Breakthrough Treatments: Semaglutide and Tirzepatide
Semaglutide (Wegovy®) and Tirzepatide (Zepbound®) have emerged as effective peptide-based drugs for weight management, with FDA approvals for chronic weight management and obesity treatment, respectively. Both drugs, initially developed for type 2 diabetes, are injectable and work by increasing satiety through the regulation of appetite-sensing neurocircuits.
Comparative Efficacy: Semaglutide vs. Tirzepatide
Clinical studies and meta-analyses suggest that Tirzepatide may offer greater weight loss (up to 22%) compared to Semaglutide (15-18%). Both drugs share similar gastrointestinal side effects, such as nausea, due to their overlapping molecular modes of action.
Innovative Monotherapies and Combination Therapies
The future of obesity medications includes novel monotherapies, drug combination concepts, and dual/triple hormone receptor agonists. Early clinical data indicates that targeting more than one peptide receptor could enhance weight loss efficacy and cardiovascular benefits, while also aiming to mitigate common side effects like nausea.
Emerging Injectable Obesity Pharmacotherapies
Pharmaceutical companies are developing long-acting amylin analogues and injectable dual GLP-1 receptor and glucagon receptor agonists, among others, to differentiate from currently approved weight loss medications. These include Cagrilintide, AZD6234, Petrelintide, and GUBamy, with several in phase-2/3 clinical trials.
Advancements in Oral Drug Formulations
The development of oral medications, such as an oral semaglutide formulation (Rybelsus®), is set to change the obesity treatment landscape by providing alternative options. Non-peptide once-daily oral GLP-1 receptor agonists are also in clinical development.
Sarcopenia and Its Impact on Anti-obesity Drug Development
Sarcopenic obesity, characterized by the co-existence of obesity and sarcopenia, poses a public health concern. The pharmaceutical industry is focusing on developing drugs that promote sustainable and healthy weight loss while preventing or reversing muscle mass loss.
Key Endpoints in Translational Diet-induced Obese Rodent Models
Diet-induced obese (DIO) mice and rats serve as standard translational obesity models in preclinical drug discovery, with major outcomes including body weight and adiposity. These models help characterize the efficacy of weight loss drugs like Semaglutide and Tirzepatide.
Preclinical Mode-of-action (MoA) Studies
Anti-obesity medications vary in their mode of action, with some suppressing appetite and others increasing energy expenditure. Food intake serves as an important endpoint in assessing potential anti-obesity efficacy.
Gubra’s Expertise: Profiling and Developing Anti-Obesity Drugs
Gubra, a leading Contract Research Organization, specializes in obesity pharmacology and peptide drug discovery. With over 16 years of experience, Gubra has profiled numerous anti-obesity drug candidates and is involved in significant research collaborations and clinical trials, including the development of GUBamy, a long-acting amylin agonist analogue.
