Peptide Name
Tirzepatide
Updated February 2026
Tirzepatide Dosing Protocol
Complete tirzepatide research dosing protocol with phase-by-phase titration schedule (2.5 mg to 15 mg), reconstitution math, side effect profile, and trial references.
Half-life
~5 days
Dose range
2.5 mg to 15 mg weekly
Status
FDA-approved
Developer
Eli Lilly and Company
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Quick Reference Card
Aliases
LY3298176, Mounjaro (T2D), Zepbound (obesity/OSA)
Category / Class
Metabolic - Dual Agonist (GIP / GLP-1)
Half-Life
~5 days
Dosing Frequency
Once weekly (subcutaneous injection)
Dose Range
2.5 mg - 15 mg per week
Common Vial Sizes
5 mg, 10 mg, 15 mg, 30 mg, 60 mg
Route of Administration
Subcutaneous (SubQ)
Regulatory Status
FDA-approved - Mounjaro for type 2 diabetes (May 2022); Zepbound for chronic weight management (November 2023) and moderate-to-severe obstructive sleep apnea with obesity (December 2024).
Developer
Eli Lilly and Company
Key Stat
SURMOUNT-1: Up to 22.5% body weight reduction at 72 weeks (15 mg). SURMOUNT-5: -20.2% vs -13.7% for semaglutide head-to-head at 72 weeks.
What Is Tirzepatide?
Tirzepatide (LY3298176) is an FDA-approved dual GIP/GLP-1 receptor agonist developed by Eli Lilly that simultaneously activates receptors for two key incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This dual mechanism distinguishes it from single-agonist compounds like semaglutide (GLP-1 only) and positions it between semaglutide and the investigational triple agonist retatrutide (GLP-1/GIP/Glucagon) in the incretin therapy landscape.
Structurally, tirzepatide is a 39-amino acid synthetic peptide engineered from the native GIP sequence. It is conjugated to a C20 fatty diacid moiety (eicosanedioic acid) via a hydrophilic linker at the lysine residue at position 20. This acylation enables high-affinity albumin binding in the bloodstream, extending its elimination half-life to approximately 5 days and supporting once-weekly subcutaneous dosing. Tirzepatide binds GIP receptors with affinity comparable to endogenous GIP while exhibiting approximately 5-fold lower affinity for GLP-1 receptors compared to native GLP-1.
Tirzepatide was first approved by the FDA in May 2022 under the brand name Mounjaro for the treatment of type 2 diabetes. It subsequently received FDA approval as Zepbound in November 2023 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity, and in December 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity. The SUMMIT trial (NEJM, 2024) demonstrated cardiovascular benefit in patients with heart failure with preserved ejection fraction (HFpEF) and obesity, and the SURPASS-CVOT cardiovascular outcomes trial is ongoing. As of February 2026, it is the first and only FDA-approved dual GIP/GLP-1 receptor agonist.
Tirzepatide is FDA-approved for specific indications. In the grey market research context, lyophilized research-grade tirzepatide is available in vial form. All information on this page is for educational and research reference purposes only.
How Tirzepatide Works: Dual Incretin Receptor Agonism
Tirzepatide's therapeutic effects arise from simultaneous activation of two receptor targets, each contributing complementary metabolic and appetite-regulating actions.
2-Pathway Mechanism Infographic
GIP Receptor (Glucose-Dependent Insulinotropic Polypeptide)
GIP receptors are expressed on pancreatic beta cells, adipose tissue, bone, and regions of the central nervous system. Tirzepatide activates GIP receptors with affinity comparable to endogenous GIP, making it a potent GIP agonist. GIP receptor activation enhances glucose-dependent insulin secretion from pancreatic beta cells, improves insulin sensitivity in adipose tissue by increasing lipoprotein lipase activity and adiponectin levels, and may contribute to appetite regulation through central nervous system signaling in brain regions that do not overlap with GLP-1 receptor expression. This complementary CNS distribution is hypothesized to contribute to tirzepatide's greater weight reduction versus GLP-1-only compounds.
