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Pills for the Fats

Posted on April 10, 2023 | No Comments on Pills for the Fats

Obesity is now a growing concern, for the young and old alike. It is the harbinger of other diseases like diabetes, hypertension, stroke, heart attack and peripheral vascular diseases. Genetic factors play an important role but cultural, socioeconomic, behavioral and situational factors play a greater role in carving the modern Venus of Willendorf (she was the obese model during the prehistoric era).

Losing weight is truly a challenge. Easier said than done, so they say. A lot of fad diets have come and gone but only to make us realize that there are really no hard and fast rules when it comes to weight loss. The doctor and the patient may have different expectations during obesity treatment. Doctors are concerned that weight loss could help avert cardiovascular complications, but patients are often hoping for a greatly improved appearance.

Common conditions associated with obesity are cancer (endometrial, ovarian, breast, gallbladder, prostate and colon), menstrual irregularities, infertility, gallbladder disease, obstructive sleep apnea, osteoarthritis, gout and thromboembolic disease.

Numerous treatments are available for obesity. Behavioral treatment, surgery and pharmacological therapy are widely used with varying success rates. Older anorectic agents (drugs that cause loss of appetite, the opposite of orexigenic agents which cause increase in appetite) have significant side effects in association with cardiovascular complications and have been pulled out of the market.

Proper nutrition (by avoiding the extremes of dense and empty calorie foods) together with regular exercise are still the cornerstone of long-term weight loss. However, it would entail a highly disciplined and motivated individual to adhere to a prescribed medical nutritional therapy. Failure to lose weight with lifestyle modification may lead to pharmacotherapy to help shed off those extra pounds.

There are several slimming pills swarming the media, internet and weight loss centers. At present, there are only three approved anti-obesity agents, Orlistat, Sibutramine and Phentermine.

Orlistat, the first lipase inhibitor labeled by the FDA for treatment of obesity, is a potent and irreversible inhibitor of gastric and pancreatic lipases, thus preventing the absorption of about 30 percent of dietary fat. These lipases are enzymes which aid in the digestion of dietary fats making them more absorbable in the intestines as free fatty acids. Orlistat as a locally acting agent, undergoes minimal systemic absorption and its interaction with other medications to cause adverse reactions is very nil. However, there is decreased absorption of lipid-soluble vitamins (A, D, E and K). This digestive inhibitor may have a role in creating the negative energy balance brought by the decreased fat absorption and is necessary for subsequent weight loss.

Based on Orlistat’s mechanism of action, its side effects will mainly be on the gastrointestinal tract for patients consuming a high fat diet. Side effects included flatus with discharge, oily spotting and oily stool, fecal urgency, fecal incontinence and abdominal pain. Lipid-soluble vitamin concentrations may change during therapy but rarely need supplementation. Orlistat does not appear to interfere with the efficacy of other chronically administered medications (i.e., antihypertensive agents, warfarin and oral contraceptives). Its recommended dose is 120mg tablet three times a day given during or less than an hour after a fat-containing meal.

Sibutramine is a combined reuptake inhibitor of both serotonin (5-hydroxytryptamine) and norepinephrine and acts centrally to enhance satiety or suppress appetite. This agent may also stimulate thermogenesis leading to increased energy expenditure. Therefore, Sibutramine works in two ways by helping in reducing the amount of food intake and also reducing the slowing of metabolism as a response to weight loss. This dual effect could contribute greatly up to the weight maintenance phase.

According to clinical trials, most common adverse events experienced by patients on Sibutramine are
dry mouth, anorexia, constipation, insomnia, dizziness and anxiety. However these were noted to be mild to moderate in severity and transient in duration. There was also note of minor rise in pulse rate (one to two beats per minute) and small rise in blood pressure (4mmHg). For this reason, it is not recommended for patients with uncontrolled hypertension or in patients having fast heartbeats. It is recommended that Sibutramine be started at a low dose of 10mg once a day with careful monitoring of blood pressure. A weight loss effect may offset any pro-hypertension effect and allow the drug to be tolerated. Extra care must be employed when considering dose increase.

This is chemically similar to amphetamine and acts as an appetite suppressant or “anorectic” agent. Hunger cravings are reduced as this active ingredient acts on the central nervous system. Side effects that may occur while taking phentermine are restlessness, nervousness, difficulty sleeping, changes in sex drive, constipation, diarrhea, dizziness, exaggerated feelings of depression or elation, headache, high blood pressure, hives, increased heart rate, stomach or intestinal problems, throbbing heartbeat, tremors, or unpleasant taste.
Users of phentermine are very susceptible to developing physical and psychological addiction to it. It is strongly advised that patients using this drug adhere to the prescribed dosage and duration of its intake to avoid development of tolerance. Phentermine may react badly with alcohol and this combination should be avoided. Diabetic patients who are on insulin and taking Phentermine may need increased doses of insulin and therefore should seek doctor’s consult when using this pill.

Phentermine is available in tablets and extended-release capsules. It usually is taken as a single daily dose in the morning or three times a day 30 minutes before meals.

Diabetes and Anti-Obesity Pills, Do They Match?
Obesity begets diabetes. This noxious twirl of two risk factors leads to a lurid path of cardiovascular events. Weight loss is very vital and could improve the health of overweight or obese people who have type 2 diabetes and help lower their risk for heart problems.

The XENDOS (Xenical in the Prevention of Diabetes in Obese Subjects) study showed the strongest evidence for improved glycemic control and 37 percent risk reduction of diabetes incidence over four years using Orlistat. The mechanism of this fat-blocking drug in preventing diabetes is attributed to sustained weight loss (modest weight loss of six percent) in obese subjects leading to significant improvement in blood sugar and insulin metabolism. There was also pronounced improvement in the lipid parameters of the Orlistat-treated patients compared to placebo-treated patients. This independent pharmacologic lipid-lowering effect of Orlistat is probably related to the mechanism of action in reducing the absorption of dietary fat.

In a multicenter study by McNulty et al, Sibutramine was an effective anti-obesity agent in type 2 diabetic patients, of whom nearly 20 percent achieved weight loss of > 10 percent, and over 50 percent achieved a loss of > five percent. Patients losing >10 percent showed improvements in glycemic control that were comparable with those achieved by oral hypoglycemic agents. Thus, Sibutramine is a potentially valuable adjunct to the medical management of appropriately selected obese type 2 diabetic patients. Several authors cited that the overall cardiovascular impact of sibutramine is favorable.

Would these anti-munchee pills solve the “diabesity” epidemic? It could never be overly-emphasized that above all, lifestyle modification, proper nutrition and regular exercise are still the key points. Merely taking anti-obesity pills would always lead to weight management failure. These agents are just adjuncts. The adverse events for each drug must be weighed against the benefits.

Weight loss remains a big challenge. Understanding how obesity could lead to various devastating complications would probably be enough to make you get up and start burning those fats and leave those stubborn pounds behind!

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