II. Indications
- See GLP-1 Agonist
-
Type II Diabetes Mellitus
- Very effective for weight loss in comorbid Obesity
- May be used in combination with Basal insulin (e.g. Lantus)
-
Insulin deficiency and Insulin Resistance
- Adjunct to Glucophage, Sulfonylureas, Glitazones
- Weight Loss
- At least 50% of weight regained on stopping GLP-1 agents
- Semaglutide High Dose (Wegovy) with mean weight loss 13% body weight (at least 5% in most patients)
III. Contraindications
- See GLP-1 Agonist
- Type I Diabetes Mellitus
- Medullary Thyroid Carcinoma (personal or Family History)
- Multiple Endocrine Neoplasia syndrome type 2 (active)
- Concurrent prandial Insulin (Bolus Insulin)
- Basal insulin (e.g. Lantus) may be used
- Severe Gastrointestinal Diseases or Gastroparesis
- Relative contraindication due to the high Incidence of gastrointestinal side effects with GLP-1 Agonists
IV. Mechanism
- See GLP-1 Agonist
-
Glucagon-Like Peptide 1 (GLP-1) Agonist, an Incretin Mimetic, derived from Gila monster Saliva
- Increases Glucose dependent Insulin secretion
- Inhibits Glucagon secretion
- Delays gastric emptying
- Decreases food intake (improves satiety and decreases appetite)
- Direct effects at the Hypothalamus, Nucleus Accumbens, ventral tegmental areas and Vagus Nerve
V. Medications
- Precautions
- All GLP-1 Agonists are expensive ($600 to $1300 per month in 2024)
- GLP-1 shortages (esp. Semaglutide and Tirzepatide) have resulted in many online resellers
- Buy from only licensed pharmacies (U.S.), and appropriately accredited (e.g. compounding pharmacy)
- Certificates of analysis confirm active ingredient
- Semaglutide Standard Injection (Ozempic, Diabetes Mellitus)
- Once weekly injection
- Lowers Hemoglobin A1C 1.5%
- 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)
- Semglutide High Dose (Wegovy, weight loss in Obesity only)
- Indicated only in Obesity (do NOT Semglutide High Dose for Diabetes Mellitus alone)
- Associated with mean weight loss 13% body weight (at least 5% in most patients)
- Semaglutide Oral (Rybelsus)
- First oral GLP-1 Agonist
- Lowers Hemoglobin A1C 1%
- Associated with short term weight loss <10 pounds
- Gastrointestinal adverse effects may be prolonged
VI. Dosing
- Give subcutaneous doses in the upper arm, Abdomen or thigh (and rotate injection sites)
- Semaglutide Standard Injection (Ozempic, Diabetes Mellitus)
- Once weekly injection
- May be given at any time of day (regardless of meal times)
- Start at 0.25 mg injected SQ weekly, and slowly titrate to maximum of 1.0 mg injected weekly
- Semglutide High Dose (Wegovy, weight loss in Obesity only)
- Indicated only in Obesity (do NOT use this dosing for Diabetes Mellitus alone)
- Start at 0.25 mg injected SQ weekly, and slowly titrate over first 16 weeks to max 2.4 mg weekly
- Increase dose monthly (0.5, 1, 1.7, 2.4 mg) over the first 16 weeks, then continue at 2.4 mg
- Target dose 2.4 mg/week costs $1400/month in 2021
- Semaglutide Oral (Rybelsus)
- Take once orally daily with NO more than 4 ounces of water
- Take at least 30 minutes before first food, water or medication of the day
VII. Adverse Effects
- See GLP-1 Agonist
-
Nausea or Vomiting
- Gastrointestinal adverse effects may be prolonged with Semaglutide Oral (Rybelsus)
- Eat smaller meals and more slowly, stopping before fullness (satiety)
- Consider short-term Ondansetron
- Consider dose reduction until tolerated
- Diarrhea
- Dizziness
- Headache
-
Hypoglycemia
- Alone, GLP-1 Agonists do not significantly increase risk of Hypoglycemia
- Avoid combination with Bolus Insulin (Mealtime Insulin) or Insulin Secretagogues (e.g. Sulfonylureas)
- With Sulfonylurea: 14.4% at 5 mcg, 35.7% at 10 mcg
- With Metformin: 4.5% at 5 mcg, 5.3% at 10 mcg
- Pancreatitis (occurs with all GLP-1 Agonists)
- Gallbladder disease (Cholelithiasis, Cholecystitis, Choledocholithiasis)
