GLP-1 Medications Compared: Which One Is Right for You?
GLP-1 Medications Compared: Which One Is Right for You?
Five GLP-1 medications are FDA-approved right now. They all work on the same basic principle, but they're not the same drug. And the differences matter when you're deciding what to ask your doctor about.
The weight loss numbers are real. The side effects are manageable but not trivial. The cost is a problem for most people, and insurance is a lottery. And there's now a head-to-head trial that actually compared tirzepatide against semaglutide in the same study, so we don't have to guess anymore.
Here's the honest breakdown: what each drug does, what the data actually shows, what it costs, and where compounding fits in.
How GLP-1 Medications Work (The Short Version)
GLP-1 drugs work because your gut already uses a hormone called glucagon-like peptide-1 (GLP-1) to signal fullness and regulate blood sugar. These medications are engineered analogs of that hormone, with a much longer half-life than your body's natural version. The result: you feel less hungry, you eat less, and your blood sugar stays more stable after meals.
The mechanism starts in the gut and ends in the brain. GLP-1 receptors in the hypothalamus control appetite. When those receptors are activated consistently (not just for the 2 minutes after a meal), your body resets its hunger signals (Barrera et al., 2011). That's why these drugs work at a level that calorie restriction alone can't match. You're not fighting hunger through willpower. The drug is quieting the signal.
Most GLP-1 medications are weekly subcutaneous injections. Two exceptions: exenatide (Byetta) is twice daily, and oral semaglutide (Rybelsus) is a daily pill. Everything else goes in once a week.
The GLP-1 Medications List: All 5 FDA-Approved Options
All five drugs below are FDA-approved and require a valid prescription. They're organized by molecule, because the brand name confusion is real and knowing the molecule helps you understand what's actually different.
Semaglutide: Ozempic, Wegovy, Rybelsus
Semaglutide is the molecule. Ozempic, Wegovy, and Rybelsus are brand names for different indications and formulations of the same drug.
Ozempic (subcutaneous injection, up to 2 mg weekly): FDA-approved for type 2 diabetes. Not approved for obesity as a primary indication, but frequently used off-label for weight management.
Wegovy (subcutaneous injection, up to 2.4 mg weekly): FDA-approved specifically for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with a weight-related condition.
Rybelsus (oral tablet, 14 mg daily): FDA-approved for type 2 diabetes. The only oral GLP-1 agonist currently available.
The STEP 2 trial showed semaglutide 2.4 mg produced a mean body weight reduction of about 10% in adults with type 2 diabetes and obesity over 68 weeks, significantly more than the 1.0 mg diabetes dose (Davies et al., 2021). For context, that's about 20 pounds on a 200-pound person. Without the diabetes complication, the weight loss is higher. The STEP 1 trial (non-diabetic participants) showed approximately 14.9% mean body weight reduction at 68 weeks (Wilding et al., 2021).
Tirzepatide: Mounjaro, Zepbound
Tirzepatide is different from semaglutide in one significant way: it activates two receptors instead of one. It hits both the GLP-1 receptor and the GIP (glucose-dependent insulinotropic polypeptide) receptor. GIP is the other main incretin hormone, and activating both pathways together appears to produce meaningfully greater weight loss than GLP-1 activation alone (Yabe & Seino, 2011).
Mounjaro (subcutaneous injection, up to 15 mg weekly): FDA-approved for type 2 diabetes.
Zepbound (subcutaneous injection, up to 15 mg weekly): FDA-approved for chronic weight management.
The SURPASS-4 trial compared tirzepatide against insulin glargine in high-cardiovascular-risk patients with type 2 diabetes. Tirzepatide showed superior HbA1c reduction and significant weight loss of up to 11.7% (Del Prato et al., 2021). In the SURMOUNT-1 trial focused on weight management, tirzepatide 15 mg produced a mean body weight reduction of 22.5% at 72 weeks. That's roughly 50 pounds for a person starting at 220 pounds (Jastreboff et al., 2022).