GLP-1 Receptor (Glucagon-Like Peptide-1)
GLP-1 receptors are found on pancreatic beta cells, the gastrointestinal tract, and in the central and peripheral nervous systems. Tirzepatide activates GLP-1 receptors with approximately 5-fold lower affinity than native GLP-1 but still produces clinically meaningful effects. GLP-1 pathway activation delays gastric emptying (reducing postprandial glucose spikes), stimulates glucose-dependent insulin secretion, suppresses inappropriate glucagon release, and activates anorexigenic (appetite-suppressing) signaling pathways in the brain. This is the same pathway targeted by semaglutide (Ozempic/Wegovy).
The simultaneous activation of both GIP and GLP-1 pathways produces synergistic effects that exceed what either receptor achieves alone. In preclinical models, the combination produced greater weight reduction and metabolic improvement than GLP-1 receptor monoagonism. Clinically, this translates to superior glycemic control (HbA1c reductions of up to -2.30%) and greater weight loss (-22.5% at 72 weeks in SURMOUNT-1) compared to semaglutide. Tirzepatide also enhances first- and second-phase insulin secretion and improves insulin sensitivity, as demonstrated in hyperinsulinemic euglycemic clamp studies.
Tirzepatide Dosing Protocol & Titration Schedule
Phase 1 - Initiation
Weeks 1-4
2.5 mg once weekly
Starting dose for tolerability assessment. Not intended as a therapeutic dose for glycemic control or weight loss.
Phase 2 - Early Escalation
Weeks 5-8
5 mg once weekly
First maintenance dose. GI side effects (nausea) may begin. Meaningful glycemic and weight effects start.
Phase 3 - Mid Escalation
Weeks 9-12
7.5 mg once weekly
Transitional dose. Appetite suppression typically becomes more noticeable.
Phase 4 - Therapeutic Range
Weeks 13-16
10 mg once weekly
Second maintenance dose. Significant weight loss and HbA1c improvement expected.
Phase 5 - High Escalation
Weeks 17-20
12.5 mg once weekly
Transitional dose toward maximum. GI effects may recur during escalation.
Phase 6 - Maximum Studied Dose
Weeks 21+
15 mg once weekly
Maximum FDA-approved dose. 22.5% average weight loss at 72 weeks (SURMOUNT-1).
Important Titration Notes
Titration pacing matters. Escalation occurs in 2.5 mg increments at minimum 4-week intervals. Rushing escalation significantly increases the frequency and severity of GI side effects, particularly nausea and vomiting. Most GI adverse events occur during the dose-escalation period and decrease over time at each stable dose level.
Three maintenance doses: The FDA-approved maintenance doses are 5 mg, 10 mg, and 15 mg weekly. The 2.5 mg, 7.5 mg, and 12.5 mg doses serve as transitional escalation steps. Not all protocols escalate to 15 mg - dose is individualized based on tolerability and response.
Dose flexibility: If GI side effects are significant at a new dose level, remaining at the current dose for an additional 4 weeks before re-attempting escalation is a standard approach from clinical trial protocols.
Missed dose guidance: Per the Mounjaro prescribing information, if a dose is missed, it should be administered as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.
Steady state: With a 5-day half-life, steady-state plasma concentrations are achieved after approximately 4 weeks of once-weekly dosing, with approximately 1.6-fold accumulation.
