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Tirzepatide

Also known as: Mounjaro, Zepbound, LY3298176

Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist developed by Eli Lilly. FDA-approved as Mounjaro for type 2 diabetes and Zepbound for chronic weight management, it has demonstrated unusual weight loss of up to 22.5% in clinical trials.

Last updated: February 1, 2025Reviewed by: PeptideHub Research Team

Tirzepatide is a 4,813.45 Da research peptide. Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist developed by Eli Lilly. FDA-approved as Mounjaro for type 2 diabetes and Zepbound for chronic weight management, it has demonstrated unusual weight loss of up to 22.5% in clinical trials.

Also called: Mounjaro, Zepbound, LY3298176

4,813.45

Molecular Weight

Daltons

3

Strong Evidence

benefits

5

Studies Cited

peer-reviewed

2500-2500

Typical Dose

mcg

Overview

Tirzepatide is a novel synthetic peptide that functions as a dual agonist of both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. Developed by Eli Lilly and Company, it represents the first molecule in a new pharmacological class; dual incretin agonists. Tirzepatide received FDA approval in May 2022 as Mounjaro for the treatment of type 2 diabetes mellitus, and in November 2023 as Zepbound for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity. The SURPASS and SURMOUNT clinical trial programs demonstrated notable efficacy, with participants achieving up to 22.5% body weight reduction, surpassing all existing approved weight-loss medications. Tirzepatide's dual mechanism is thought to provide additive or complementary metabolic benefits beyond what GLP-1-only agonists achieve, including superior glycemic control, greater weight loss, and improved cardiovascular risk factors. The molecule is based on a 39-amino acid sequence incorporating a C20 fatty diacid moiety that binds albumin, extending its half-life to approximately 5 days and enabling once-weekly subcutaneous dosing.

Key Takeaways: Tirzepatide

  • Strongest evidence supports Tirzepatide for superior weight loss and type 2 diabetes control
  • Research doses typically range from 2500 to 2500 mcg via subcutaneous injection
  • 3 benefits with strong evidence, 3 moderate, 0 preliminary
  • Half-life: Approximately 5 days (enabling once-weekly dosing)
  • 5 cited research studies in this guide

Mechanism of Action

Tirzepatide simultaneously activates two incretin hormone receptors: GIP-R and GLP-1R. At the GLP-1 receptor, it mimics the effects of native GLP-1 — enhancing glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and reducing appetite through hypothalamic signaling. At the GIP receptor, it activates complementary pathways that enhance insulin secretion, improve insulin sensitivity in adipose tissue, and may promote more favorable fat metabolism and distribution. The dual mechanism creates additive metabolic effects: GLP-1R activation provides potent appetite suppression and glycemic control, while GIP-R activation contributes additional insulin sensitization and may modulate central appetite circuits through distinct hypothalamic pathways. Tirzepatide has biased agonism at GIP-R (preferring cAMP signaling over beta-arrestin recruitment), which may contribute to its efficacy profile. The C20 fatty diacid modification enables non-covalent albumin binding in circulation, dramatically extending the half-life from minutes (native incretins) to approximately 5 days. Weight loss is mediated through central appetite suppression (reduced caloric intake), slowed gastric emptying (enhanced satiety), and improved metabolic partitioning favoring fat oxidation over storage.

Research Benefits

Tirzepatide at a Glance

Primary mechanism:

Tirzepatide simultaneously activates two incretin hormone receptors: GIP-R and GLP-1R.

Top researched benefits:
Superior Weight LossType 2 Diabetes ControlCardiovascular Risk ReductionImproved Insulin SensitivityFatty Liver ImprovementObstructive Sleep Apnea

Superior Weight Loss

Strong Evidence

SURMOUNT-1 trial demonstrated up to 22.5% body weight reduction at the highest dose (15 mg) over 72 weeks, the largest weight loss achieved by any approved pharmaceutical agent in clinical trials.

Type 2 Diabetes Control

Strong Evidence

SURPASS trials showed HbA1c reductions of up to 2.58% and up to 50% of patients achieving HbA1c below 5.7% (normal range). Superior to semaglutide 1 mg in head-to-head comparison (SURPASS-2).

