What are the indications for use of GLP-1 (Glucagon-like peptide-1) receptor agonists like semaglutide (Ozempic)?

Indications for GLP-1 Receptor Agonists Like Monjaro (Tirzepatide)

Tirzepatide is FDA-approved for two primary indications: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity. 1

Primary FDA-Approved Indications

Type 2 Diabetes Mellitus

• Tirzepatide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, achieving HbA1c reductions of 1.87-2.24% with 23.0-62.4% of patients reaching HbA1c <5.7% 1
• The American Diabetes Association recommends tirzepatide as first-line therapy for patients with type 2 diabetes and obesity due to its superior efficacy, achieving 20.9% weight loss and greater HbA1c reduction compared to semaglutide 1
• The medication works through dual GIP and GLP-1 receptor activation, suppressing appetite, delaying gastric emptying, enhancing insulin secretion, reducing glucagon, and increasing energy expenditure 1

Chronic Weight Management

• Tirzepatide is approved for chronic weight management in adults with BMI ≥30 kg/m² (obesity) or BMI ≥27 kg/m² with at least one weight-related comorbidity such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease 1
• Tirzepatide demonstrates superior weight loss of 20.9% at 72 weeks compared to semaglutide's 14.9%, representing a 6% absolute advantage 1
• The medication must be used in conjunction with lifestyle modifications including a 500-kcal reduction below daily requirements and minimum 150 minutes/week of physical activity 1

Cardiovascular and Cardiometabolic Benefits

Cardiovascular Risk Reduction

• Tirzepatide provides cardioprotective effects through improved lipid profiles, blood pressure reduction, and anti-inflammatory mechanisms 1
• The medication produces broader cardiometabolic improvements including blood pressure reduction through multiple mechanisms and liver fat reduction with significant decreases in both hepatic steatosis and visceral adipose tissue 1
• For patients with established cardiovascular disease, semaglutide 2.4mg may be preferred over tirzepatide due to proven cardiovascular outcome benefits, reducing composite cardiovascular death, nonfatal MI, or nonfatal stroke by 20% (HR 0.80) 1

Metabolic Improvements Beyond Glucose Control

• Tirzepatide achieves statistically significant advantages over semaglutide including greater waist circumference reduction, superior triglyceride reduction, and better fasting glucose control 1
• Both tirzepatide and semaglutide improve blood pressure, lipid profiles, and insulin sensitivity, with potential requirements for antihypertensive adjustment 1

Special Clinical Scenarios

NAFLD/NASH Management

• GLP-1 receptor agonists, including tirzepatide, potentially decrease hepatic steatosis in patients with NAFLD, with semaglutide showing the most robust evidence achieving NASH resolution in 59% of patients at 0.4mg/d versus 17% on placebo 2
• These medications allow the possibility of treating diabetes, cardiovascular disease, and NASH simultaneously 2

Renal Protection

• GLP-1 receptor agonists reduce albuminuria and slow eGFR decline, with no dose adjustment required for tirzepatide across all stages of CKD 1
• The MACE risk reduction with GLP-1 receptor agonists is significantly greater for those with eGFR <60 ml/min/1.73 m² than for those with eGFR ≥60 ml/min/1.73 m² 1

Absolute Contraindications

Tirzepatide is absolutely contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2), based on animal studies showing thyroid C-cell tumors 1, 3

Important Clinical Caveats

Not Indicated For

• Type 1 diabetes mellitus 3
• Treatment of diabetic ketoacidosis 3
• Patients with recent heart failure decompensation should avoid GLP-1 receptor agonists 2

Use With Caution

• History of pancreatitis - consider alternative antidiabetic therapy, as tirzepatide has not been studied in patients with a history of pancreatitis 3, 4
• Severe gastroparesis or GI motility disorders, as tirzepatide may worsen symptoms through delayed gastric emptying 1
• Patients on insulin or insulin secretagogues require dose reduction to prevent hypoglycemia 1

Monitoring Requirements

• Regular monitoring for pancreatitis, gallbladder disease, and severe gastrointestinal motility complications 1
• Blood pressure monitoring as weight loss may necessitate antihypertensive medication adjustment 1
• Women using oral contraceptives should switch to non-oral methods or add barrier contraception for 4 weeks after initiation and each dose escalation 1