- Increased by one in 357 patients over 3 years of medication use
- Increased with longer use, higher dose and when GLP-1 Agonist is used for weight loss
- Faillie (2016) JAMA Intern Med 176(10): 1474-81 +PMID: 27478902 [PubMed]
- Increased Heart Rate
- Heart Rate rises in 10-20 bpm in 40% of patients on Semaglutide Injection (Wegovy)
- Subcutaneous Fat Loss
- Desired weight loss (esp. Semaglutide) may result in loose, sagging skin ("Ozempic face")
-
Diabetic Retinopathy complications (increased Retinal Hemorrhage)
- Increased risk of Retinopathy complications (esp. if pre-existing Retinopathy)
- Occurs with Semaglutide, Liraglutide, Dulaglutide
- Paradoxically attributed to better Blood Glucose control
- Other serious but uncommon effects (<1%)
- Acute Kidney Injury
- Angioedema
- Suicidality (case reports, FDA is investigating as of 2024)
VIII. Safety
- Unknown safety in Lactation
- Most GLP-1 Agonists have unknown safety in pregnancy (avoid)
- High dose weight loss GLP-1 Agonists (e.g. Saxena, Wegovy) are considered Pregnancy Category X
- Stop Semaglutide at least 2 months before planned conception
- Monitor patients with renal dysfunction
- Periodic Renal Function testing
- May present with increased gastrointestinal adverse effects
IX. Efficacy
- Semaglutide Standard Injection (Ozempic) lowers Hemoglobin A1C 1.5%
- Semaglutide Oral (Rybelsus) lowers Hemoglobin A1C 1%
- Semaglutide is also associated with decreased Cardiovascular Risk
- Reduces Cardiovascular Risk at 0.5 mg weekly dose
- However, does not decrease overall mortality or cardiovascular mortality (unlike Liraglutide)
- Semaglutide weekly reduces risk of CKD Progression (NNT 20)
- Semglutide High Dose (Wegovy)
- Mean weight loss 13% body weight (at least 5% in most patients)
- Weight loss sustained >1 year while on Semaglutide
- Expect 10-12% weight loss at one year (twice the weight loss of Saxenda)
- Stop medication if inadequate weight loss (<5% at 12 weeks of 2.5 mg/week)
- References
X. Drug Interactions
- Avoid using 2 Incretins (e.g. Byetta with Januvia) in combination
- Raises cost, risk of Pancreatitis without significant benefit
- (2012) Presc Lett 19(8): 45
- Concurrent prandial Insulin (Bolus Insulin)
- Basal insulin (e.g. Lantus) may be used
XI. Resources
- Semaglutide Standard Injection: Ozempic (DailyMed)
- Semglutide High Dose: Wegovy (DailyMed)
- Semaglutide Oral: Rybelsus (DailyMed)
XII. References
- (2024) Presc Lett 31(7): 38
- (2024) Presc Lett 31(2): 8-9
- (2022) Presc Lett 30(2): 7
- (2019) Presc Lett 26(11):62-3
- (2019) Presc Lett 26(8):46
- (2018) Presc Lett 25(2)
- (2014) Presc Lett 21(12): 69
- (2012) Presc Lett 19(3): 15
- Nordt and Kaucher (2023) EM:Rap 23(9)
- Dungan (2005) Clin Diabetes 23: 56-62 [PubMed]
- Ezzo (2006) Am Fam Physician 73 [PubMed]
- Fineman (2003) Diabetes Care 26:2370-7 [PubMed]
- Jones (2007) Am Fam Physician 75:1831-5 [PubMed]
- Joy (2005) Ann Pharmacol 39:110-8 [PubMed]
- Vaughan (2024) Am Fam Physician 109(4): 333-42 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
| ozempic (on 1/6/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| OZEMPIC 0.25-0.5 MG/DOSE (2 MG/1.5 ML) PEN | $571.53 per ml | |
| OZEMPIC 0.25-0.5 MG/DOSE (2 MG/3 ML) PEN | $300.06 per ml | |
| OZEMPIC 1 MG/DOSE (2 MG/1.5 ML) PEN | $285.23 per ml | |
| OZEMPIC 1 MG/DOSE (4 MG/3 ML) PEN | $287.01 per ml | |
| OZEMPIC 2 MG/DOSE (8 MG/3 ML) PEN | $285.85 per ml | |
| rybelsus (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| RYBELSUS 14 MG TABLET | $28.58 each | |
| RYBELSUS 3 MG TABLET | $28.58 each | |
| RYBELSUS 7 MG TABLET | $28.57 each | |
| wegovy (on 2/22/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| WEGOVY 0.25 MG/0.5 ML PEN | $657.38 per ml | |
| WEGOVY 0.5 MG/0.5 ML PEN | $644.43 per ml | |
| WEGOVY 1 MG/0.5 ML PEN | $644.07 per ml | |
| WEGOVY 1.7 MG/0.75 ML PEN | $431.69 per ml | |
| WEGOVY 2.4 MG/0.75 ML PEN | $431.80 per ml | |