Tirzepatide Reconstitution Guide
Vial Size: 5 mg
BAC Water: 1.0 mL
Concentration: 5,000 mcg/mL (5.0 mg/mL)
2.5 mg: 0.50 mL (50 units)
5 mg: 1.00 mL (100 units)
7.5 mg: N/A - exceeds vial
10 mg: N/A
15 mg: N/A
Vial Size: 10 mg
BAC Water: 1.0 mL
Concentration: 10,000 mcg/mL (10.0 mg/mL)
2.5 mg: 0.25 mL (25 units)
5 mg: 0.50 mL (50 units)
7.5 mg: 0.75 mL (75 units)
10 mg: 1.00 mL (100 units)
15 mg: N/A - exceeds vial
Vial Size: 10 mg
BAC Water: 2.0 mL
Concentration: 5,000 mcg/mL (5.0 mg/mL)
2.5 mg: 0.50 mL (50 units)
5 mg: 1.00 mL (100 units)
7.5 mg: N/A - exceeds vial
10 mg: N/A
15 mg: N/A
Vial Size: 15 mg
BAC Water: 1.5 mL
Concentration: 10,000 mcg/mL (10.0 mg/mL)
2.5 mg: 0.25 mL (25 units)
5 mg: 0.50 mL (50 units)
7.5 mg: 0.75 mL (75 units)
10 mg: 1.00 mL (100 units)
15 mg: 1.50 mL - full vial
Vial Size: 30 mg
BAC Water: 2.0 mL
Concentration: 15,000 mcg/mL (15.0 mg/mL)
2.5 mg: 0.17 mL (17 units)
5 mg: 0.33 mL (33 units)
7.5 mg: 0.50 mL (50 units)
10 mg: 0.67 mL (67 units)
15 mg: 1.00 mL (100 units)
Vial Size: 30 mg
BAC Water: 3.0 mL
Concentration: 10,000 mcg/mL (10.0 mg/mL)
2.5 mg: 0.25 mL (25 units)
5 mg: 0.50 mL (50 units)
7.5 mg: 0.75 mL (75 units)
10 mg: 1.00 mL (100 units)
15 mg: 1.50 mL - split draw
Vial Size: 60 mg
BAC Water: 4.0 mL
Concentration: 15,000 mcg/mL (15.0 mg/mL)
2.5 mg: 0.17 mL (17 units)
5 mg: 0.33 mL (33 units)
7.5 mg: 0.50 mL (50 units)
10 mg: 0.67 mL (67 units)
15 mg: 1.00 mL (100 units)
Reconstitution Step-by-Step
- Allow the lyophilized tirzepatide vial and bacteriostatic water to reach room temperature (5-10 minutes).
- Clean both vial stoppers with alcohol swabs and allow to air dry for approximately 10-15 seconds.
- Draw the calculated volume of bacteriostatic water using a sterile syringe.
- Inject water slowly down the inside vial wall. Do not spray directly onto the lyophilized powder.
- Gently swirl until dissolved (typically 1-3 minutes). Do not shake. The solution should be clear, colorless to slightly yellow, and free of visible particles.
- Label the vial with peptide name, concentration (mg/mL), and reconstitution date.
- Refrigerate at 2-8C (35.6-46.4F) and use within 28 days.
Tirzepatide Side Effects - What Clinical Trials Show
Tirzepatide's side effect profile is consistent with incretin-based therapies, with gastrointestinal events being the most common adverse effects. Importantly, these are dose-dependent and predominantly occur during the dose-escalation period.
Common gastrointestinal effects: Across the SURPASS and SURMOUNT clinical trial programs, GI adverse events were reported by 33% to 53% of tirzepatide-treated participants, compared to 19-22% on placebo. In the SURPASS-2 head-to-head trial against semaglutide (NEJM), nausea was reported in 17-22% of tirzepatide participants (vs 18% semaglutide), diarrhea in 13-16% (vs 12%), and vomiting in 6-10% (vs 8%). A meta-analysis across the SURPASS trials found pooled incidence rates of approximately 20% for nausea, 16% for diarrhea, and 9% for vomiting across all tirzepatide doses. Decreased appetite (7-9%) and dyspepsia (~7%) were also common. Most events were mild to moderate in severity and decreased over time at each stable dose level.
Dose-dependent pattern: GI adverse events increased with dose. A meta-analysis of 10 trials (6,836 participants) found that overall GI event rates were 39% at 5 mg, 46% at 10 mg, and 49% at 15 mg. Nausea and diarrhea were the most frequent events at every dose.
