Retatrutide Recomposition: Dual-Axis Protocol for Fat Loss Without Muscle Loss

Why Retatrutide Works—And Why That's a Problem

Retatrutide produces 24% body weight loss in 48 weeks[^1]. That's not a typo. It beats semaglutide (~15%) and tirzepatide (~21%) because it does something fundamentally different: it activates three receptor systems simultaneously instead of just one or two.

Think of it like turning up three separate dials on your metabolism:

Dial 1: Appetite Control (GLP-1 receptors)
Makes eating less feel natural instead of forced. Patients describe "food noise" disappearing—that constant mental background hum of thinking about the next meal just goes quiet. You're not white-knuckling hunger; you're genuinely satisfied eating half what you used to.

Dial 2: Nutrient Efficiency (GIP receptors)
Improves how your body uses the limited food you do eat. Insulin works better, meaning calories get utilized efficiently rather than wasted. Your metabolic machinery stays functional even as total intake drops dramatically.

Dial 3: Metabolism Boost (Glucagon receptors)
This is the one that makes retatrutide different—and dangerous. Glucagon raises your baseline metabolic rate (you burn more just existing) and actively breaks down stored fat. It's why retatrutide produces that unprecedented 24% weight loss[^2].

Here's the problem: glucagon doesn't have a "just fat" setting.

When it signals "unlock storage and burn it," your body pulls from whatever's available—fat, muscle, connective tissue. Think of it like having two bank accounts: one filled with fat, one filled with muscle. Retatrutide says "we need money, withdraw from both accounts." Without intervention, you lose weight fast but you also lose the muscle you spent years building.

This is where most people using retatrutide alone end up: dramatic scale weight loss, but poor body composition. Less fat, yes. But also less muscle, lower strength, slower metabolism, and a body now primed to regain fat quickly.

The solution isn't to avoid retatrutide. It's to make the fat account easy to access while locking down the muscle account.

Your Body Already Has a Plan: The Daily Metabolic Rhythm

Here's what most people miss: your body isn't static throughout the day. It already operates on a natural rhythm that alternates between two metabolic modes.

Morning = Breakdown Mode

You wake up after not eating for 10-16 hours. Your body needs energy but there's no food coming in. So it flips into breakdown mode:

• Fat stores unlock and mobilize for energy
• Your cells shift to burning fat preferentially
• Mental clarity peaks (evolutionarily, this is when you'd be hunting or foraging)
• Insulin sensitivity is high (your body is ready to use glucose efficiently when it arrives)

This is called AMPK activation—think of AMPK as a cellular fuel gauge that says "we're low on energy, start breaking things down." It's a catabolic state: breaking down exceeds building up.

For fat loss, this mode is perfect. The problem? Without guidance, it burns muscle just as readily as fat.

Evening = Building Mode

After you eat, especially in the evening and during sleep, your body shifts to building mode:

• Protein synthesis ramps up—muscle tissue repairs and grows
• Growth hormone pulses during deep sleep drive restoration
• Your parasympathetic nervous system takes over (rest, digest, restore)
• Glycogen stores refill in muscles and liver
• Connective tissue repairs damage from training

This is called mTOR activation—the signal that says "we have resources, build and repair." It's an anabolic state: building up exceeds breaking down.

For muscle preservation and recovery, this window is critical.

What Retatrutide Does to This Rhythm

Retatrutide jacks breakdown mode up to 11 through glucagon signaling. You're mobilizing fat aggressively, appetite is crushed, metabolism is elevated. But it also kills building mode: the chronic caloric deficit (often 50-70% below baseline) and constant AMPK activation suppress mTOR signaling.

Result: You're in breakdown mode nearly 24/7 with no repair window. Fat loss is rapid but muscle loss follows.

The dual-axis fix: Amplify what you want during breakdown mode (fat mobilization) while restoring what you need during building mode (muscle protection).

The Four-Compound Stack: Engineering Selective Fat Loss

This protocol uses four compounds synchronized to your natural metabolic rhythm. Each one has a specific job.

Morning Axis: Making Fat the Easy Target

L-Carnitine (500mg, fasted)

When retatrutide unlocks fat through glucagon signaling, that fat needs to actually reach your mitochondria—the cellular furnaces where it gets burned. L-Carnitine is the shuttle that transports it there.

