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Semaglutide

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Semaglutide, Ozempic, Rybelsus, Wegovy

  • See Also
  1. GLP-1 Agonist
  2. Type II Diabetes Medications
  3. Obesity Medication
  4. Dulaglutide
  5. Exenatide
  6. Liraglutide
  7. Lixisenatide
  8. Tirzepatide
  • Indications
  1. See GLP-1 Agonist
  2. Type II Diabetes Mellitus
    1. Very effective for weight loss in comorbid Obesity
    2. May be used in combination with Basal insulin (e.g. Lantus)
  3. Insulin deficiency and Insulin Resistance
    1. Adjunct to Glucophage, Sulfonylureas, Glitazones
  4. Weight Loss
    1. At least 50% of weight regained on stopping GLP-1 agents
    2. Semaglutide High Dose (Wegovy) with mean weight loss 13% body weight (at least 5% in most patients)
  • Contraindications
  1. See GLP-1 Agonist
  2. Type I Diabetes Mellitus
  3. Medullary Thyroid Carcinoma (personal or Family History)
  4. Multiple Endocrine Neoplasia syndrome type 2 (active)
  5. Concurrent prandial Insulin (Bolus Insulin)
    1. Basal insulin (e.g. Lantus) may be used
  6. Severe Gastrointestinal Diseases or Gastroparesis
    1. Relative contraindication due to the high Incidence of gastrointestinal side effects with GLP-1 Agonists
  • Mechanism
  1. See GLP-1 Agonist
  2. Glucagon-Like Peptide 1 (GLP-1) Agonist, an Incretin Mimetic, derived from Gila monster Saliva
    1. Increases Glucose dependent Insulin secretion
    2. Inhibits Glucagon secretion
    3. Delays gastric emptying
    4. Decreases food intake (improves satiety and decreases appetite)
      1. Direct effects at the Hypothalamus, Nucleus Accumbens, ventral tegmental areas and Vagus Nerve
  • Medications
  1. Precautions
    1. All GLP-1 Agonists are expensive ($600 to $1300 per month in 2024)
    2. GLP-1 shortages (esp. Semaglutide and Tirzepatide) have resulted in many online resellers
      1. Buy from only licensed pharmacies (U.S.), and appropriately accredited (e.g. compounding pharmacy)
      2. Certificates of analysis confirm active ingredient
  2. Semaglutide Standard Injection (Ozempic, Diabetes Mellitus)
    1. Once weekly injection
    2. Lowers Hemoglobin A1C 1.5%
    3. Available in multidose pens: 0.25 or 0.5 mg dose (2 mg/1.5 ml), 1 mg dose (2 mg/1.5 ml or 4 mg/3 ml)
  3. Semglutide High Dose (Wegovy, weight loss in Obesity only)
    1. Indicated only in Obesity (do NOT Semglutide High Dose for Diabetes Mellitus alone)
    2. Associated with mean weight loss 13% body weight (at least 5% in most patients)
  4. Semaglutide Oral (Rybelsus)
    1. First oral GLP-1 Agonist
    2. Lowers Hemoglobin A1C 1%
    3. Associated with short term weight loss <10 pounds
    4. Gastrointestinal adverse effects may be prolonged
  • Dosing
  1. Give subcutaneous doses in the upper arm, Abdomen or thigh (and rotate injection sites)
  2. Semaglutide Standard Injection (Ozempic, Diabetes Mellitus)
    1. Once weekly injection
    2. May be given at any time of day (regardless of meal times)
    3. Start at 0.25 mg injected SQ weekly, and slowly titrate to maximum of 1.0 mg injected weekly
  3. Semglutide High Dose (Wegovy, weight loss in Obesity only)
    1. Indicated only in Obesity (do NOT use this dosing for Diabetes Mellitus alone)
    2. Start at 0.25 mg injected SQ weekly, and slowly titrate over first 16 weeks to max 2.4 mg weekly
    3. Increase dose monthly (0.5, 1, 1.7, 2.4 mg) over the first 16 weeks, then continue at 2.4 mg
    4. Target dose 2.4 mg/week costs $1400/month in 2021
  4. Semaglutide Oral (Rybelsus)
    1. Take once orally daily with NO more than 4 ounces of water
    2. Take at least 30 minutes before first food, water or medication of the day
  • Adverse Effects
  1. See GLP-1 Agonist
  2. Nausea or Vomiting
    1. Gastrointestinal adverse effects may be prolonged with Semaglutide Oral (Rybelsus)
    2. Eat smaller meals and more slowly, stopping before fullness (satiety)
    3. Consider short-term Ondansetron
    4. Consider dose reduction until tolerated
  3. Diarrhea
  4. Dizziness
  5. Headache
  6. Hypoglycemia
    1. Alone, GLP-1 Agonists do not significantly increase risk of Hypoglycemia
