Centrally Acting Agents for Obesity: Past, Present, and Future

Area of Science:

• Pharmacology
• Endocrinology
• Neuroscience

Background:

• Obesity was historically viewed as a behavioral issue, treatable with counseling and short-term medication.
• Recognition of obesity as a chronic disease by scientific (1985) and medical (2013) communities spurred the need for long-term pharmacotherapies.
• Early obesity drugs like amphetamines were withdrawn due to safety and addiction concerns, highlighting the need for safer, long-term solutions.

Purpose of the Study:

• To review current and emerging central nervous system (CNS) acting pharmacotherapies for obesity.
• To evaluate the mechanisms of action and efficacy of novel anti-obesity medications.
• To discuss the future trajectory of obesity drug development, including centrally and peripherally acting agents.

Main Methods:

• Review of scientific literature on CNS-acting anti-obesity drugs.
• Evaluation of pharmacotherapies targeting neurotransmitter pathways and hormonal signaling.
• Analysis of drugs in various stages of clinical trials, from Phase III to early development.

Main Results:

• Current therapies like phentermine/topiramate and bupropion/naltrexone utilize synergistic mechanisms to reduce appetite and promote weight loss.
• Selective serotonin receptor agonists (e.g., lorcaserin) and glucagon-like-peptide-1 (GLP-1) receptor agonists (e.g., liraglutide) are effective treatments.
• Emerging drugs such as tesofensine, semaglutide, and setmelanotide show promise for future obesity management.

Conclusions:

• Pharmacotherapy for obesity has significantly advanced, moving beyond short-term interventions to long-term, safe treatment options.
• Future obesity drug development is expected to focus on novel centrally acting combinations and drugs targeting peripheral tissues.
• Continued research into the complex interplay between the CNS, gut, and adipose tissue will drive the creation of more targeted and effective obesity pharmacotherapies.