Who should use weight loss pills?
A multi-pronged approach to weight loss is often needed which should initially involve only calorie restricted diet and exercise. It is only when these measures fail to meet the desired target body weight that more aggressive measures like the use of weight loss drugs can be considered. The use of medication to lose weight is not indicated for every person. It should be considered in any individual who is not responding to lifestyle changes with :
- a Body Mass Index (BMI) > 27 with a high risk of developing obesity-related diseases
- a Body Mass Index (BMI) > 30
Individuals on medications for the treatment of obesity (weight loss drugs) should actively continue with the lifestyle modification measures aimed at weight loss.
How do weight loss pills work?
These drugs have an effect through various mechanisms which ultimately assist with weight loss.
- The most thoroughly explored approach is appetite suppression with medications acting through alteration of monoamine neurotransmitters or cannabinoid receptor systems in the central nervous system (brain).
- Another major approach is to reduce nutrient absorption from the gastrointestinal (GI) tract. It is mainly the absorption of fats that are targeted.
- Increasing metabolism is also an attractive approach to promote weight loss.
Medications exerting actions through these mechanisms form the basis for all currently used anti-obesity agents. Despite the attractive benefits of weight loss medication, most of the currently available drugs are associated with significant health risks. Hence anti-obesity drugs are to be prescribed only when the advantages outweigh the risks associated with the use of the medication.
Centrally acting appetite suppressing drugs
Appetite-suppressing drugs, also called anorexiants, reduce appetite by causing early satiety (feeling of satisfaction or fullness after food intake) and subsequently reducing hunger. This helps patients to reduce calorie intake without a sense of deprivation. These drugs mainly exert the effect on appetite by modulating the neurotransmission of three monoamines namely norepinephrine, serotonin (5-hydroxytryptamine or 5-HT) and dopamine. The main drawback of appetite suppressants are that the effects of the drugs are short-lived and wear off after discontinuation. The individuals are likely to regain weight if the drug is discontinued at the same time use of most appetite suppressants beyond 3 months is associated with significant toxicities. The prominent appetite suppressing agents are :
- Sympathomimetic agents
- Cannabinoid receptor antagonists
Sympathomimetic agents primarily include amphetamine derivatives like :
These drugs function by stimulating norepinephrine release or by blocking its reuptake. Phenylpropanolamine, which was commonly used in over-the-counter appetite suppressant preparations, was associated with hemorrhagic strokes in young women and increase in blood pressure.
Fenfluramine and dexfenfluramine primarily exerts action by increasing serotonin levels in brain. These drugs were commonly used previously in slimming centers because of its ability to suppress appetite. However, the effectiveness of these drugs gradually declines if its used continuously beyond a period of 3 months. These drugs have very less brain stimulating property but can produce a sense of relaxed state of mind (tranquillizing role). Use of these drugs is associated with certain cardiac valvular abnormalities more so in patients with carcinoid syndrome (conditions associated with increased serum level of serotonin).
Sympathomimetic drugs are associated with stimulant effect on central nervous system and can potentially cause disturbances in sleep. These drugs are also associated with significant potential for abuse, mood disturbances, and cardiovascular toxicity. As a result, most of the sympathomimetic drugs have been withdrawn from markets or are available only for highly restricted use in most countries. Amphetamine derivatives are thus no longer recommended for routine for the treatment of obesity.
Sibutramine acts by inhibiting reuptake of serotonin and norepinephrine. It is effective in suppressing appetite and also promotes fat breakdown by increasing metabolism and heat generation in the body. These effects of sibutramine are responsible for reducing the body weight. Sibutramine can produce a loss of about 10 to 20 pounds (approximately 5 to 10 kgs) over a period of 12 months and it can maintain the weight loss for about 2 years. Unlike other appetite suppressants which were popular previously, sibutramine is not pharmacologically related to amphetamine and has no addictive potential.
The undesirable effects of sibutramine are constipation, sleep disturbance, alterations in the heart rate and blood pressure, acute cardiovascular complications, mood disturbances, and dry mouth. Use of sibutramine is contraindicated in patients with uncontrolled hypertension (high blood pressure) and ischemic heart disease. Sibutramine has been withdrawn from markets in several countries including the United States, due to a high incidence of the cardiovascular complications like myocardial infarction (heart attack) and stroke.
Cannabinoid receptor antagonist
Cannabinoid receptor antagonists like rimonabant has effect on reducing weight by suppressing appetite and also by increasing metabolism. The most common side effects include depression, anxiety and significant nausea. The drug was never approved in the United States and Canada even though it was available in the Europe. The manufacturer has discontinued the drug worldwide due to serious psychiatric side effects.
Peripherally acting weight loss drugs
These drugs affect sites other than the brain and its hormones. One of the more common of these agents is a lipase inhibitor. Other peripherally acting weight loss drugs include fiber supplements and diabetes medication.
Orlistat is the only approved weight loss medication which is widely used at present. It is a synthetic derivative of a lipase inhibitor called lipostatin which is produced naturally by the fungi Streptomyces toxytricini. Orlistat inhibits absorption of fat by blocking the action of lipase enzymes (fat dissolving enzymes) produced in the body. In this way, orlistat reduces the absorption of certain fats from the gut. Significant weight-loss can be obtained with continuous use of orlistat. Orlistat can reduce a 10% weight loss over a period of 12 months.
The drug is taken three times a day with meal. The best results are obtained with orlistat when the total fat intake is evenly distributed between the three meals and when the total fat intake is kept at about 30% of the total calorie requirement. The protein, carbohydrate and fat content in diet should also be ideally kept balanced for best results. The effect on fat digestion returns to normal levels with in 2 to 3 days after discontinuation of the treatment.
Orlistat is free of any serious systemic side effects as the drug is minimally absorbed. Undesirable effects of orlistat are mainly due to the presence of undigested fat in the stools. The fecal fat increases considerably after starting the therapy leading to significant gastrointestinal side effects in about 10% of the patients. The adverse effects of orlistat mostly includes flatulence, fatty stool, pain in the abdomen, fecal urgency, deficiency of fat soluble vitamins and foul smelling stools. The intensity of side effects generally diminishes with control of dietary fat intake. The GI side effects may be minimized with concomitant intake of Psyllium mucilloid along with orlistat. Potential deficiency of vitamin A and E can be prevented with its supplementation at least 2 hours before the intake of a meal along with the drug.
Olestra (sucrose polymer) which is used as a fat substitute may be used as a fat substitute which is neither digested nor absorbed. Fiber supplements like glucomannan and guar gum can form an indigestible gel-like substance which may be of use in reducing absorption of nutrients from intestines. This may have supplementary roles in the treatment of obesity. These supplements have to be taken thrice daily with food. Unwanted side effects are predominantly gastrointestinal in nature and include nausea, flatulence, abdominal bloating and diarrhea.
The biguanides, like metformin, is associated with reduction of absorption of glucose from intestine. At the same time it helps increase utilization of glucose in the peripheral tissues mainly in muscles and fat tissue. Metformin is a popular antidiabetic drug and it may be of some use in reducing weight, especially in obese diabetic patients.