Semaglutide vs Tirzepatide vs Retatrutide

Compare GLP-1 drugs based on your tolerance and goals.

Semaglutide, tirzepatide, and retatrutide work through different receptor combinations — single, dual, and triple agonism — which changes everything about how they affect fat loss, muscle preservation, and metabolic breadth. This tool compares dosing protocols sourced from clinical trials, and the support stacks that optimize results for each compound. Select a compound below to see its complete protocol.

Semaglutide

Ozempic, Wegovy

beginner

The gentle starter

Reduces appetite and slows digestion for steady but indiscriminate weight loss

Intensity

2/5

Tolerability

4/5

Support

2/4

Metabolic Scope

FDA Approved

GLP-1 only: satiety and insulin sensitivity

Weight Loss Ratio

60% fat40% lean

Tirzepatide

Mounjaro, Zepbound

intermediate

The fast track

Dual-action appetite control with enhanced fat loss - more powerful but requires attention to muscle protection

Intensity

4/5

Tolerability

3/5

Support

3/4

Metabolic Scope

FDA Approved

GLP-1 + GIP: deeper metabolic rebalancing with improved nutrient partitioning

Weight Loss Ratio

67% fat33% lean

Retatrutide

Investigational (Phase 2)

advanced

The heavy hitter

Triple-action for maximum fat loss - requires meticulous muscle protection and supervised approach

Intensity

5/5

Tolerability

2/5

Support

4/4

Metabolic Scope

Phase 3

GLP-1 + GIP + Glucagon: whole-system metabolic rewiring with enhanced fat oxidation

Weight Loss Ratio

70% fat30% lean

GLP-1

Satiety

GIP

Insulin

Glucagon

Energy

Intensity

2/5

Tolerability

4/5

Support Needed

2/4

Metabolic

1/5

Data source:STEP-1Non-diabetic obesity68 weeks

How It Works

GLP-1 Receptor Activation

Semaglutide activates the GLP-1 receptor, the gut–brain hormone pathway that reduces appetite, slows stomach emptying, and improves insulin signaling as a byproduct.

What This Means

Smaller hunger signals, earlier fullness, flatter post-meal glucose spikes. If you just 'let it run,' you'll lose lean mass at a rapid rate and may experience side effects caused by reducing intake drastically

Weight Loss Ratio

60% fat loss40% lean loss

20-30%

Visceral Fat

↓10-15%

Resting Energy Expenditure

What % of People Hit Each Milestone?

86%

lost ≥5%

69%

lost ≥10%

50%

lost ≥15%

33%

lost ≥20%

Based on STEP-1 trial data (68 weeks, non-diabetic obesity)

Expected Weight Loss by Dose

Dose	Weeks	Expected Loss	Notes
0.25 mg	0–4	~1%	Early titration
0.5 mg	4–8	2–3%	Appetite suppression begins
1.0 mg	8–12	4–6%	Noticeable trajectory
1.7 mg	12–16	7–9%	Most reach ≥5%
2.4 mg	16–68	12–15%	Full effect

Complete Protocol Guide

Start

Week 1-4

Assess Tolerance

0.25 mg weekly for 4 weeks

What Happens

Appetite suppression begins

Early GI side effects

1-2% weight loss

Hunger stabilizes

Build

Week 5-12+

Progressive Escalation

Increase every 4 weeks: 0.5 → 1.0 → 1.7 → 2.4 mg

What Happens

Fat loss begins

3-5% total weight loss

Improved glycemic markers

Strength preserved with support

Maintain

Month 3-6+

Optimization Phase

Lowest dose that controls appetite without hurting training

What Happens

Visceral fat ↓ 20-25%

10-12% total weight loss

REE down 10-15%

Steady metabolism with training

Medical Disclaimer

The content in this GLP-1 comparison guide is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider before beginning any new protocol, supplement, or medication.

Maximum Dose

2.4 mg weekly

Do not exceed this dosage. Always follow your healthcare provider's guidance.

Key Guidance

Dose Considerations

Only increase if appetite returns or fat loss stalls. Slow and steady wins.

