Ozempic. Wegovy. Mounjaro. Zepbound. These names are everywhere right now — and for good reason. GLP-1 agonists are the most effective weight loss drugs we’ve ever had.
But there’s a lot of confusion out there. Let’s clear it up.
What Are GLP-1 Agonists?
GLP-1 (glucagon-like peptide-1) is a hormone your body naturally produces after eating. It does a few things:
- Signals fullness — tells your brain you’re satisfied
- Slows stomach emptying — food stays in your gut longer
- Increases insulin release — helps regulate blood sugar
- Decreases glucagon — reduces sugar release from your liver
GLP-1 agonists are drugs that mimic this hormone, but they’re much more powerful and last much longer than your natural GLP-1.
The result: you eat less because you genuinely feel full, not because you’re white-knuckling through hunger.
The Big Three
Semaglutide (Ozempic, Wegovy, Rybelsus)
What it is: A GLP-1 agonist — mimics one hormone.
Brand names:
- Ozempic — injectable, FDA-approved for diabetes
- Wegovy — injectable, FDA-approved for weight loss (higher dose)
- Rybelsus — oral tablet, FDA-approved for diabetes
Weight loss: ~15% of body weight on average in clinical trials. Some people lose more, some less.
Dosing: Weekly injection. You start low (0.25mg) and titrate up over weeks to minimize side effects. Maintenance dose is typically 1mg (Ozempic) or 2.4mg (Wegovy).
The bottom line: The original modern weight loss drug. Well-studied, effective, and widely available. The benchmark everything else is compared to.
Tirzepatide (Mounjaro, Zepbound)
What it is: A dual agonist — mimics TWO hormones (GLP-1 and GIP).
Brand names:
- Mounjaro — FDA-approved for diabetes
- Zepbound — FDA-approved for weight loss
Weight loss: ~20-22% of body weight on average — significantly more than semaglutide.
Why it works better: GIP (glucose-dependent insulinotropic polypeptide) adds additional appetite suppression and metabolic effects. Two hormones > one hormone.
Dosing: Weekly injection. Start at 2.5mg, titrate up to 5mg, 7.5mg, 10mg, 12.5mg, or 15mg depending on response and tolerance.
The bottom line: Currently the most effective weight loss drug on the market. If semaglutide isn’t getting you where you want to be, tirzepatide is the next step.
Retatrutide (Investigational)
What it is: A triple agonist — mimics THREE hormones (GLP-1, GIP, and glucagon).
Status: Still in clinical trials. Not yet FDA-approved.
Weight loss: ~24% of body weight in Phase 2 trials — potentially the most powerful yet.
Why it might work even better: Adding glucagon receptor activation increases energy expenditure (you burn more calories) on top of the appetite suppression.
The catch: We need more data. Phase 3 trials are ongoing. Side effect profile at high doses needs more study.
The bottom line: The next frontier. If the Phase 3 data holds up, this could be a game-changer. But it’s not available yet outside of clinical trials.
How Do They Compare?
| Drug | Mechanism | Avg Weight Loss | Status |
|---|---|---|---|
| Semaglutide | GLP-1 | ~15% | Available |
| Tirzepatide | GLP-1 + GIP | ~20-22% | Available |
| Retatrutide | GLP-1 + GIP + Glucagon | ~24% | Trials |
Simple version: Tirzepatide is stronger than semaglutide. Retatrutide looks even stronger but isn’t available yet.
Side Effects
All GLP-1 agonists share similar side effects because they work the same way. Most are GI-related:
Common:
- Nausea (especially when starting or increasing dose)
- Vomiting
- Diarrhea or constipation
- Decreased appetite (that’s… kind of the point)
Less common:
- Acid reflux / GERD
- Fatigue
- Injection site reactions
Rare but serious:
- Pancreatitis (inflammation of the pancreas)
- Gallbladder issues
- Thyroid tumors (seen in rodents, unclear in humans — boxed warning)
The pattern: Side effects are worst when you start or increase your dose. They usually improve over 2-4 weeks. This is why you titrate slowly.
Pro tip: Eating smaller meals, avoiding greasy/fatty foods, and staying hydrated helps a lot with the GI side effects.
Muscle Loss: The Real Concern
Here’s something that doesn’t get talked about enough: you will lose muscle on these drugs if you’re not careful.
Rapid weight loss — from any cause — leads to muscle loss alongside fat loss. Studies show about 25-40% of weight lost on GLP-1 agonists can be lean mass (muscle).
Why this matters:
- Muscle is metabolically active — losing it lowers your metabolism
- Muscle is critical for longevity and functional health
- You don’t want to end up “skinny fat”
How to minimize muscle loss:
- Lift weights — resistance training is non-negotiable
- Eat enough protein — 0.7-1g per pound of body weight
- Don’t crash diet on top of the drug — you’re already in a deficit
- Lose weight at a reasonable pace — faster isn’t always better
If you’re taking a GLP-1 agonist and NOT lifting weights and eating adequate protein, you’re making a mistake.
Who Should Consider These?
Good candidates:
- BMI ≥30 (obese)
- BMI ≥27 with weight-related health issues (diabetes, high blood pressure, sleep apnea)
- People who’ve tried diet and exercise without success
- Those with metabolic dysfunction
Not ideal for:
- People who just want to lose 10 vanity pounds
- Anyone with history of thyroid cancer or MEN2 syndrome
- People with history of pancreatitis
- Pregnant or breastfeeding women
The honest take: These are powerful drugs with real side effects. They’re not for cosmetic weight loss in otherwise healthy people. They’re medical tools for people with significant weight-related health issues.
How to Get Them
Legitimate routes:
- Prescription from your doctor — for approved indications
- Telehealth weight loss clinics — many now prescribe these
- Compounding pharmacies — can compound semaglutide (gray area, variable quality)
What to avoid:
- Random online peptide vendors (quality unknown)
- “Research chemical” semaglutide (not for human use)
- Anything from overseas with no quality testing
Cost reality: Without insurance, these drugs are expensive ($800-1500/month). With insurance coverage, costs vary widely. Some telehealth clinics and compounding pharmacies offer more affordable options.
The Bottom Line
GLP-1 agonists are genuinely revolutionary. For people with obesity and metabolic disease, they offer something we’ve never had: effective, sustainable weight loss without constant hunger.
Key takeaways:
- Semaglutide — the original, well-proven, ~15% weight loss
- Tirzepatide — more effective, ~20-22% weight loss, dual mechanism
- Retatrutide — potentially most effective, but not available yet
- Side effects are real — mostly GI, worst at the start
- Protect your muscle — lift weights, eat protein, or you’ll regret it
- These are medical tools — not casual weight loss shortcuts
If you’re considering one of these, talk to a doctor who understands them. Get bloodwork. Have a plan for nutrition and exercise. Don’t just take the drug and hope for the best.
This content is for educational purposes only and does not constitute medical advice. Consult a healthcare provider before starting any medication.