Future Obesity Therapies: From Multi-Agonists to New Drug Targets

Dr Arun Kumar C. Singh, Director Endocrinology, Metro Heath Institute Faridabad

Dual and triple agonists are expanding obesity treatment, while newer targets and drug combinations may offer further options for weight managemen

Obesity is a complex disease influenced by genetic, environmental, metabolic and hormonal factors. As knowledge of these factors has grown, treatment has evolved from older medicines such as amphetamines to newer therapies that target appetite and metabolic pathways.

Incretin-based treatments are an important part of this progress. Dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists and triple GLP-1/GIP/glucagon receptor agonists are being developed to act on more than one pathway. A systematic review and meta-analysis of 10 randomized controlled trials involving 3,236 participants found that tirzepatide, retatrutide, and mazdutide were associated with greater reductions in body weight, waist circumference, glycated hemoglobin, and fasting plasma glucose than placebo. However, adverse events, particularly gastrointestinal events, were more common with these treatments.

Research is also moving beyond incretin-based therapies. Potential future targets include growth differentiation factor 15 (GDF15) and its receptor glial cell-line derived neurotrophic factor receptor α-like (GFRAL), inhibin βE (INHBE), and bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Multi-target drugs and drug combinations are also being explored as ways to improve weight loss and address some limitations of current treatments.

Another area of development is the use of oral formulations, which may offer greater convenience. Advances in multi-omics and artificial intelligence may also support more personalized approaches to obesity treatment in the future.

Overall, the treatment landscape for obesity is moving toward therapies that act on multiple pathways, with dual and triple agonists already showing promising results and several newer targets being explored for future treatment.

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