Dimitar Marinov, Ph.D.
Dimitar Marinov, Ph.D.Tirzepatide side effects are of significant interest to researchers due to the peptide's novel nature and immense potential, particularly in weight loss and glycemic control settings.
When interested in tirzepatide research, understanding the potential adverse effects is crucial to ensuring the safety of any future experiments.
This informative guide will break down the main side effects linked to tirzepatide according to the available research. Further, we provide essential information on appropriate dosing and administration to mitigate the main tirzepatide risks during research.
Keep reading to also learn about our most trusted source for obtaining research-grade tirzepatide online.
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What is Tirzepatide?
Tirzepatide (LY3298176) is a novel peptide and a first-in-class dual incretin mimetic. It was developed and patented in 2016 by the American pharmaceutical company Eli Lilly and Co [1].
The peptide works by stimulating the receptors for the hormones known as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) [2]. GIP and GLP-1 are incretins, which means they stimulate insulin secretion by the beta-cells in the exocrine pancreas.
Thanks to its dual GIP/GLP-1 action, tirzepatide is highly effective at stimulating insulin production and lowering blood sugar levels. In fact, it is considered superior at improving glycemic control compared to GLP-1 mimetics [3, 4].
The unprecedented effectiveness and favorable safety record of tirzepatide have secured its 2022 approval by the United States Food and Drug Administration (FDA) for improving glycemic control in type 2 diabetes (T2D) patients [1].
In addition, the peptide also activates GLP-1 and GIP receptors in tissues outside the exocrine pancreas, including the brain, the heart, white adipose tissue, the digestive tract, and several other organs [5, 6].
This is why tirzepatide appears to have broad therapeutic potential including weight loss, appetite suppression, cardioprotection, and more.
However, it is yet to be approved for any indications beyond glycemic control. As of writing, tirzepatide is FDA-approved only under the brand name Mounjaro for therapy in T2D patients.
In addition, non-prescription tirzepatide can be purchased by qualified scientists and laboratory professionals as a reference material for research purposes.
What Does Tirzepatide Do?
In this section, we discuss the range of effects and uses of this powerful GIP/GLP-1 co-agonist. While tirzepatide research is already indicated for use in type 2 diabetes, its weight loss and cardioprotective effects, while proven in a handful of studies, are still subject to investigation in clinical trials.
Improved Glycemic Control in T2D
Tirzepatide's FDA approval for type 2 diabetes was granted following completion of five phase-3 trials in the SURPASS global clinical development program.
SURPASS demonstrated that tirzepatide is safe and highly effective in improving glycemic control and inducing weight loss in T2D patients when used as a stand-alone therapy or as an add-on to other diabetes medicines [3, 7, 8, 9, 10].
In these five phase-3 trials, the efficacy of various tirzepatide doses were compared to a placebo, a GLP-1 receptor agonist (1mg semaglutide), and two long-acting insulin analogs.
The results showed that all doses (5mg, 10mg and 15mg/weekly) had a greater effect on glycemic control and glycated hemoglobin (HbA1c) levels when compared to placebo or the GLP-1 receptor agonist.
Furthermore, 10mg and 15mg tirzepatide had a greater HbA1c lowering effect than either of the insulin analogs [3, 7, 8, 9, 10].
The largest of the trials lasted 12 months and included over 3000 participants. The researchers reported that the mean HbA1c changes from baseline were -2·43% at 10mg tirzepatide and -2·58% at 15mg tirzepatide, compared to -1·44% with insulin glargine [9].
Tirzepatide for Weight Loss
The largest meta-analysis to date on the weight loss potential of tirzepatide included ten randomized controlled trials and a total of 9873 patients with type 2 diabetes and/or chronic weight conditions like obesity [11].
The results showed that tirzepatide significantly reduced body weight compared to all three alternatives: placebo, GLP-1 receptor agonists, and insulin.
A sub-analysis revealed that all three doses of tirzepatide (5mg, 10mg, and 15mg) effectively reduced body weight. Compared to the placebo, 15mg/weekly of tirzepatide appeared most effective as the subjects lost an average of -24lb (10.9kg) among all trials.
Interestingly, 10mg of tirzepatide was almost as effective as the sub-analysis revealed a -23lb (10.5kg) weight loss. On the other hand, 15mg tirzepatide led to significantly greater weight loss than 10mg when compared to GLP-1 receptor agonists.
Regarding safety, the incidence of adverse events and discontinuation rate of the study drug were greater in the tirzepatide group, but serious adverse events and hypoglycemia were lower.
Gastrointestinal adverse events such as diarrhea, nausea, vomiting, and decreased appetite were more common with tirzepatide than placebo or basal insulin but similar to GLP-1 receptor agonists [11].
Tirzepatide and Cardioprotection
Research reveals that tirzepatide is capable of improving diabetics’ lipoprotein profiles, which are major indicators of cardiovascular health and risk of heart disease.
One trial showed that tirzepatide dose-dependently decreased levels of apolipoprotein B (apoB) and apolipoprotein C-III (apoC-III) compared to placebo [12].
Specifically, tirzepatide at the 10mg and 15mg doses reduced large triglyceride-rich lipoprotein particles (TRLP) and small low-density lipoprotein particles (LDLP), thereby reducing overall atherogenic risk. Further, the reduction in apoC-III levels with tirzepatide was more pronounced in patients with high baseline triglycerides, which are considered a high-risk factor for heart disease [12].
More research is needed to investigate whether tirzepatide can lead to a clinically meaningful reduction in heart disease risk in patients with or without T2D.
