Tirzepatide vs Semaglutide: Which Weight Loss Medication Is Better?

Tirzepatide (Mounjaro, Zepbound) produces significantly more weight loss than semaglutide (Wegovy, Ozempic) - averaging 20-22% vs 15-17% of total body weight in clinical trials. However, tirzepatide may cause slightly more gastrointestinal side effects and costs about the same or slightly more. Both are highly effective GLP-1 receptor agonists for weight loss, with the choice depending on your priorities, tolerance, and access.

This comprehensive comparison covers everything you need to know about tirzepatide and semaglutide to make an informed decision about which medication is right for you.

Table of Contents

• Quick Overview: Key Differences
• What Are Tirzepatide and Semaglutide?
• How They Work
• Effectiveness: Weight Loss Comparison
• Side Effects Comparison
• Dosing and Administration
• Weight Loss Timeline
• Cost Comparison
• Who Should Choose Each Medication?
• Availability and Access
• Switching Between Medications
• Frequently Asked Questions

Quick Overview: Key Differences

Factor	Tirzepatide (Mounjaro/Zepbound)	Semaglutide (Wegovy/Ozempic)
Average Weight Loss	20-22% of body weight	15-17% of body weight
Mechanism	Dual GLP-1 and GIP agonist	Single GLP-1 agonist
Dosing	Once weekly injection	Once weekly injection
FDA Approval for Weight Loss	Zepbound (2023)	Wegovy (2021)
GI Side Effects	Slightly higher frequency	Moderate frequency
Brand-Name Cost	$1,000-$1,600/month	$900-$1,500/month
Compounded Cost	$300-$500/month	$200-$400/month
Time on Market	Newer (2022)	Longer track record (2017)

What Are Tirzepatide and Semaglutide?

Semaglutide (Wegovy, Ozempic, Rybelsus)

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist originally approved for type 2 diabetes in 2017 (Ozempic) and subsequently approved for chronic weight management in 2021 (Wegovy) (Source: FDA).

Available forms:

• Injectable: Ozempic (diabetes), Wegovy (weight loss)
• Oral tablet: Rybelsus (diabetes)
• Compounded injectable: Various strengths

For comprehensive information about semaglutide, see our complete semaglutide guide.

Tirzepatide (Mounjaro, Zepbound)

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist approved for type 2 diabetes in 2022 (Mounjaro) and for chronic weight management in 2023 (Zepbound) (Source: FDA).

Available forms:

• Injectable: Mounjaro (diabetes), Zepbound (weight loss)
• Compounded injectable: Various strengths
• No oral form currently available

The Key Difference: Dual vs Single Mechanism

The fundamental difference between these medications lies in their mechanism:

• Semaglutide: Activates only GLP-1 receptors
• Tirzepatide: Activates both GLP-1 and GIP receptors

This dual action is why tirzepatide produces greater weight loss, though both medications work through similar pathways to reduce appetite and improve metabolic health.

How They Work

Shared Mechanisms (GLP-1 Effects)

Both medications activate GLP-1 receptors, which leads to:

• Appetite suppression: Signals to the brain that you're full, reducing hunger
• Delayed gastric emptying: Food stays in your stomach longer, prolonging satiety
• Blood sugar regulation: Increases insulin when blood sugar is high, reduces glucagon
• Reduced food cravings: Decreases desire for high-calorie foods

Tirzepatide's Additional GIP Action

Tirzepatide's activation of GIP receptors adds several effects:

• Enhanced insulin sensitivity: Cells respond better to insulin
• Improved fat metabolism: Better breakdown and utilization of stored fat
• Additional appetite regulation: Works through complementary pathways
• Potential metabolic benefits: May have additional effects on metabolism beyond GLP-1 alone

The combination of GIP and GLP-1 activation appears to have synergistic effects, resulting in greater weight loss than GLP-1 activation alone (Source: SURMOUNT-1 Trial, NEJM).

