What are GLP-1 Agonists?

GLP-1 (Glucagon-Like Peptide-1) agonists are medications that mimic the action of the natural hormone GLP-1, which is released after eating. Originally developed for type 2 diabetes, higher-dose GLP-1 agonists have been approved for chronic weight management and are revolutionizing obesity treatment.

How do GLP-1 Agonists Work for Weight Loss?

• Suppress Appetite: Act on brain centers to reduce hunger and increase feelings of fullness
• Slow Gastric Emptying: Food stays in stomach longer → prolonged satiety
• Reduce Food Cravings: Especially for high-fat, high-sugar foods
• Improve Blood Sugar Control: Stimulate insulin release, suppress glucagon

FDA-Approved GLP-1 for Weight Loss:

1. Semaglutide (Wegovy®):

• Dose: 2.4 mg subcutaneous injection once weekly
• Weight Loss: Average 15-20% body weight over 68 weeks
• Also available as: Ozempic® (lower dose for diabetes)

2. Liraglutide (Saxenda®):

• Dose: 3.0 mg subcutaneous injection daily
• Weight Loss: Average 8-10% body weight
• Also available as: Victoza® (lower dose for diabetes)

3. Tirzepatide (Zepbound®):

• Dual Agonist: GLP-1 + GIP (glucose-dependent insulinotropic polypeptide)
• Dose: Up to 15 mg subcutaneous injection once weekly
• Weight Loss: Average 20-25% body weight (highest of all)
• Also available as: Mounjaro® (for diabetes)

Who is a Candidate for GLP-1 for Weight Loss?

• BMI ≥30 (obesity)
• OR BMI ≥27 with weight-related comorbidity: Type 2 diabetes, high blood pressure, high cholesterol, sleep apnea, etc.
• Failed lifestyle modifications alone (diet + exercise)

Benefits Beyond Weight Loss:

• Cardiovascular: Reduced risk of heart attack, stroke, cardiovascular death (proven with semaglutide)
• Blood Sugar: Improved glycemic control; can prevent or delay type 2 diabetes
• Blood Pressure: Reduction in systolic/diastolic BP
• Liver: Improvement in fatty liver disease (NAFLD/NASH)
• Kidney: May slow progression of chronic kidney disease
• Sleep Apnea: Improvement with weight loss

Side Effects:

Common (Gastrointestinal):

• Nausea (Most Common): Usually improves over time
• Vomiting, diarrhea, constipation
• Abdominal pain, bloating
• Decreased appetite (intended effect)

Less Common but Serious:

• Pancreatitis: Severe abdominal pain → stop medication, seek medical care
• Gallstones/Cholecystitis: Rapid weight loss increases risk
• Gastroparesis: Severe delayed gastric emptying (rare; usually resolves after stopping)
• Hypoglycemia: If combined with insulin or sulfonylureas (adjust doses)
• Thyroid C-Cell Tumors: Seen in rodent studies; theoretical risk in humans (contraindicated if personal/family history of medullary thyroid cancer or MEN2)
• Suicidal Thoughts: Rare; FDA investigating

Contraindications:

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
• Pregnancy or planning pregnancy (stop 2 months before conception)
• History of severe pancreatitis
• Diabetic retinopathy (worsening risk with rapid glucose improvement)

Dosing and Titration:

• Start Low, Go Slow: Gradual dose escalation over weeks to months to minimize nausea
• Example (Semaglutide/Wegovy®):
  • Start: 0.25 mg weekly for 4 weeks
  • → 0.5 mg weekly for 4 weeks
  • → 1.0 mg weekly for 4 weeks
  • → 1.7 mg weekly for 4 weeks
  • → 2.4 mg weekly (maintenance)
• Injections: Subcutaneous (belly, thigh, upper arm)

Cost and Insurance:

• Very Expensive: $1,000-$1,500/month without insurance
• Insurance Coverage: Variable; many insurers cover for diabetes but NOT obesity (changing)
• Medicare: Does NOT cover weight loss medications (as of 2024)
• Manufacturer savings programs, coupons may be available

What Happens After Stopping?

• Weight Regain: Most patients regain significant weight after stopping (often 2/3 of weight lost)
• Long-Term Use: GLP-1 agonists are intended for chronic, long-term management (like blood pressure meds)
• Lifestyle Maintenance: Diet + exercise remain essential even while on medication

Practical Tips:

• Manage Nausea: Eat smaller, more frequent meals; avoid greasy/spicy foods; stay hydrated
• Stay Hydrated: Especially if experiencing diarrhea/vomiting
• Report Severe Abdominal Pain: Could indicate pancreatitis or gallstones
• Rotate Injection Sites
• Maintain Protein Intake: To preserve muscle mass during weight loss
• Exercise: Resistance training helps maintain muscle

Monitoring:

• Weight, BMI: Every visit
• Blood Pressure, Heart Rate
• HbA1c, Fasting Glucose: If diabetic or prediabetic
• Lipid Panel: Monitor improvement
• Liver Enzymes: If fatty liver disease
• Assess for Side Effects