Advantages

Most forgiving - easiest to start and adjust.
Well-studied with good safety profile.

Watch Out For

Effects of a 'blunt-instrument' that catabolizes muscle as the driving force is slowed gastric emptying.
Fatigue, lethargy, and reduced libido are common side effects.

Clinical Monitoring Framework

Lean Mass (DXA/BIA)

>10% relative lean mass loss

Frequency:Baseline + every 3-6 months

Action:Reassess diet, slow titration, intensify resistance training

Strength Metrics

>10% strength drop without recovery

Frequency:Monthly to quarterly

Action:Hold dose, reduce training volume, review nutrition

Protein Intake

<1.2 g/kg trending

Frequency:Weekly logs

Action:Nutrition consult, meal plan revision, protein supplementation

Resting Heart Rate

+10 bpm above baseline

Frequency:Weekly

Action:Evaluate hydration, training stress, consider dose adjustment

REE/Metabolic Rate

>15% drop beyond adaptation

Frequency:Every 3-6 months

Action:Examine lean mass loss, adjust caloric intake

Clinical Evidence

GLP-1

Satiety

GIP

Insulin

Glucagon

Energy

Intensity

4/5

Tolerability

3/5

Support Needed

3/4

Metabolic

3/5

Data source:SURMOUNT-1Non-diabetic obesity72 weeks

How It Works

Dual GIP/GLP-1 Receptor Activation

Tirzepatide hits two incretin receptors: GLP-1 (satiety, gastric slowing) and GIP, which enhances insulin's effectiveness and imrpoves HbA1c levels, augmenting weight loss.

What This Means

In practice it feels like semaglutide with more punch—but less reliant on simply 'not eating' by improving glycemic control. Great for fat loss, but it will still catabolize muscle if you don't guard it.

Weight Loss Ratio

67% fat loss33% lean loss

25-35%

Visceral Fat

↓8-12%

Resting Energy Expenditure

What % of People Hit Each Milestone?

>95%

lost ≥5%

91%

lost ≥10%

83%

lost ≥15%

57%

lost ≥20%

36%

lost ≥25%

Based on SURMOUNT-1 trial data (72 weeks, non-diabetic obesity)

Expected Weight Loss by Dose

Dose	Weeks	Expected Loss	Notes
2.5 mg	0–4	~2%	Starting dose
5 mg	4–8	4–6%	Entry therapeutic
7.5 mg	8–12	8–10%	Building
10 mg	12–16	12–15%	Strong effect
15 mg	16–72	18–21%	Maximum dose

Complete Protocol Guide

Start

Week 1-4

Assess Tolerance

2.5-5 mg weekly for 4 weeks

What Happens

Appetite ↓ sharply

Glucose stabilizes

2-4% weight loss

GI symptoms if escalated too fast

Build

Week 5-12+

Progressive Escalation

Increase every 4 weeks: 7.5 → 10 → 12.5 → 15 mg

What Happens

Fat loss 6-8%

Energy steady via GIP

Lean retention high

Sleep/breathing improves

Maintain

Month 3-6+

Optimization Phase

Lowest dose keeping hunger controlled and training normal

What Happens

10-15% total weight loss

Visceral fat ↓ 25-35%

Metabolic adaptation mild

Performance sustained with support

Medical Disclaimer

Maximum Dose

15 mg weekly

Do not exceed this dosage. Always follow your healthcare provider's guidance.

Key Guidance

Dose Considerations

More powerful than sema - watch muscle loss if support isn't dialed in

Advantages

Faster fat loss than semaglutide in head-to-head studies.
Strong glucose control for diabetics.