Effectiveness: Weight Loss Comparison

Clinical Trial Results

Tirzepatide (SURMOUNT-1 Trial, 72 weeks)

15 mg dose (highest maintenance dose):

• Average weight loss: 20.9% of total body weight (about 48 pounds for a 230-pound person)
• ≥5% weight loss: 91% of participants
• ≥10% weight loss: 83% of participants
• ≥15% weight loss: 71% of participants
• ≥20% weight loss: 57% of participants
• ≥25% weight loss: 40% of participants

10 mg dose:

• Average weight loss: 19.5% of total body weight

5 mg dose (lowest maintenance dose):

• Average weight loss: 15.0% of total body weight

Source: SURMOUNT-1 Clinical Trial, New England Journal of Medicine

Semaglutide (STEP 1 Trial, 68 weeks)

2.4 mg dose (maintenance dose):

• Average weight loss: 14.9% of total body weight (about 33 pounds for a 220-pound person)
• ≥5% weight loss: 86% of participants
• ≥10% weight loss: 69% of participants
• ≥15% weight loss: 50% of participants
• ≥20% weight loss: 32% of participants

Source: STEP 1 Clinical Trial, New England Journal of Medicine

Head-to-Head Comparison

Weight Loss Milestone	Tirzepatide 15mg	Semaglutide 2.4mg	Difference
Average Total	20.9%	14.9%	+6 percentage points
≥5% Loss	91%	86%	+5 percentage points
≥10% Loss	83%	69%	+14 percentage points
≥15% Loss	71%	50%	+21 percentage points
≥20% Loss	57%	32%	+25 percentage points

Real-World Effectiveness

Both medications demonstrate effectiveness in real-world clinical practice that closely matches clinical trial results. Healthcare providers report:

• Consistent results: Most patients achieve significant weight loss on either medication
• Tirzepatide edge: Generally produces 5-7 percentage points more weight loss
• Individual variation: Some people respond exceptionally to either medication
• Both highly effective: Either medication far exceeds traditional weight loss methods

Bottom Line: Which Is More Effective?

Tirzepatide is more effective, producing about 40% more weight loss on average (21% vs 15%). For a 200-pound person, this translates to approximately 42 pounds lost with tirzepatide vs 30 pounds with semaglutide - a difference of 12 pounds.

However, semaglutide still produces excellent results and may be the better choice for some individuals based on side effect profile, cost, or availability.

Side Effects Comparison

Gastrointestinal Side Effects

Both medications cause similar types of side effects, but tirzepatide tends to have slightly higher rates:

Side Effect	Tirzepatide (15mg)	Semaglutide (2.4mg)
Nausea	33%	20-30%
Diarrhea	23%	15-20%
Vomiting	12%	8-12%
Constipation	11%	10-15%
Abdominal Pain	9%	5-10%

Discontinuation Due to Side Effects

• Tirzepatide: 6.2% of participants discontinued due to adverse events in SURMOUNT-1
• Semaglutide: 4.5% of participants discontinued due to adverse events in STEP 1

The slightly higher discontinuation rate with tirzepatide reflects the somewhat higher frequency of GI side effects.

Managing Side Effects

Side effect management strategies are similar for both medications:

• Start with low doses and increase gradually
• Eat smaller, more frequent meals
• Avoid fatty, greasy, or spicy foods
• Stay well-hydrated
• Most side effects improve within 2-4 weeks

For comprehensive side effect management strategies, see our guide to managing semaglutide side effects (strategies apply to tirzepatide as well).

Serious Side Effects

Both medications share similar warnings for rare but serious side effects:

• Pancreatitis: Risk is low (0.1-0.2%) but requires immediate medical attention if severe abdominal pain occurs
• Gallbladder issues: Rapid weight loss can increase gallstone risk
• Thyroid C-cell tumors: Black box warning (seen in rodent studies, not confirmed in humans)
• Diabetic retinopathy: Possible worsening in people with existing eye disease
• Kidney problems: Dehydration from GI side effects can worsen kidney function

Which Has Fewer Side Effects?

