Do Diet Pills Really Work?

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The answer is yes. But there’s some scary (and, um, unsavory) info in the fine print.

Diet drugs have come a long way since the addictive amphetamines of the 1950s. And while each new generation of skinny pills has so far proven more dangerous than effective – remember fen-phen and ephedra? – experts continue their search for a safe diet pill that works. Enter Alli, a new formulation proven to block dietary fat absorption; as of this month, it will be available at your local drugstore, no prescription required. Also on the horizon: the awaited FDA approval of Zimulti, a new prescription pill that not only promises to help slim you down but also improve cholesterol.

But while these diet pills offer hope for trimming America’s ever-expanding waistline, experts caution that there’s no miracle potion out there to automatically shrink you back into your college jeans. “These diet drugs work only if you also change your lifestyle, and that means following the same old advice of dieting and exercising,” says Caroline Apovian, M.D., of the Nutrition and Weight Management Center at Boston University Medical Center. The medications also come with some real health risks, ranging from nausea and diarrhea to hypertension and depression. Here’s the scoop on the five newest weight-loss pills on the market.

Alli (orlistat)

THE SKINNY: Created originally as the prescription drug Xenical, orlistat is now available in a lower-dose version, Alli, which was granted FDA approval to be sold over the counter earlier this year. The drug, which you take up to three times a day with meals, prevents you from digesting 25 percent of the fat you consume (by attaching to some of the enzymes responsible for breaking down fat from food). The amount of fat calories blocked will depend on how much fat you eat, but most patients block 100 to 200 calories per day.

So, how does that play out in pounds? Subjects who took Alli for six months lost 50 percent more weight – say, 15 pounds versus 10 – than those who only dieted, according to a study done by GlaxoSmithKline (GSK) Consumer Healthcare, the drug’s manufacturer. It also appeared to inspire positive lifestyle changes: “We found that 80 percent of Alli-takers really stuck to a reduced-fat diet, and 50 percent started exercising for longer periods of time,” says Vidhu Bansal, director of Medical Affairs at GSK Consumer Healthcare. A starter pack of Alli — which includes a month’s supply of pills, a dietary guidelines guide, a calorie and fat counter, and a food journal – costs about $54.

THE RISKS: If you eat too much fat (more than 30 percent of your calories, or roughly 15 grams of fat per meal), you’ll likely experience loose, oily stools, since the excess fat that is blocked from absorption is quickly excreted. “My patients on Xenical often find that when they eat a high-fat meal, several hours later they may have diarrhea or loose stools. In extreme cases, they can’t control their bowels – they’ll leak all over their pants,” says Caroline Cederquist, M.D., a spokesperson for the American Society of Bariatric Physicians (ASBP). (People who took Alli were less likely to experience these side effects.) Taking either drug may also put you at risk for vitamin loss. “You need enough fat in your diet to absorb fat-soluble vitamins such as A and D,” adds Loren Wissner Greene, M.D., an obesity specialist at the New York University School of Medicine in New York City.

IS THIS PILL FOR YOU? Alli is intended for people who are overweight, generally defined as those with a body mass index (BMI) – a measure of body fat based on height and weight – of at least 25. (You can calculate your BMI at “Alli, like Xenical, will be useful for people who eat out often and don’t have much control over the amount of fat they are served,” says Cederquist. “So if you eat more fat than you intended, you’ll get rid of it.” The drug also works as a splurge deterrent — the side effects are so unpleasant that you’ll want to avoid fatty foods. But experts do have fears about misuse: “I worry that a slim woman who just wants to lose 5 pounds to fit into her bikini will use it as a way to eat anything she wants while still getting skinnied up,” says Greene. The problem with this? A normal-weight woman who takes Alli places herself at an unnecessary risk of suffering side effects such as loss of bowel control and vitamin loss, whereas for an overweight woman, the health risks of carrying around extra pounds – such as heart disease and diabetes – may outweigh these side effects.

Meridia (sibutramine)

THE SKINNY: This prescription weight-loss drug acts on the brain’s appetite-control center to make you feel fuller faster – so you’ll likely eat less, says Madelyn Fernstrom, Ph.D., of the Weight Management Center at the University of Pittsburgh Medical Center. It works by altering levels of serotonin and norepinephrine, two chemicals that help regulate satiety. People on sibutramine lost about 10 pounds more in a year than those taking a placebo, according to a study review.

THE RISKS: Meridia can raise blood pressure, increasing the risk of heart attack or stroke. In fact, it was temporarily banned in Italy five years ago, after 50 adverse reactions. And in 2002, the nonprofit group Public Citizen petitioned the FDA to ban it in the United States, citing evidence that Meridia was associated with 29 deaths and hundreds of reactions such as rapid heart rate, high blood pressure, and heart palpitations. The FDA stated that while it wouldn’t ban the drug, it would monitor the pill’s safety. (Abbott, Meridia’s manufacturer, maintains that the drug is safe, based on clinical trials of more than 12,000 patients.)

IS THIS PILL FOR YOU? Meridia is approved for obese people (having a BMI of 30 or higher) and those who are overweight (with a BMI of 27 or higher) who also have other health risk factors such as diabetes or high cholesterol. (Meridia may help these conditions by facilitating weight loss.) “It’s most effective in people who complain of never feeling full,” says Fernstrom. “It takes away that bottomless-pit feeling.” Since Meridia may increase blood pressure, some doctors prescribe it to those under the age of 40 with no other heart disease risk factors. “I’ll put patients on Meridia – but I’ll check their blood pressure once or twice a month,” says Michael Steelman, M.D., a spokesperson for the ASBP. “I also often lower the dose initially to reduce side effects.”