Watch Out For

Higher chance of GI side effects.
Will catabolize muscle if anabolic support isn't dialed

Clinical Monitoring Framework

Lean Mass (DXA/BIA)

>10% relative lean mass loss

Frequency:Baseline + every 3-6 months

Action:Hold dose escalation, boost protein to ≥1.8 g/kg, increase resistance training frequency

Strength Metrics

>10% strength drop

Frequency:Monthly to quarterly

Action:Freeze at current dose, deload training, review anabolic support

Protein Intake

<1.6 g/kg

Frequency:Weekly logs

Action:Immediate nutrition intervention, protein shakes between meals

Resting Heart Rate

+8 bpm above baseline

Frequency:Weekly

Action:Monitor for GIP-related effects, adjust training volume

Clinical Evidence

GLP-1

Satiety

GIP

Insulin

Glucagon

Energy

Intensity

5/5

Tolerability

2/5

Support Needed

4/4

Metabolic

5/5

Data source:Phase 2 (NEJM 2023)Type 2 diabetes48 weeks

How It Works

Triple Agonist: GLP-1 / GIP / Glucagon

Retatrutide adds glucagon to GLP-1 and GIP. Glucagon raises resting energy expenditure and mobilizes fat—exactly what you want for a hard cut—but it can pull on lean tissue if you aren't anabolic enough.

What This Means

GLP-1/GIP handle appetite and glucose; glucagon increases energy expenditure and lipolysis. The clinical lever is aggressive fat loss only when you steer fuel in the morning and backfill anabolism at night.

Weight Loss Ratio

70% fat loss30% lean loss

30-40%

Visceral Fat

↓6-10%

Resting Energy Expenditure

−18 to −20 cm at 8–12 mg

Waist Reduction

What % of People Hit Each Milestone?

100%

lost ≥5%

93%

lost ≥10%

83%

lost ≥15%

63%

lost ≥20%

~40%

lost ≥25%

~25%

lost ≥30%

Based on Phase 2 (NEJM 2023) trial data (48 weeks, type 2 diabetes)

Expected Weight Loss by Dose

Dose	Weeks	Expected Loss	Notes
0.5–1 mg	0–4	~3%	Activation phase
2 mg	4–8	5–7%	Early response
4 mg	8–12	10–12%	Similar to full sema
8 mg	12–24	18–20%	Large effect
12 mg	24–48	22–24%	Maximum; no plateau

Complete Protocol Guide

Start

Week 1-4

Assess Tolerance

0.5-2 mg weekly, hold each step ≥4 weeks

What Happens

Appetite & thermogenesis begin

3-5% weight loss

HR ↑ 2-4 bpm

Watch for early strength dip

Build

Week 5-12+

Progressive Escalation

Advance only after plateau: 1 → 2 → 3 → 4 up to 12 mg

What Happens

Fat oxidation ↑, liver fat ↓

8-10% weight loss

Visceral fat drops rapidly

Lean preserved ONLY with tight support

Maintain

Month 3-6+

Optimization Phase

Lowest dose keeping appetite/weight trending

What Happens

Full thermogenic drive

Visceral fat ↓ 40%

18-24% total weight loss

Lean risk highest - monitor closely

Medical Disclaimer

Maximum Dose

12 mg weekly

Do not exceed this dosage. Always follow your healthcare provider's guidance.

Key Guidance

Dose Considerations

Glucagon boosts energy expenditure but can catabolize muscle and increase need for carbohydrate intake if training too hard - slow titration essential.

Advantages

Highest fat loss potential of any available option.
Impacts metabolism and drives fat oxidation with glucagon.

Watch Out For

Side effects highly sensitive to dose escalation.
Elevated heart-rate during initial titration phases.

Clinical Monitoring Framework

Lean Mass (DXA/BIA)

>10% relative lean mass loss

Frequency:Baseline + every 3 months

Action:STOP escalation immediately, reduce to previous dose, verify anabolic support

Strength Metrics

>8% strength drop

Frequency:Every 2 weeks

Action:Freeze dose for 4+ weeks, review protein/training, consider dose reduction

Protein Intake

<1.6 g/kg

Frequency:Daily tracking

Action:Emergency intervention - protein shakes mandatory, pause escalation

Resting Heart Rate

+12 bpm above baseline

Frequency:Daily (morning)

Action:Glucagon effect assessment, reduce training stress, hydration check

RMR/Metabolic Rate

>10% drop (glucagon should offset)