Semaglutide has a slightly better side effect profile, with lower rates of nausea, diarrhea, and discontinuation. However, the difference is modest, and many people tolerate tirzepatide very well despite the slightly higher rates.

Dosing and Administration

Tirzepatide Dosing Schedule

Timeframe	Dose	Purpose
Weeks 1-4	2.5 mg weekly	Initiation dose
Weeks 5-8	5 mg weekly	First increase (minimum maintenance dose)
Weeks 9-12	7.5 mg weekly	Second increase
Weeks 13-16	10 mg weekly	Third increase
Weeks 17-20	12.5 mg weekly	Fourth increase
Week 21+	15 mg weekly	Maximum maintenance dose

Source: Zepbound Prescribing Information, FDA

Semaglutide Dosing Schedule

Timeframe	Dose	Purpose
Weeks 1-4	0.25 mg weekly	Initiation dose
Weeks 5-8	0.5 mg weekly	First increase
Weeks 9-12	1.0 mg weekly	Second increase
Weeks 13-16	1.7 mg weekly	Third increase
Week 17+	2.4 mg weekly	Maintenance dose

Key Dosing Differences

• Escalation period: Tirzepatide takes 20 weeks to reach max dose vs 16 weeks for semaglutide
• Number of doses: Tirzepatide has 6 dose levels vs 5 for semaglutide
• Flexibility: Both allow staying at lower doses if tolerated and effective
• Administration: Both are once-weekly subcutaneous injections

Weight Loss Timeline

Tirzepatide Timeline

• Month 1: 2-6 pounds (starting at low dose)
• Month 3: 8-15 pounds total
• Month 6: 18-30 pounds total (10-13% body weight)
• Month 12: 35-50 pounds total (15-20% body weight)
• Month 18: 45-60+ pounds total (20-25% body weight at max dose)

Semaglutide Timeline

• Month 1: 2-5 pounds (starting at low dose)
• Month 3: 6-12 pounds total
• Month 6: 15-25 pounds total (8-12% body weight)
• Month 12: 25-40 pounds total (12-16% body weight)
• Month 18: 30-45 pounds total (15-20% body weight)

For a detailed week-by-week semaglutide timeline, see our complete timeline guide.

Time to Peak Results

• Tirzepatide: Peak weight loss typically occurs around 72-84 weeks (18-21 months)
• Semaglutide: Peak weight loss typically occurs around 60-68 weeks (15-17 months)

Cost Comparison

Brand-Name Pricing

Medication	Monthly Cost (Retail)	Annual Cost
Zepbound (tirzepatide)	$1,060-$1,600	$12,720-$19,200
Mounjaro (tirzepatide)	$1,000-$1,100	$12,000-$13,200
Wegovy (semaglutide)	$1,349-$1,595	$16,188-$19,140
Ozempic (semaglutide)	$900-$1,000	$10,800-$12,000

Compounded Pricing

Medication	Monthly Cost	Annual Cost
Compounded tirzepatide	$300-$500	$3,600-$6,000
Compounded semaglutide	$200-$400	$2,400-$4,800

Insurance Coverage

• For diabetes: Both Mounjaro and Ozempic are often covered with copays ranging from $25-$500/month
• For weight loss: Coverage for Zepbound and Wegovy is limited; many plans exclude weight loss medications
• Medicare: Does not cover weight loss medications (as of 2025)

Cost-Effectiveness Considerations

Per pound lost:

• Tirzepatide (brand): ~$250-300 per pound lost (48 pounds at $14,000/year)
• Semaglutide (brand): ~$400-450 per pound lost (33 pounds at $14,000/year)
• Tirzepatide (compounded): ~$75-100 per pound lost
• Semaglutide (compounded): ~$75-100 per pound lost

While tirzepatide costs slightly more in absolute terms, it may be more cost-effective per pound lost due to greater weight loss.

For detailed cost breakdowns and savings strategies, see our semaglutide cost guide.

