Description

Tirzepatide Peptide

 

CAS Number	2023788-19-2
Other Names	LY3298176, GIP/GLP-1 RA, Mounjaro, CHEBI:194186, LY-3298176,
IUPAC Name	20-[[(1R)-4-[2-[2-[2-[2-[2-[2-[[(5S)-5-[[(2S)-5-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-2-methylpropanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-2-methylpropanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[2-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[(2S)-2-[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-20-oxoicosanoic acid
Molecular Formula	C₂₂₅H₃₄₈N₄₈O₆₈
Molecular Weight	4813
Purity	≥99% Pure (LC-MS)
Liquid Availability	N/A
Powder Availability	5 milligrams, 10 milligrams (lyophilized/freeze-dried)
Storage Condition	Store cold, keep refrigerated. Do NOT freeze.
Terms	All products are for laboratory developmental research USE ONLY. Products are not for human consumption.

**Important Information: Each peptide comes lyophilized/freeze-dried and must be reconstituted with Bacteriostatic Water in order to be dispensable in liquid form.

Watch How To Reconstitute Peptide Video Here

What is Tirzepatide?

Tirzepatide is a 39-amino acid synthetic peptide that exhibits agonistic activity at both the GLP-1 and the glucose-dependent insulinotropic polypeptide (GIP) receptors. The peptide is composed of a bioactive N-terminal GIP sequence and an exenatide-like C-terminal sequence. In order to extend the half life of the drug, the combined sequences are conjugated to a fatty acid chain to promote binding with albumin.

 

Main Research Findings

1) Varying doses of tirzepatide were able to successfully reduce body weight in test subjects with a BMI of 30 or more.

2) Administration of tirzepatide successfully lowered the weight of test subjects diagnosed with type 2 diabetes and obesity.

3) Treatment with tirzepatide results in a significant improvements in glycemic control after 40 weeks of subcutaneous administration of the peptide

 

Selected Data

1) The research team of Jastreboff et. Al examined the efficacy of a once-weekly subcutaneous injection of tirzepatide in obese patients who were not diagnosed with type 2 diabetes. Participants were included in the study if they were 18 years of age or older with a BMI of 30 or more, or a BMI of 27 with a weight-related comorbidity (hypertension, dyslipidemia, cardiovascular disease, etc.). Participants of the study were excluded if they were diagnosed with diabetes, underwent previous surgery for obesity or had a planned obesity-related surgery, or experienced a change in body weight greater than 5 kg, within 90 days of the screening. After meeting the necessary criteria the participants went through a 2-week screening period followed by random assignment in a 1:1:1:1 ratio. The test subjects were then administered either a placebo compound, or experimental doses of tirzepatide varying from 5, 10, or 15 mg [1].

Each treatment was administered once-weekly via subcutaneous injection over the course of a 72 week treatment period. The research team followed a dose escalation procedure that lasted up to 20 weeks. Tirzepatide was initiated at a dose of 2.5 mg and was increased by 2.5 mg every 4 weeks until each group reached their assignment maintenance dosage. The peptide was meant to be used in addition to other lifestyle interventions such as lifestyle counseling sessions led by a variety of dieticians and qualified health care professionals to assist the participants in adhering to a balanced diet and increased activity levels. All test subjects that were not deemed prediabetic during their baseline assessment proceeded to a 4-week safety follow-up period after the 72-week experimental treatment period ended. If test subjects were deemed prediabetic during their baseline assessment they proceeded to an additional 2-year trial treatment period.

The primary endpoints assessed through this study were the percentage change in body weight from baseline to week 72, as well as a reduction in body weight of 5% or more by week 72. The secondary endpoints assessed included the reduction in body weight of 10%, 15%, and 20% or more at week 72. Additional secondary endpoints included the change in waist circumference, systolic blood pressure, physical function, and fasting lipid and insulin levels from baseline to week 72. It is also important to mention that a subgroup of 255 underwent dual-energy x-ray absorptiometry in order to assess total body-fat mass and closely observe changes in body composition from baseline to week 72 [1].

2) Using combined data gathered from clinical trials, a systematic review and meta-analysis was performed by the research team of Tang et. Al in order to examine the clinical efficacy and safety of tirzepatide in a sample of people diagnosed with type 2 diabetes. First and foremost, it was established that the researchers both reported and executed their review and analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. 12 week long randomized control trials were included in the initial assessment phase in order to assess and compare the efficacy and safety of tirzepatide in comparison to a placebo compound or other hypoglycemic treatments in participants. Inclusion criteria required participants to be at least 18 years old and diagnosed with type 2 diabetes according to the World Health Organization or the American Diabetes Association criteria [2].