Frequency:Every 2-3 months

Action:Investigate lean mass loss, caloric adequacy, thyroid panel

Visual Assessment

'Stringy' appearance emerging

Frequency:Weekly photos

Action:Immediate dose hold, anabolic support review, nutrition consult

Clinical Evidence

Full Compound Comparison

Characteristic	Semaglutide	Tirzepatide	Retatrutide
Brand Names	Ozempic, Wegovy	Mounjaro, Zepbound	Investigational (Phase 2)
Mechanism	GLP-1 Receptor Activation	Dual GIP/GLP-1 Receptor Activation	Triple Agonist: GLP-1 / GIP / Glucagon
Approval Status	🟢 FDA Approved	🟢 FDA Approved	🟡 Phase 3 Ongoing
Key Trial	STEP-1	SURMOUNT-1	Phase 2 (NEJM 2023)
Trial Duration	68 weeks	72 weeks	48 weeks
Starting Dose	0.25 mg	2.5 mg	0.5–1 mg
Maximum Dose	2.4 mg weekly	15 mg weekly	12 mg weekly
Avg. Weight Loss	12–15%	18–21%	22–24%
Fat Loss Ratio	60% fat / 40% lean	67% fat / 33% lean	70% fat / 30% lean
Visceral Fat Reduction	20-30%	25-35%	30-40%

Weight Loss Threshold Achievement

Percentage of trial participants reaching each weight loss threshold at maximum dose

Threshold	Semaglutide	Tirzepatide	Retatrutide
≥5%	86%	>95%	100%
≥10%	69%	91%	93%
≥15%	50%	83%	83%
≥20%	33%	57%	63%
≥25%	—	36%	~40%

Data from STEP-1 (semaglutide), SURMOUNT-1 (tirzepatide), and Phase 2 NEJM 2023 (retatrutide)

Frequently Asked Questions

Which is better for weight loss: semaglutide or tirzepatide?

Clinical trials show tirzepatide produces more weight loss than semaglutide. In the SURMOUNT-1 trial, tirzepatide 15mg achieved 21% weight loss versus 15% for semaglutide 2.4mg in STEP-1. However, individual response varies, and semaglutide has a longer safety track record with more real-world data.

What is the maximum dose of each GLP-1 medication?

Semaglutide maximum is 2.4mg weekly (Wegovy). Tirzepatide maximum is 15mg weekly (Mounjaro/Zepbound). Retatrutide has been studied up to 12mg weekly in Phase 2 trials. All require slow dose escalation over 16-20 weeks to reach maximum tolerated dose.

How do semaglutide brand names compare: Ozempic vs Wegovy?

Ozempic (0.25-2mg doses) is FDA-approved for type 2 diabetes. Wegovy (0.25-2.4mg doses) is FDA-approved for weight loss. They contain the same active ingredient (semaglutide) but Wegovy goes to a higher maximum dose and is specifically indicated for obesity treatment.

What makes tirzepatide different from semaglutide?

Tirzepatide activates two receptors (GLP-1 and GIP) while semaglutide only activates GLP-1. The dual-agonist mechanism provides both appetite suppression and improved fat metabolism, leading to 40% more weight loss on average in head-to-head comparisons.

Is retatrutide available yet?

Retatrutide is not yet FDA-approved. It completed Phase 2 trials (published NEJM 2023) showing up to 24% weight loss. Phase 3 TRIUMPH trials with 1,500+ participants are ongoing, with results expected in 2027. Currently only available through clinical trials or compounding.

Which GLP-1 has the fewest side effects?

Semaglutide generally has a slightly better tolerability profile than tirzepatide, with lower rates of nausea and vomiting in trials. However, all GLP-1 agonists cause similar GI side effects. Slow dose escalation (4 weeks per step) significantly reduces side effect severity regardless of which compound you use.

Clinical Trial Sources

STEP-1 Trial (Semaglutide): Wilding et al., NEJM 2021. 1,961 participants, 68 weeks. Semaglutide 2.4mg vs placebo. Mean weight loss: -14.9% vs -2.4%.
SURMOUNT-1 Trial (Tirzepatide): Jastreboff et al., NEJM 2022. 2,539 participants, 72 weeks. Tirzepatide 5/10/15mg vs placebo. Mean weight loss: -15% to -21% vs -3%.
Phase 2 Trial (Retatrutide): Jastreboff et al., NEJM 2023. 338 participants with type 2 diabetes, 48 weeks. Retatrutide 1-12mg vs placebo. Mean weight loss: up to -24%.

