Tirzepatide (Mounjaro/Zepbound)
Overview
Mechanism of Action: Tirzepatide is a dual GIP (Glucose-dependent Insulinotropic Polypeptide) and GLP-1 (Glucagon-Like Peptide-1) receptor agonist. This means it acts on both the GIP and GLP-1 receptors, which are involved in insulin secretion and appetite regulation. By stimulating these receptors, tirzepatide enhances insulin secretion in response to meals, suppresses glucagon secretion, and slows gastric emptying, which can lead to reduced appetite and caloric intake.
Use in Diabetes Treatment: Tirzepatide is primarily used for the management of type 2 diabetes. It has been shown to effectively lower blood glucose levels and also contribute to significant weight loss in patients. Its dual action on GIP and GLP-1 receptors is thought to contribute to its effectiveness in controlling blood sugar levels.
Administration: Tirzepatide is administered through subcutaneous injection. The dosing frequency can vary depending on the formulation and the patient’s treatment plan.
Clinical Trials and Efficacy: Clinical trials have demonstrated that tirzepatide is effective in lowering HbA1c (a measure of blood sugar control over time) and aiding weight loss. It has been compared favorably with other GLP-1 receptor agonists and has shown significant benefits in terms of both glycemic control and weight reduction.
Side Effects: Common side effects of tirzepatide may include gastrointestinal symptoms such as nausea, diarrhea, reduced appetite, and vomiting. As with all medications, it’s essential for individuals to be aware of potential side effects and discuss them with their healthcare provider.
Approval and Availability: Tirzepatide had received regulatory approval in several regions, including the United States, for the treatment of type 2 diabetes. Its availability and specific indications can vary by region.
Potential for Weight Management: Given its significant effects on weight, tirzepatide is also being explored for use in weight management, similar to some GLP-1 receptor agonists like semaglutide.
Lilly is ramping up production - Big Time
Eli Lilly and Company is significantly investing in the manufacturing of tirzepatide. The company has announced plans to construct a new high-tech manufacturing site in Alzey, Rhineland-Palatinate, Germany, with an investment of $2.5 billion. This facility is intended to expand Lilly’s global parenteral (injectable) product and device manufacturing network, supporting increased demand for its medicines, including those for diabetes and obesity.
Additionally, Lilly has invested over $11 billion in its global manufacturing footprint over the past three years. This investment aims to ensure the safe and reliable supply of Lilly’s innovative medicines, addressing growth expected from potential new medicines to treat diabetes, obesity, Alzheimer’s disease, cancer, and autoimmune conditions.
Furthermore, the company plans to invest an additional $450 million to expand the capacity of a plant in North Carolina, U.S. This expansion is part of its efforts to boost production ahead of an expected increase in demand.
RECENT PAPERS from PubMed – November 11, 2023 – Tirzepatide and Cancer
- Tirzepatide as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer October 10, 2024CONCLUSION: Tirzepatide decreased both mouse weight and tumor growth via effects on metabolic and immune pathways in the EC tumors that differed between obese and lean mice. This novel weight loss treatment deserves further evaluation as an innovative strategy in the management of EC.Weimin Kong
- The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database August 14, 2024CONCLUSIONS: TZP was associated with an increased risk of specific AE. However, its safety profile was similar to that of GLP-1RA, without increased risk of pancreato-biliary AE, diabetic retinopathy, and medullary thyroid cancer.I Caruso
- A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma August 1, 2024The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic […]Byung-Kwan Jeong
- Tirzepatide use and the risk of cancer among individuals with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials June 26, 2024CONCLUSIONS: Preliminary evidence from our analysis suggests that tirzepatide may not affect the risk ofcancer among individuals with T2DM. However, our results should be interpreted with extra caution, based on the several limitations of our "hypothesis-generating" analysis Future, well-designed studies are warranted to answer this important research question.Djordje S Popovic
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) June 9, 2024Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma […]European Association for the Study of the Liver (EASL)
- Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity June 6, 2024The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits of GLP-1RA in select patient populations. In ongoing trials investigators are interrogating the efficacy of these agents for new indications, including metabolic liver disease, peripheral artery disease, Parkinson disease, and Alzheimer disease. […]Daniel J Drucker
