Cardiovascular effects of antiobesity drugs: are the new medicines all the same?

Waiting for a definite answer from well-designed randomized prospective clinical trials, the impact of the new antiobesity drugs -liraglutide, bupropion/naltrexone, phentermine/topiramate and lorcaserin- on cardiovascular outcomes remains uncertain. What has been learned from previous experience with older medicines is that antiobesity drugs may influence cardiovascular health not only causing weight reduction but also through direct actions on the cardiovascular system. Therefore, in the present review, we examine what is known, mainly from preclinical investigations, about the cardiovascular pharmacology of the new antiobesity medicines with the aim of highlighting potential mechanistic differences. We will show that the two active substances of the bupropion/naltrexone combination both exert beneficial and unwanted cardiovascular effects. Indeed, bupropion exerts anti-inflammatory effects but at the same time it does increase heart rate and blood pressure by potentiating catecholaminergic neurotransmission, whereas naltrexone reduces TLR4-dependent inflammation and has potential protective effects in stroke but also impairs cardiac adaption to ischemia and the beneficial opioid protective effects mediated in the endothelium. On the contrary, with the only exception of a small increase in heat rate, liraglutide only exerts favorable cardiovascular effects by protecting myocardium and brain from ischemic damage, improving heart contractility, lowering blood pressure and reducing atherogenesis. As far as the phentermine/topiramate combination is concerned, no direct cardiovascular beneficial effect is expected for phentermine (as this drug is an amphetamine derivative), whereas topiramate may exert cardioprotective and neuroprotective effects in ischemia and anti-inflammatory and antiatherogenic actions. Finally, lorcaserin, a selective 5HT_2C receptor agonist, does not seem to exert significant direct effects on the cardiovascular system though at very high concentrations this drug may also interact with other serotonin receptor subtypes and exert unwanted cardiovascular effects. In conclusion, the final effect of the new antiobesity drugs on cardiovascular outcomes will be a balance between possible (but still unproved) beneficial effects of weight loss and "mixed" weight-independent drug-specific effects. Therefore comparative studies will be required to establish which one of the new medicines is more appropriate in patients with specific cardiovascular diseases.