All percentage values represent mean weight change from baseline in intention-to-treat populations.

Semaglutide vs Tirzepatide vs Retatrutide

Compare GLP-1 drugs based on your tolerance and goals.

Semaglutide

Ozempic, Wegovy

beginner

The gentle starter

Reduces appetite and slows digestion for steady but indiscriminate weight loss

Intensity

2/5

Tolerability

4/5

Support

2/4

Metabolic Scope

FDA Approved

GLP-1 only: satiety and insulin sensitivity

Weight Loss Ratio

60% fat40% lean

Tirzepatide

Mounjaro, Zepbound

intermediate

The fast track

Dual-action appetite control with enhanced fat loss - more powerful but requires attention to muscle protection

Intensity

4/5

Tolerability

3/5

Support

3/4

Metabolic Scope

FDA Approved

GLP-1 + GIP: deeper metabolic rebalancing with improved nutrient partitioning

Weight Loss Ratio

67% fat33% lean

Retatrutide

Investigational (Phase 2)

advanced

The heavy hitter

Triple-action for maximum fat loss - requires meticulous muscle protection and supervised approach

Intensity

5/5

Tolerability

2/5

Support

4/4

Metabolic Scope

Phase 3

GLP-1 + GIP + Glucagon: whole-system metabolic rewiring with enhanced fat oxidation

Weight Loss Ratio

70% fat30% lean

GLP-1

Satiety

GIP

Insulin

Glucagon

Energy

Intensity

2/5

Tolerability

4/5

Support Needed

2/4

Metabolic

1/5

Data source:STEP-1Non-diabetic obesity68 weeks

How It Works

GLP-1 Receptor Activation

Semaglutide activates the GLP-1 receptor, the gut–brain hormone pathway that reduces appetite, slows stomach emptying, and improves insulin signaling as a byproduct.

What This Means

Weight Loss Ratio

60% fat loss40% lean loss

20-30%

Visceral Fat

↓10-15%

Resting Energy Expenditure

What % of People Hit Each Milestone?

86%

lost ≥5%

69%

lost ≥10%

50%

lost ≥15%

33%

lost ≥20%

Based on STEP-1 trial data (68 weeks, non-diabetic obesity)

Expected Weight Loss by Dose

Dose	Weeks	Expected Loss	Notes
0.25 mg	0–4	~1%	Early titration
0.5 mg	4–8	2–3%	Appetite suppression begins
1.0 mg	8–12	4–6%	Noticeable trajectory
1.7 mg	12–16	7–9%	Most reach ≥5%
2.4 mg	16–68	12–15%	Full effect

Complete Protocol Guide

Start

Week 1-4

Assess Tolerance

0.25 mg weekly for 4 weeks

What Happens

Appetite suppression begins

Early GI side effects

1-2% weight loss

Hunger stabilizes

Build

Week 5-12+

Progressive Escalation

Increase every 4 weeks: 0.5 → 1.0 → 1.7 → 2.4 mg

What Happens

Fat loss begins

3-5% total weight loss

Improved glycemic markers

Strength preserved with support

Maintain

Month 3-6+

Optimization Phase

Lowest dose that controls appetite without hurting training

What Happens

Visceral fat ↓ 20-25%

10-12% total weight loss

REE down 10-15%

Steady metabolism with training

Medical Disclaimer

Maximum Dose

2.4 mg weekly

Do not exceed this dosage. Always follow your healthcare provider's guidance.

Key Guidance

Dose Considerations

Only increase if appetite returns or fat loss stalls. Slow and steady wins.

Advantages

Most forgiving - easiest to start and adjust.
Well-studied with good safety profile.

Watch Out For

Effects of a 'blunt-instrument' that catabolizes muscle as the driving force is slowed gastric emptying.
Fatigue, lethargy, and reduced libido are common side effects.

