Protocols · Metabolism/Weight Loss
Reta Advanced Weight Loss Protocol
Triple GLP-1/GIP/Glucagon Receptor Agonist | Class II/III Obesity
Typical Dose
0.5–12mg weekly
Graduated titration over 28+ weeks
Route
Subcutaneous
Abdomen, thigh, or posterior arm; rotate sites
Cycle
Ongoing
28-week titration, then maintenance
Storage
2–8°C refrigerated
Protect from light; use within 28 days post-reconstitution
Patient version available. Share ?view=patient with patients for the plain-language handout.
Overview
Reta is a triple agonist targeting GLP-1, GIP, and glucagon receptors, designed for higher-magnitude weight reduction than mono- or dual-incretin therapies. In Phase 2 data (Jastreboff et al., NEJM 2023), 48-week mean weight reduction reached approximately 24% at the 12mg dose, with continued downward trajectory suggesting non-plateaued response. This protocol is intended for patients with Class II obesity (BMI ≥35) or Class III obesity (BMI ≥40), or Class I obesity with significant metabolic comorbidity (T2DM, MASLD, OSA, hypertension) who have failed prior GLP-1 monotherapy or require deeper adiposity reduction.
The clinical goal is durable, substantial fat-mass loss with concurrent improvement in glycemic control, hepatic steatosis, lipid panel, and blood pressure. Unlike pure incretin agonists, the glucagon receptor component drives hepatic lipid oxidation and increases resting energy expenditure — a mechanism distinct from appetite suppression alone. Patients selected for this protocol should be capable of tolerating aggressive titration, willing to engage with resistance training and protein-forward nutrition to preserve lean mass, and committed to extended monitoring.
This stack uses three Reta strengths (10mg, 15mg, 30mg vials) to enable a graduated titration from initiation through maintenance without product waste or repeated reconstitution errors.
Key Benefits
Mean 20–24% total body weight loss at 48 weeks in Phase 2 data — exceeding both Sema and Tirz. Adds glucagon-mediated energy expenditure and hepatic lipid clearance on top of GLP-1/GIP appetite suppression.
Mechanism of Action
Balanced agonism at GLP-1, GIP, and glucagon receptors. GLP-1/GIP drive satiety and delayed gastric emptying; glucagon receptor activation increases resting metabolic rate and hepatic fatty acid oxidation.
Molecular Information
Weight
~4,731 Da
Length
39 amino acids
Type
Triple agonist peptide (GLP-1R / GIPR / GCGR)
* Lipidated synthetic peptide engineered for once-weekly subcutaneous administration.
Pharmacokinetics
Research Indications
Class II/III ObesityMOST EFFECTIVE
24% mean weight loss
48-week Phase 2 data at 12mg dose, with non-plateaued downward trajectory.
Higher magnitude than Sema/Tirz
Glucagon component adds caloric expenditure to GLP-1/GIP appetite suppression.
Post-failure of mono GLP-1
Effective option when Sema or Tirz response is insufficient.
Type 2 DiabetesEFFECTIVE
HbA1c reduction
0.4–0.8% reduction in dysglycemic patients by week 8; further improvement through week 24.
Glucose-dependent insulin
GLP-1R and GIP-R co-activation improves insulin secretion without hypoglycemia in monotherapy.
MASLD / Hepatic SteatosisEMERGING
Direct hepatic lipid oxidation
Glucagon receptor activation drives fatty acid oxidation in hepatocytes — a mechanism absent in GLP-1/GIP-only agents.
ALT/GGT improvement
Measurable by week 12 in patients with baseline elevation.
Metabolic SyndromeEFFECTIVE
Lipid panel
Triglyceride reduction and LDL improvement parallel weight loss timeline.
Blood pressure
Meaningful reductions by week 24 in hypertensive responders.
Research Protocols
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Initiation (Weeks 1–4) | 0.5mg | Once weekly | SC (10mg vial) |
| Early Titration (Weeks 5–12) | 1–2mg | Once weekly | SC (10mg vial) |
| Mid Titration (Weeks 13–20) | 4–6mg | Once weekly | SC (15mg vial) |
| Late Titration (Weeks 21–28) | 8–10mg | Once weekly | SC (30mg vial) |
| Standard Maintenance | 8–10mg | Once weekly | SC (30mg vial) |
| High-BMI Maintenance | 12mg | Once weekly | SC (30mg vial) |
| Strong Early Responder | 8mg | Once weekly | SC (30mg vial) |
Timing · Administer on the same day each week. Hold any dose an additional 4 weeks if GI tolerability is borderline. Re-evaluate non-responders at week 20.