Liraglutide: Victoza, Saxenda
Liraglutide is the older sibling in this family. It was among the first GLP-1 agonists widely used and gave researchers the foundational data that made semaglutide and tirzepatide possible.
Victoza (subcutaneous injection, up to 1.8 mg daily): FDA-approved for type 2 diabetes and, uniquely, for cardiovascular risk reduction in adults with type 2 diabetes and established cardiovascular disease.
Saxenda (subcutaneous injection, 3 mg daily): FDA-approved for chronic weight management.
Liraglutide requires a daily injection, which is the main practical disadvantage compared to weekly options. In direct comparison to semaglutide (O'Neil et al., 2018), semaglutide produced approximately 2-3x more weight loss than liraglutide at comparable doses. Liraglutide still works, but it's harder to use and less effective by the numbers.
Liraglutide's pharmacokinetics in patients with kidney disease have been studied (Jacobsen et al., 2009), and no dose adjustment is generally required, which makes it a viable option for patients with renal impairment.
Dulaglutide: Trulicity
Trulicity (subcutaneous injection, up to 4.5 mg weekly): FDA-approved for type 2 diabetes and for cardiovascular risk reduction in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors.
Dulaglutide produces modest weight loss, typically 3-5% in diabetes trials, meaningfully less than semaglutide or tirzepatide. Its advantage is its cardiovascular outcomes data and a strong track record with patients who are already on complex medication regimens.
The SURPASS-CVOT trial is comparing tirzepatide directly against dulaglutide for cardiovascular outcomes in over 13,000 patients with type 2 diabetes and established cardiovascular disease (Nicholls et al., 2023). Results are expected to clarify the cardiovascular advantage, if any, of tirzepatide versus older GLP-1 agents.
Exenatide: Byetta, Bydureon BCise
Byetta (subcutaneous injection, 10 mcg twice daily): FDA-approved for type 2 diabetes. Requires twice-daily dosing, which is a significant practical disadvantage.
Bydureon BCise (subcutaneous injection, 2 mg weekly): An extended-release version of exenatide approved for type 2 diabetes.
Exenatide produces the least weight loss of the five molecules discussed here. Its place in modern practice is mainly in patients who have already been stabilized on it, are tolerating it well, and for whom switching would disrupt an otherwise stable regimen.
SURMOUNT-5: The First Head-to-Head Trial
In the first direct head-to-head randomized trial, tirzepatide produced 20% mean body weight reduction versus 14% for semaglutide at maximum approved doses. Same population, same endpoints, different results.
Source: SURMOUNT-5 Trial, 2024
Head-to-Head: Semaglutide vs. Tirzepatide
For years, clinicians compared semaglutide and tirzepatide using data from different trials, different populations, and different designs. That comparison was always rough. Now there's a direct answer.
For a deeper look at the mechanism differences, see our semaglutide vs tirzepatide breakdown. But here's the headline number from the most important trial.
The SURMOUNT-5 trial was a randomized, head-to-head comparison of tirzepatide (maximum 15 mg) versus semaglutide (maximum 2.4 mg) in adults with overweight or obesity without type 2 diabetes. This is the cleanest possible comparison: same trial, same population, same endpoints.
The results: tirzepatide produced approximately 20% mean body weight reduction versus about 14% for semaglutide at week 72. That's a meaningful gap. For a 250-pound person, tirzepatide's advantage translates to roughly 15 more pounds of weight loss.
This tracks with what the earlier separate trials suggested. Tirzepatide's dual-mechanism activation appears to produce more weight loss at maximum dose. That said, semaglutide's numbers are not small. A 14% mean body weight reduction at 2.4 mg is still highly significant compared to lifestyle intervention alone.
One important caveat: more weight loss doesn't automatically mean tirzepatide is the better choice for your specific situation. Diabetes indication, insurance coverage, side effect tolerance, cost, and your starting metabolic picture all factor in. But if pure weight loss efficacy is the question, the data now has a clear answer.
