New Weight-Loss Drugs

Posted by Mark Abramowicz, M.D.

Well, not all new. One is a combination of 2 old drugs, and the other resembles a disgraced older drug in its mechanism of action. Not so closely that the FDA refused to approve it, but enough so that we will have to say something about it in the next issue of The Medical Letter, when we take up both of these new products.

The combination of old drugs matches up phentermine, the sympathomimetic component of “fen-phen”, with the antiepileptic topiramate, which, numerous authors have noted, causes weight loss in patients who take it to prevent seizures. Weight loss (in addition to a decrease in seizures) is not the only thing topiramate causes in patients with epilepsy; it also causes difficulties in memory, concentration, and attention. That sounds less than ideal, but any drug that produces weight loss without doing any really terrible damage has a multi-billion-dollar upside, so here it is, being marketed for weight loss, with phentermine.

Sympathomimetics like phentermine are among the oldest drugs used to produce weight loss, and they undeniably reduce appetite and calorie intake, at least for a while. They may also produce a number of unwanted effects. One of the sympathomimetic drugs marketed as an aid in weight loss is methamphetamine, which has, of course, gone on to become a multi-billion-dollar success in another venue.

The all-new drug with the slightly concerning mechanism of action is lorcaserin, which is a serotonin receptor agonist. Fenfluramine, the other half of phen-fen, was also a serotonin receptor agonist, but the kind of serotonin stimulation fenfluramine caused had 2 serious side effects: it led to serious damage to heart valves, and in some patients it caused primary pulmonary hypertension. Lorcaserin is thought to stimulate a different serotonin receptor, but sometimes these receptor target identities can be difficult to pin down. We will try to sort all this out for our readers in the next issue of The Medical Letter.

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