Tirzepatide Side Effects | A-Z Guide
Researchers have evaluated tirzepatide's safety and efficacy in various populations. It has a favorable safety record based on phase 3 clinical trials and post-marketing surveillance.
Nevertheless, researchers should consider that tirzepatide can increase the risk of certain adverse effects. Below researchers will find information on the incidence of the most common tirzepatide side effects, contraindications, and other potential adverse reactions.
Common Tirzepatide Side Effects
As of writing, the latest meta-analysis on tirzepatide side effects included data from ten trials involving 6836 participants. The most commonly reported adverse events were gastrointestinal complaints, with the incidence being dose-dependent.
Nausea and diarrhea were the most frequent gastrointestinal side effects at all doses of tirzepatide. The total rates of gastrointestinal adverse events were 39%, 46%, and 49% for the 5mg, 10mg, and 15mg doses, respectively.
Nausea was the most common and occurred in 13.27%, 17.89%, and 24.08% of study participants taking the 5mg, 10mg, and 15mg doses, respectively. The rate of diarrhea was similar. The discontinuation rate of the drug due to adverse events was highest at the 15mg dose (10%).
Further, the incidence of mild hypoglycemia (blood glucose < 70mg/dL) was highest at the 10mg dose of tirzepatide, registering at 22.6% [13].
Based on the research to date, the risk of severe hypoglycemia increases only when tirzepatide is used as an add-on to other glucose-lowering agents.
Other common side effects have included indigestion, headache, constipation, abdominal pain, dyspepsia, vomiting, and injection site reactions, such as redness or itching at the injection site.
Serious Adverse Events Associated with Tirzepatide
Tirzepatide researchers have found that serious side effects tend to occur in less than 1% of test subjects and include cholelithiasis, cholecystitis, and pancreatitis. Interestingly, the incidence of these serious effects tended to decrease with higher doses.
Tirzepatide may also cause hypersensitivity reactions, which tend to affect 2-4% of the subjects in most studies [13].
Potential Risks and Contraindications of Tirzepatide Therapy
Experts advise pregnant and lactating women to avoid the use of tirzepatide. Additionally, studies in rats have shown an elevated risk of medullary thyroid carcinoma in rodents exposed to the peptide. It remains uncertain whether similar effects would occur in humans, though the research to date has not borne that out.
Nevertheless, a medical history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 constitutes a tirzepatide contraindication [14].
Tirzepatide Cycle | Safety Concerns
There is currently no established rationale for administering tirzepatide in successive cycles.
Tirzepatide has been studied only as a long-term therapy, as most studies have lasted from 12 to 72 weeks [11]. There is a lack of data showing that tirzepatide should be cycled, and the safety of administering the peptide in successive cycles is unknown.
As mentioned, the longest trial to date lasted 72 weeks. Interestingly, the researchers reported a higher incidence of nausea and constipation with the 10mg tirzepatide group (33.3%) compared to the 15mg group (31%) [15].
The incidence of constipation was also higher in the 10mg group, while the subjects on 15mg/weekly were much more likely to experience diarrhea.
There were no cases of thyroid cancer in either of the groups and the incidence of serious side effects was no greater than placebo [15].
Based on the available data, tirzepatide can be administered to test subjects safely for prolonged periods.
Tirzepatide Dosage Guide
When designing a dosing protocol for tirzepatide, researchers should consider important factors like the study objective, nature of test subjects, and intended duration.
Researchers should note that tirzepatide has a long half-life of five days due to its ability to bind to plasma albumin. It is designed for once-weekly subcutaneous administration [16, 17].
At the beginning of each study, researchers should start with a low weekly dose and titrate up to gauge the subject’s response and minimize side effects. It may take several months before achieving the full dose.
As a reference, researchers can rely on the latest data on tirzepatide dosing, which is based on clinical trials in patients suffering from T2D and/or chronic weight issues like obesity.
According to current tirzepatide dosing guidelines, the initial dose should not exceed 2.5mg once weekly for the first four weeks. It should then be increased at 2.5mg increments every four weeks until achieving the full weekly, which itself should not exceed 15mg/weekly [18, 19].
Based on the latest scientific data, here is a sample tirzepatide dosing protocol for weight loss:
- Tirzepatide Dose: Initiate at 2.5mg/weekly for the first four weeks of the study period, followed by an increase to 5mg/weekly in weeks 5-8, 7.5mg/weekly in weeks 9-12, and 10mg/daily in weeks 13-16. Depending on the test subject’s response and tolerance, consider increasing further to 12.5mg/weekly in weeks 17-20, and 15mg in weeks 21 and beyond.
- Frequency: Once weekly; subcutaneously.
- Study Duration: 24-72 weeks.
- Notes: Do not exceed a weekly tirzepatide dose of 15mg.
Where to Buy Tirzepatide Online? | 2024 Edition
To avoid the risk of receiving a low-purity peptide product, we advise researchers to buy only from vendors whose peptides are produced in accredited facilities and tested by a third-party laboratory for purity.
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Limitless Life
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Side Effects of Tirzepatide | Verdict
Tirzepatide is a novel, dual GIP and GLP-1 receptor agonist that has shown unprecedented efficacy in the management of T2D. It is also a promising weight loss agent for the management of conditions like overweight and obesity.
While generally well-tolerated, tirzepatide at higher doses may cause gastrointestinal symptoms, including nausea, diarrhea, constipation, and decreased appetite.
Researchers need to be aware of these potential side effects and take appropriate measures to mitigate or address these during experimentation.
When considering buying tirzepatide for research, we recommend sourcing the compound from a reputable supplier like our top-rated vendor.
Luis Daniel López Murillo, PhD