Orforglipron (Foundayo)

See GLP-1 Agonist
Not yet FDA approved for Type 2 Diabetes as of May 2026
1. Orforglipron lowers Hemoglobin A1C 1% more than Placebo
Weight Loss
1. At least 50% of weight regained on stopping GLP-1 agents
2. Similar efficacy to Semaglutide 25 mg/day with 11% more weight loss than Placebo

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)
1. Basal insulin (e.g. Lantus) may be used
Severe Gastrointestinal Diseases or Gastroparesis
1. Relative contraindication due to the high Incidence of gastrointestinal side effects with GLP-1 Agonists

See GLP-1 Agonist
Oral GLP-1 (similar to Semaglutide; other GLP1 Agonists are injectable)
1. Orforglipron is a unique, non-peptide small molecule agent
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

Orforglipron (Foundayo) film coated tablets: 0.8, 2.5, 5.5, 9, 14.5, 17.2 mg
Precautions
1. All GLP-1 Agonists are expensive ($600 to $1300 per month without insurance, $150 to $500 with insurance)
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

Instructions
1. Take once daily with or without food (contrast with Semaglutide)
2. Swallow tablets whole, and do not break, crush or chew
Start: 0.8 mg orally daily
Titration (>30 days between dose increase): 2.5 mg, 5.5 mg, 9 mg, 14.5 mg, 17.2 mg
Maximum: 17.2 mg/day

See GLP-1 Agonist
Diarrhea
Dizziness
Headache
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
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)
Acute Pancreatitis (occurs with all GLP-1 Agonists)
1. Singh (2013) JAMA Intern Med 173(7):534-9 [PubMed]
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]
Subcutaneous Fat Loss
1. Desired weight loss may result in loose, sagging skin ("Ozempic face")
Diabetic Retinopathy complications (increased Retinal Hemorrhage)
1. Increased risk of Retinopathy complications (esp. if pre-existing Retinopathy)
2. GLP1-Agonist class effect (esp. Semaglutide, Liraglutide, Dulaglutide)
3. Paradoxically attributed to better Blood Glucose control
Other serious but uncommon effects (<1%)
1. Acute Kidney Injury
2. Angioedema or Anaphylaxis

Strong CYP3A4 Inhibitors (e.g. Clarithromycin)
1. Maximum Orforglipron dose: 9 mg
Strong CYP3A4 Inducers (e.g. Carbamazepine)
1. Discontinue strong CYP3A4 Inducers or avoid Orforglipron