GI Side Effects Are Common — Plan for Them
Nausea, diarrhea, vomiting, and constipation are the most common side effects across the GLP-1 class. They typically peak during dose escalation and diminish at stable maintenance doses. The FDA adverse event database has logged over 54,000 reports across the class.
Eat smaller meals, avoid high-fat foods during dose increases, and never rush the escalation schedule. Pancreatitis is rare but documented — tell your provider immediately if you develop severe upper abdominal pain.
Source: Davies et al., Lancet, 2021; FDA FAERS Database, 2025
GLP-1 Side Effects: What to Expect
The most common side effects are gastrointestinal: nausea, diarrhea, vomiting, constipation. The FDA's adverse event database has logged over 54,000 reports across the GLP-1 class, with nausea appearing most frequently.
These side effects are manageable for most people. They typically peak during dose escalation and diminish once you've been at a stable dose for a few weeks. Standard mitigation: eat smaller portions, eat slowly, avoid high-fat or spicy meals during dose increases, and don't skip the escalation schedule to rush to maximum dose.
By drug:
Semaglutide (Wegovy) in STEP trials: nausea in about 44% of participants, vomiting in 25%, diarrhea in 30%.
Tirzepatide (Zepbound) in SURMOUNT trials: nausea in 25-28%, vomiting in 8-13%, diarrhea in 19-23%. The GI side effect profile appears somewhat lower than semaglutide at comparable weight loss levels.
For a full breakdown of what to expect on semaglutide specifically, see our Ozempic side effects guide.
The more serious risks are rare but real. Pancreatitis is a known adverse event (uncommon, but not trivial). If you develop sudden, severe upper abdominal pain while on a GLP-1, stop the medication and go to the ER. The label contraindication that matters most for most patients: a personal or family history of medullary thyroid carcinoma or MEN2 syndrome. If that applies to you, GLP-1 agonists are contraindicated.
A recent large-scale analysis of 215,970 GLP-1 users versus comparator drugs (Xie et al., 2025) showed that GLP-1 use was associated with reduced risk of neurocognitive disorders, cardiovascular events, and substance use disorders, and increased risk of gastrointestinal conditions. The class is clearly not neutral on GI risk; plan for that.
Comparing Weight Loss Efficacy: The Numbers
Here's what the clinical trial evidence shows for mean body weight reduction at maximum approved doses:
| Drug | Max Dose | Trial | Mean Weight Loss |
|---|---|---|---|
| Tirzepatide | 15 mg weekly | SURMOUNT-1 | ~22.5% (~50 lbs at 220 lbs) |
| Semaglutide | 2.4 mg weekly | STEP 1 | ~14.9% (~30 lbs at 200 lbs) |
| Semaglutide | 1.0 mg weekly | SUSTAIN 1 | ~4-6% (diabetes dose) |
| Liraglutide | 3.0 mg daily | Phase 2 | ~6-8% |
| Dulaglutide | 4.5 mg weekly | Various | ~3-5% |
| Exenatide | 2 mg weekly | Various | ~2-3% |
These are mean values from clinical trials. Your individual response will vary. Patients who exercise regularly, follow a protein-forward diet, and stay on stable dosing consistently tend to outperform trial averages.
GLP-1 Drug Costs at a Glance
List price without insurance (monthly)
| Drug | Indication | Monthly Cost |
|---|---|---|
| Wegovy (semaglutide 2.4mg) | Weight loss | ~$1,350 |
| Zepbound (tirzepatide 15mg) | Weight loss | ~$1,060 |
| Ozempic (semaglutide) | Type 2 diabetes | ~$900 |
| Mounjaro (tirzepatide) | Type 2 diabetes | ~$1,000 |
| Victoza/Saxenda (liraglutide) | T2D / weight loss | ~$600-900 |
Source: Manufacturer list prices, 2025. Savings programs may reduce costs significantly.
Cost, Insurance, and Access
This is the question that actually determines whether you can use these drugs. And the honest answer is complicated.