Who Should Choose Each Medication?

Choose Tirzepatide If:

• ✅ You want maximum weight loss: Willing to accept slightly higher side effect risk for better results
• ✅ You need to lose 50+ pounds: The extra 5-7 percentage points of weight loss makes a meaningful difference
• ✅ You tolerated semaglutide well but want more: Switching to tirzepatide can produce additional weight loss
• ✅ Cost isn't the primary concern: Tirzepatide costs about the same or slightly more
• ✅ You have type 2 diabetes and obesity: Excellent blood sugar control plus weight loss
• ✅ You're willing to try the newer medication: Tirzepatide is newer but has strong clinical trial data

Choose Semaglutide If:

• ✅ You're concerned about side effects: Slightly lower rates of nausea and GI symptoms
• ✅ You want a longer track record: Semaglutide has been used since 2017 (vs 2022 for tirzepatide)
• ✅ You prefer oral medication: Rybelsus offers a needle-free option (tirzepatide has no oral form)
• ✅ You want slightly lower cost: Compounded semaglutide is typically $100-200/month less
• ✅ Excellent results are enough: 15% weight loss is still transformative for most people
• ✅ Your insurance covers it: If you have coverage for Wegovy, that may be most affordable

Either Medication Works Well If:

• You have a BMI ≥30 or BMI ≥27 with comorbidities
• Traditional weight loss methods haven't worked
• You're committed to long-term treatment (1-2+ years)
• You're willing to make lifestyle improvements alongside medication
• You don't have contraindications (thyroid cancer history, etc.)

Availability and Access

Current Supply Status

Semaglutide:

• On FDA drug shortage list since 2022
• Wegovy availability improving but still intermittent
• Ozempic also experiencing shortages
• Compounded versions widely available due to shortage status

Tirzepatide:

• Generally better availability than semaglutide
• Most doses of Mounjaro and Zepbound in stock
• Compounded versions available from some pharmacies
• Newer manufacturing means capacity is still growing

How to Access Each Medication

Brand-name options:

• Prescription from your doctor or specialist
• Telehealth services (often easiest for weight loss indications)
• Fill at retail pharmacy or use specialty pharmacy
• Apply manufacturer savings cards if eligible (up to $650/month off)

Compounded options:

• Telehealth platforms offering compounded medications
• Prescription required from licensed provider
• Sourced from 503B FDA-registered compounding pharmacies
• Typically includes ongoing medical oversight

Our programs offer both compounded semaglutide and compounded tirzepatide from 503B FDA-registered pharmacies with full medical support.

Switching Between Medications

Semaglutide to Tirzepatide

Many patients switch from semaglutide to tirzepatide to achieve additional weight loss. The typical approach:

• Stop semaglutide: Take your last dose on your regular schedule
• Wait 1 week: Allow one week between last semaglutide and first tirzepatide dose
• Start tirzepatide at 2.5 mg: Begin at the initiation dose even if you were on high-dose semaglutide
• Escalate normally: Follow the standard titration schedule
• Monitor for side effects: Some people experience renewed GI symptoms when switching

Expected additional weight loss: People who switch typically lose an additional 5-10% of their body weight on tirzepatide.

Tirzepatide to Semaglutide

Less common, but sometimes done due to:

• Side effects on tirzepatide
• Cost considerations
• Supply issues
• Insurance coverage changes

Approach:

• Stop tirzepatide and wait 1 week
• Start semaglutide at appropriate dose based on prior tirzepatide dose (discuss with provider)
• May maintain weight loss but unlikely to lose more

Frequently Asked Questions

Which medication causes more weight loss?

Tirzepatide produces significantly more weight loss - averaging 20-22% of total body weight compared to semaglutide's 15-17%. This translates to about 40% more weight loss with tirzepatide. However, both medications produce excellent results far exceeding traditional weight loss methods.

Is tirzepatide safer than semaglutide?

