Table 3.

Ten Takeaway Messages Regarding Anti-Obesity Drug Development. Shown are takeaway messages regarding current and future anti-obesity drug development.

1.	Examples of common body tissue targets of anti-obesity drug development include the central nervous system, gastrointestinal systems, and adipose tissue, with a continuing “emerging concept that the development of anti-obesity agents must not only reduce fat mass (adiposity), but must also correct fat dysfunction (adiposopathy)” [59].
2.	Glucagon-like peptide-1 (GLP-1) is an intestinal peptide secreted by the ileum and large intestine that, after food intake, increases pancreatic insulin release (“incretin”) and decreases glucagon secretion. Therapeutic long-acting GLP-1 receptor agonists (GLP-1 RAs) reduce glucose levels, decrease hunger, increase satiety, slow gastric emptying, increase adipogenesis and lipogenesis [122] (potentially improving fat functionality and helping to correct adiposopathy), and decrease hepatic glucose production. Some GLP-1 RAs function as anti-obesity and/or anti-diabetes medications when used alone or when used as a component of dual or triple mechanistic therapeutics.
3.	Glucose-dependent insulinotropic polypeptide (i.e., GIP — formerly known as gastric inhibitory peptide) is an incretin secreted by the small intestine (i.e., duodenum and jejunum) that increases pancreatic insulin release. GIP receptor agonists are a component of anti-obesity and anti-diabetes agents serving as polyagonists (i.e., promoting multiple physiologic responses).
4.	Glucagon receptor (GCGR) agonists may increase glucose levels via promotion of gluconeogenesis and inhibition of insulin. While glucagon is not an incretin, GCGR agonists may reduce hunger, increase satiety, have catabolic and thermogenic effects, increase energy expenditure, increase lipolysis and fatty acid oxidation, and reduce cholesterol and triglyceride levels. Combination GCG-RA and GLP-1 receptor agonist (RA) often result in a net reduction in glucose and body weight.
5.	Tirzepatide is an approved anti-diabetes agent and an investigational anti-obesity drug in development and is a unimolecular GLP-1 and GIP RA.
6.	Paradoxically, dual GLP-1 RA and GIP antagonists are also in development as anti-obesity therapeutic agents.
7.	Oxyntomodulin acting agents have dual GLP-1 RA and glucagon RA activity.
8.	Agents that facilitate browning of adipocytes have the potential to increase energy expenditure.
9.	The development of anti-obesity medications is following the path of drug development of other metabolic diseases.
10.	Clinical cardiovascular outcome trial support for cardiovascular benefits is likely the binary switch that will transform the current limited use of anti-obesity medications into future standards of care for patients with obesity.