The primary outcome of efficacy measured in the study was the change in HbA1c levels in comparison to baseline values. The secondary outcomes of efficacy included proportion of participants with HbA1c levels of less than 7.0%, less than 6.5%, or less than 5.7%, fasting serum glucose, body weight changes of greater than 5%, greater than 10%, or greater than 15%, fasting lipid profile, blood pressure, HOMA2-IR , and the occurrence of adverse events leading to hypoglycemia, gastrointestinal events, pancreatitis, or a major adverse cardiovascular event-4. It is important to mention that severe hypoglycemia in the participants was marked as the onset of cognitive impairments that ultimately resulted in the need for assistance in the active intake of various resuscitation measures such as carbohydrates and glucose [2].

3) The goal of the study conducted by Dahl et. Al was to examine how a once-weekly subcutaneous administration of tirzepatide would affect glycemic control in patients with type 2 diabetes in comparison to a placebo compound or titrated insulin glargine. Inclusion criteria for the participants included adults with a type 2 diabetes diagnosis, a baseline HbA1x of 7% to 10.5%, and a BMI of at least 23 while receiving once-daily doses of insulin glargine, either with or without metformin. Participants were excluded if there was the presence of type 1 diabetes detected, if they had a history of pancreatitis, proliferative diabetic retinopathy, nonproliferative diabetic retinopathy with acute treatment, diabetic maculopathy, hepatitis, gastroparesis, hypoglycemia unawareness, abnormal glomerular filtration rate, or the use of any antihyperglycemic medication 3 month prior to the initial start date of the study. Following screening the patients were randomized in a 1:1:1:1 ratio and administered either 5 mg, 10 mg, or 15 mg of tirzepatide, or a placebo compound of the same volume. The treatments were administered once-weekly via subcutaneous injection over an experimental period of
40 weeks [3].

The first four weeks of the study included a 4-week insulin stabilization period, followed by a 36-week insulin titration period while the experimental treatment or placebo compound were administered once a week using single-dose pens. All of the test subjects continue to receive a 100 U/mL insulin glargine once a day throughout the 40 week treatment period while closely measuring fasting blood glucose. The insulin glargine dose remained unchanged for the first 4 weeks of treatment in order to lower the risk of a hypoglycemic episode. For the remainder of the treatment period, test subjects of all groups were instructed to self-adjust their insulin dosage as needed, in response to their self-measured blood glucose values collected multiple times per day. In order to enhance gastrointestinal tolerability of tirzepatide the doses were gradually increased starting at a 2.5 mg dose that was advanced by 2.5 mg every 4 weeks until the target dose for each patient was reached. It is also important to mention that any participants using metformin at the beginning of the study were allowed to continue medication use as needed. Rescue therapy using glucose-lowering agents was only permitted in accordance with strict experimental protocol.

The primary efficacy endpoint measured in this study was the change in HbA1c levels from baseline to week 40 after 5 mg, 10 mg, and 15 mg doses of tirzepatide were administered to the test subjects. Secondary outcomes measured included the mean change from baseline in HbA1c levels as well as changes in body weight greater than 5%, 10%, or 15%, fasting serum glucose, and the comparison between the percent of patients the achieved HbA1c levels less than 7.0% and the percent of patients that achieved HbA1c levels less than 5.7%. The research team also recorded the daily mean change in the average 7-point self-monitored blood glucose and insulin glargine dose as well as the mean change in fasting lipids, BMI, and waist circumference. It is important to note that any significantly symptomatic occurrences of hypo- or hyperglycemia were reported by the researchers [3].

 

Discussion

1) Out of the 2539 participants included in the study conducted by Jastreboff et. Al, 86.0% completed the primary trial treatment period while 81.9% accurately adhered to the treatment as assigned. The various baseline values collected from each participant were similar; the mean age of the subjects was 44.9 years, primarily white and female; the mean body weight was 104.8 kg while the mean BMI was 38 and mean waist circumference was 114.1 cm. By week 72, the experimental group receiving 5 mg doses of tirzepatide experienced a -15.0% decrease in body weight, the 10 mg treatment group experienced a -19.5% decrease in body weight, and the 15 mg treatment group experienced a 20.9% decrease in body weight. This was in comparison to the placebo group that only experienced a -3.1% reduction in body weight. Significant weight loss effects of tirzepatide were apparent in the test subjects as soon as 20 weeks into the 72 week experimental treatment period.

