Introduction:
Obesity is a widespread and severe health issue affecting over 13 percent of adults globally. It reduces the quality of life and increases the risk of diseases like diabetes, heart problems, liver issues, and more, often leading to premature death. To address obesity, one of the main approaches is lifestyle-based therapy, which involves personalized diet, exercise, and counseling. However, this typically results in a modest weight loss of five to ten percent, which can offer some health improvements, but more significant weight loss is more beneficial.
Historically, most approved anti-obesity medications have only provided a modest weight reduction and some significant side effects. However, a recently approved medication called Semaglutide (Tirzepatide) has shown better results than older medications.
What Is Tirzepatide?
Tirzepatide, a newly approved medication by the FDA (Food and Drug Administration), is primarily intended for treating type 2 diabetes mellitus (T2DM). However, owing to its notable effectiveness in promoting weight loss, there is potential interest in its off-label use for managing obesity. It operates as a GLP-1 (glucagon-like peptide-1) agonist and a GIP (glucose-dependent insulinotropic polypeptide) agonist, aiming to provide similar benefits to GLP-1 drugs like Semaglutide. Currently, it is prescribed as a second-line treatment for diabetes, following a pattern similar to GLP-1 medications, and it is administered via a once-weekly subcutaneous injection. The FDA approved Tirzepatide in May 2022.
Tirzepatide marks a significant milestone as the first medication with dual action on GIP and GLP-1 receptors, designed for treating type 2 diabetes, obesity, and nonalcoholic steatohepatitis. This groundbreaking GLP-1 or GIP receptor agonist gained FDA approval to enhance blood sugar management in adults with T2DM alongside diet and exercise. Notably, Tirzepatide demonstrated superior efficacy in lowering hemoglobin A1C levels compared to other medications.
How Does Tirzepatide Work?
Tirzepatide, a synthetic peptide composed of 39 amino acids, is a dual agonist for the gastric inhibitory polypeptide and glucagon-like peptide receptors. It stimulates insulin release from the pancreas, effectively reducing hyperglycemia. Additionally, Tirzepatide boosts adiponectin levels. Its unique dual agonist activity substantially reduces hyperglycemia compared to using GLP-1 agonists alone, and it also helps lower appetite.
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It boasts an approximate 80 percent bioavailability, with peak serum levels achieved anywhere from eight to 72 hours after administration.
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Tirzepatide exhibits a mean apparent steady-state volume of distribution of roughly 10.3 liters. It binds strongly to plasma albumin, with a 99 % binding rate.
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Following injection, the peptide structure undergoes proteolytic cleavage. Additionally, the C20 fatty diacid composition experiences beta-oxidation and amide hydrolysis.
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Tirzepatide has a half-life of five days, allowing for once-weekly dosing. It is eliminated through urine and feces in metabolite forms.
How Can Tirzepatide Help With Obesity?
Tirzepatide has emerged as a promising option for obesity management. While initially developed and approved for type 2 diabetes, its potent effects on weight loss have garnered interest in its off-label use for obesity. It works as the following:
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Weight Reduction: Tirzepatide has shown weight loss benefits in clinical trials. It operates as a dual agonist for the GLP-1 and GLIP receptors, which helps reduce appetite and food intake while promoting a feeling of fullness. This combination effect leads to substantial weight loss.
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Metabolic Improvements: Tirzepatide can improve metabolic parameters in addition to weight loss. It helps control sugar levels, reduces insulin resistance, and may lower the risk of developing obesity-related comorbidities, such as type 2 diabetes and cardiovascular disease.
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Comprehensive Treatment: Tirzepatide is often considered a part of a comprehensive obesity management plan. This plan typically includes dietary modifications, increased physical activity, and behavioral counseling. Tirzepatide complements these lifestyle changes to enhance weight loss results.
Why Is Tirzepatide Used in Obesity Treatment?
Achieving and maintaining significant weight reduction is the main objective of obesity treatment. Numerous trials have showcased the promising impact of Trizepatide on weight control in individuals with type 2 diabetes. The effectiveness of Trizepatide in achieving meaningful weight loss is studied under SURMOUNT trials. In this trial, treatment allocation is based on factors related to the potential impact of diabetes therapy on weight. The ultimate objective in weight management is to sustain the lost weight over the long term. However, achieving this goal is often hindered by a multitude of factors. Current guidelines suggest incorporating Anti-obesity medication for individuals who have responded well to lifestyle interventions but still need further weight reduction or struggle to maintain lost weight.
In a recent trial, Tirzepatide demonstrated significant improvement in cardiovascular and metabolic risk factors, such as waist circumference, insulin levels, lipid profiles, and blood pressure, compared to a placebo group. People treated with Tirzepatide experienced a substantial reduction in fat mass, which was about three times greater than the reduction in lean mass, leading to overall improved body composition. This fat-to-lean mass ratio aligns with results seen in lifestyle-based and surgical treatments for obesity.
Regarding safety, the tripeptide profile was consistent with previous findings in clinical trials for type 2 diabetes and similar to other medications of the same class. As is typical for such medications, mild-to-moderate gastrointestinal side effects were most commonly reported, especially during the initial dose-escalation phase. Compared with other medications like Semaglutide and Dulaglutide, Tirzepatide at minimal dose showed dose-dependent weight reduction, surpassing the weight loss observed with their selective GLP-1 receptor agonists. The FDA granted Trizepatide a ‘fast-track’ designation for evaluation as a treatment for obesity and being overweight. It is approved Trizepatide as an adjunct therapy, in combination with diet and exercise, for improving glycemic control in adults with type 2 diabetes.
What Are the Adverse Effects of Tirzepatide?
Some common adverse effects are:
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Nausea.
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Diarrhea.
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Vomiting.
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Abdominal discomfort.
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Hypoglycemia (low blood sugar levels).
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Injection site reactions like itchiness, redness, or swelling.
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Undesired weight loss.
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Pancreatitis (inflammation of the pancreas-rare).
Tirzepatide contains a boxed warning due to its increased cancer risk, hypersensitivity reactions, hypoglycemia, and medullary thyroid carcinoma.
Conclusion:
Tirzepatide has shown promise as a treatment option for individuals with type 2 diabetes and obesity, significantly improving cardiovascular and metabolic risk factors, including body composition and glycemic control. While it can bring about positive outcomes, it is essential to be aware of the potential side effects, although they are rare. Tirzepatide should be used only after consulting a doctor who can assess an individual’s health and needs and monitor side effects. The FDA has approved Tirzepatide for obesity treatment due to its potential avenue for improving metabolic health and overall well-being under medical supervision.