Cardiovascular effects: A modest resting heart rate increase of approximately 2-4 bpm has been observed with tirzepatide. The SUMMIT trial (NEJM, 2024) demonstrated cardiovascular benefit in HFpEF patients - a 38% reduction in the composite of cardiovascular death or worsening heart failure (HR 0.62; 95% CI 0.41-0.95). Tirzepatide also reduced systolic blood pressure by ~5 mmHg in the SUMMIT analysis. The SURPASS-CVOT trial is ongoing.
Injection site reactions: Reported in approximately 3-7% of participants across trials, typically redness, itching, or mild irritation at the injection site.
Discontinuation rates: Drug discontinuation due to adverse events was highest at the 15 mg dose (approximately 10%) and lower at 5 mg (approximately 5%). In SURMOUNT-1 (obesity, 72 weeks), overall discontinuation rates due to adverse events ranged from 4.3% (5 mg) to 7.1% (15 mg) vs 2.6% on placebo.
Contraindications: Tirzepatide carries a boxed warning for thyroid C-cell tumors based on rodent studies. It is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). It should not be used in patients with a history of pancreatitis. Gallbladder-related events (cholelithiasis, cholecystitis) have been reported.
Tirzepatide Clinical Trial Results
Jastreboff et al., NEJM 2022 (SURMOUNT-1)
Phase 3 • 72 weeks
2,539 adults with obesity, no diabetes
15 mg: -22.5% body weight; 10 mg: -21.4%; 5 mg: -16.0%. 96% of 10 mg and 15 mg groups lost >=5%.
Aronne et al., NEJM 2025 (SURMOUNT-5)
Phase 3b • 72 weeks
751 adults with obesity, no diabetes (head-to-head vs semaglutide)
Tirzepatide: -20.2% vs semaglutide: -13.7% (P<0.001). Waist circumference: -18.4 cm vs -13.0 cm.
Frias et al., NEJM 2021 (SURPASS-2)
Phase 3 • 40 weeks
1,879 adults with T2D (vs semaglutide 1 mg)
All tirzepatide doses superior to semaglutide. HbA1c: up to -2.30%; weight: up to -11.2 kg. Up to 92% reached HbA1c <7%.
Rosenstock et al., Lancet 2021 (SURPASS-1)
Phase 3 • 40 weeks
478 adults with T2D (monotherapy vs placebo)
All doses superior to placebo. Up to 52% achieved HbA1c <5.7% (non-diabetic range).
Dahl et al., JAMA 2022 (SURPASS-5)
Phase 3 • 40 weeks
475 adults with T2D + insulin glargine
HbA1c: -2.11% (5 mg) to -2.34% (15 mg). Weight: -5.4 to -8.8 kg. 85-90% reached HbA1c <7%.
Packer et al., NEJM 2024 (SUMMIT)
Phase 3 • 104 weeks median
731 patients with HFpEF + obesity
38% reduction in CV death or worsening HF (HR 0.62). KCCQ-CSS improved by +6.9 points vs placebo at 52 weeks.
Malhotra et al., NEJM 2024 (SURMOUNT-OSA)
Phase 3 • 52 weeks
469 adults with moderate-to-severe OSA + obesity
AHI reduced by 25.3-29.3 events/hour (vs 5.3-5.5 placebo). Weight loss: ~45-50 lbs vs 4-6 lbs.
Tirzepatide has one of the most extensive clinical development programs in the incretin therapy landscape. The SURPASS program (type 2 diabetes) enrolled more than 19,000 participants across 10 trials, leading to Mounjaro's FDA approval in May 2022. The SURMOUNT program (obesity) secured Zepbound's approval in November 2023 for weight management and December 2024 for obstructive sleep apnea. The SUMMIT trial, published in NEJM in November 2024, established cardiovascular benefit in obesity-related HFpEF. The SURPASS-CVOT cardiovascular outcomes trial (NCT04255433) is ongoing and expected to further define tirzepatide's long-term cardiovascular safety profile. The SURMOUNT-MMO study is evaluating long-term outcomes in adults with obesity.
