Do diet pills really work?

With almost 70 percent of the U.S. population overweight or obese, it’s no surprise that the number one New Year’s resolution each year is to lose weight. Now that you or someone you know has made this resolution, what are you going to do about it?
Roughly 50 percent of people make New Year’s resolutions, and 71 percent of people maintain their resolve for the first two weeks. In six months, about half are still working toward their goals, at least to some degree. So about half of us make resolutions and about half of us stick to them at least halfway through the year (1). The good news is that people who make resolutions are about 10 times more likely to reach their objectives than those who don’t (2). So don’t give up!
Wouldn’t it be nice if we had a silver bullet that would help us lose weight without much thought? Are diet pills at least part of the answer? Diet pills, both medications and supplements, have a checkered past. But don’t despair, the armament of diet pills is beginning to grow. Two drugs were approved in 1999: Xenical (orlistat) and Meridia (sibutramine). Meridia was subsequently withdrawn due to side effects. Since then, the options have expanded with the 2012 approval of two additional drugs: Qsymia (phentermine-topiramate combination) and Belviq (lorcaserin). And finally, we have two new medications, approved in the latter half of 2014: Contrave (naltrexone-buproprion) and Saxenda (liraglutide). At this point, you need a playbook to keep them straight.
How do we evaluate weight-loss drugs? There are two important parameters: effectiveness in weight loss and impact on health. Drugs considered modestly effective cause at least 5 percent weight loss. Those that cause 10 percent weight loss are considered very good. Those that cause over 15 percent weight loss are considered excellent.
Let’s look at the history of diet drugs, along with evidence on the two newest entrants.
DIET PILL’S BLACK EYE
Unfortunately, diet pills’ track records have made both the medical community and the population at large leery. One of the most notorious medications was Fen-phen (fenfluramine-phentermine combination). While this drug combination helped people lose weight, it also had some serious side effects, pulmonary hypertension and heart valve defects resulting in serious adverse events and even mortality in some patients who took the drug. It was withdrawn from the market in 1997 by the FDA (3). Fenfluramine was blamed for causing these side effects, not phentermine. The reason I highlight this is that another more recent combination uses phentermine.
In terms of supplements, green coffee bean extract had been touted for its weight-loss capabilities based on a small 2012 study funded by the manufacturer (4). However, the FTC took this study to task, noting that the lead investigator changed the weights of patients, altered the length of the trial and could not determine which patients actually took supplement or placebo. In 2014, the journal responsible for publishing the research retracted the results (5).
This brings up another point. Green coffee bean supplements were promoted on a TV medical talk show. A recent study looked at the validity of advice given on these shows. Research evidence that supported the shows’ claims was found only half the time, and it was usually only from small studies or case studies. Unfortunately, the magnitude of benefit, the side effects, conflicts of interest and costs were highlighted on the shows no more than 20 percent of the time (6). So caveat emptor or, as “The Doctors” show says many times, consult your physician.
DRUGS WITH LONGER
TRACK RECORDS
There have been two established drugs since 1999: Xenical (orlistat) and Meridia (sibutramine). In a meta-analysis (a group of 14 randomized controlled trials, 11 with orlistat and 3 with sibutramine), results showed that there was a mean reduction in weight of 2.9 percent with orlistat and 4.6 percent with sibutramine (7). Also, there were only 12 percent of patients on orlistat and 15 percent of patients on sibutramine who achieved greater than 10 percent body weight reduction when compared to placebo. To boot, both drugs have side effects. Orlistat is known for causing gastrointestinal (GI) side effects.
Another smaller trial with Alli (orlistat over the counter) found that those who followed diet and exercise regimens while taking the drug saw a median 5 percent reduction in weight over a two-month period. The patients were satisfied or very satisfied with the results, despite GI side effects after three months of study duration (8).
Orlistat assessment: modest efficacy and mild-to-moderate side effect profile.
Sibutramine was taken off the market in 2010 due to increased risk of cardiovascular events (3).
NEWLY APPROVED DRUGS BETTER?
Two drugs are recent enough that they don’t have track records in the marketplace. In September 2014, Contrave (naltrexone-bupropion) was approved by the FDA (3). In a large randomized controlled phase 3 trial, naltrexone-bupropion demonstrated significant effectiveness over placebo (9). The mean weight lost was 5.0 percent in the low-dose drug and 6.1 percent in the high-dose drug, whereas the placebo demonstrated a 1.6 percent reduction. These results were seen over 56 weeks. Nausea was the most common side effect, occurring in 30 percent of patients. The drug did also raise blood pressure 1.5 mmHg initially. There is an ongoing study intended to demonstrate no increased risk of heart attack, and interim results have been good.
There is a black box warning that patients may have suicidal thoughts because of bupropion, an antidepressant. Ultimately, Contrave reduces weight by an additional 4.1 percent over placebo (3). This medication can be used for those who are obese (BMI>30 kg/m2) or who have a BMI>27 kg/m2 with an additional weight-related disease, such as diabetes or high blood pressure.
Naltrexone-bupropion assessment: modest effectiveness and mild-moderate potential side effect profile. If the drug does not reduce the weight when using maintenance dose by at least 5 percent in 12 weeks, it should be discontinued according to the FDA (3).
The latest drug, Saxenda (liraglutide), was approved in December 2014. In a randomized controlled trial with a 56-week duration, liraglutide resulted in a 6.2 percent reduction in weight, whereas the placebo had 0.2 percent reduction in weight (10). Interestingly, the researchers required that all participants have a pre-trial period of lifestyle modifications, which resulted in a 6 percent weight loss prior to the trial. The treatment population is the same as for naltrexone-bupropion, either obese (BMI>30 kg/m2) or a BMI>27 kg/m2 with an additional weight-related disease, such as diabetes or high blood pressure. Liraglutide is an injectable diabetes drug in the class referred to as GLP-1 agonists. The dose is higher for weight-loss patients. The side effect profile was mainly associated with GI distress.
Liraglutide assessment: modest effectiveness and mild side effect profile.
Interestingly, metformin has been used as an off-label weight-loss drug as well, meaning not approved by the FDA for that use, but at the discretion of the physician.
Your best recourse is always lifestyle changes, but a diet drug could help jump start your resolution to lose weight. The medications have very similar modest effectiveness and mild-to-moderate side effect profiles. However, the newer drugs do not have post-marketing safety data yet. Even if you start a diet medication, diet and exercise are highly recommended or else the results may not be achieved with medication alone. I can’t stress it enough: always consult your doctor before starting a weight-loss drug.
REFERENCES:
(1) statisticbrain.com. (2) J Clin Psychol. 2002 Apr;58(4):397-405. (3) FDA.gov. (4) Diabetes Metab Syndr Obes. 2012;5:21-7. (5) Diabetes Metab Syndr Obes. 2014;7:467. (6) BMJ. 2014;349:g7346. (7) Int J Obes Relat Metab Disord. 2003;27:1437-1446. (8) Obesity (Silver Spring). 2008;16:623-629. (9) Lancet. 2010;376:595-605. (10) Int J Obes (Lond). 2013;37:1443-1451.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management.  For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.