Both medications have similar safety profiles with comparable rates of serious side effects. Tirzepatide has slightly higher rates of nausea and GI symptoms but similar rates of serious complications. Semaglutide has a longer track record (2017 vs 2022), but tirzepatide's clinical trials demonstrated good safety. Both are considered safe when used appropriately under medical supervision.

Which medication costs less?

Compounded semaglutide typically costs $100-200 less per month than compounded tirzepatide ($200-400/month vs $300-500/month). Brand-name costs are similar, with both ranging from $900-1,600/month. However, tirzepatide may be more cost-effective per pound lost due to greater weight loss.

Can I switch from semaglutide to tirzepatide?

Yes, many people successfully switch from semaglutide to tirzepatide to achieve additional weight loss. Wait one week after your last semaglutide dose, then start tirzepatide at the 2.5 mg initiation dose. Most people lose an additional 5-10% of body weight after switching.

Does tirzepatide have more side effects?

Tirzepatide has slightly higher rates of gastrointestinal side effects, particularly nausea (33% vs 20-30%) and diarrhea (23% vs 15-20%). The discontinuation rate due to side effects is also slightly higher (6.2% vs 4.5%). However, most people tolerate both medications well, and side effects typically improve within 2-4 weeks.

Which medication works faster?

Both medications have similar timelines for initial weight loss, with 2-5 pounds lost in the first month. The difference becomes more apparent over time, with tirzepatide producing progressively more weight loss. By 12 months, tirzepatide users typically lose 35-50 pounds vs 25-40 pounds with semaglutide.

Is tirzepatide FDA approved for weight loss?

Yes, tirzepatide was approved by the FDA for chronic weight management under the brand name Zepbound in November 2023. It's also approved for type 2 diabetes under the brand name Mounjaro (approved May 2022).

Can I take both medications together?

No, you should not take tirzepatide and semaglutide together. Both medications work through overlapping mechanisms (GLP-1 activation), and combining them would significantly increase the risk of side effects without providing additional benefit. Choose one or the other based on your goals and tolerance.

Which is better for diabetes control?

Both medications provide excellent blood sugar control for type 2 diabetes. Clinical trials show tirzepatide produces slightly better A1C reductions (average 2.0-2.3% reduction vs 1.5-1.8% for semaglutide). However, both are highly effective for diabetes management alongside weight loss.

Will insurance cover tirzepatide or semaglutide?

Insurance coverage varies significantly. For diabetes (Mounjaro/Ozempic), coverage is common with copays typically $25-500/month. For weight loss (Zepbound/Wegovy), coverage is limited - many plans exclude weight loss medications entirely. Medicare does not cover either medication for weight loss. Check with your specific plan for coverage details.

Conclusion: Which Should You Choose?

Both tirzepatide and semaglutide are highly effective medications that produce transformative weight loss results. The choice between them depends on your priorities:

Choose tirzepatide if:

• You want the absolute maximum weight loss (20-22% vs 15-17%)
• You're willing to accept slightly higher side effect rates
• You need to lose significant weight (50+ pounds)
• You've tried semaglutide with good tolerance but want more results

Choose semaglutide if:

• You want a slightly better side effect profile
• You prefer a medication with a longer track record
• You want the option of oral administration (Rybelsus)
• Excellent results (15% weight loss) are sufficient for your goals
• You want the lowest cost option

The honest truth: Both medications work exceptionally well. Many people would achieve their weight loss goals with either option. The 5-7 percentage point difference in weight loss is meaningful but not necessarily decisive for everyone.

Ready to get started?

Explore our medication options:

• Compounded Semaglutide - Starting at $249/month with medical support
• Compounded Tirzepatide - Starting at $349/month with medical support

Both programs include:

• Initial consultation with licensed healthcare provider
• Medication from 503B FDA-registered pharmacies
• Injection supplies and detailed instructions
• Ongoing medical oversight and dose adjustments
• No hidden fees or long-term contracts

For more information about how these medications work, see our complete guide to semaglutide.