The average change in weight at week 72 after treatment with tirzepatide was -16%. The subjects treated with 5 mg of the peptide experienced a reduction in weight by 16.1 kg; the subjects treated with 10 mg of the peptide experienced a 22.2 kg reduction in weight, and the 15 mg treatment group lost an average of 23.6 kg. The average weight loss observed in the placebo group was only 2.4 kg. Additionally, 85%, 89%, and 91% of the patients in the 5 mg, 10 mg, and 15 mg tirzepatide treatment groups, respectively, had a reduction in weight loss of 5% or more by week 72. In comparison to the placebo group, a larger proportion of the subjects receiving an active dose of tirzepatide experienced a weight loss of 10%, 15%, and 20% or more [1].

In regards to the secondary endpoints measured, tirzepatide elicited significant benefits in respect to changes in waist circumference, blood pressure, lipid levels and fasting insulin levels. By week 72 of the study, 95.3% of the study participants deemed prediabetic at baseline had returned to normoglycemic levels. This was compared to this placebo group where only 61.9% of study participants returned to normoglycemic levels. The reduction of total body fat was an average of 33.9% in the participants treated with varying doses of tirzepatide, in comparison with an average of 8.2% total body fat loss recorded in the placebo group. Through the use of dual-energy x-ray absorptiometry the research team was able to determine that the ratio of total fat mass to total lean mass decreased from 0.93 at baseline to 0.70 after 72 weeks of treatment with tirzepatide. Again, this was compared to the ratio of total fat mass to total lean mass measured in the placebo group that only decreased from 0.95 at baseline to 0.88 after 72 weeks of treatment [1].

Figure 1: changes in (A) overall percent change in body weight from baseline, (B) percent change in body weight by week, (C) participants who met the weight-reduction targets (treatment-regimen estimand), and (D) participants who met the weight-reduction targets (efficacy estimand).

2) The meta-analysis performed by the research team of Tang et. Al compared and related various studies investigating the correlation between administration of tirzepatide and reduced levels of HbA1c, body weight, and blood pressure. Starting with HbA1c levels, all of the studies included in the meta-analysis reported a significant change in levels of HbA1c from baseline. When comparing all experimental groups and all placebo groups included in the meta-analysis, an average of 62.6% of participants administered tirzepatide achieved an HbA1c target level of less than 7%, while 41.2% of the participants administered a placebo compound achieved the target level. Additionally, an average of 56.2% of all participants administered tirzepatide achieved an HbA1c target level of less than 6.5%, compared to only 27.6% of the participants administered a placebo compound [2].

In all subjects treated with tirzepatide, body weight decreased across all groups involved in the meta-analysis. The average change in body weight in the experimental group ranged from -7.25 kg to -10.36 kg and from 2.3 kg to -5.7kg in the control group. The mean treatment differences versus the control differences were found to range from -3.66 kg to -12.66 kg. The reduction of body weight was observed regardless of whether tirzepatide was administered to the test subject as monotherapy or add-on therapy. All of the studies included in the meta-analysis included the number of participants that achieved greater than a 5%, 10%, or 15% reduction in body weight. The research team mentioned that the percentage of patients that achieved the target levels was significantly higher in the groups treated with tirzepatide in comparison to the control groups. It is also important to note that several of the studies included in the meta-analysis experienced a change in blood pressure. In comparison to the patients treated with a placebo compound, administration of tirzepatide resulted in a decrease in both systolic blood pressure and diastolic blood pressure, regardless of whether the peptide was used as a monotherapy or an add-on therapy [2].

3) The results of the study conducted by Dahl et. Al reported that out of the 586 patients assessed for eligibility, 475 were able to successfully receive administration of a treatment dose while 451 (94.9%) participants completed the 40-week treatment period. At week 40, the patients receiving a 10 mg dose of tirzepatide experienced a -2.40% mean change from baseline in HbA1c levels. The patients receiving a 15 mg dose of the peptide experienced a -2.34% mean change from baseline. These results were compared to the placebo group that only had a -0.86% mean change from baseline. The research team also measured the amount of patients receiving an experimental dose of tirzepatide that achieved the predetermined target levels of 7%, 6.5%, and 5.7%. In comparison to the placebo group, a significant proportion of test subjects administered 5 mg, 10 mg, and 15 mg doses of the peptide achieved a target HbA1c level of less than 7.0%, while participants in the 10 mg and 15 mg treatment groups were able to reach the target level of less than 5.7% [3].