Without enough carnitine, freed fat just circulates in your blood doing nothing. It's like having firewood delivered to your house but no way to get it into the fireplace. A 37-trial meta-analysis confirmed L-carnitine supplementation produces consistent fat mass reduction during caloric restriction[^3][^4].

The key: take it after a 16-hour fast when your body's fat-transport enzyme (CPT1) expression peaks. Fasted state matters—taking it with food kills the effect.

MOTS-c (5-10mg, 3x/week before training)

MOTS-c is a signal molecule from your mitochondrial DNA that activates the same AMPK system retatrutide is already cranking up. But it does something critical: it tells your muscles "stay responsive to the limited food coming in."

What this means practically:

• Your muscles keep pulling in glucose from the small amount you're eating
• Fat oxidation during training increases
• Energy stays high despite the deficit
• Insulin sensitivity improves

Research shows MOTS-c preserves lean tissue during weight loss while promoting fat oxidation[^5][^6]. During retatrutide's enforced deficit, this keeps your muscles metabolically active instead of shutting down to conserve energy.

Dosing before demanding training sessions leverages its 4-hour active window precisely when you need it.

Evening Axis: Protecting What You've Built

Tesamorelin (1-2mg, after dinner)

Tesamorelin tells your pituitary to pulse growth hormone—but unlike injecting GH directly, this preserves your natural feedback loops and circadian timing.

What this does:

• Creates a strong GH pulse during early sleep when protein synthesis peaks
• Sends a clear "protect and build muscle" signal to counter retatrutide's catabolic pressure
• Preferentially targets visceral abdominal fat (GH mobilizes this specifically)
• Supports collagen synthesis so connective tissue stays intact

Clinical trials show tesamorelin reduces visceral fat by 15-20% without impairing glucose metabolism[^7][^8]. Critically, the GH pulse makes muscle "metabolically expensive" to break down—your body prioritizes preserving it even during aggressive deficit.

Timing matters: 60-90 minutes after dinner aligns with natural GH pulse timing during slow-wave sleep.

NAD+ Precursors (500-1000mg NMN or NR, midday)

NAD+ is the electron carrier in cellular respiration—the process that converts food and oxygen into ATP (cellular energy). During retatrutide's metabolic stress, your mitochondria work harder with less fuel. NAD+ ensures they have the cofactors to sustain energy production without accumulating damage.

Practically:

• Energy stays stable despite eating way less
• Recovery capacity between training sessions is preserved
• DNA repair processes continue (NAD+ activates longevity enzymes called sirtuins)
• Mitochondria don't burn out from overwork

Dose at midday when endogenous NAD+ naturally troughs due to circadian rhythms—supplementing when levels are lowest maximizes the boost.

How The System Actually Works: The Two-Account Strategy

Here's what's happening when everything's running:

Morning (Breakdown Mode - AMPK Dominant)

[Retatrutide] → Glucagon activates → Fat stores unlock
            ↓
[L-Carnitine] → Freed fat transported into mitochondria
            ↓
[MOTS-c] → AMPK activation → Fat burning prioritized
            ↓
[NAD+] → Energy production sustained
            ↓
Result: Fat becomes abundant, easy fuel source

Evening (Building Mode - mTOR Dominant)

[Protein intake] → Amino acids available for repair
            ↓
[Tesamorelin] → GH pulse → Strong anabolic signal
            ↓
Result: Muscle preservation signal during sleep

The insight: Retatrutide creates the massive energy deficit—you're burning way more than you're eating. Your body has to pay that bill somehow. We're making the fat account easy to access (morning compounds make it abundant and readily available) while locking down the muscle account (evening compounds signal "this is valuable, don't touch it").

Physics still applies—the deficit happens. We just engineer which account pays for it.

The Protocol: Implementation and Timing

Morning Routine (Fasted, 16+ Hours Ideal)

6:00 AM

• L-Carnitine: 500mg subcutaneous or intramuscular
• Wait 30-60 minutes before training or eating

6:30 AM (Monday/Wednesday/Friday, pre-training)

• MOTS-c: 5-10mg subcutaneous

Why fasted: Fat transport enzyme (CPT1) expression peaks after 16-hour fast. Breaking fast too early blunts the effect.

