-1 therapy, as these agents are not contraindicated in mild hepatic enzyme elevations. 1
• In fact, GLP-1 receptor agonists may improve hepatic steatosis in patients with obesity. 1

Critical Screening Questions Before Initiation

Absolute Contraindications to Rule Out

You must ask about personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2). 3, 1 The patient's relative has hyperthyroidism, but you need to specifically clarify:

• "Has anyone in your family ever been diagnosed with medullary thyroid cancer or thyroid tumors?" 3
• "Have you or any family members been diagnosed with multiple endocrine neoplasia syndrome?" 3
• If either answer is yes, GLP-1 therapy is absolutely contraindicated. 3, 1

Additional Essential Questions

Gastrointestinal history: 1

• "Do you have a history of gastroparesis or severe delayed stomach emptying?" (relative contraindication) 1
• "Have you had problems with your gallbladder or gallstones?" (active gallbladder disease is a consideration that may prompt caution) 1
• "Do you have a history of pancreatitis?" (use clinical judgment) 1

Pregnancy planning: 1

• "Are you planning to become pregnant in the near future?" (GLP-1s should be discontinued if pregnancy is being considered) 1
• "Are you currently breastfeeding?" (contraindication) 1

Diabetic complications: 1

• "Have you been told you have diabetic eye disease or retinopathy?" (caution with semaglutide or dulaglutide in proliferative retinopathy) 1
• Proteinuria is already documented, which actually favors GLP-1 use for renal protection. 1

Medication reconciliation:

• "Are you taking any diabetes medications, particularly insulin or sulfonylureas?" (need dose adjustment to prevent hypoglycemia) 1
• "Are you on any other GLP-1 medications or DPP-4 inhibitors?" (should not be combined) 1

Recommended Agent Selection

Semaglutide 2.4 mg weekly (Wegovy) or liraglutide 3.0 mg daily (Saxenda) are the preferred options for obesity management. 1

• Semaglutide offers superior weight loss (approximately 15% body weight reduction vs 8% with liraglutide) and once-weekly dosing convenience. 4, 5
• Liraglutide has specific evidence for migraine reduction in this exact patient population (obesity with chronic migraine). 2
• Both agents reduce cardiovascular events in high-risk patients. 1

Given the migraine component, starting with liraglutide 3.0 mg may provide dual benefit for weight loss and headache reduction. 2

Titration Protocol

For liraglutide: 1

• Week 1: 0.6 mg daily
• Week 2: 1.2 mg daily
• Week 3: 1.8 mg daily
• Week 4: 2.4 mg daily
• Week 5+: 3.0 mg daily (maintenance)

For semaglutide: 1

• Weeks 1-4: 0.25 mg weekly
• Weeks 5-8: 0.5 mg weekly
• Weeks 9-12: 1.0 mg weekly
• Weeks 13-16: 1.7 mg weekly
• Week 17+: 2.4 mg weekly (maintenance)

Slow titration is essential to minimize gastrointestinal side effects (nausea, vomiting). 1

Monitoring and Management

Blood pressure monitoring: 1

• GLP-1 therapy may improve hypertension through weight loss, but continue current antihypertensive therapy. 1
• Monitor BP regularly as weight loss may allow medication reduction. 1

Renal function: 1

• Proteinuria should be monitored as GLP-1s may provide renoprotective effects. 1
• If starting or up-titrating ACE inhibitor/ARB concurrently, use clinical judgment regarding timing. 1

Hypoglycemia surveillance: 1

• If patient is on insulin or sulfonylureas, doses must be reduced and patient counseled on hypoglycemia symptoms. 1
• GLP-1s alone carry very low hypoglycemia risk due to glucose-dependent insulin secretion. 1

Gastrointestinal effects: 1

• Nausea occurs in approximately 40% of patients on liraglutide (vs 14.8% placebo). 1
• Vomiting occurs in 16% (vs 4.3% placebo). 1
• These effects typically diminish over time with gradual titration. 1

Common Pitfalls to Avoid

Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors. 1 This is a common prescribing error that provides no additional benefit and increases side effects.

Do not miss doses during titration. 1 If more than 2 consecutive doses are missed, consider resuming at the same dose if previously well-tolerated, or lowering the dose. If 3+ doses missed, restart titration schedule. 1

Do not ignore the family history of thyroid disease. 3 While hyperthyroidism in a relative is not a contraindication, you must specifically rule out MTC or MEN2 family history. 3

Do not forget to counsel about delayed gastric emptying effects on other medications. 1 Oral medications requiring rapid onset may have altered absorption. 1