Clinical Monitoring Framework

Lean Mass (DXA/BIA)

>10% relative lean mass loss

Frequency:Baseline + every 3-6 months

Action:Reassess diet, slow titration, intensify resistance training

Strength Metrics

>10% strength drop without recovery

Frequency:Monthly to quarterly

Action:Hold dose, reduce training volume, review nutrition

Protein Intake

<1.2 g/kg trending

Frequency:Weekly logs

Action:Nutrition consult, meal plan revision, protein supplementation

Resting Heart Rate

+10 bpm above baseline

Frequency:Weekly

Action:Evaluate hydration, training stress, consider dose adjustment

REE/Metabolic Rate

>15% drop beyond adaptation

Frequency:Every 3-6 months

Action:Examine lean mass loss, adjust caloric intake

Clinical Evidence

GLP-1

Satiety

GIP

Insulin

Glucagon

Energy

Intensity

4/5

Tolerability

3/5

Support Needed

3/4

Metabolic

3/5

Data source:SURMOUNT-1Non-diabetic obesity72 weeks

How It Works

Dual GIP/GLP-1 Receptor Activation

Tirzepatide hits two incretin receptors: GLP-1 (satiety, gastric slowing) and GIP, which enhances insulin's effectiveness and imrpoves HbA1c levels, augmenting weight loss.

What This Means

Weight Loss Ratio

67% fat loss33% lean loss

25-35%

Visceral Fat

↓8-12%

Resting Energy Expenditure

What % of People Hit Each Milestone?

>95%

lost ≥5%

91%

lost ≥10%

83%

lost ≥15%

57%

lost ≥20%

36%

lost ≥25%

Based on SURMOUNT-1 trial data (72 weeks, non-diabetic obesity)

Expected Weight Loss by Dose

Dose	Weeks	Expected Loss	Notes
2.5 mg	0–4	~2%	Starting dose
5 mg	4–8	4–6%	Entry therapeutic
7.5 mg	8–12	8–10%	Building
10 mg	12–16	12–15%	Strong effect
15 mg	16–72	18–21%	Maximum dose

Complete Protocol Guide

Start

Week 1-4

Assess Tolerance

2.5-5 mg weekly for 4 weeks

What Happens

Appetite ↓ sharply

Glucose stabilizes

2-4% weight loss

GI symptoms if escalated too fast

Build

Week 5-12+

Progressive Escalation

Increase every 4 weeks: 7.5 → 10 → 12.5 → 15 mg

What Happens

Fat loss 6-8%

Energy steady via GIP

Lean retention high

Sleep/breathing improves

Maintain

Month 3-6+

Optimization Phase

Lowest dose keeping hunger controlled and training normal

What Happens

10-15% total weight loss

Visceral fat ↓ 25-35%

Metabolic adaptation mild

Performance sustained with support

Medical Disclaimer

Maximum Dose

15 mg weekly

Do not exceed this dosage. Always follow your healthcare provider's guidance.

Key Guidance

Dose Considerations

More powerful than sema - watch muscle loss if support isn't dialed in

Advantages

Faster fat loss than semaglutide in head-to-head studies.
Strong glucose control for diabetics.

Watch Out For

Higher chance of GI side effects.
Will catabolize muscle if anabolic support isn't dialed

Clinical Monitoring Framework

Lean Mass (DXA/BIA)

>10% relative lean mass loss

Frequency:Baseline + every 3-6 months

Action:Hold dose escalation, boost protein to ≥1.8 g/kg, increase resistance training frequency

Strength Metrics

>10% strength drop

Frequency:Monthly to quarterly

Action:Freeze at current dose, deload training, review anabolic support

Protein Intake

<1.6 g/kg

Frequency:Weekly logs

Action:Immediate nutrition intervention, protein shakes between meals

Resting Heart Rate

+8 bpm above baseline

Frequency:Weekly

Action:Monitor for GIP-related effects, adjust training volume

Clinical Evidence

GLP-1

Satiety

GIP

Insulin

Glucagon

Energy

Intensity

5/5

Tolerability

2/5

Support Needed

4/4

Metabolic

5/5

Data source:Phase 2 (NEJM 2023)Type 2 diabetes48 weeks

How It Works

Triple Agonist: GLP-1 / GIP / Glucagon

What This Means

Weight Loss Ratio

70% fat loss30% lean loss

30-40%

Visceral Fat

↓6-10%

Resting Energy Expenditure

−18 to −20 cm at 8–12 mg

Waist Reduction

What % of People Hit Each Milestone?

