The problem
To a cynic like me, epidemic is an overused word -- most often overused by someone holding out their hat while looking for a handout for their particular cause or special interest -- but in the case of obesity, it's spot-on.

Roughly 30% of all adults in America are obese (and two-thirds of everyone in the country qualify as either obese or overweight), and the percentages keep rising -- particularly among minorities and children. According to data presented by the Centers for Disease Control, roughly 9% of all medical spending can be attributed to excess body weight -- a whopping $93 billion a year and growing.

What's more, we all know the tagalong risks that go with obesity -- heart disease, diabetes, sleep apnea, lower quality of life, etc. Even if you don't believe the stats, look around the next time you're at a mall or out in public. On even such a superficial level, it's clear that obesity is a problem.

While obesity is a serious medical issue, that doesn't mean that it's somehow off-limits to those seeking profits in the stock market. Accordingly, I believe there are at least a few separate avenues that investors can explore in the hunt for profitable means of reversing this serious trend in our society, and I'll look at them in this commentary and another one tomorrow.

Modifying one's diet is almost always the first line of attack in obesity. Odds are, almost every single person reading these words has tried to diet at least once in their life. There are no shortages of crackpot theories and fads in the diet world, though most drain more weight from your wallet in the form of self-help books than they drain from your waist.

Though dieting is most often accomplished via a self-help book or a long-term physician-guided program, there are two significant publicly traded dieting angles. Weight Watchers (NYSE:WTW) and NutriSystem (AMEX:NSI) are generally acknowledged as the leaders in dieting or behavior-modification approaches, or both.

To its credit, Weight Watchers is the only dieting system that has the support of long-term clinical studies. In other words, there's proof that it works. Unfortunately, as I highlighted in an earlier piece, that clinical proof isn't helping profitability too much these days. What's worse, the company has a high debt load, and valuation on the shares is pretty steep.

While results from Weight Watchers have been a little thin, NutriSystem is growing strong of late. With prepackaged meals that take a lot of the hassle and confusion out of dieting, there is certainly a convenience angle to the company's approach.

That angle seems to be paying off; sales were up nearly 90% in the fourth quarter, and management expects 100% growth for the first quarter. Although NutriSystem's revenue and market cap ($39 million and $182 million, respectively) are tiny compared with Weight Watchers ($1 billion and $4.3 billion), NutriSystem's numbers are growing much faster.

That said, NutriSystem can't produce the clinical data that Weight Watchers has. Without that data, many dieticians question how many NutriSystem dieters are able to maintain their weight loss once they switch back to preparing meals for themselves after eating the company's prepared meals.

Although there are things to like about NutriSystem (including its growth, profitability, and strong return on equity), the stock was trading at about $1 a share late last year, though shares have moved up to more than $6 each since then, and the company is still pretty small. That said, there are aspects that make it intriguing for further due diligence -- the stock is barely covered, there's good insider ownership, and the company has no debt. I don't know about you, but that sounds to me like maybe it's worth at least a second look.

When diets fail (as they often do), some people look to their doctor for help, and the next step might be pharmaceuticals. Drugs are a treatment option with obvious appeal. There's no pain, no sweat, and no hard work involved. Given that many people with obesity are obese precisely because they're not willing (or in some cases, able) to exercise, a weight loss pill is an obvious winner.

For all of their obvious appeal, weight-loss drugs have been tricky. Most compounds have failed to produce any meaningful sustained weight loss, and some of those that have led to weight loss have also proved to be too dangerous to use.

For years now, Wyeth (NYSE:WYE) has been under a cloud of lawsuits as former users of Pondimin and Redux have lined up to get compensated for the side effects of the drugs. Many pharmaceutical companies have taken the "Wyeth lesson" to heart and won't advance early stage obesity compounds if they show even a hint of potentially serious side effects.

