Liraglutide

Aka: Liraglutide, Victoza, Saxenda, Xultophy

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II. 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. Liraglutide High Dose (Saxenda) results in weight loss up to 9.7 to 13 lb (4.4 to 5.9 kg) over Placebo

III. 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

IV. 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

V. 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. Liraglutide Standard Dose (Victoza)
    1. Single daily injection
    2. Available in Multidose pens 18 mg/3 ml that deliver doses in 0.6 mg increments (0.6, 1.2 and 1.8 mg)
    3. Approved in 2019 for use in age 10 years and older with Type 2 Diabetes Mellitus
  3. Liraglutide High Dose (Saxenda)
    1. FDA approved as an Obesity Medication with release in 2015
    2. Results in weight loss up to 9.7 to 13 lb (4.4 to 5.9 kg) over Placebo
    3. Available in Multidose pens 18 mg/3 ml that deliver doses in 0.6 mg increments (0.6, 1.2, 1.8, 2.4 and 3 mg)
    4. Indicated only in Obesity (with or without Diabetes Mellitus)
      1. Do not use high dose Liraglutide (Saxenda) for Diabetes Mellitus alone
      2. Consider in Type II Diabetes Mellitus in which an Obesity Medication is being considered
  4. Combination: Insulin Degludec with Liraglutide (Xultophy)
    1. Addition of Liraglutide, may spare basal Insulin Dosing
    2. However, limits titration of basal Insulin Dosing (fixed dose combinations)
    3. Very expensive ($760 to 950 per month in 2024)

VI. Dosing

  1. Give subcutaneous doses in the upper arm, Abdomen or thigh (and rotate injection sites)
  2. Liraglutide Standard Dose (Victoza)
    1. Approved in 2019 for use in age 10 years and older with Type 2 Diabetes Mellitus (same dosing as adults)
    2. Start 0.6 mg SQ daily for 1 week
    3. Next: Increase to 1.2 mg SQ daily
    4. May increase, as needed, to 1.8 mg SQ daily
  3. Liraglutide High Dose (Saxenda) for Obesity (with or without Diabetes Mellitus)
    1. Saxenda is dosed up to 3 mg daily (contrast with 1.8 mg with Victoza)
    2. Start at 0.6 mg SQ daily
    3. May increase weekly as tolerated in 0.6 mg increments (0.6, 1.2, 1.8, 2.4 and 3 mg)
    4. Maximum: 3.0 mg SQ daily

VII. Adverse Effects

  1. See GLP-1 Agonist
  2. Nausea or Vomiting
    1. More common with Liraglutide High Dose (Saxenda)
    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 (transient)
  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. Diabetic Retinopathy complications (increased Retinal Hemorrhage)
    1. Occurs with Semaglutide, Liraglutide, Dulaglutide
    2. Paradoxically attributed to better Blood Glucose control
  10. Subcutaneous Fat Loss
    1. Desired weight loss (esp. Semaglutide) may result in loose, sagging skin ("Ozempic face")
  11. Other serious but uncommon effects (<1%)
    1. Acute Kidney Injury
    2. Angioedema
    3. Suicidality (case reports, FDA is investigating as of 2024)

VIII. 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

IX. Efficacy

  1. Liraglutide (high dose) is among the most ideal GLP-1 Agonists
    1. Offers potent Glucose control and weight loss, cardiovascular protection, easy preparation
    2. Liraglutide is, however, dosed daily (contrast with Dulaglutide dosed weekly, but with similar benefits)
  2. Lowers Hemoglobin A1C 1.5%
  3. Liraglutide is also associated with decreased Cardiovascular Risk
    1. Liraglutide has the best evidence for cardiovascular benefit of any GLP-1 Agonist
    2. Reduces Cardiovascular Risk at 1.8 mg daily dose or 1.5 mg weekly dose
    3. Reduces overall mortality and cardiovascular mortality
  4. May reduce hypoalbuminuria (NNT 83), but does not delay Hemodialysis
    1. Mann (2017) N Engl J Med 377(9):839-48 [PubMed]

X. 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

XI. Resources

  1. Liraglutide: Victoza (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4
  2. Liraglutide High Dose: Saxenda (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3946d389-0926-4f77-a708-0acb8153b143

XII. 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(12):2213-4 [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]

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Related Studies

Cost: Medications

victoza (on 1/6/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
VICTOZA 2-PAK 18 MG/3 ML PEN $113.59 per ml
VICTOZA 3-PAK 18 MG/3 ML PEN $113.52 per ml
saxenda (on 8/17/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
SAXENDA 18 MG/3 ML PEN $86.24 per ml
xultophy (on 1/6/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
XULTOPHY 100 UNIT-3.6 MG/ML PEN $75.69 per ml
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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