100%

lost ≥5%

93%

lost ≥10%

83%

lost ≥15%

63%

lost ≥20%

~40%

lost ≥25%

~25%

lost ≥30%

Based on Phase 2 (NEJM 2023) trial data (48 weeks, type 2 diabetes)

Expected Weight Loss by Dose

Dose	Weeks	Expected Loss	Notes
0.5–1 mg	0–4	~3%	Activation phase
2 mg	4–8	5–7%	Early response
4 mg	8–12	10–12%	Similar to full sema
8 mg	12–24	18–20%	Large effect
12 mg	24–48	22–24%	Maximum; no plateau

Complete Protocol Guide

Start

Week 1-4

Assess Tolerance

0.5-2 mg weekly, hold each step ≥4 weeks

What Happens

Appetite & thermogenesis begin

3-5% weight loss

HR ↑ 2-4 bpm

Watch for early strength dip

Build

Week 5-12+

Progressive Escalation

Advance only after plateau: 1 → 2 → 3 → 4 up to 12 mg

What Happens

Fat oxidation ↑, liver fat ↓

8-10% weight loss

Visceral fat drops rapidly

Lean preserved ONLY with tight support

Maintain

Month 3-6+

Optimization Phase

Lowest dose keeping appetite/weight trending

What Happens

Full thermogenic drive

Visceral fat ↓ 40%

18-24% total weight loss

Lean risk highest - monitor closely

Medical Disclaimer

Maximum Dose

12 mg weekly

Do not exceed this dosage. Always follow your healthcare provider's guidance.

Key Guidance

Dose Considerations

Glucagon boosts energy expenditure but can catabolize muscle and increase need for carbohydrate intake if training too hard - slow titration essential.

Advantages

Highest fat loss potential of any available option.
Impacts metabolism and drives fat oxidation with glucagon.

Watch Out For

Side effects highly sensitive to dose escalation.
Elevated heart-rate during initial titration phases.

Clinical Monitoring Framework

Lean Mass (DXA/BIA)

>10% relative lean mass loss

Frequency:Baseline + every 3 months

Action:STOP escalation immediately, reduce to previous dose, verify anabolic support

Strength Metrics

>8% strength drop

Frequency:Every 2 weeks

Action:Freeze dose for 4+ weeks, review protein/training, consider dose reduction

Protein Intake

<1.6 g/kg

Frequency:Daily tracking

Action:Emergency intervention - protein shakes mandatory, pause escalation

Resting Heart Rate

+12 bpm above baseline

Frequency:Daily (morning)

Action:Glucagon effect assessment, reduce training stress, hydration check

RMR/Metabolic Rate

>10% drop (glucagon should offset)

Frequency:Every 2-3 months

Action:Investigate lean mass loss, caloric adequacy, thyroid panel

Visual Assessment

'Stringy' appearance emerging

Frequency:Weekly photos

Action:Immediate dose hold, anabolic support review, nutrition consult

Clinical Evidence

Full Compound Comparison

Characteristic	Semaglutide	Tirzepatide	Retatrutide
Brand Names	Ozempic, Wegovy	Mounjaro, Zepbound	Investigational (Phase 2)
Mechanism	GLP-1 Receptor Activation	Dual GIP/GLP-1 Receptor Activation	Triple Agonist: GLP-1 / GIP / Glucagon
Approval Status	🟢 FDA Approved	🟢 FDA Approved	🟡 Phase 3 Ongoing
Key Trial	STEP-1	SURMOUNT-1	Phase 2 (NEJM 2023)
Trial Duration	68 weeks	72 weeks	48 weeks
Starting Dose	0.25 mg	2.5 mg	0.5–1 mg
Maximum Dose	2.4 mg weekly	15 mg weekly	12 mg weekly
Avg. Weight Loss	12–15%	18–21%	22–24%
Fat Loss Ratio	60% fat / 40% lean	67% fat / 33% lean	70% fat / 30% lean
Visceral Fat Reduction	20-30%	25-35%	30-40%