Midday

1:00 PM

• NAD+ precursor (NMN or NR): 500-1000mg oral
• Times with natural NAD+ circadian trough

Evening Routine

7:00 PM

• Dinner: High protein (40-50g), moderate carb
• Provides substrate for nighttime repair

8:30 PM (60-90 minutes after dinner)

• Tesamorelin: 1-2mg subcutaneous
• Aligns GH pulse with upcoming sleep cycle

Retatrutide Titration (Separate Schedule)

Don't rush this. Side effects and catabolic pressure scale with dose:

• Weeks 1-4: 0.5mg weekly (assess appetite/GI response)
• Weeks 5-8: 1mg weekly (if well-tolerated)
• Weeks 9-12: 1.5-2mg weekly (glucagon effects prominent here)
• Maintenance: 2-4mg weekly (lowest effective dose)

Ultra-slow titration reduces side effects and gives you time to layer in the support stack. Muscle loss risk increases dramatically above 1.5mg without support.

Non-Negotiable: Protein

1.6-2.2g per kg bodyweight daily, spread across at least 4 meals.

For 80kg person: 130-175g protein daily, 30-45g per meal minimum.

Protein is the structural signal that tells your body you can afford to rebuild. Skip this and no peptide stack will save your muscle. Evening meal can bias higher (50g) to support the mTOR window.

Training Structure

Resistance Training: 3-4x/week

• Maintain intensity (weight on bar is the feedback signal)
• Volume can drop 10-20% during deep deficit weeks
• If major lifts drop >15%, freeze retatrutide dose immediately

Zone-2 Cardio: 2-3x/week, 30-45 minutes

• Heart rate: 60-70% max (conversational pace)
• Enhances fat oxidation machinery and insulin sensitivity
• Fasted AM sessions optional but amplify AMPK bias

What to Track

Weekly:

• Body weight (same time/conditions)
• Strength on 3-5 key lifts
• Subjective energy (1-10)
• Hunger levels (1-10)

Bi-weekly:

• Body composition (DEXA or InBody)
• Waist circumference
• Visceral fat area if available

Monthly Labs:

• Fasting glucose, HbA1c
• Lipid panel
• Liver enzymes (AST/ALT)
• IGF-1 (if using Tesamorelin >8 weeks)
• Thyroid panel (TSH, Free T3, Free T4)

This data tells you when to advance, freeze, or pause. Never operate blind.

Timeline: What Actually Happens

Weeks 1-4: Adaptation

• Weight: 5-8 lbs initial loss (water/glycogen)
• Appetite: Suppression kicks in, eating becomes effortless
• Energy: L-Carnitine + MOTS-c improve fasted training feel
• Body comp: 2-3% fat reduction, lean mass stable if protein target met
• Strength: Maintained or slight improvement

Weeks 5-8: Acceleration

• Weight: Fat loss accelerates significantly
• Appetite: Nearly fully suppressed, may need reminders to eat
• Energy: Adaptation complete, energy stable despite large deficit
• Body comp: 4-6% additional fat loss, waist circumference drops noticeably
• Strength: 95-100% baseline. If dropping below 90%, freeze retatrutide

Weeks 9-12: Refinement

• Weight: Loss rate stabilizes but stays consistent
• Body comp: 3-4% more fat loss from stubborn depots (visceral, lower abdominal)
• Strength: May see 5-10% decrease due to reduced leverages from body weight loss, not actual muscle loss
• Recovery: Tesamorelin's effects fully expressed, recovery feels good despite deficit

Weeks 13-24: Maintenance Recomp

• Retatrutide: Maintain at lowest effective dose (2-4mg)
• Stack: Continue full protocol or shift to maintenance (L-Carnitine + NAD+ daily, MOTS-c/Tesamorelin 2x/week)
• Body comp: Focus shifts from aggressive fat loss to refinement and metabolic flexibility
• Outcome: 12-18% total fat loss with 90-95% lean mass retention

Compare this to retatrutide alone: Similar fat loss but typically 15-25% lean mass loss, strength decreases of 20-30%, metabolic adaptation requiring higher doses over time.

