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Metabolic

Semaglutide

GLP-1 Receptor Agonist - Prescriber Reference

Clinical Disclaimer: This guide is for educational purposes only and does not constitute medical advice. Prescribers should exercise independent clinical judgment and verify all information before making treatment decisions.

What is Semaglutide?

Semaglutide is a GLP-1 receptor agonist that mimics the effects of naturally occurring GLP-1, a hormone that regulates appetite and glucose metabolism. It is available in FDA-approved formulations (Ozempic, Wegovy, Rybelsus) and through compounding pharmacies.

Structure: Modified GLP-1 analog with 94% homology to native GLP-1

Mechanism of Action

Glucose Regulation

  • Stimulates glucose-dependent insulin secretion
  • Suppresses glucagon release
  • Slows gastric emptying

Appetite and Weight

  • Acts on hypothalamic receptors to reduce appetite
  • Increases satiety signaling
  • Reduces food cravings and reward-driven eating

Cardiovascular Effects

  • Demonstrated cardiovascular benefit in type 2 diabetes
  • Reduces major adverse cardiovascular events (MACE)
  • Modest blood pressure reduction

FDA-Approved Indications

Type 2 Diabetes (Ozempic, Rybelsus)

  • Adjunct to diet and exercise
  • Improves glycemic control
  • Cardiovascular risk reduction

Chronic Weight Management (Wegovy)

  • BMI ≥30 kg/m² (obesity)
  • BMI ≥27 kg/m² with weight-related comorbidity
  • Adjunct to lifestyle intervention

Dosing Protocols

For Diabetes (Ozempic - Weekly SC Injection)

  • Week 1-4: 0.25 mg weekly (initiation)
  • Week 5-8: 0.5 mg weekly
  • Maintenance: 1.0 mg weekly (max 2.0 mg weekly)

For Weight Management (Wegovy - Weekly SC Injection)

  • 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)

Compounded Formulations

  • Dosing varies by preparation
  • Follow compounding pharmacy guidance
  • Titration approach similar to branded products

Patient Selection Criteria

Good Candidates

  • BMI ≥27 with comorbidity or BMI ≥30
  • Type 2 diabetes seeking improved control
  • Motivated for lifestyle modification
  • No contraindications

Contraindications

  • Absolute: Personal/family history of medullary thyroid carcinoma, MEN2 syndrome
  • Relative: History of pancreatitis, severe gastroparesis, pregnancy

Safety Profile

Common Adverse Effects (>5%)

  • Nausea (most common, typically transient)
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Injection site reactions

Serious Adverse Effects (Rare)

  • Pancreatitis
  • Gallbladder disease
  • Acute kidney injury (usually from dehydration)
  • Diabetic retinopathy complications (in diabetics)
  • Hypoglycemia (mainly with sulfonylureas/insulin)

Black Box Warning

Risk of thyroid C-cell tumors observed in rodents. Contraindicated in patients with personal or family history of medullary thyroid carcinoma or MEN2.

Monitoring Parameters

Baseline

  • HbA1c, fasting glucose
  • Renal function (BMP)
  • Lipid panel
  • Thyroid examination
  • Weight, BMI, vital signs

Ongoing (Every 3-6 months)

  • Weight and BMI
  • HbA1c (diabetics)
  • Renal function
  • Adverse effect assessment
  • Lifestyle adherence

Drug Interactions

Clinical Significance

  • Sulfonylureas/Insulin: Increased hypoglycemia risk; consider dose reduction
  • Oral medications: Delayed absorption due to slowed gastric emptying
  • Warfarin: Monitor INR more frequently

Timing Considerations

  • Take oral medications at least 1 hour before semaglutide
  • Monitor diabetes medications for hypoglycemia

Compounding Considerations

Quality Requirements

  • Certificate of Analysis (identity, purity, potency)
  • Sterility testing
  • Endotoxin testing
  • Appropriate beyond-use dating
  • Proper storage requirements

Regulatory Note

Compounded semaglutide is NOT FDA-approved. Prescribers should inform patients of this distinction and document informed consent.

Clinical Pearls

  1. Slow titration reduces GI effects: Follow escalation schedule; slower if needed
  2. Hydration is key: Encourage fluid intake to prevent dehydration and AKI
  3. Set realistic expectations: Average weight loss 10-15% over 68 weeks
  4. Lifestyle matters: Medication works best with diet and exercise
  5. Monitor for gallbladder issues: Rapid weight loss increases risk
  6. Maintenance therapy: Weight regain common upon discontinuation

References

  1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
  2. Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834-1844.
  3. Davies M, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity. Lancet. 2021;397(10278):971-984.
  4. FDA Prescribing Information for Ozempic, Wegovy, Rybelsus.