Improved Insulin Sensitivity

Strong Evidence

The dual GIP/GLP-1 mechanism improves insulin sensitivity beyond what GLP-1-only agonists achieve, with particular benefits in adipose tissue insulin signaling.

Cardiovascular Risk Reduction

Moderate Evidence

Clinical data shows significant improvements in cardiovascular risk factors including blood pressure, triglycerides, and inflammatory markers. Dedicated cardiovascular outcome data is emerging.

Fatty Liver Improvement

Moderate Evidence

Studies show significant reductions in liver fat content and improvement in NASH/NAFLD markers, likely through combined weight loss and direct metabolic effects.

Obstructive Sleep Apnea

Moderate Evidence

SURMOUNT-OSA trial showed tirzepatide significantly reduced apnea-hypopnea index (AHI) in adults with obesity and moderate-to-severe obstructive sleep apnea.

Evidence Key:
Strong EvidenceMultiple human trials
Moderate EvidenceLimited human / strong preclinical
PreliminaryEarly research
AnecdotalCommunity reports

Research Dosing Protocols

Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.

Research ProtocolDose RangeRoute
Starting dose25002500 mcgSubcutaneous injection
Escalation doses500010000 mcgSubcutaneous injection
Maximum dose1500015000 mcgSubcutaneous injection

Frequency

Once weekly

Timing

Any time of day, with or without meals. Same day each week preferred.

Cycle Length

Ongoing; chronic treatment for sustained weight management

Research Notes

  • 1Standard dose escalation: 2.5 mg × 4 weeks → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg.
  • 2Each dose level is maintained for at least 4 weeks before escalation.
  • 3Gradual escalation is critical to minimize GI side effects (nausea, vomiting).
  • 4Mounjaro and Zepbound are the same molecule with different indications and labeling.
  • 5Available as pre-filled single-dose pen injectors in the approved pharmaceutical form.
  • 6Weight regain is common after discontinuation — treatment is typically long-term.
  • 7Monitor for pancreatitis, thyroid C-cell tumors (boxed warning), and gallbladder events.

Reconstitution Guide

Standard Reconstitution

Vial Size

5 mg

Bacteriostatic Water

1 mL

Concentration

50 mcg

per 0.1 mL (10 units)

Step-by-Step Guide

1

Gather Materials

Tirzepatide vial, bacteriostatic water, alcohol swabs, insulin syringes.

2

Equilibrate Temperature

Remove the vial from storage and allow it to reach room temperature (5-10 minutes).

3

Sanitize

Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.

4

Draw Water

Draw 1 mL of bacteriostatic water into a syringe.

5

Add Water to Vial

Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.

6

Mix Gently

Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.

7

Store Properly

Refrigerate at Refrigerated (2-8°C / 36-46°F). Approved product: store in refrigerator until use.. Approved product: use by expiration date on pen. Compounded preparations vary..

Storage Temperature

Refrigerated (2-8°C / 36-46°F). Approved product: store in refrigerator until use.

Shelf Life

Approved product: use by expiration date on pen. Compounded preparations vary.

Important Notes

  • Mounjaro/Zepbound comes as pre-filled single-dose pen injectors; no reconstitution needed.
  • Compounded tirzepatide may require reconstitution from lyophilized powder.
  • If using compounded product, reconstitute with bacteriostatic water per provider instructions.
  • Do not freeze reconstituted solution.
  • Protect from light and extreme temperatures.

