Title:Cardiovascular Effects of Current and Future Anti-Obesity Drugs
Volume: 12
Issue: 3
Author(s): Simon Comerma-Steffensen, Martin Grann, Charlotte U. Andersen, Jorgen Rungby and Ulf Simonsen
Affiliation:
Keywords:
Antiobesity drugs, brown adipose tissue, cardiovascular effects, incretins, TRPV1, SLGT2.
Abstract: The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia,
hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and
may result in reduction of expected remaining lifespan. We have reviewed the adverse effects on the cardiovascular system
of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential
pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased
cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn
due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine
alone or in combination with topiramate and lorcaserin, although cardiovascular side effects need to be clarified regarding
phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and
metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential
of nebivolol remains unexplored. Pathways with anti-obesity potential include sirtuin activation, blockade of transient receptor
potential (TRPV1) channels, acetyl-CoA carboxylase 1 and 2 inhibitors, uncoupling protein activators, bile acids,
crotonins, CB1 antagonists, but the cardiovascular profile remains to be investigated. For type 2 diabetes, new drug classes
with possible advantageous cardiovascular profiles, e.g. GLP-1 analogues and sodium-glucose co-transport type 2 inhibitors,
are associated with weight loss and are currently being evaluated as anti-obesity drugs.
