Dominique Adair, MS, RD

*courtesy of HFPN.com*

Weight loss drugs, referred to as pharmacotherapy, have been popularly used since the 1950s, though long before that there were products available claiming to contain sanitized tapeworms available for purchase. Following several drugs such as dinitrophenol and the amphetamine-like compounds that posed serious side effects, the weight-loss drugs most commonly used today are appetite suppressants and nutrient absorption blockers.

While lifestyle measures remain the cornerstone of prevention and treatment of obesity, adding anti-obesity agents is considered by some physicians for obese patients who did not achieve sufficient weight loss after lifestyle modifications. Often positioned as an adjunct to diet and exercise, weight loss drugs are meant to supplement these behavior interventions and not to replace them. This article will review these classes of drugs, how they work, and the criteria with which physicians prescribe them to their patients.

Classes of Drugs

Today, most commonly prescribed weight loss drugs are either appetite suppressants or fat absorption blockers. For both, the goal of pharmacological intervention is to decrease feeding behavior and reduce weight. Appetite suppressants facilitate weight loss by tricking the body into believing that it is not hungry or that it is full. Most of them decrease appetite by increasing serotonin or catecholamine — two brain chemicals that affect mood and appetite. For example, the drug Subutrimine acts by increasing noradrenaline and serotonin levels in the hypothalamus, nucleus accumbens and the brainstem, all regions associated with energy homeostasis (1). Other centrally acting drugs that also work through the modification of neurotransmitters are presently being aggressively researched to determine if these novel approaches lead to clinically meaningful weight loss and improvements in comorbid conditions such as diabetes and cardiovascular disorders.

Clinical experience data on the success of these drugs suggests that weight loss produced by any one agent is limited and rarely exceeds 10% of the starting weight (2). This initial drop also plateaus. The ‘ceiling effect’ observed is probably due to adaptive changes as the body continues to maintain a balance in favor of energy conservation or the body’s metabolic “slow-down” in response to chronic underfeeding. One approach that some weight loss specialists have adopted to overcome this issue is to develop combination therapies that tackle the problem through more than one mechanism in an effort to minimize the impact of these adaptive changes.

Fat absorption inhibitors work by preventing the body from breaking down and absorbing ingested fat. These medications act on the gastrointestinal system and work by blocking the action of lipase, the fat-digesting enzyme, thereby reducing fat absorption in the gut. The non-absorbed fat is then eliminated in bowel movements. It also blocks the availability of fat-soluble vitamins (vitamins A, D, E, and K), so patients may also take a vitamin supplement (3).

The most commonly prescribed fat absorption blocker is the prescription drug Orlistat (brand name Xenical). Research has explored the effectiveness of Orlistat compared to other drug treatments, placebo, or behavior-focused interventions. Avenell et al. carried out a systematic review of trials involving a combination of diets, drug therapy, exercise, and behavior therapy and concluded that adding Orlistat to a dietary intervention improved weight loss by 3.26kg up to 24 months (4). Research also indicates that Orlistat reduces cholesterol and blood pressure levels and improves glycemic control when compared to placebo (5).

As of 2007, Orlistat became available over-the-counter (OTC). Sold as the brand name “Alli,” which is half the strength (60mg versus 120mg) of the prescription drug, Orlistat was the first clinically-proven OTC product to be combined with a comprehensive support program. Research indicates that both Orlistat and Alli can improve weight loss if used alongside behavioral and lifestyle interventions, however due to unpleasant side effects (urgent bowel movements, diarrhea, and gas with oily spotting/anal leakage) there remain problems with adherence and much variability in patient outcomes.

The Best Candidates

While each physician develops their own specific criteria for prescribing weight loss drugs, guidelines do exist. The National Heart Lung and Blood Institute’s evidence statement on pharmacotherapy for weight loss asserts:

“Weight loss drugs approved by the FDA may only be used as part of a comprehensive weight loss program, including dietary therapy and physical activity, for patients with a BMI of 30 with no concomitant obesity-related risk factors or diseases, and for patients with a BMI of 27 with concomitant obesity-related risk factors or diseases. Weight loss drugs should never be used without concomitant lifestyle modifications. Concomitant assessment of drug therapy for efficacy and safety is necessary. If the drug is efficacious in helping the patient lose and/or maintain weight loss and there are no serious adverse effects, it can be continued. If not, it should be discontinued” (6).

Before selecting a medication(s), physicians will also consider health history, possible side effects, and potential interaction of weight-loss drugs with other prescribed and OTC medications.

It is extremely important for physicians to emphasize to their patients that weight-loss drugs don’t replace the need for changes in eating habits and activity level. In fact, several studies on drug intervention alone demonstrate that once patients stop taking the drug, they may have a higher rate of regain compared with people who also have some behavior modification support (7).

Weight-Loss Drugs and the Fitness Professional

When combined with a low-calorie diet and regular exercise, weight-loss drugs produce an average weight loss of 5% to 10% of total body weight within a year, a typical initial goal for any weight-loss effort. Losing 5% to 10% of total weight may not seem like much, but even modest weight loss can improve health by:

* Decreasing blood pressure
* Decreasing lipid levels
* Decreasing blood glucose levels
* Increasing insulin sensitivity

With interventions that combine lifestyle behavior change and pharmacotherapy, it is difficult to determine how much of weight loss success can be attributed to each. Regardless, both during drug intervention and after, lifestyle behaviors, as supported by fitness professionals, remain an exceptionally important part of the success equation.

References:

(1) Sargent B and Moore, NA. New central targets for the treatment of obesity. Br J Clin Pharmacol. 2009 December; 68(6): 852–860.
(2) Tziomalos K, Krassas GE, Tzotzas T. The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009; 5: 441–452.
(3) Hollywood A, Ogden J. Taking Orlistat: Predicting Weight Loss over 6 MonthsObes. 2011;2011:806896. Epub 2010 Nov 11.
(4) Avenell A, Brown TJ, McGee MA, et al. What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions. Journal of Human Nutrition and Dietetics. 2004;17(4):293–316
(5) Padwal R, Li SK, Lau DCW. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. International Journal of Obesity. 2003;27(12):1437–1446
(6) http://www.nhlbi.nih.gov/guidelines/obesity/e_txtbk/txgd/4325.htm last accessed 12.12.10.
(7) Warziski Turk, M Randomized Clinical Trials of Weight-Loss Maintenance: A Review. J Cardiovasc Nurs. 2009; 24(1): 58–80.