Storage & Handling
Lyophilized (powder, sealed)
-20C (-4F) or below (freezer)
Long-term - up to 12+ months
Lyophilized (powder, sealed)
2-8C (35.6-46.4F) (refrigerator)
Several months
Lyophilized (powder, sealed)
Room temperature (during shipping)
Stable for several weeks - peptide powders tolerate short-term temperature fluctuations
Reconstituted (solution)
2-8C (35.6-46.4F) (refrigerator)
Use within 28 days (conservative recommendation)
Reconstituted (solution)
-20C (-4F) (frozen aliquots)
3-4 months
Protect reconstituted solutions from light. Do not freeze reconstituted tirzepatide - freezing damages the peptide structure and reduces potency. For long-term storage of unreconstituted powder, use single-use aliquots before freezing. Bacteriostatic water (0.9% benzyl alcohol) is preferred for multi-dose workflows; sterile water should only be used if the entire vial will be consumed in a single session.
Tirzepatide vs. Semaglutide vs. Retatrutide
Receptor Targets
Tirzepatide: GLP-1 + GIP (dual)
Semaglutide: GLP-1 only (single)
Retatrutide: GLP-1 + GIP + Glucagon (triple)
Half-Life
Tirzepatide: ~5 days
Semaglutide: ~7 days
Retatrutide: ~6 days
Dosing Frequency
Tirzepatide: Once weekly
Semaglutide: Once weekly
Retatrutide: Once weekly
Max Studied Dose
Tirzepatide: 15 mg/week
Semaglutide: 2.4 mg/week
Retatrutide: 12 mg/week
Peak Weight Loss (Trials)
Tirzepatide: -22.5% at 72 weeks (SURMOUNT-1)
Semaglutide: -15.8% at 68 weeks (STEP-1)
Retatrutide: -28.7% at 68 weeks (TRIUMPH-4)
FDA Status (Feb 2026)
Tirzepatide: Approved (T2D, obesity, OSA)
Semaglutide: Approved (T2D, obesity)
Retatrutide: Investigational - Phase 3
Head-to-Head vs Semaglutide
Tirzepatide: -20.2% vs -13.7% (SURMOUNT-5)
Semaglutide: -
Retatrutide: Not yet tested head-to-head
HFpEF Benefit
Tirzepatide: Yes - SUMMIT (HR 0.62)
Semaglutide: Yes - STEP-HFpEF
Retatrutide: Not yet studied
Unique Advantage
Tirzepatide: Dual agonism balances efficacy and tolerability; FDA-approved for 3 indications
Semaglutide: Longest clinical track record; CV outcomes data (SELECT trial)
Retatrutide: Triple agonism increases energy expenditure via glucagon; highest weight loss
Tirzepatide occupies a unique middle position in the incretin therapy landscape: FDA-approved and clinically validated like semaglutide, but with superior weight loss demonstrated head-to-head in SURMOUNT-5 (-20.2% vs -13.7% at 72 weeks). Retatrutide's triple agonism shows higher peak weight loss in Phase 2/3 data (-28.7%) but remains investigational as of February 2026.
These compounds are not interchangeable. Reconstitution math, dose ranges, and concentration targets differ significantly.
See the retatrutide protocol and semaglutide protocol for compound-specific guides.
Frequently Asked Questions - Tirzepatide
Q1: What is the starting dose of tirzepatide?
The starting dose of tirzepatide is 2.5 mg administered once weekly via subcutaneous injection for the first 4 weeks. This dose is intended for tolerability assessment and initiation, not as a therapeutic dose for glycemic control or weight management. After 4 weeks, the dose is escalated to 5 mg weekly, which is the first maintenance dose. Further escalation occurs in 2.5 mg increments at minimum 4-week intervals up to a maximum of 15 mg weekly, based on individual tolerability and response.
Q2: What is tirzepatide's half-life?
