Drugs for losing weight

The problem of obesity has taken on epidemic proportions over the last few years. In 1998, a report by the UK’s National Institute for Clinical Excellence (NICE) revealed that 17 out of 100 men and 21 out of 100 women were obese. At this time, about half of the UK’s adult population is overweight or obese – and rising. As obesity rates increase, so do the numbers suffering from obesity-related diseases such as cardiovascular disease, hypertension, certain cancers (including colorectal and breast cancer), joint disease and, in particular, type 2 diabetes (J La State Med Soc, 2005; 157 [Spec No 1]: S50-5).

In most cases, a sensible combination of dieting and exercise should be sufficient to shed those extra pounds. But when this fails, appetite-suppressant drugs are often prescribed as a last resort to those who are dangerously obese.

Of the wide variety of anti-obesity agents available, the three most commonly prescribed are orlistat (Xenical), sibutramine (Reductil) and fluoxetine (Prozac).

Orlistat is a weight-loss drug that works by suppressing the appetite. It is designed to reduce the amount of fat taken up from food and to eliminate it directly from out of your body via your stools.

However, this ‘fat-grabbing’ ability means that the drug also reduces the absorption of the fat-soluble vitamins (A, D, E and K) and beta-carotene – so much so that Roche, which makes Xenical, has urged patients to take a multivitamin supplement containing those vitamins and beta-carotene. The US Food and Drug Administration also recommends that orlistat not be taken by those who have digestive difficulties. A study carried out in Turkey, looking at the effect of orlistat in severely obese adolescents, found that gastrointestinal side-effects occurred in one in three cases (Eur J Pediatr, 2004 ; 163: 738-41).

Orlistat can also interact with the blood-thinner warfarin. In the case of a 66-year-old man taking warfarin, orlistat was found to enhance the effect of warfarin, which could lead to serious bleeding complications. Doctors say this could be due to the reduced uptake of fat-soluble vitamins, especially vitamin K, necessary for the production of the blood-clotting factor prothrombin (Ann Pharmacother, 2003; 37: 510-2).

Other groups who need to exercise caution when taking orlistat are those with gallbladder problems, pregnant or breastfeeding women and diabetics, as the drug can affect blood sugar control.

Another frequently prescribed anti-obesity drug is the appetite-suppressant sibutramine (Reductil). It works by reducing hunger cravings by altering two chemical messengers in the brain – specifically, it acts on noradrenaline (norepinephrine) and serotonin to promote feelings of being full.

Sibutramine, however, can increase blood pressure and heart rate. For this reason, it is not recommended for patients who already have high blood pressure or cardiac arrhythmias (heartbeat irregularities). Other common side-effects of the drug are dry mouth, constipation, headaches and insomnia.

As a serotonin and noradrenaline reuptake inhibitor, sibutramine should not be used with certain types of antidepressants (monoamine oxidase inhibitors and noradrenergics). Caution is also advised in prescribing it to patients taking SSRIs (selective serotonin reuptake inhibitors) (Drugs Today [Barc], 2004; 40: 41-54).

The third most commonly prescribed drug for weight loss is fluoxetine, better known as Prozac. Originally intended to treat depression, doctors noticed that those taking Prozac felt less hungry. This was substantiated by a Canadian study showing that fluoxetine improves insulin-mediated sugar disposal in obese patients (Int J Obes Relat Metab Disord, 1997; 21: 97-102).

However, the drug can also activate anorexia in some users (Pharmacopsychiatry, 2005; 38: 69-77). More alarming, the FDA has issued an alert on the potential risk of suicide with fluoxetine in paediatric patients. Indeed, taking any antidepressants can increase suicidal thoughts and actions in about one out of 50 people 18 or under (FDA Alert [05/2005]: Suicidality in Pediatric Patients).