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

Coulter, Ann A.; Rebello, Candida J.; Greenway, Frank L.

doi:10.1007/s40265-018-0946-y

Cited by 151Pharmacology and Obesity TreatmentRegulation of Appetite and ObesityBariatric Surgery and Outcomes

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

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Coulter, Ann A., Rebello, Candida J., Greenway, Frank L.·2018·Drugs

DOI 10.1007/s40265-018-0946-yPMC PMC6095132

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Abstract

For many years, obesity was believed to be a condition of overeating that could be resolved through counseling and short-term drug treatment. Obesity was not recognized as a chronic disease until 1985 by the scientific community, and 2013 by the medical community. Pharmacotherapy for obesity has advanced remarkably since the first class of drugs, amphetamines, were approved for short-term use. Most amphetamines were removed from the obesity market due to adverse events and potential for addiction, and it became apparent that obesity pharmacotherapies were needed that could safely be administered over the long term. This review of central nervous system (CNS) acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite. In the synergistic mechanism of bupropion/naltrexone, naltrexone blocks the feed-back inhibitory circuit of bupropion to give greater weight loss. Lorcaserin, a selective agonist of a serotonin receptor that regulates food intake, and the glucagon-like-peptide-1 (GLP-1) receptor agonist liraglutide are reviewed. Future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for obesity. Another potential new pharmacotherapy, setmelanotide, is a melanocortin-4 receptor agonist, which is still in an early stage of development. As our understanding of the communication between the CNS, gut, adipose tissue, and other organs evolves, it is anticipated that obesity drug development will move toward new centrally acting combinations and then to drugs acting on peripheral target tissues.

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Suicidal ideation is associated with the use of various weight reduction drugs.
“Suicidal ideation is associated with the use of various weight reduction drugs [67,68].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [67]
Many anti-obesity drugs used for morbid obesity were removed from the market because of long-term side effects, especially cardiovascular problems.
“During the last few decades, some anti-obesity drugs were used to treat morbid obesity; however, many of them were removed from the market owing to long-term side effects, particularly cardiovascular issues [12].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [12]
Based on several clinical studies documenting the effects of liraglutide on weight loss, it has been approved for the treatment of obesity at a dose of 3.0 mg/day in the form of subcutaneous injections.
“Based on several clinical studies documenting the effects of liraglutide, a long-lasting GLP-1RAs, on weight loss, it has been approved for the treatment of obesity at a dose of 3.0 mg/day in the form of subcutaneous injections [88].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [88]
Both peripheral and central mechanisms are associated with the weight-loss effects of liraglutide.
“Both peripheral and central mechanisms were found to be associated with the weight-loss effects of liraglutide [88].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [88]

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Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
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“Thus, there is a necessity for developing more effective novel treatment approaches that address these central nervous system processes (2,9,10).”
Background
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“derivatives, cannabinoid receptor blockers, and serotonin reuptake inhibitors, have been withdrawn due to their unfavorable adverse event (AE) profiles (Table 1).(22,28)”
Background
Obesity medications in development
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Potential contributors to variation in weight‐loss response to liraglutide
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Authors: Coulter, A. A., Rebello, C. J., & Greenway, F. L.
Affiliations: Pennington Biomedical Research Center (US)
Corresponding author: Greenway, Frank L.
ORCID: Coulter, Ann A.
Rebello, Candida J.
Greenway, Frank L.
Venue: Drugs
Publisher: Springer Science and Business Media LLC
Published: 2018-07
Volume: 78
Issue: 11
Pages: 1113-1132
ISSN: 0012-6667 (ISSN-L)
1179-1950
DOI: 10.1007/s40265-018-0946-y
PMC: PMC6095132
OpenAlex: W2884008074
Cited by: 151
References: 135
Citations by year: 2026: 12 · 2025: 20 · 2024: 24 · 2023: 21 · 2022: 20 · 2021: 29 · 2020: 14 · 2019: 6 · 2018: 5
FWCI: 1.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Drugs (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Center for Complementary and Integrative Health (T32 A T004094)
National Institute of General Medical Sciences (1 U54 GM104940)
Topics: Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
Keywords: obesity pharmacotherapy, anti-obesity drugs, phentermine/topiramate, naltrexone/bupropion, lorcaserin, liraglutide, semaglutide, setmelanotide, melanocortin-4 receptor agonist, GLP-1 receptor agonists, serotonin receptor agonists, appetite regulation, drug development
MeSH terms: Animals, Appetite Regulation, Central Nervous System Agents, Humans, Obesity, Weight Loss, Anti-Obesity Agents

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