Weight Loss Threshold Achievement

Percentage of trial participants reaching each weight loss threshold at maximum dose

Threshold	Semaglutide	Tirzepatide	Retatrutide
≥5%	86%	>95%	100%
≥10%	69%	91%	93%
≥15%	50%	83%	83%
≥20%	33%	57%	63%
≥25%	—	36%	~40%

Data from STEP-1 (semaglutide), SURMOUNT-1 (tirzepatide), and Phase 2 NEJM 2023 (retatrutide)

Frequently Asked Questions

Which is better for weight loss: semaglutide or tirzepatide?

What is the maximum dose of each GLP-1 medication?

How do semaglutide brand names compare: Ozempic vs Wegovy?

What makes tirzepatide different from semaglutide?

Is retatrutide available yet?

Which GLP-1 has the fewest side effects?

Clinical Trial Sources

STEP-1 Trial (Semaglutide): Wilding et al., NEJM 2021. 1,961 participants, 68 weeks. Semaglutide 2.4mg vs placebo. Mean weight loss: -14.9% vs -2.4%.
SURMOUNT-1 Trial (Tirzepatide): Jastreboff et al., NEJM 2022. 2,539 participants, 72 weeks. Tirzepatide 5/10/15mg vs placebo. Mean weight loss: -15% to -21% vs -3%.
Phase 2 Trial (Retatrutide): Jastreboff et al., NEJM 2023. 338 participants with type 2 diabetes, 48 weeks. Retatrutide 1-12mg vs placebo. Mean weight loss: up to -24%.

All percentage values represent mean weight change from baseline in intention-to-treat populations.

Semaglutide vs Tirzepatide vs Retatrutide

Semaglutide

The gentle starter

Tirzepatide

The fast track

Retatrutide

The heavy hitter

How It Works

GLP-1 Receptor Activation

What This Means

What % of People Hit Each Milestone?

Expected Weight Loss by Dose

Complete Protocol Guide

Start

Build

Maintain

Advantages

Watch Out For

Clinical Monitoring Framework

Clinical Evidence

FDA & Regulatory Documentation

Clinical Guidelines & Perioperative Management

Semaglutide Research

Clinical Trials & Dose-Specific Safety Data

Dosing Strategies & Optimization

How It Works

Dual GIP/GLP-1 Receptor Activation

What This Means

What % of People Hit Each Milestone?

Expected Weight Loss by Dose

Complete Protocol Guide

Start

Build

Maintain

Advantages

Watch Out For

Clinical Monitoring Framework

Clinical Evidence

FDA & Regulatory Documentation

Clinical Guidelines & Perioperative Management

Tirzepatide Research

Clinical Trials & Dose-Specific Safety Data

Dosing Strategies & Optimization

How It Works

Triple Agonist: GLP-1 / GIP / Glucagon

What This Means

What % of People Hit Each Milestone?

Expected Weight Loss by Dose

Complete Protocol Guide

Start

Build

Maintain

Advantages

Watch Out For

Clinical Monitoring Framework

Clinical Evidence

Retatrutide Research

Clinical Trials & Dose-Specific Safety Data

Dosing Strategies & Optimization

Full Compound Comparison

Weight Loss Threshold Achievement

Frequently Asked Questions

Which is better for weight loss: semaglutide or tirzepatide?

What is the maximum dose of each GLP-1 medication?

How do semaglutide brand names compare: Ozempic vs Wegovy?

What makes tirzepatide different from semaglutide?

Is retatrutide available yet?

Which GLP-1 has the fewest side effects?

Clinical Trial Sources

Semaglutide vs Tirzepatide vs Retatrutide

Semaglutide

The gentle starter

Tirzepatide

The fast track

Retatrutide

The heavy hitter

How It Works

GLP-1 Receptor Activation

What This Means

What % of People Hit Each Milestone?