The Fight Against Obesity Escalates: New Drugs on the Horizon and Metabolic Implications

Abstract

Purpose of Review

There is currently a steep rise in the global prevalence of obesity. Pharmaceutical therapy is a valuable component of conservative obesity therapy. Herein, medications currently in the phase of preclinical or clinical testing are reviewed, along with an overview of the mechanisms that regulate energy intake and expenditure. In addition, the current and potential future directions of obesity drug therapy are discussed.

Recent Findings

Although the current arsenal of obesity pharmacotherapy is limited, a considerable number of agents that exert their actions through a variety of pharmacodynamic targets and mechanisms are in the pipeline. This expansion shapes a potential near future of obesity conservative management, characterized by tailored combined therapeutic regimens, targeting not only weight loss but also improved overall health outcomes.

Summary

The progress regarding the elucidation of the mechanisms which regulate the bodily energy equilibrium has led to medications which mimic hormonal adaptations that follow bariatric surgery, in the quest for a “Medical bypass.” These, combined with agents which could increase energy expenditure, point to a brilliant future in the conservative treatment of obesity.

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Abbreviations

AgRP:

Agouti-related peptide

BAT:

Brown adipose tissue

BMI:

Body mass index

cGMP:

Cyclic guanosine monophosphate

CVD:

Cardiovascular disease

DACRA:

Dual amylin/calcitonin receptor agonists

DIO:

Diet-induced obesity

DPP4:

Dipeptidyl-peptidase-4

EE :

Energy expenditure

EI:

Energy intake

FDA:

Food and Drug Administration

GCGR :

Glucagon receptor

GHSR1a:

Growth hormone secretagogue receptor type 1a

GIP:

Glucose-dependent insulinotropic peptide

GLP-1:

Glucagon-like peptide 1

GLP1R:

Glucagon-like peptide 1 receptor

GOAT:

Ghrelin-O-acyltransferase

NPY:

Neuropeptide Y

OXM:

Oxyntomodulin

POMC:

Proopiomelanocortin

PYY:

Peptide tyrosine-tyrosine

RYGB:

Roux-en-Y gastric bypass

SCT:

Secretin

SG:

Sleeve gastrectomy

T2DM:

Type 2 diabetes mellitus

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Tsilingiris, D., Liatis, S., Dalamaga, M. et al. The Fight Against Obesity Escalates: New Drugs on the Horizon and Metabolic Implications. Curr Obes Rep 9, 136–149 (2020). https://doi.org/10.1007/s13679-020-00378-x

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Keywords

  • Appetite
  • Energy expenditure
  • Gut peptides
  • Medical bypass
  • Obesity
  • Semaglutide
  • Weight loss