The drug isn’t cheap – it’s about $120 per month. And Meridia, like other diet drugs, often isn’t covered by insurance. As a result, some doctors prescribe antidepressants such as Effexor, Cymbalta, or Wellbutrin instead, since they also work by altering brain chemical levels and are more likely to be covered by insurance. But antidepressants might not have the exact same effect: “They help ease any depression that may cause overeating, but they won’t necessarily control cravings,” says Fernstrom.

Zimulti (rimonabant)

THE SKINNY: Available in Europe since mid-2006 as Acomplia, rimonabant is currently under review by the FDA for prescription use here under the name Zimulti. It works on the brain’s endocannabinoid system — a system that plays a crucial role in regulating food intake and energy expenditure. The drug helps shut off appetite by reducing levels of insulin, a hormone that promotes fat storage, explains Louis Aronne, M.D., director of the Comprehensive Weight Control Program at the New York–Presbyterian Hospital/Weill Cornell Medical Center in New York City. Diabetics who took rimonabant for six months lost two-and-a-half times more weight (15 pounds versus 6 pounds) than those taking a placebo, according to a study sponsored by Sanofi Aventis, the drug’s manufacturer. Rimonabant was also found to significantly lower blood sugar, raise HDL (”good”) cholesterol, and lower triglycerides (harmful fats in the blood linked to heart disease).

THE RISKS: People who took rimonabant were slightly more likely to suffer anxiety and depression. “Since this drug works by inhibiting the pleasure center of the brain, it may trigger or exacerbate these conditions,” explains George Blackburn, M.D., director of the Center for the Study of Nutrition Medicine at the Beth Israel Deaconness Medical Center in Boston. Some experts question whether rimonabant is safe for people with even mild depression. “I would be comfortable with prescribing Zimulti to patients as long as I’m monitoring them for any mood changes,” says endocrinologist and obesity specialist Scott Isaacs, M.D., author of The Leptin Boost Diet.

IS THIS PILL FOR YOU? Clinically obese people with low levels of HDL cholesterol and high levels of triglycerides, who also have no history of anxiety or depression, are the best candidates for this drug, says Apovian.

Glucophage (metformin) and Byetta (exenatide)

THE SKINNY: These two diabetes drugs are also being prescribed by obesity specialists to aid weight loss in diabetics. Glucophage lowers glucose levels and increases insulin sensitivity, so you’ll be less hungry and less likely to overeat, explains Cederquist. It’s often used with Byetta, an injectable diabetes drug that delays the movement of food from your stomach into your small intestine, so it may extend fullness and help you to eat less. About 80 percent of women who took metformin with astragalus while following a modified carbohydrate diet lost about 10 percent of their body weight within a year, a New York Medical College study found. And just over 90 percent of them had kept the weight off four years later. According to another study, diabetics who had a weekly injection of Byetta alone lost 8 pounds after 15 weeks.

THE RISKS: Both drugs can initially cause nausea, upset stomach, and diarrhea – which may be partly responsible for weight loss, says Isaacs.

IS THIS PILL FOR YOU? These medications are for people who are diabetic or those who are overweight (having a BMI of 25 or more) and also have elevated blood sugar levels and diabetes. Since both drugs are approved to treat diabetes, they’re more likely than the other diet pills to be covered by insurance. “We also use these drugs in women who have polycystic ovarian syndrome (PCOS), a hormonal condition linked with insulin resistance that may cause weight gain, acne, and irregular periods,” says Fernstrom. “Once we get sufferers’ insulin under control, their PCOS symptoms improve and they often lose weight.”

What about supplements?

Think these “natural” weight-loss aids are a safe option? Think again. You’ve heard and seen their benefits extolled on infomercials – from “lose 30 pounds in 30 days” promises to miraculous before-and-after photos – and they’re sold everywhere, from your local drugstore to the Internet. But just because these dietary or weight-loss supplements claim to be made with herbs and other naturally occurring ingredients doesn’t mean you can take them without worry. “Dietary-supplement companies aren’t required to show clinical data on their efficacy and safety to the FDA, which means we have no idea whether they work or if they’re safe,” says Michael Steelman, M.D., an obesity specialist in Oklahoma City.

Take bitter orange extract, a substance that has replaced ephedra as an ingredient in many weight-loss supplements. (Ephedra was banned in 2004 after causing more than 16,000 adverse events, including several cases of stroke and death.) Two products containing bitter orange – Advantra Z and Xenadrine EFX – were found to increase heart rate, and Xenadrine increased blood pressure by 7 percent to 12 percent in participants in a University of California San Francisco study. What’s more, bitter orange doesn’t appear to help people lose weight, according to a research review. And while there may be some truth to the weight-loss promises of hoodia, a cactuslike plant said to be used by African bushmen to stave off hunger, a lot of the products that claim to be made with hoodia don’t actually contain much or any at all, says Lona Sandon, R.D., a spokesperson for the American Dietetic Association. Hoodia’s a protected plant, and many experts suspect that companies replace some or all of it with another species of the same plant. Whether hoodia itself is harmless is unclear, but products that use it often contain other potentially dangerous ingredients, such as bitter orange.

To find out more about these and other common supplement ingredients such as hydroxycitric acid (HCA, found in Hydroxycut) and chromium (found in Trimspa), visit

There are two supplements that may have some safe body fat – and weight-loss potential: green tea extract and conjugated linoleic acid (CLA). Green tea contains EGCG, an antioxidant that may help boost metabolism, according to some studies. CLA, found naturally in dairy, was shown to reduce body fat in one small study, though participants’ weights stayed the same. But the amounts found in EGCG and CLA supplements vary and some may not be effective, says George Blackburn, M.D., an obesity specialist at Harvard Medical School. Instead, he suggests getting these compounds through food, whether by including green tea at breakfast or by adding an extra glass of skim milk to your daily diet.

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