Peptide Comparison
ExenatidevsRetatrutide
First-in-class GLP-1 receptor agonist derived from Gila monster venom (Byetta/Bydureon), FDA-approved for type 2 diabetes with demonstrated cardiovascular safety in the 14,752-patient EXSCEL trial and available in both twice-daily and once-weekly formulations
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
Exenatide
5–10 mcg
Retatrutide
1–12 mg
Frequency
Exenatide
Once weekly
Retatrutide
Once weekly
Administration
Exenatide
Subcutaneous injection
Retatrutide
Subcutaneous injection
Cycle Length
Exenatide
Ongoing/indefinite
Retatrutide
12+ weeks
Onset Speed
Exenatide
Gradual (3-4 weeks)
Retatrutide
Moderate (1-2 weeks)
Evidence Level
Exenatide
Strong human trials (Phase 3 or FDA approved)
Retatrutide
Moderate human trials (Phase 1-2)
Efficacy
Benefit
ratings
Weight
Weight Management
Weight Loss Power
Metabolic Health
Appetite Control
Technical Data
Compound
specifications
Exenatide
Molecular Formula
C184H282N50O60S
Molecular Weight
4,187 Da
Half-Life
Byetta: ~2.4 hours (immediate-release); Bydureon: ~7 weeks effective duration via PLGA microsphere technology; Tmax ~2.1 hours (Byetta)
Bioavailability
65–75% after subcutaneous injection (Byetta); microsphere sustained release for Bydureon
CAS Number
183321-74-6
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
Exenatide
Retatrutide
Applications
Best
suited for
Exenatide
Type 2 diabetes patients inadequately controlled on metformin seeking add-on therapy with weight loss benefit
Exenatide is particularly well-suited for individuals focused on type 2 diabetes patients inadequately controlled on metformin seeking add-on therapy with weight loss benefit. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Patients preferring once-weekly dosing convenience (Bydureon 2 mg) over daily injections for improved adherence
Exenatide is particularly well-suited for individuals focused on patients preferring once-weekly dosing convenience (bydureon 2 mg) over daily injections for improved adherence. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Overweight or obese type 2 diabetes patients (BMI >27) requiring glycemic control without weight gain
Exenatide is particularly well-suited for individuals focused on overweight or obese type 2 diabetes patients (bmi >27) requiring glycemic control without weight gain. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Patients with established cardiovascular disease who need a GLP-1 RA with demonstrated cardiovascular safety
Exenatide is particularly well-suited for individuals focused on patients with established cardiovascular disease who need a glp-1 ra with demonstrated cardiovascular safety. 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
Exenatide
Common
- Nausea
- Vomiting and diarrhea
- Injection site nodules (Bydureon)
- Decreased appetite and constipation
Uncommon
- Hypoglycemia
Serious
- Acute pancreatitis
- Renal impairment
Retatrutide
Common
- Nausea
- Diarrhea
- Constipation
- Decreased appetite
Uncommon
- Increased heart rate
- Injection site reactions
Serious
- Pancreatitis
- Gallbladder problems
Research Status
Safety
& evidence
Exenatide
Evidence Level
Strong human trials (Phase 3 or FDA approved)
FDA Status
FDA approved for this use
Safety Overview
Exenatide is an FDA-approved GLP-1 receptor agonist with post-market safety data spanning 15+ years, though some safety concerns have emerged. Nausea affects 30-45% of patients, dose-dependent and typically improves within 1-2 weeks but can lead to treatment discontinuation in 5% of patients. Pancreatitis risk, while rare (0.1-0.2%), is increased and contraindicated in patients with history of acute pancreatitis. Thyroid C-cell tumor risk identified in rodent studies supports clinical vigilance in patients with personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2—absolute contraindication. Acute kidney injury has been reported in 0.3-1% of patients, particularly with concurrent NSAID or ACE inhibitor use. Hypoglycemia risk is minimal when used as monotherapy but increases substantially when combined with insulin or sulfonylureas.
Contraindications
- xPersonal or family history of medullary thyroid carcinoma (MTC) — black box warning based on animal data
- xMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- xPrior serious hypersensitivity reaction to exenatide or any excipient
- xSevere renal impairment (eGFR <15 mL/min) or end-stage renal disease
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 Exenatide if...
- Type 2 diabetes patients inadequately controlled on metformin seeking add-on therapy with weight loss benefit
- Patients preferring once-weekly dosing convenience (Bydureon 2 mg) over daily injections for improved adherence
- Overweight or obese type 2 diabetes patients (BMI >27) requiring glycemic control without weight gain
- Patients with established cardiovascular disease who need a GLP-1 RA with demonstrated cardiovascular safety
Choose Retatrutide if...
- Significant weight loss
- Type 2 diabetes management
- Metabolic health improvement
- Body composition optimization