Cardiovascular effects of current and future anti-obesity drugs.
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 Fenfluramine, and sibutramine were withdrawn due to increased cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems.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.
Simon
S
Comerma-Steffensen
Martin
M
Grann
Charlotte U
CU
Andersen
Jorgen
J
Rungby
Department of Biomedicine- Pharmacology, Aarhus University, Wilhelm Meyers Alle 4, 8000 Aarhus C, Denmark. us@farm.au.dk.
Ulf
U
Simonsen
D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D055808:Drug Discovery / Q000639:trends; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D015995:Prevalence; D012307:Risk Factors
D019440:Anti-Obesity Agents; D015507:Drugs, Investigational; D007004:Hypoglycemic Agents