Peptide Comparison
OrforglipronvsRetatrutide
First oral non-peptide GLP-1 receptor agonist for diabetes and obesity
The world's first triple-action weight loss peptide that simultaneously activates three hormone receptors—GIP, GLP-1, and glucagon—delivering unprecedented weight loss results of up to 24% body weight in clinical trials.
At a Glance
Quick
comparison
Dose Range
Orforglipron
12 mg–36 mg mg
Retatrutide
1–12 mg
Frequency
Orforglipron
Once daily
Retatrutide
Once weekly
Administration
Orforglipron
oral
Retatrutide
Subcutaneous injection
Cycle Length
Orforglipron
Ongoing/indefinite
Retatrutide
12+ weeks
Onset Speed
Orforglipron
Moderate (1-2 weeks)
Retatrutide
Moderate (1-2 weeks)
Evidence Level
Orforglipron
Strong human trials (Phase 3 or FDA approved)
Retatrutide
Moderate human trials (Phase 1-2)
Efficacy
Benefit
ratings
Weight Management
Blood Sugar Control
Cardiovascular Health
Weight Loss Power
Metabolic Health
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
Retatrutide
Molecular Formula
C221H342N46O68
Molecular Weight
4731 g/mol
Half-Life
~6 days (allows once-weekly dosing)
Bioavailability
High via subcutaneous injection
CAS Number
2381089-83-2
Protocols
Dosing
tiers
Orforglipron
Retatrutide
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.
Retatrutide
Significant Obesity Management
If you need to lose a substantial amount of weight, retatrutide is showing unprecedented results. Phase 2 trials demonstrated average weight loss of 24% at the highest dose—that's nearly 60 pounds for someone weighing 250 lbs. No other medication has matched this.
Type 2 Diabetes with Obesity
Retatrutide tackles both problems at once. It dramatically improves blood sugar control (HbA1c reductions of up to 2%) while delivering major weight loss. The dual benefit makes it especially valuable for diabetics struggling with weight.
Metabolic Syndrome Warriors
If you're dealing with the cluster of issues that includes high blood sugar, excess belly fat, abnormal cholesterol, and high blood pressure, retatrutide's triple mechanism attacks multiple aspects of metabolic dysfunction simultaneously.
Fatty Liver Disease (MASLD)
Early research shows retatrutide may significantly reduce liver fat. For people with non-alcoholic fatty liver disease, this peptide offers hope through weight loss plus direct metabolic improvements that benefit liver health.
Safety Profile
Side
effects
Orforglipron
Common
- Nausea
- Constipation
- Diarrhea
- Vomiting
Uncommon
- Heart Rate Increase
Serious
- Pancreatitis Risk
Retatrutide
Common
- Nausea
- Diarrhea
- Constipation
- Decreased appetite
Uncommon
- Increased heart rate
- Injection site reactions
Serious
- Pancreatitis
- Gallbladder problems
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)
Retatrutide
Evidence Level
Moderate human trials (Phase 1-2)
FDA Status
Research compound
Safety Overview
Retatrutide has shown a generally favorable safety profile in Phase 1 and Phase 2 clinical trials involving over 600 participants. Most side effects are gastrointestinal and tend to improve over time. The medication appears well-tolerated when doses are increased gradually. No major safety signals have emerged, but larger Phase 3 trials are still ongoing.
Contraindications
- xPersonal or family history of medullary thyroid carcinoma (MTC)
- xMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- xPregnancy or planning to become pregnant
- xHistory of severe pancreatitis
- xKnown allergy to GLP-1 receptor agonists
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 Retatrutide if...
- Significant weight loss
- Type 2 diabetes management
- Metabolic health improvement
- Body composition optimization