List prices without insurance:
- Wegovy (semaglutide 2.4 mg): approximately $1,350/month
- Zepbound (tirzepatide 15 mg): approximately $1,060/month
- Ozempic (semaglutide, diabetes indication): approximately $900/month
- Mounjaro (tirzepatide, diabetes indication): approximately $1,000/month
- Victoza/Saxenda (liraglutide): approximately $600-$900/month
Insurance coverage: the real story:
If you have a type 2 diabetes diagnosis, insurance coverage for Ozempic or Mounjaro is substantially more likely. Commercial insurance plans cover these at rates similar to other diabetes medications.
For weight management specifically (Wegovy and Zepbound), coverage is patchwork at best. Many commercial plans do not cover anti-obesity medications. Medicare Part D was prohibited by law from covering most obesity drugs until recent policy changes, but coverage is still inconsistent. If your insurer doesn't cover it, you're paying list price or finding another path.
Manufacturer savings programs:
Both Eli Lilly (Zepbound, Mounjaro) and Novo Nordisk (Wegovy, Ozempic) offer savings programs for commercially insured patients. As of 2025, eligible patients have accessed these drugs for as little as $25-$50/month through these programs. These programs have income limits and insurance requirements. Ask your provider or check the manufacturer website directly.
Compounding pharmacies:
During the FDA drug shortage period for semaglutide and tirzepatide (which ran from 2022 into 2025), FDA guidance allowed 503A and 503B compounding pharmacies to produce these drugs legally. The FDA has been phasing out this authorization as shortage designations are resolved.
Compounded versions can be significantly cheaper, often $200-$400/month for semaglutide. But the quality controls are not equivalent to branded products, and the FDA has issued warnings about illegitimate compounders. If you're considering compounding, use only a licensed 503A pharmacy that your physician has vetted, and make sure the compound matches what was approved during the shortage period.
At HEXIS, we work with each patient to navigate coverage, savings programs, and legitimate access pathways. Your protocol starts with labs and an honest conversation about what's actually accessible for your situation. Not a sales pitch for the most expensive option on the market.
When to Choose an Older GLP-1
Semaglutide and tirzepatide get most of the attention, but liraglutide and dulaglutide still have a legitimate clinical role.
You might use an older agent when:
- Insurance covers it and doesn't cover newer options. If your plan covers Victoza or Trulicity but not Ozempic or Wegovy, the older drug at a fraction of the cost may be the practical starting point.
- You've been stable on it and it's working. There's no reason to switch a patient who's tolerating liraglutide well and achieving their goals.
- Cardiovascular risk reduction is the primary objective. Liraglutide's LEADER trial showed cardiovascular mortality benefit in high-risk patients. That's established outcomes data.
- Renal impairment is a concern. Liraglutide pharmacokinetics are well-characterized in kidney disease (Jacobsen et al., 2009), and it doesn't require dose adjustment for most stages.
The oral semaglutide option (Rybelsus) also has a specific role for patients with needle phobia or strong preference for pills over injections. The PIONEER 4 trial showed oral semaglutide 14 mg was superior to subcutaneous liraglutide on HbA1c reduction at 52 weeks (Pratley et al., 2019), which is a significant finding for a pill versus an injection.
“GLP-1 drugs treat obesity the way blood pressure medications treat hypertension. They work while you're taking them.”
What Happens When You Stop
Most of the weight returns.
This isn't a HEXIS opinion. It's what the STEP 4 trial showed. Patients who stopped semaglutide after 20 weeks regained approximately two-thirds of their lost weight within a year. Similar data has emerged for tirzepatide.
GLP-1 drugs treat obesity the way blood pressure medications treat hypertension. They work while you're taking them. Stop the medication, and the underlying physiology reasserts itself. Your appetite returns. Your hunger set point goes back up.
This has a few implications for how you think about treatment:
First, if you start a GLP-1, think of it as a long-term commitment, not a 6-month course. The people who do best are those who use the appetite suppression window to build better movement habits and protein intake, so if and when they do taper off, they have a physiological and behavioral foundation that makes maintenance more achievable.
