Targeting Energy Expenditure-Drugs for Obesity Treatment

Abstract

Obesity and overweight are associated with lethal diseases. In this context, obese and overweight individuals infected by COVID-19 are at greater risk of dying. Obesity is treated by three main pharmaceutical approaches, namely suppressing appetite, reducing energy intake by impairing absorption, and increasing energy expenditure. Most compounds used for the latter were first envisaged for other medical uses. However, several candidates are now being developed explicitly for targeting obesity by increasing energy expenditure. This review analyzes the compounds that show anti-obesity activity exerted through the energy expenditure pathway. They are classified on the basis of their development status: FDA-approved, Withdrawn, Clinical Trials, and Under Development. The chemical nature, target, mechanisms of action, and description of the current stage of development are described for each one.

Keywords: FDA-approved; clinical trials; energy expenditure; energy metabolism; obesity; thermogenesis; treatments under development; withdrawn treatments.

Figure 1

Excess intake of calories causes overweight and obesity. There are three main pharmacological strategies to achieve a caloric deficit. Two of them aim to prevent the storage of excess calories, first by acting on the central nervous system to cause an anorexic effect and regulate appetite, and second by inducing early excretion and thus preventing ingested food from becoming a useful source of calories. The third strategy, and the topic of this review, is the use of drugs that increase energy expenditure by causing the body to use calories already stored in the form of fat.

Figure 2

Drugs, their targets, and their metabolic outcomes focusing on energy expenditure effect.

Figure 3

Chemical structures of drugs that increase energy expenditure that are approved by the FDA and withdrawn from the market.

Figure 4

Drugs that increase energy expenditure in clinical trials.

Figure 5

Drugs under development that increase energy expenditure.