Weight Loss Drugs Enter the Era of Precision Multi-Target Therapies with abinScience Metabolic Research Tools

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Multi-Target Synergistic Agonists

While GLP-1-based drugs have shown efficacy in weight management, challenges such as efficacy plateaus, poor tolerability in some individuals, and side effects like nausea persist. As a result, multi-target synergistic agonists have emerged as a promising direction for drug development. Current research focuses include:

1. GLP-1 + GIP: Tirzepatide

Glucose-dependent insulinotropic polypeptide (GIP) enhances insulin secretion and improves β-cell function, complementing GLP-1’s effects while reducing gastrointestinal side effects. Tirzepatide, developed by Eli Lilly, is considered an advanced version of GLP-1 agonists. Approved by the FDA in 2022 for type 2 diabetes, it demonstrated an average weight loss of up to 22.5% in phase III trials, surpassing Semaglutide’s performance.

Figure 1. Mechanism of Action of Tirzepatide (Source: zhuanlan.zhihu.com)

2. GLP-1 + Glucagon: Survodutide

Glucagon promotes fat breakdown and energy expenditure, complementing GLP-1’s appetite suppression and glucose control. This combination enables a dual-pathway approach to weight loss: reduced intake and enhanced metabolism. Survodutide, developed by Boehringer Ingelheim, entered phase III trials in 2024 to evaluate its weight loss efficacy and safety compared to Semaglutide.

Figure 2. Mechanism of Action of GCGR/GLP-1R Dual Agonists in Metabolic-Associated Fatty Liver Disease (DOI: 10.1080/13543784.2024.2441865)

3. GLP-1 + Amylin: CagriSema

Amylin delays gastric emptying and enhances satiety, potentially amplifying GLP-1’s appetite-suppressing effects. CagriSema, developed by Novo Nordisk, combines GLP-1 and Amylin strategies. In phase III trials, it achieved over 16% weight loss, outperforming Semaglutide alone but falling short of the anticipated 25% target.

Figure 3. CagriSema Phase II Clinical Results (Source: medsci.cn)

4. GLP-1 + GIP + Glucagon: Retatrutide

Retatrutide, a triple agonist targeting GLP-1, GIP, and Glucagon receptors, addresses appetite suppression, glucose control, and metabolism enhancement. Developed by Eli Lilly, it achieved an average weight loss of 24.2% over 48 weeks in a 2023 NEJM-published phase II trial, approaching the efficacy of bariatric surgery.

Figure 4. Mechanism of Action of Retatrutide (Source: zhuanlan.zhihu.com)

Emerging Targets

New targets for metabolic syndrome are under exploration, with small molecules and protein drugs targeting FGF21, MC4R, and others entering preclinical stages.

abinScience specializes in developing and producing high-quality bioreagents, offering innovative tools and solutions for researchers worldwide. abinScience provides a comprehensive product portfolio for autoimmune diseases, infectious diseases, neuroscience, and immune target research. Our offerings include antibodies, recombinant proteins, assay kits, and functional research tools, known for their high sensitivity and specificity, supporting interdisciplinary life science research.

Below is a selection of abinScience’s protein and antibody products for metabolic pathway research. Contact our team for more product details!