Peptide Comparison
ExenatidevsSemaglutide
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 revolutionary once-weekly GLP-1 medication that helps your body feel full faster and longer, leading to significant weight loss while also protecting your heart—FDA approved and backed by some of the largest clinical trials in obesity medicine history.
At a Glance
Quick
comparison
Dose Range
Exenatide
5–10 mcg
Semaglutide
0.25–2.4 mg
Frequency
Exenatide
Once weekly
Semaglutide
Once weekly
Administration
Exenatide
Subcutaneous injection
Semaglutide
Subcutaneous injection
Cycle Length
Exenatide
Ongoing/indefinite
Semaglutide
Ongoing/indefinite
Onset Speed
Exenatide
Gradual (3-4 weeks)
Semaglutide
Moderate (1-2 weeks)
Evidence Level
Exenatide
Strong human trials (Phase 3 or FDA approved)
Semaglutide
Strong human trials (Phase 3 or FDA approved)
Efficacy
Benefit
ratings
Weight
Weight Management
Weight Loss
Appetite Control
Heart Protection
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
Semaglutide
Molecular Formula
C187H291N45O59
Molecular Weight
4113.58 g/mol
Half-Life
Approximately 7 days (168 hours)
Bioavailability
89% (subcutaneous); 0.4-1% (oral, with absorption enhancer)
CAS Number
910463-68-2
Protocols
Dosing
tiers
Exenatide
Semaglutide
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.
Semaglutide
People with Obesity Seeking Significant Weight Loss
If your BMI is 30 or higher (or 27+ with weight-related health conditions), semaglutide is currently one of the most effective non-surgical weight loss options available. Clinical trials show average weight loss of 15% of body weight—that's 30+ pounds for someone starting at 200 pounds.
Those Who've Struggled with Diet and Exercise Alone
Semaglutide works by changing the biological signals that drive hunger and cravings. If you've tried to lose weight through willpower alone and found yourself constantly battling hunger, this medication addresses that underlying biology rather than just telling you to eat less.
People with Type 2 Diabetes Needing Better Control
Originally developed for diabetes, semaglutide excellently controls blood sugar while also promoting weight loss—addressing two major health concerns simultaneously. It can often allow people to reduce or eliminate other diabetes medications.
Individuals at High Cardiovascular Risk
The SELECT trial proved that semaglutide reduces heart attacks, strokes, and cardiovascular death by 20% in people with obesity and existing heart disease—even without diabetes. It's one of the few weight loss medications proven to improve hard cardiovascular outcomes.
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
Semaglutide
Common
- Nausea
- Constipation or Diarrhea
- Decreased Appetite
- Vomiting
Uncommon
- Gallbladder Problems
- Hair Loss (Telogen Effluvium)
Serious
- Pancreatitis
- Thyroid Tumors (Theoretical Risk)
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
Semaglutide
Evidence Level
Strong human trials (Phase 3 or FDA approved)
FDA Status
FDA approved for this use
Safety Overview
Semaglutide has been studied in over 20,000 participants across multiple large clinical trials, making it one of the most thoroughly researched weight loss medications available. The FDA approved it after rigorous review of safety data. While GI side effects are common (especially early on), serious side effects are rare. The SELECT trial showed it actually reduces cardiovascular events, adding a safety benefit beyond just weight loss.
Contraindications
- xPersonal or family history of medullary thyroid carcinoma (MTC)
- xMultiple Endocrine Neoplasia syndrome type 2 (MEN2)
- xHistory of serious allergic reaction to semaglutide
- xCurrent or recent pancreatitis
- xPregnancy or planning to become pregnant
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 Semaglutide if...
- Significant weight loss
- Long-term weight management
- Cardiovascular risk reduction
- Blood sugar control