Safety: When to Stop and What to Watch

⚠️ Medical Supervision Required This protocol should only be undertaken under qualified medical supervision. Self-administration without oversight may pose serious health risks.

Common Side Effects (Manageable)

Retatrutide:

• Nausea (weeks 1-3, improves with slow titration)
• Constipation (increase fiber, hydration, magnesium)
• Fatigue (NAD+ and electrolytes help)
• Injection site reactions (rotate sites, insulin syringes)

Support Stack:

• Mild injection site redness (normal, 24-hour resolution)
• Transient headaches from NAD+ (start lower, titrate up)
• Fishy body odor with L-Carnitine (dose-dependent, reduce if bothersome)

Serious Warning Signs (Stop Immediately, Seek Medical Care)

Cardiovascular:

• Resting heart rate >100 bpm
• New irregular heartbeat or palpitations
• Chest pain or pressure

Metabolic:

• Severe nausea/vomiting preventing hydration
• Severe upper abdominal pain radiating to back (pancreatitis risk)
• Persistent hypoglycemia (<70 mg/dL with symptoms)

Musculoskeletal:

• Strength loss >20% over 2 weeks despite protocol compliance
• Persistent muscle cramping or twitching
• New joint pain or swelling (possible fluid retention from GH)

Endocrine:

• Cold intolerance, severe fatigue, depression (thyroid)
• Severe water retention or facial swelling

Dose Adjustment Triggers

Freeze retatrutide (don't advance) if:

• Nausea interferes with daily function
• Energy consistently <5/10 despite full stack
• Lean mass declining >1% every 2 weeks
• Liver enzymes elevated but <2x upper limit

Reduce retatrutide 25-50% if:

• Strength drops >15% from baseline
• Severe GI symptoms despite slow titration
• Thyroid markers shifting unfavorably (Free T3 dropping)

Pause entire protocol if:

• Any serious warning signs above
• Pregnancy or planning pregnancy
• New thyroid disorder diagnosis
• Pancreatitis symptoms

Absolute Contraindications

Do not use this protocol if you have:

• Personal/family history of medullary thyroid carcinoma (MTC)
• Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Active eating disorder or history of disordered eating
• Severe depression or suicidal ideation
• Type 1 diabetes (requires specialist oversight)
• History of pancreatitis
• Severe kidney disease (CrCl <30 mL/min)
• Pregnancy or breastfeeding

Why This Actually Works: The Engineering Behind It

Traditional retatrutide use produces rapid weight loss but poor body composition because the energy deficit pulls from all tissues indiscriminately. Your body doesn't care that you spent three years building those biceps—it just sees available fuel.

This protocol solves that through metabolic steering:

Morning strategy: L-Carnitine shuttles freed fat into mitochondria. MOTS-c activates AMPK system-wide and keeps muscles responsive to limited incoming calories. NAD+ sustains energy production. Result: Fat becomes the abundant, easy-to-access fuel source. When your body needs energy, fat is right there, ready to burn.

Evening strategy: Protein intake provides amino acids. Tesamorelin creates strong GH pulse during sleep. Result: Muscle receives clear "this is valuable, protect it" signal. When your body evaluates what to preserve during deficit, muscle becomes metabolically "expensive" to break down relative to readily available fat.

Circadian alignment: Timing interventions to natural AMPK/mTOR oscillations amplifies each axis rather than fighting your biology. You're not overriding your circadian rhythm—you're enhancing it.

The outcome: Your body still experiences retatrutide's aggressive deficit (thermodynamics doesn't change), but the deficit is routed almost entirely through fat oxidation pathways while muscle receives protective anabolic signaling.

It's not about "tricking" your body. It's about making fat loss the path of least resistance while making muscle preservation the default response.

Getting Started: The Practical Steps

Step 1: Medical Consultation

Find a physician experienced with peptide protocols and GLP-1 therapies. Required baseline labs:

• Comprehensive metabolic panel
• Lipid panel (total, LDL, HDL, triglycerides)
• HbA1c
• Thyroid panel (TSH, Free T3, Free T4)
• Liver enzymes (AST, ALT)

Step 2: Source Quality Compounds

Only pharmaceutical-grade or research-grade peptides from verified suppliers with certificates of analysis (CoA). Contaminated or underdosed peptides create safety risks and guarantee poor outcomes.

