Drugs for obesity – which of them are approved?
There has been a dramatic worldwide rise in the prevalence of obesity, which is associated with substantial morbidity and mortality from cardiovascular and other diseases. There are standardized cut-off points for the recommendation of various treatments, beginning conservatively with diet, exercise, behavior modification, medications, and after failure of these treatments, consideration of bariatric surgery. Reduction of food intake, increase in physical activity, and individualized lifestyle strategies are recommended once BMI exceeds 25. In addition, pharmacotherapy is appropriate when BMI reaches 30 (or 27 with he existence of comorbidities). Bariatric surgery is not recommended until BMI reaches 40 (or 35 with comorbidities).
Indications for pharmacotherapy
Pharmacotherapy is indicated for patients who have BMI more than 30 without comorbidities or more than 27 with at least one comorbidity. Comorbidities include coronary artery disease, other atherosclerotic disease, type 2 diabetes, and sleep apnea. Additional cardiovascular risk factors include cigarette smoking, hypertension (>140/90 mm Hg), elevated low-density lipoprotein (LDL) cholesterol level (>130 mg/ml), decreased high-density lipoprotein (HDL) cholesterol level (< 35 mg/ml), impaired fasting glucose (100–125 mg/ml), family history of premature coronary heart disease and advancing age (> 45 years for men and > 55 years for women). Three or more cardiovascular risk factors in an obese patient are assumed to confer the same risk as comorbidity. Patients who achieve a weight loss of more than 0.5 kg/week in the first month of pharmacotherapy are more likely to have a sustained and substantial response to longer-term treatment. This information can be used to optimize treatment and prevent excessive cost.
To lose weight even when being teated with drugs, an individual must go into negative energy balance in which the energy intake of food is less than the energy needed for daily activities.
Drugs used for obesity treatment can be divided into two main groups:
- drugs that act primarily on the central nervous system to reduce food intake
- drugs that act outside the brain
Drugs approved for a long-term treatment are Orlistat (Xenical) and Sibutramine (Merindia, Reductil) whereas drugs approved for a short-term treatment include Benzphetamine (Didrex), Diethylpropion (Tenuate, Tepanil, Dospan), Phendimetrazine (Bontril PDM, Plegine, X-trozine, Prelu-2), Phentermine (Adipex-P, Fastin, Obenix, Oby-Cap, Oby-Trim, Zantryl, Lonamin).
Orlistat is a non-absorbable pancreatic lipase inhibitor that reduces dietary fat absorption by about 30% at a dose of 120 mg taken three times each day. Randomized trials have shown that patients receiving orlistat have a weight loss of about 10% over a 12-month period, compared with a 5% weight reduction with placebo. Weight loss is sustained for at least 4 years with continued therapy. In addition to inducing weight loss, orlistat lowers LDL level by about 6%, although this reduction is not accompanied by an increase in HDL cholesterol level. Orlistat also reduces the risk of developing diabetes by about two thirds in at-risk obese subjects and lowers glycosylated hemoglobin levels by about 0.5% in obese patients who have type 2 diabetes. One disadvantage of orlistat is that it must be taken three times a day. It may have gastro-intestinal side effects.
Sibutramine is a serotonin-norepinephrine re-uptake inhibitor. It is approved by the US FDA for long-term use. In a clinical study lasting six months, 67% patients achieved a 5% weight loss and 35% patients lost 10% or more weight. It also causes reduction in triglyceride, total cholesterol and low density lipoprotein cholesterol level and an increase in high density lipoprotein cholesterol level.
Sympathomimetic drugs include Benzphetamine, Diethylpropion, Phendimetrazine and Phentermine. They suppress appetite by blocking the re-uptake of norepinephrine from synaptic granules. All of these drugs are taken orally.
The epidemic of obesity has became a worldwide issue, now including the developing nations. A lot of drugs are undergoing clinical trials. Many of them can have serious side effects, so they should be taken after consulting the physician who will naturally recommend the approved drugs. Medications are one of the options for the treatment of obesity and, to be efficient, should be combined with diet control and regular supervised exercise program.