Tirzepatide has an elimination half-life of approximately 5 days (approximately 120 hours), as established by population pharmacokinetic analysis across 19 pooled studies. This extended half-life is enabled by its C20 fatty diacid conjugation, which promotes high-affinity albumin binding (99% protein bound). The 5-day half-life supports once-weekly dosing, with steady-state concentrations achieved after approximately 4 weeks of administration and approximately 1.6-fold drug accumulation.
Q3: How much weight can you lose on tirzepatide?
In the pivotal SURMOUNT-1 trial (NEJM, 2022) involving 2,539 adults with obesity and no diabetes, participants on 15 mg tirzepatide lost an average of 22.5% of body weight (approximately 52 lbs) at 72 weeks. The 10 mg group lost 21.4% and the 5 mg group lost 16.0%. In the head-to-head SURMOUNT-5 trial (NEJM, 2025), tirzepatide achieved -20.2% weight loss vs -13.7% for semaglutide at 72 weeks - demonstrating clear superiority over the leading GLP-1 monotherapy.
Q4: How do you reconstitute tirzepatide?
For research-grade lyophilized tirzepatide, add bacteriostatic water to the vial at a calculated volume to achieve your target concentration. A common approach: for a 30 mg vial, add 3.0 mL BAC water to produce a 10 mg/mL concentration. Inject water slowly down the inside vial wall, gently swirl (never shake), and refrigerate at 2-8C. Use within 28 days. For exact syringe units at any vial size or water volume, use the PepPal Reconstitution Calculator (https://www.peppal.app/calculator). See the reconstitution table above for common vial/dose combinations.
Q5: Is tirzepatide FDA-approved?
Yes. Tirzepatide is FDA-approved under two brand names. Mounjaro was approved in May 2022 as an adjunct to diet and exercise for glycemic control in adults with type 2 diabetes. Zepbound was approved in November 2023 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity, and in December 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity. It is the first and only dual GIP/GLP-1 receptor agonist with FDA approval.
Q6: What are the most common side effects of tirzepatide?
Gastrointestinal side effects are most common: nausea (17-22%), diarrhea (13-16%), vomiting (6-10%), decreased appetite (7-9%), and dyspepsia (~7%). These are dose-dependent and occur most frequently during the escalation period. A meta-analysis of 10 trials found overall GI event rates of 39% at 5 mg, 46% at 10 mg, and 49% at 15 mg. Most events are mild to moderate and decrease over time at stable doses. Discontinuation due to adverse events ranges from ~5% (5 mg) to ~10% (15 mg). Tirzepatide carries a boxed warning for thyroid C-cell tumors (rodent studies) and is contraindicated with MTC/MEN 2 history.
Q7: How does tirzepatide compare to semaglutide?
Tirzepatide is a dual GIP/GLP-1 agonist while semaglutide activates GLP-1 receptors only. In the head-to-head SURMOUNT-5 trial (NEJM, 2025), tirzepatide achieved significantly greater weight loss (-20.2% vs -13.7%) and waist circumference reduction (-18.4 cm vs -13.0 cm) than semaglutide at 72 weeks. In SURPASS-2 (T2D patients), all tirzepatide doses showed superior HbA1c and weight reductions versus semaglutide 1 mg. GI side effect profiles are generally similar between the two compounds.
Q8: What vial sizes are available for research-grade tirzepatide?
Research-grade lyophilized tirzepatide is commonly available in vial sizes of 5 mg, 10 mg, 15 mg, 30 mg, and 60 mg from grey market suppliers. The 30 mg vial is the most popular size for research protocols as it accommodates the full titration range (2.5-15 mg) from a single vial when reconstituted with an appropriate water volume.
Q9: How much bacteriostatic water should be added to tirzepatide?
The BAC water volume depends on your vial size and desired concentration. For a 30 mg vial, 3.0 mL of BAC water produces a 10,000 mcg/mL (10 mg/mL) concentration with straightforward dosing math: 2.5 mg = 25 units, 5 mg = 50 units, 10 mg = 100 units. For a 10 mg vial, 1.0 mL produces 10 mg/mL or 2.0 mL produces 5 mg/mL. Use the PepPal calculator (https://www.peppal.app/calculator) for custom configurations.