Peptide Interactions
- Semaglutide— Do not combine incretin agonists — overlapping GLP-1R activation.AVOID
- Tirzepatide— Overlapping GLP-1/GIP agonism; switch rather than stack.AVOID
- Sulfonylureas / Insulin— Hypoglycemia risk — preemptive dose reduction required.MONITOR
- BPC-157— May offset GI side effects during titration; supports gut healing.SYNERGISTIC
- Tesofensine— Additive anorexigenic and cardiovascular effects; HR elevation compounded.AVOID
- CJC-1295 / Ipamorelin— GH axis support may aid lean mass preservation during rapid weight loss.SYNERGISTIC
- Levothyroxine— Delayed gastric emptying may alter absorption; recheck TSH at 12 weeks.MONITOR
- Warfarin— Altered absorption from delayed gastric emptying — increase INR monitoring.MONITOR
- AOD-9604— No known interaction; minimal additive benefit.COMPATIBLE
How to Reconstitute
- 1
Gather supplies: Reta vial (10mg, 15mg, or 30mg), bacteriostatic water, alcohol swabs, syringes, and sharps container.
- 2
Wash hands thoroughly and disinfect work surface.
- 3
Wipe both the BAC water vial and the Reta vial septum with separate alcohol swabs.
- 4
For 10mg vial: draw 2mL bacteriostatic water (yields 5mg/mL). For 15mg vial: draw 1.5mL (yields 10mg/mL). For 30mg vial: draw 2mL (yields 15mg/mL).
- 5
Inject the BAC water slowly down the inner wall of the Reta vial — do not spray directly onto the peptide powder.
- 6
Gently swirl or roll the vial between palms. Do not shake vigorously — agitation can denature the peptide.
- 7
Allow 2–5 minutes for full dissolution. The solution should be clear and colorless with no visible particulate.
- 8
Label the vial with reconstitution date and concentration.
- 9
Store reconstituted vial refrigerated at 2–8°C, protected from light.
- 10
Calculate draw volume based on prescribed dose and vial concentration. Verify with second source before injecting.
- 11
Inject subcutaneously into abdomen, thigh, or posterior arm. Rotate sites weekly to avoid lipohypertrophy.
- 12
Use reconstituted product within 28 days; discard any unused solution after that window.
Quality Indicators
Clear, colorless solution
Fully dissolved peptide with no visible particulate or cloudiness.
Intact vacuum seal
Audible hiss when first piercing the septum confirms sterile integrity.
Slight foaming after reconstitution
Acceptable if it dissipates within 2–5 minutes. Persistent foam suggests over-agitation.
Cloudiness or particulate
Do not inject. Indicates contamination, denaturation, or precipitation.
Yellow or amber discoloration
Discard. Suggests degradation from heat exposure or expiry.
What to Expect
Week 1–2: Mild nausea or early satiety; appetite suppression begins.
Week 4: 2–4% body weight loss; GI symptoms most prominent during dose escalations.
Week 8: 5–8% body weight loss; reduced food noise commonly reported; HbA1c improving.
Week 12: 8–12% body weight loss; triglycerides and ALT measurably improving.
Week 24: 15–18% body weight loss in responders; lipids, BP, and hepatic markers significantly improved.
Week 48: 20–24% mean body weight loss; downward trajectory often continuing.
Resting heart rate may rise 3–8 bpm due to glucagon receptor activation.
Hair shedding (telogen effluvium) possible during rapid loss phase; usually self-limited.
Lean mass loss likely without adequate protein (1.4–1.8 g/kg) and resistance training.
~10–15% of patients show partial or no response — re-evaluate at week 20 if <5% loss.
Side Effects & Safety
- Nausea, vomiting, constipation, dyspepsia, early satiety (worst in first 2–4 weeks of each escalation)
- Increased resting heart rate (3–8 bpm, glucagon-mediated)
- Transient transaminase elevations
- Injection site reactions (erythema, induration)
- Fatigue and dehydration during titration
- Hair shedding (telogen effluvium) with rapid weight loss
- Sarcopenia risk if protein intake inadequate
When to Stop & Call Provider
- Severe persistent abdominal pain radiating to back (possible pancreatitis)
- RUQ pain, fever, or jaundice (possible cholelithiasis/cholecystitis)
- Persistent vomiting with inability to maintain hydration
- Resting heart rate >100 bpm or new palpitations
- Signs of severe dehydration or acute kidney injury
- Pregnancy or active conception attempt
References
Triple–Hormone-Receptor Agonist Retatrutide for Obesity — Phase 2 Trial
Phase 2 RCT demonstrating dose-dependent weight loss up to ~24% at 12mg/week at 48 weeks, with continued downward trajectory suggesting non-plateaued response.
Retatrutide for Type 2 Diabetes — Phase 2 Trial
Dose-ranging trial in T2DM showing meaningful HbA1c reductions and weight loss across 1–12mg doses, with acceptable tolerability when titrated.
TRIUMPH Phase 3 Program
Ongoing Phase 3 program evaluating retatrutide in obesity, T2DM, MASLD, and cardiovascular outcomes. Results pending; not yet FDA-approved.