Use our Peptide Calculator to calculate exact reconstitution volumes and dosing for each compound in the protocol.

Step 3: Layer Gradually

Don't start everything at once:

• Weeks 1-2: L-Carnitine + NAD+ (establishes fat oxidation baseline, tests injection tolerance)
• Week 3: Add retatrutide at 0.5mg (assess GI/appetite response)
• Week 4: Add MOTS-c on training days
• Week 5: Add Tesamorelin (completes dual-axis protocol)

Step 4: Track Everything

Create a tracking system (spreadsheet or app):

• Daily: Weight, energy (1-10), hunger (1-10)
• Weekly: Strength on key lifts
• Bi-weekly: Body composition measurements
• Monthly: Lab results

This data determines when to advance, freeze, or pause. It's your feedback system.

Step 5: Titrate Based on Data, Not Schedule

Don't advance retatrutide on a fixed timeline. Advance when:

• Current dose well-tolerated for 2+ weeks
• Lean mass stable or increasing
• Strength maintained at 95%+ baseline
• Energy acceptable (>6/10)

Freeze or reduce when any of these reverse.

The Bottom Line: Recomposition Without Compromise

Retatrutide represents a breakthrough—24% weight loss changes lives for people struggling with obesity[^1]. But for anyone who's built muscle and metabolic capacity, weight loss alone isn't the goal.

The goal is selective fat loss while protecting what you've built.

Most people using retatrutide alone achieve dramatic scale weight loss but emerge weaker, with poor body composition, and a metabolism primed to regain fat. That's not recomposition—that's just smaller.

This dual-axis protocol is designed for people who understand that body composition matters more than scale weight. You're not trying to get smaller. You're trying to become leaner, stronger, and more metabolically efficient.

The four-compound stack isn't optional if that's your goal:

• L-Carnitine routes freed fat to where it burns
• MOTS-c keeps muscle metabolically responsive despite deficit
• Tesamorelin creates anabolic protection during sleep
• NAD+ sustains energy machinery under metabolic stress

Together, synchronized to your circadian rhythm, they create a system where fat loss and muscle preservation happen simultaneously—not through genetics or willpower, but through metabolic engineering aligned with how your body naturally operates.

If you're on retatrutide or planning to start, this is how you do it without losing what you've spent years building.

References

[^1]: Jastreboff AM, Aronne LJ, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine. 2023. https://doi.org/10.1056/NEJMoa2301972

[^2]: Thomas MK, Nikooienejad A, et al. Efficacy and safety of Retatrutide, a novel GLP-1, GIP and glucagon receptor agonist. Nature Medicine. 2024. https://doi.org/10.1038/s41591-024-03018-2

[^3]: Fielding R, Riede L, et al. L-Carnitine Supplementation in Recovery after Exercise. Nutrients. 2018.

[^4]: Pooyandjoo M, Nouhi M, et al. Effect of L-Carnitine Supplementation on Weight Loss and Body Composition: Systematic Review and Meta-Analysis. Clinical Nutrition. 2020. https://pubmed.ncbi.nlm.nih.gov/32359762/

[^5]: Lee C, Zeng J, et al. The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance. Cell Metabolism. 2015. https://doi.org/10.1016/j.cmet.2015.02.009

[^6]: Lu H, Tang S, et al. Mitochondria-Derived Peptide MOTS-c: Effects and Mechanisms. Journal of Translational Medicine. 2023. https://doi.org/10.1186/s12967-023-03885-2

[^7]: Stanley TL, Chen CY, et al. Safety and metabolic effects of tesamorelin, a growth-hormone-releasing factor in obese subjects. Metabolism. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513535/

[^8]: Stanley TL, Falutz J, et al. Effect of Tesamorelin on Visceral Fat and Liver Fat in HIV-Infected Patients with Abdominal Fat Accumulation. JAMA. 2014. https://pubmed.ncbi.nlm.nih.gov/25038357/