What conditions are Glucagon-like peptide-1 (GLP-1) agonists approved for in adults?

GLP-1 Agonists: FDA-Approved Indications

GLP-1 receptor agonists are FDA-approved for two primary conditions: type 2 diabetes mellitus and chronic weight management in adults with obesity or overweight with weight-related complications. 1, 2, 1

Type 2 Diabetes Mellitus

GLP-1 agonists are approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 1, 2, 1 Dulaglutide (Trulicity) extends this indication to pediatric patients 10 years of age and older with type 2 diabetes. 2

For cardiovascular risk reduction, specific GLP-1 agonists are approved to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. 1, 2, 1 This represents a critical indication beyond glycemic control alone, with semaglutide demonstrating a 26% reduction in composite cardiovascular outcomes (HR 0.74,95% CI 0.58-0.95). 3

Key Limitations for Diabetes Use

• Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis 1
• Has not been studied in patients with a history of pancreatitis; consider alternative antidiabetic therapy in these patients 1, 2, 1
• Not recommended in patients with severe gastrointestinal disease, including severe gastroparesis 2

Chronic Weight Management (Obesity)

Semaglutide 2.4 mg (Wegovy) and liraglutide 3.0 mg (Saxenda) are FDA-approved for chronic weight management in adults with: 3

• BMI ≥30 kg/m² (obesity), OR
• BMI ≥27 kg/m² with at least one weight-related comorbidity such as hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease 3, 4

These medications must be used as an adjunct to a reduced-calorie diet and increased physical activity. 3 The American Gastroenterological Association conditionally recommends semaglutide 2.4 mg with lifestyle modifications, noting it may be prioritized over other approved anti-obesity medications for most patients given the magnitude of net benefit (14.9% weight loss at 68 weeks versus 2.4% with placebo). 3

Tirzepatide (Zepbound) is FDA-approved for obesity treatment as of November 2023, demonstrating superior weight loss of 20.9% compared to semaglutide's 14.9%. 4

Cardiovascular Benefits in Obesity Without Diabetes

Semaglutide 2.4 mg is approved to decrease the risk of cardiovascular disease events in adults with overweight or obesity without diabetes, based on the SELECT study showing a 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80). 4

Critical Contraindications Across All Indications

Absolute contraindication: Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 1, 2, 1 This stems from rodent studies showing thyroid C-cell tumors, though human relevance remains undetermined. 1

Additional contraindication: Known hypersensitivity to the GLP-1 agonist or any product components. 1

Available GLP-1 Agonist Formulations

Currently approved agents include: 5, 6

• Twice daily: Exenatide (Byetta)
• Once daily: Lixisenatide, liraglutide (Victoza for diabetes, Saxenda for weight loss)
• Once weekly: Exenatide extended-release, dulaglutide (Trulicity), albiglutide, semaglutide (Ozempic for diabetes, Wegovy for weight loss)
• Oral daily: Semaglutide (Rybelsus) - approved only for type 2 diabetes, not obesity 5, 7

Tirzepatide (Mounjaro for diabetes, Zepbound for obesity) is technically a dual GIP/GLP-1 receptor agonist, representing a distinct drug class with once-weekly subcutaneous administration. 3, 4

Clinical Decision Framework

For type 2 diabetes with inadequate glycemic control: The American Diabetes Association strongly recommends adding an SGLT-2 inhibitor or GLP-1 agonist to metformin and lifestyle modifications, with GLP-1 agonists preferred to reduce all-cause mortality, MACE, and stroke. 3 GLP-1 agonists are particularly preferred in patients with advanced CKD (eGFR <30 mL/min/1.73 m²) due to lower hypoglycemia risk. 3

For obesity management: Guidelines recommend initiating an anti-obesity medication in patients with inadequate response to lifestyle modifications who meet BMI criteria, with semaglutide 2.4 mg or tirzepatide prioritized based on magnitude of weight loss needed and cardiovascular risk profile. 3, 4