Peptide Comparison
OrforglipronvsTirzepatide
First oral non-peptide GLP-1 receptor agonist for diabetes and obesity
The dual-action powerhouse that targets both GIP and GLP-1 receptors, delivering the most dramatic weight loss results ever seen in a medication—averaging over 20% body weight reduction while also crushing blood sugar levels in people with diabetes.
At a Glance
Quick
comparison
Dose Range
Orforglipron
12 mg–36 mg mg
Tirzepatide
2.5–15 mg
Frequency
Orforglipron
Once daily
Tirzepatide
Once weekly
Administration
Orforglipron
oral
Tirzepatide
Subcutaneous injection
Cycle Length
Orforglipron
Ongoing/indefinite
Tirzepatide
Ongoing/indefinite
Onset Speed
Orforglipron
Moderate (1-2 weeks)
Tirzepatide
Moderate (1-2 weeks)
Evidence Level
Orforglipron
Strong human trials (Phase 3 or FDA approved)
Tirzepatide
Strong human trials (Phase 3 or FDA approved)
Efficacy
Benefit
ratings
Weight Management
Blood Sugar Control
Cardiovascular Health
Weight Loss
Appetite Control
Technical Data
Compound
specifications
Orforglipron
Molecular Formula
C48H48F2N10O5
Molecular Weight
883.0 Da
Half-Life
25-68 hours (dose-dependent; enables once-daily oral dosing)
Bioavailability
~79% oral bioavailability (food-independent)
CAS Number
2212020-52-3
Tirzepatide
Molecular Formula
C225H348N48O68
Molecular Weight
4813.45 g/mol
Half-Life
Approximately 5 days (120 hours)
Bioavailability
~80% (subcutaneous)
CAS Number
2023788-19-2
Protocols
Dosing
tiers
Orforglipron
Tirzepatide
Applications
Best
suited for
Orforglipron
Oral GLP-1 receptor agonism without injection burden
Orforglipron is particularly well-suited for individuals focused on oral glp-1 receptor agonism without injection burden. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Weight management in obesity with or without type 2 diabetes
Orforglipron is particularly well-suited for individuals focused on weight management in obesity with or without type 2 diabetes. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Glycemic control in type 2 diabetes as add-on to metformin
Orforglipron is particularly well-suited for individuals focused on glycemic control in type 2 diabetes as add-on to metformin. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Cardiovascular risk reduction through weight loss and metabolic improvements
Orforglipron is particularly well-suited for individuals focused on cardiovascular risk reduction through weight loss and metabolic improvements. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Tirzepatide
People Who Want Maximum Weight Loss Results
If you're serious about losing significant weight, tirzepatide delivers results that were previously only achievable through bariatric surgery. Clinical trials showed average weight loss exceeding 20% of body weight—that's 50+ pounds for someone starting at 250 pounds. No other medication comes close.
Those Who Haven't Succeeded with Semaglutide
Thanks to its dual GIP/GLP-1 mechanism, tirzepatide often works better for people who had limited results with GLP-1-only drugs like semaglutide. The added GIP activation provides extra metabolic benefits that can break through plateaus and deliver superior weight loss.
People with Type 2 Diabetes Needing Aggressive Control
Head-to-head trials proved tirzepatide beats semaglutide for blood sugar control. The average HbA1c reduction of over 2 percentage points means many people can dramatically reduce or eliminate other diabetes medications. It's a genuine game-changer for metabolic health.
Individuals Looking to Transform Their Relationship with Food
Tirzepatide doesn't just reduce hunger—it fundamentally changes how food appeals to you. Users describe feeling free from constant food thoughts, finding it easy to stop eating when satisfied, and losing interest in formerly irresistible treats. It's not willpower—it's biochemistry working for you.
Safety Profile
Side
effects
Orforglipron
Common
- Nausea
- Constipation
- Diarrhea
- Vomiting
Uncommon
- Heart Rate Increase
Serious
- Pancreatitis Risk
Tirzepatide
Common
- Nausea
- Diarrhea
- Decreased Appetite
- Vomiting
Uncommon
- Gallbladder Problems
- Hair Thinning (Telogen Effluvium)
Serious
- Pancreatitis
- Thyroid Tumors (Theoretical Risk)
Research Status
Safety
& evidence
Orforglipron
Evidence Level
Strong human trials (Phase 3 or FDA approved)
FDA Status
Research compound
Safety Overview
Orforglipron (MK-0731) completed Phase II trials for type 2 diabetes with favorable safety profile at oral doses of 10-40 mg daily. Gastrointestinal side effects (nausea, vomiting) occurred in 20-30% of subjects but were dose-dependent and generally mild. As a GLP-1 receptor agonist, risks include potential medullary thyroid carcinoma (black box warning category) and acute pancreatitis, requiring thyroid screening before treatment initiation and patient education on symptoms.
Contraindications
- xPersonal or family history of medullary thyroid carcinoma (GLP-1 class precaution)
- xMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- xKnown hypersensitivity to orforglipron or excipients
- xHistory of pancreatitis (use with caution)
Tirzepatide
Evidence Level
Strong human trials (Phase 3 or FDA approved)
FDA Status
FDA approved for this use
Safety Overview
Tirzepatide has been extensively studied in the SURPASS (diabetes) and SURMOUNT (obesity) trial programs, involving thousands of participants over multiple years. The FDA approved it after thorough safety review. While GI side effects are common (especially during dose increases), they're typically mild to moderate and improve over time. Serious adverse events are rare. The SURPASS-CVOT trial is ongoing to evaluate long-term cardiovascular outcomes.
Contraindications
- xPersonal or family history of medullary thyroid carcinoma (MTC)
- xMultiple Endocrine Neoplasia syndrome type 2 (MEN2)
- xHistory of serious allergic reaction to tirzepatide or any GLP-1/GIP medication
- xCurrent or recent pancreatitis
- xPregnancy or planning to become pregnant
Decision Guide
Which is
right for you?
Choose Orforglipron if...
- Oral GLP-1 receptor agonism without injection burden
- Weight management in obesity with or without type 2 diabetes
- Glycemic control in type 2 diabetes as add-on to metformin
- Cardiovascular risk reduction through weight loss and metabolic improvements
Choose Tirzepatide if...
- Maximum weight loss results
- Long-term obesity management
- Type 2 diabetes control
- Metabolic health improvement