    2. Avoid combination with Bolus Insulin (Mealtime Insulin) or Insulin Secretagogues (e.g. Sulfonylureas)
    3. With Sulfonylurea: 14.4% at 5 mcg, 35.7% at 10 mcg
    4. With Metformin: 4.5% at 5 mcg, 5.3% at 10 mcg
  7. Pancreatitis (occurs with all GLP-1 Agonists)
    1. Singh (2013) JAMA Intern Med 173(7):534-9 [PubMed]
  8. Gallbladder disease (Cholelithiasis, Cholecystitis, Choledocholithiasis)
    1. Increased by one in 357 patients over 3 years of medication use
    2. Increased with longer use, higher dose and when GLP-1 Agonist is used for weight loss
    3. Faillie (2016) JAMA Intern Med 176(10): 1474-81 +PMID: 27478902 [PubMed]
  9. Increased Heart Rate
    1. Heart Rate rises in 10-20 bpm in 40% of patients on Semaglutide Injection (Wegovy)
  10. Subcutaneous Fat Loss
    1. Desired weight loss (esp. Semaglutide) may result in loose, sagging skin ("Ozempic face")
  11. Diabetic Retinopathy complications (increased Retinal Hemorrhage)
    1. Increased risk of Retinopathy complications (esp. if pre-existing Retinopathy)
    2. Occurs with Semaglutide, Liraglutide, Dulaglutide
    3. Paradoxically attributed to better Blood Glucose control
  12. Other serious but uncommon effects (<1%)
    1. Acute Kidney Injury
    2. Angioedema
    3. Suicidality (case reports, FDA is investigating as of 2024)
  • Safety
  1. Unknown safety in Lactation
  2. Most GLP-1 Agonists have unknown safety in pregnancy (avoid)
    1. High dose weight loss GLP-1 Agonists (e.g. Saxena, Wegovy) are considered Pregnancy Category X
    2. Stop Semaglutide at least 2 months before planned conception
  3. Monitor patients with renal dysfunction
    1. Periodic Renal Function testing
    2. May present with increased gastrointestinal adverse effects
  • Efficacy
  1. Semaglutide Standard Injection (Ozempic) lowers Hemoglobin A1C 1.5%
    1. Semaglutide Oral (Rybelsus) lowers Hemoglobin A1C 1%
  2. Semaglutide is also associated with decreased Cardiovascular Risk
    1. Reduces Cardiovascular Risk at 0.5 mg weekly dose
    2. However, does not decrease overall mortality or cardiovascular mortality (unlike Liraglutide)
  3. Semaglutide weekly reduces risk of CKD Progression (NNT 20)
    1. Perkovic (2024) N Engl J Med 391(2):109-21 +PMID: 38785209 [PubMed]
  4. Semglutide High Dose (Wegovy)
    1. Mean weight loss 13% body weight (at least 5% in most patients)
    2. Weight loss sustained >1 year while on Semaglutide
    3. Expect 10-12% weight loss at one year (twice the weight loss of Saxenda)
    4. Stop medication if inadequate weight loss (<5% at 12 weeks of 2.5 mg/week)
    5. References
      1. (2021) Presc Lett 28(8): 45
      2. Bald (2023) Am Fam Physician 107(1): 90-1 [PubMed]
      3. Capehorn (2020) Diabetes Metab 46:100-9 +PMID: 31539622 [PubMed]
      4. Garvey (2022) Nat Med 28:2083-91 +PMID: 36216945 [PubMed]
      5. Wilding (2021) N Engl J Med 384:989-1002 +PMID: 33567185 [PubMed]
  • Drug Interactions
  1. Avoid using 2 Incretins (e.g. Byetta with Januvia) in combination
    1. Raises cost, risk of Pancreatitis without significant benefit
    2. (2012) Presc Lett 19(8): 45
  2. Concurrent prandial Insulin (Bolus Insulin)
    1. Basal insulin (e.g. Lantus) may be used
  • Resources
  1. Semaglutide Standard Injection: Ozempic (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79
  2. Semglutide High Dose: Wegovy (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
  3. Semaglutide Oral: Rybelsus (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98
  • References
  1. (2024) Presc Lett 31(7): 38
  2. (2024) Presc Lett 31(2): 8-9
  3. (2022) Presc Lett 30(2): 7
  4. (2019) Presc Lett 26(11):62-3
  5. (2019) Presc Lett 26(8):46
  6. (2018) Presc Lett 25(2)
  7. (2014) Presc Lett 21(12): 69
  8. (2012) Presc Lett 19(3): 15
  9. Nordt and Kaucher (2023) EM:Rap 23(9)
  10. Dungan (2005) Clin Diabetes 23: 56-62 [PubMed]
  11. Ezzo (2006) Am Fam Physician 73 [PubMed]
  12. Fineman (2003) Diabetes Care 26:2370-7 [PubMed]
  13. Jones (2007) Am Fam Physician 75:1831-5 [PubMed]
  14. Joy (2005) Ann Pharmacol 39:110-8 [PubMed]
  15. Vaughan (2024) Am Fam Physician 109(4): 333-42 [PubMed]