Tirzepatide (Mounjaro) - a novel Pharmacotherapeutic Agent for Obesity

Abstract

Obesity and its consequential morbidities are a major global burden. with Pakistan having a national obesity risk of  6.5/10.⁽¹⁾ Raised BMI (body mass index-an index of weight to height ratio) along with obesity is one  the  prime risk factors that lead to numerous other non-transmissible diseases like heart diseases, Type 2 diabetes, osteoarthritis and certain carcinomas (Breast, ovarian, colon, liver, prostate, gall bladder). Lifestyle interventions can only produce modest (~5-10%) weight loss, necessitating other antiobesity interventions. Therefore, pharmacological approaches to losing weight are in the limelight. The  U.S. (FDA) Food and Drug Administration has also authorized pharmacological treatment as a new treatment option to incorporate into weight management programme with concomitant dietary and physical behavioral remodeling in patients having 27 kg/m2 or higher BMI along with incidence of any of the following obesity-related comorbidities: T2DM, hypertension, or hypercholesterolemia ^(2).As of 2021 around 5 antiobesity  medications (AOMs) have been approved by FDA so far but a recent randomized,  placebo controlled double blind trial has incredibly unveiled the potential effects of tirzepatide as an antiobesity drug.

Tirzepatide (Mounjaro) is an exclusive and the only dual receptor agonist the mimicking actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and therefore referred as “twincretin”. This drug, originally used to treat T2DM, has now been incredibly effective in treating obesity. According to a recent randomized control trial, 85% of participants with a 5.0 mg dose, 89% participants with a 10 mg dose and 91% participants with a  15 mg dose showed a significant reduction in weight⁽³⁾ which is a corroborating evidence supporting tirzepatide as antiobesity drug. According to SURPASS-2 clinical trial, comparing efficacy of tirzepatide to semaglutide (a selective GLP-1 receptor agonist), tirzepatide was proven to reduce body weight and A1C levels more effectively than semaglutide demonstrating it to be better in treating not only diabetes but obesity⁽⁴⁾. The SURMOUNT-1 trial, depicting the efficacy of tirzepatide, showed significant weight reduction of up to 22.5 % in obese adults ⁽⁵⁾

Some of the adverse effects noted with its use were gastrointestinal events like nausea, vomiting and diarrhea. A few contraindications are gallbladder disease, pancreatitis, genetic predisposition of medullary thyroid carcinoma and MEN (multiple endocrine neoplasia) Type 2.

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