Safety & Side Effects

Reported Side Effects

  • !Nausea (most common, 12-33% depending on dose, usually improves with continued use)
  • !Diarrhea (12-21%)
  • !Vomiting (5-13%)
  • !Decreased appetite (expected pharmacological effect)
  • !Constipation (6-11%)
  • !Abdominal pain
  • !Injection site reactions (mild)
  • !Dyspepsia / acid reflux
  • !Fatigue
  • !Pancreatitis (rare but serious, seek immediate medical attention)
  • !Gallbladder events (cholelithiasis, cholecystitis)
  • !Boxed warning: thyroid C-cell tumors (observed in rodents, relevance to humans unknown)

Potential Interactions

  • Slows gastric emptying — may affect absorption of oral medications. Take time-sensitive oral medications 1 hour before tirzepatide.
  • May increase the risk of hypoglycemia when combined with insulin or sulfonylureas, dose reduction of these agents may be needed.
  • Oral contraceptives: switch to non-oral contraception or barrier method for 4 weeks after initiation and each dose escalation due to delayed gastric emptying.
  • Not recommended with other GLP-1 receptor agonists (overlapping mechanism, increased GI risk).
  • Caution with medications that cause nausea or GI effects (additive).
  • Monitor warfarin INR more closely due to potential absorption changes.

Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.

Research Studies

The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.

Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)

Jastreboff AM, et al.2022New England Journal of Medicine
PMID: 35658024

Landmark Phase III trial showing tirzepatide achieved 15 mg dose produced 22.5% mean weight reduction at 72 weeks in adults with obesity, with 63% of participants losing ≥20% body weight.

Tirzepatide versus semaglutide in type 2 diabetes (SURPASS-2)

Frías JP, et al.2021New England Journal of Medicine
PMID: 34170647

Head-to-head trial demonstrating tirzepatide superiority over semaglutide 1 mg for both HbA1c reduction and weight loss in type 2 diabetes, establishing the advantage of dual incretin agonism.

Tirzepatide for type 2 diabetes (SURPASS-1)

Rosenstock J, et al.2021New England Journal of Medicine
PMID: 34186022

Monotherapy trial showing tirzepatide produced HbA1c reductions of up to 2.07% and weight loss of up to 9.5 kg over 40 weeks, with 31-52% of patients achieving normoglycemia.

Tirzepatide and obstructive sleep apnea (SURMOUNT-OSA)

Malhotra A, et al.2024New England Journal of Medicine
PMID: 38912654

Showed tirzepatide significantly reduced the severity of obstructive sleep apnea as measured by AHI, demonstrating clinical benefits extending beyond weight loss and glycemic control.

GIP and GLP-1 receptor dual agonism: mechanistic basis for tirzepatide

Samms RJ, et al.2020Diabetes Care
PMID: 32699099

thorough review of the dual incretin mechanism, explaining how simultaneous GIP and GLP-1 receptor activation produces additive metabolic benefits beyond single-receptor agonists.

Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.

Frequently Asked Questions

Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist; a once-weekly injectable peptide that activates two incretin hormone receptors simultaneously. It is FDA-approved as Mounjaro (diabetes) and Zepbound (weight loss).

In the head-to-head SURPASS-2 trial, tirzepatide was superior to semaglutide 1 mg for both blood sugar control and weight loss. Tirzepatide's dual mechanism (GIP + GLP-1) appears to provide greater efficacy than GLP-1-only agonists like semaglutide.

In the SURMOUNT-1 trial, the average weight loss at the highest dose (15 mg) was 22.5% of body weight over 72 weeks. About 63% of participants lost 20% or more of their body weight. Results vary by individual.

Mounjaro and Zepbound contain the same molecule (tirzepatide) at the same doses. Mounjaro is approved for type 2 diabetes, while Zepbound is approved for chronic weight management. The distinction is primarily in indication and insurance coverage.

Nausea is the most common side effect and usually improves over time. Key strategies include slow dose escalation (stay at each dose for 4+ weeks), eating smaller meals, avoiding high-fat foods, staying hydrated, and not lying down immediately after eating. Your healthcare provider may adjust the escalation schedule.

Clinical trials show approximately 25-40% of weight lost is lean mass (typical for any weight loss method). Adequate protein intake (1.0-1.6 g/kg/day) and resistance training during treatment are strongly recommended to preserve muscle mass.

Weight regain is common after discontinuation. The SURMOUNT-4 trial showed participants who switched from tirzepatide to placebo regained approximately two-thirds of their lost weight over 52 weeks. Ongoing treatment is typically needed to maintain weight loss.

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Research & Educational Use Only

All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.

The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.