Second, stopping doesn't mean failure. Some patients lose a significant amount of weight, improve their metabolic risk factors substantially, and then maintain a lower weight long-term through the habits they built during treatment. But they're the exception.
If you do want to try tapering or stopping, doing it with physician oversight and a concrete plan for managing the transition gives you the best chance of holding onto what you gained.
GLP-1 Medications for Women: PCOS and Hormonal Weight
This is worth a dedicated section because the pattern shows up constantly in practice.
Women with polycystic ovarian syndrome (PCOS) have insulin resistance at the core of their condition, and GLP-1 drugs directly address that mechanism. Multiple observational studies and clinical reports document significant benefit in PCOS patients, with improvements not just in weight but in insulin sensitivity, androgen levels, and menstrual regularity.
The evidence base here is less formal than the main trial data. There's no large randomized controlled trial in PCOS specifically comparable to STEP or SURMOUNT. But the mechanistic rationale is strong, and the clinical experience reported by physicians treating women with PCOS is consistent.
For women in perimenopause who are experiencing weight gain that doesn't respond to diet and exercise the way it used to, GLP-1 drugs can be part of the picture. But this is where a registered dietitian for weight loss and a full labs panel matters, because perimenopausal weight gain has multiple drivers, and estrogen status, cortisol, thyroid function, and insulin resistance all need to be in the picture before deciding on a protocol.
The Addiction Research: A Surprising Finding
One thing the research community is increasingly focused on: GLP-1 drugs appear to reduce addictive behavior beyond food.
The large VA database analysis (Xie et al., 2025) found that GLP-1 users had significantly lower rates of alcohol use disorder, opioid use disorder, and other substance use conditions compared to matched controls. This tracks with what we know about the drug's mechanism. GLP-1 receptors are expressed in the brain's reward circuits, not just in the gut and hypothalamus.
A Phase 2 trial (NCT06651177) is actively recruiting to test tirzepatide as an adjunct to buprenorphine for opioid use disorder treatment. This research area is early, but the signal is consistent across multiple analyses.
If you're managing weight alongside alcohol consumption or other addictive behaviors, this is worth mentioning to your provider. The overlap between appetite regulation and reward circuitry may mean a GLP-1 addresses more than one problem simultaneously.
Ozempic Face, Muscle Loss, and Aesthetic Concerns
Two concerns come up regularly from patients who've done their research.
"Ozempic face" refers to the rapid facial fat loss that can occur with significant weight loss on these drugs. It's not a health problem, just a cosmetic concern. Some patients lose facial volume faster than their skin can adapt, leading to a gaunt or aged appearance. This is dose-dependent and patient-dependent. It doesn't affect everyone, and for most people the health benefits of sustained weight loss far outweigh a cosmetic side effect that fillers or time can address.
Muscle loss is a more legitimate concern. GLP-1-driven weight loss includes loss of lean mass, not just fat mass. In trials, roughly 25-40% of the total weight lost was lean tissue. That's not ideal. Muscle matters for metabolic health, insulin sensitivity, and long-term weight maintenance.
The countermeasure is resistance training and adequate protein intake. This isn't optional advice. It's essential if you're on a GLP-1. At HEXIS, protocols for patients on GLP-1 therapy include guidance on resistance training frequency and protein targets (typically 0.8-1.0 g/lb of body weight per day). The goal is fat loss, not weight loss. Those aren't the same thing.
If you're concerned about Ozempic face or muscle preservation, bring it up with your HEXIS provider early, not after you've already lost 30 pounds. GLP-1 drugs also show real benefit for people managing fatty liver and weight loss since visceral fat reduction is one of the documented effects.
Frequently Asked Questions
Is Ozempic or Mounjaro better for weight loss?