- Obesity pharmacotherapy in older adults: a narrative review of evidence May 6, 2024The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced […]Alex E Henney
- Tirzepatide, a dual incretin analog, is a boon in metabolic syndrome: an editorial March 11, 2024No abstractMainak Bardhan
- Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials February 15, 2024CONCLUSION: Tirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.Wenting Cai
- Tirzepatide attenuates mammary tumor progression in diet-induced obese mice February 8, 2024We report for the first time an anticancer benefit of tirzepatide-a dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist-in a model of obesity and breast cancer in female mice. Long-term tirzepatide treatment induced weight loss, mitigated obesity-driven changes in circulating metabolic hormone levels, and suppressed orthotopic E0771 mammary tumor growth. Relative to tirzepatide, […]Elaine M Glenny
- Psychotropic Drug-Related Weight Gain and Its Treatment January 1, 2024Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. […]Roger S McIntyre
- G protein-coupled receptors and obesity January 1, 2024G protein-coupled receptors (GPCRs) have emerged as important drug targets for various chronic diseases, including obesity and diabetes. Obesity is a complex chronic disease that requires long term management predisposing to type 2 diabetes, heart disease, and some cancers. The therapeutic landscape for GPCR as targets of anti-obesity medications has undergone significant changes with the […]Alessandro Pocai
- Glucagon-like peptide agonists: A prospective review December 14, 2023CONCLUSION: In conclusion, this review underscores the significance of GLP-1RAs, with a specific focus on semaglutide, in the management of type 2 diabetes, obesity, and beyond. By synthesizing information on their mechanisms, pharmacokinetics, efficacy, and safety, this review provides valuable insights into the potential benefits these agents offer, contributing to the ongoing discourse in the […]Zamara Mariam
- Retatrutide showing promise in obesity (and type 2 diabetes) November 10, 2023INTRODUCTION: Obesity is a major risk factor for cardiovascular disease, diabetes, osteoarthritis, and some cancers. Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes.Sheila A Doggrell
- Effect on Hemoglobin A1c (HbA1c) and Body Weight After Discontinuation of Tirzepatide, a Novel Glucose-Dependent Insulinotropic Peptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist: A Single-Center Case Series Study October 6, 2023Introduction The purpose of this study was to examine changes in blood glucose levels and body weight after discontinuation of tirzepatide, a novel long-acting dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). Methods Nine subjects (five males, four females, age 54.3±5.4 years, body mass index 33.5±3.3 kg/m²) participating with type 2 […]Mitsunobu Kubota
- Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics September 27, 2023CONCLUSION: SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.Stephen J Nicholls
- Embracing the Pros and Cons of the New Weight Loss Medications (Semaglutide, Tirzepatide, Etc.) September 2, 2023PURPOSE OF REVIEW: The history of multiple weight loss medications has been a concerning paradox based on an increased cardiovascular risk despite significant reductions in adipose tissue and weight. A new class of weight loss medications could change this past narrative based on early preliminary results of cardiovascular risk (not events-still need to be determined) […]Mark A Moyad
- GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications August 17, 2023The incretin system is an essential metabolic axis that regulates postprandial metabolism. The two incretin peptides that enable this effect are the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide 1 (GLP-1), which have cognate receptors (GIPR and GLP-1R) on islet β cells as well as in other tissues. Pharmacologic engagement of the GLP-1R is […]Jonathan E Campbell
- The Potential Utility of Tirzepatide for the Management of Polycystic Ovary Syndrome July 29, 2023Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The metabolic dysfunction associated with PCOS increases the probability of developing type 2 diabetes (T2D), endometrial cancer, and cardiovascular disease. Research has shown that the metabolic features of PCOS may be improved by weight loss following treatment with glucagon-like peptide-1 receptor […]Alekya Devi Anala
- The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets June 5, 2023The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake to facilitate glucose tolerance¹. The GLP-1 receptor (GLP-1R) is an established drug target for the treatment of diabetes and obesity², whereas the therapeutic potential of the GIP receptor (GIPR) is a subject of debate. Tirzepatide […]Kimberley El