Figure 2: (A) Change in HbA1c levels from baseline in response to varying treatment dosages of tirzepatide. (C) The proportion of patients that achieved the HbA1c target levels following administration of varying dosages of tirzepatide.

In addition to a reduction in HbA1c levels, by week 40 tirzepatide caused a significant decrease in the mean fasting serum glucose levels. Fasting serum glucose decreased by -58.2 mg/dL in the 5 mg treatment group, -64.0 mg/dL for the 10 mg treatment group, and -62.6 mg/dL for the 15-mg dose. These results were compared to the test subjects administered a placebo compound that experienced a mean change in fasting serum glucose levels of only -39.2 mg/dL. Administration of tirzepatide also led to a dramatic reduction in body weight from baseline levels. The test subjects included in the 5 mg treatment group experienced a -5.4 kg mean change in body weight, a -7.5 kg mean change in body weight was observed in the 10 mg treatment group, and finally, a -8.8 mean change in body weight in the 15 mg treatment group. After 40 weeks these values were compared to the mean change in body weight of the placebo group that experienced a mean change in body weight of 1.6 kg [3].

Figure 3: (D) Changes in fasting serum glucose from baseline to week 40 across different treatment groups. (E) Changes in body weight from baseline to week 40 across treatment groups

It is important to mention that the mean daily insulin glargine dose decreased from baseline to week 4 throughout all of the treatment groups. At the end of the 40 week experimental treatment period the mean change in insulin dose from baseline in the 5 mg treatment group was 13%, 8.1% in the 10 mg treatment group, and -11.4% in the 15 mg treatment group. These values were compared to the placebo group that experienced a 75.0% mean change in insulin dosage from baseline. All treatment doses of tirzepatide were associated with a statistically significant improvement in levels of total cholesterol, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Finally, after administration of the peptide the average change in systolic blood pressure ranged from-6.1 to -12.6 mmHg while the average changes in diastolic blood pressure ranged from -2.0 to -4.5 mmHg. These values were compared to the placebo group that only experienced a -1.7 mmHg and 2.1 mmHg decrease in systolic and diastolic blood pressure, respectively [3].

Figure 4: Change in insulin glargine dose from baseline across treatment groups.

 

Disclaimer

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

 

Citations

[1] Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PMID: 35658024.

[2] Tang Y, Zhang L, Zeng Y, Wang X, Zhang M. Efficacy and safety of tirzepatide in patients with type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Oct 28;13:1016639. doi: 10.3389/fphar.2022.1016639. PMID: 36569320; PMCID: PMC9774036.

[3] Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á. 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 Feb 8;327(6):534-545. doi: 10.1001/jama.2022.0078. PMID: 35133415; PMCID: PMC8826179.

PEPTIDES PREFER THE COLD
Keep peptide vials refrigerated at all times to reduce peptide bond breakdown. DO NOT FREEZE. Most peptides, especially shorter ones, can be preserved for weeks if careful.
Always swab the top of the vial with an alcohol wipe, rubbing alcohol or 95% ethanol before use.
Before drawing solution from any dissolved peptide vial, fill the pin with air to the same measurement you will be filling with solution, ie. if you plan to take 0.1 ml, first fill the pin with 0.1ml of air, push the air into the vial, and then draw the peptide back up to the 0.1 ml marker. Doing so will maintain even pressure in the vial. Always remember to remove air bubbles from the pin by flicking it gently, pin side up, and pushing bubbles out. In addition, push out a tiny amount of solution to ensure there is no air left in the metal tip.

ONLY MIX WITH STERILE BACTERIOSTATIC WATER
The purity and sterility of bacteriostatic water are essential to prevent contamination and to preserve the shelf-life of dissolved peptides.
Push the pin through the rubber stopper at a slight angle, so that you inject the bacteriostatic water toward the inside wall of the vial, not directly onto the powder.
Lyophilized peptide should be stored at -20°C (freezer), and the reconstituted peptide solution at 4°C (refrigerated). Do not freeze once reconstituted.
NEVER SHAKE A VIAL TO MIX.

Air bubbles are unfavorable to the stability of proteins.

Tirzepatide is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.

 

 

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09-09-2023-Umbrella-Labs-Tirzepatide-Certificate-Of-Analysis-COA.pdf

 

 

VIEW CERTIFICATES OF ANALYSIS (COA)

 

Additional information

Size	5 Milligrams, 10 Milligrams