Based on head-to-head trial data (SURMOUNT-5), tirzepatide (Mounjaro/Zepbound) produces greater mean weight loss than semaglutide (Ozempic/Wegovy) at maximum doses: approximately 20% versus 14% body weight reduction in adults without diabetes. The difference is real and meaningful, roughly 15 additional pounds for an average-sized patient. That said, Ozempic's weight loss data is still strong, and practical factors like insurance coverage and cost often determine which drug is the right starting point.
What are the most common side effects of GLP-1 medications?
Nausea is the most frequently reported side effect across the GLP-1 class, affecting 25-44% of patients in clinical trials depending on the drug and dose. Diarrhea, vomiting, and constipation are also common, especially during dose escalation. These effects typically diminish once you reach a stable maintenance dose. Serious adverse events like pancreatitis are rare but documented. If you have a history of pancreatitis or gallbladder disease, discuss this with your provider before starting.
Why doesn't my insurance cover Wegovy or Zepbound?
Most commercial insurance plans and Medicare Part D have historically excluded coverage for anti-obesity medications, even when those medications are FDA-approved. Insurance coverage is more likely if the drug is prescribed for a diabetes diagnosis (Ozempic, Mounjaro) rather than a weight management indication (Wegovy, Zepbound). This is a policy issue, not a medical one. Advocacy groups have been pushing to classify obesity as a medical condition requiring coverage parity, and some large employers are beginning to add coverage. Manufacturer savings programs can significantly reduce out-of-pocket costs for commercially insured patients.
Are compounded semaglutide and tirzepatide safe?
During the FDA shortage period, compounded versions from licensed 503A pharmacies were legal and provided a lower-cost alternative. The FDA has been tightening this guidance as shortage designations resolve. The safety concern with compounding is quality control: if a pharmacy isn't rigorously testing potency and purity, you could be getting less (or more) than the label says. Only use compounded GLP-1 drugs from a physician-supervised program with a licensed, vetted compounding pharmacy. Avoid any source that doesn't require a prescription and a provider consultation.
How long do you have to stay on a GLP-1?
Most of the weight returns when you stop. Clinical trials show about two-thirds of lost weight regained within a year of stopping. This means GLP-1 therapy is most effective as a long-term or indefinite treatment, similar to blood pressure medication. Some patients successfully taper off after building sustainable habits during treatment, but this takes intentional planning and usually works better for patients who used the medication window to fundamentally change their movement and eating patterns. Talk to your provider before stopping. Abrupt discontinuation without a plan makes weight regain more likely.
Getting Started: What a HEXIS Protocol Looks Like
If you're considering a GLP-1 medication, the conversation starts with labs.
Fasting glucose, HbA1c, fasting insulin, lipid panel, thyroid panel, and a full metabolic panel give your provider the baseline to understand whether insulin resistance is driving your weight gain, what your cardiovascular risk looks like, and whether there are contraindications to specific medications.
We don't start everyone on the same drug. Someone with a strong family history of thyroid cancer gets a different conversation than someone with PCOS and insulin resistance. Someone who's already on diabetes medication needs a different consideration than someone who's metabolically healthy and wants to lose 40 pounds.
The GLP-1 medications compared here are all effective tools. The question is which one fits your specific picture: your labs, your history, your insurance situation, and what you're trying to accomplish.
If you want to have that conversation with a HEXIS physician, schedule a consultation. We'll start with your numbers, not a generic protocol.
GLP-1 Medications Compared: The Bottom Line
- 1
Tirzepatide (Mounjaro/Zepbound) produces greater weight loss than semaglutide (Ozempic/Wegovy) — about 20% vs 14% body weight reduction in direct head-to-head trial data. The difference is real: roughly 15 extra pounds on a 200-pound person.
- 2
Cost and insurance are the real gatekeepers. Most plans don't cover weight management indications. Manufacturer savings programs can bring costs to $25-50/month for eligible patients — ask about them before assuming you can't afford treatment.
- 3
These medications treat obesity the way blood pressure drugs treat hypertension: long-term. Most weight returns when you stop. Use the appetite suppression window to build resistance training and protein habits that support you if you ever do taper off.