Q10: What is the maximum dose of tirzepatide studied?
The maximum FDA-approved dose is 15 mg once weekly. This was the highest dose evaluated across both the SURPASS (type 2 diabetes) and SURMOUNT (obesity) clinical trial programs. In SURMOUNT-1, the 15 mg dose produced 22.5% average body weight reduction at 72 weeks. In SURPASS-2, the 15 mg dose achieved HbA1c reductions of -2.30% at 40 weeks.
Q11: How should reconstituted tirzepatide be stored?
Reconstituted tirzepatide should be refrigerated at 2-8C (35.6-46.4F) and used within 28 days. Do not freeze reconstituted solution - freezing damages the peptide structure. Protect from light. Use bacteriostatic water (not sterile water) for multi-dose vials, as the benzyl alcohol preservative inhibits bacterial growth. Unreconstituted lyophilized powder can be stored long-term at -20C or for several months refrigerated.
Q12: What clinical trials has tirzepatide been studied in?
Tirzepatide has been evaluated in two major clinical trial programs. The SURPASS program (10 trials, 19,000+ participants) evaluated type 2 diabetes outcomes and led to Mounjaro's FDA approval. The SURMOUNT program evaluated obesity outcomes (SURMOUNT-1 through SURMOUNT-5) and led to Zepbound's approval for weight management and obstructive sleep apnea. The SUMMIT trial (NCT04847557, NEJM 2024) demonstrated cardiovascular benefit in HFpEF patients with obesity. The SURPASS-CVOT (NCT04255433) cardiovascular outcomes trial is ongoing.
Sources & Research
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." New England Journal of Medicine, 2022;387(3):205-216 Link.
- Frias JP, Davies MJ, Rosenstock J, et al. "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes." New England Journal of Medicine, 2021;385(6):503-515 Link.
- Aronne LJ, Horn DB, le Roux CW, et al. "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity." New England Journal of Medicine, 2025;393(1) Link.
- Packer M, Zile MR, Kramer CM, et al. "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity." New England Journal of Medicine, 2025;392(5):427-437 Link.
- Rosenstock J, Wysham C, Frias JP, et al. "Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial." The Lancet, 2021;398(10295):143-155 DOI: 10.1016/S0140-6736(21)01324-6.
- Dahl D, Onishi Y, Norwood P, et al. "Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial." JAMA, 2022;327(6):534-545 Link.
- Malhotra A, Grunstein RR, Fietze I, et al. "Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity." New England Journal of Medicine, 2024;391(13):1193-1205 DOI: 10.1056/NEJMoa2404881.
- Raj R, et al. "Adverse Events Related to Tirzepatide." Journal of the Endocrine Society, 2023;7(4):bvad016 Link.
- SURMOUNT-1. ClinicalTrials.gov Identifier: NCT04184622. Link.
- SURPASS-CVOT. ClinicalTrials.gov Identifier: NCT04255433. Link.
- SUMMIT. ClinicalTrials.gov Identifier: NCT04847557. Link.
- "Tirzepatide." Wikipedia. Link.
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View protocolDisclaimer & Affiliate Disclosure
Disclaimer: The information on this page is for educational and research reference purposes only. Tirzepatide is FDA-approved for specific medical indications (type 2 diabetes, chronic weight management, and obstructive sleep apnea) under the brand names Mounjaro and Zepbound. Research-grade lyophilized tirzepatide available from grey market suppliers is for research use only. No compounds discussed on this site are intended for unsupervised human consumption. This is not medical advice. Consult a qualified healthcare professional before considering any peptide protocol.
Affiliate Disclosure: This site contains affiliate links to vetted peptide suppliers. We may earn a commission at no extra cost to you. Our protocol content and editorial ratings are independent of affiliate relationships.