Drugmakers also face competition from the frauds, charlatans, and scam artists who offer their own unapproved "pharmaceutical" treatments for obesity. While most of these are fortunately little more than innocuous concoctions of ineffective herbs or sugar, some can actually be dangerous. While it might be nice to think that the Food and Drug Administration has the resources to shut down all of these scammers, the reality is that the crooks are usually a step or two ahead of the cops.

At present, dieters wishing to go the drug route pretty much have the choice of phentermine or two other drugs. Those two drugs on the market, Meridia from Abbott Labs (NYSE:ABT) and Xenical from Roche, have both failed to set the world on fire.

While the two drugs have different mechanisms of action -- Meridia reduces hunger while Xenical inhibits fat absorption -- both work best in conjunction with a low-calorie diet. Though it might not be fair to categorize either drug as disappointing (they do, in fact, work), they certainly haven't reached blockbuster status.

Nevertheless, there are some drugs in clinical trials that are worth watching. This list does not include existing drugs that may be explored for weight-loss potential. In particular, it seems as though many neurological compounds for conditions such as epilepsy, psychosis, and the like seem to have a weight-loss benefit. Of course, these are powerful medications (and often have unpleasant side effects), and it's quite uncertain at this point as to whether any of these compounds will be "repositioned" into obesity drugs.

I'd like to also point out that this is not a comprehensive list -- I'm sure I've overlooked at least one company with a drug in clinical studies for obesity -- so I don't want to get a bunch of nonsense emails about how I'm part of some cabal to short your little biotech/giant pharmaceutical stock into oblivion.

Sanofi-Aventis (NYSE:SNY) appears to have a real winner with Acomplia. In clinical trials, this cannabinoid receptor antagonist has been shown to lead to an average weight loss of about 19 pounds, or 8.5 kilograms, while also lowering cholesterol. Better still, roughly one-third of patients who received Acomplia lost more than 10% of their body weight. Acomplia has a tolerable side-effect profile (nausea and diarrhea) and also appears to be effective in treating nicotine and alcohol abuse.

Biotech company Amylin Pharmaceuticals (NASDAQ:AMLN) is getting into the game with its SYMLIN compound (pramlintide acetate). Recently approved for use in helping insulin-using diabetics gain better post-meal glucose control, the drug does show a positive trend of moderate weight loss with few severe side effects.

The downside with this drug, though, is that it has to be injected, and that could make patients' compliance tricky. Nevertheless, it is in phase 2 studies and is known as AC137 (to distinguish it from the insulin indication, which will carry a different label).

In an earlier stage of testing, Amylin is also developing AC162352 -- a PYY3-36 molecule. It should also be noted that another Amylin drug, exenatide, has shown strong weight-loss effects in diabetics. Though this drug is even more problematic as a weight-loss candidate (because of sometimes severe nausea and multiple injections), a long-acting formulation in development for type 2 diabetes could prove to be more appealing. It must be noted, though, that Amylin is not currently developing exenatide as an obesity drug.

Several companies also have earlier-stage drugs in development. Arena Pharmaceuticals is in phase 2 studies of APD356, a G-protein coupled receptor antagonist. Nastech is in trials with a nasally administered version of the PYY3-36 peptide and recently signed a partnership with Merck (NYSE:MRK).

Peptimmune (a spinout of Genzyme) is in phase 1 studies of its novel pancreatic lipase inhibitor, and British biotech Alizyme is in late phase 2 studies for its own lipase inhibitor (and looking to begin U.S. trials shortly).

Last but certainly not least, Amgen has moved past its leptin disappointments and has three separate obesity projects running (one of which is in phase 2).

It should also be noted that Regeneron Pharmaceuticals hasn't yet completely abandoned its drug Axokine. While antibody formation seems to mute the efficacy of the drug, it did show trends toward weight loss. That said, given that the company has no new trials planned now, investors shouldn't expect much (if anything) from this program.

Part One conclusion
As we close this first half of our two-part series on obesity, it's clear that this is a market rife with potential and problems. In particular, finding a weight-loss solution -- whether it is a diet or a drug -- that is safe, effective, and acceptable to the consumer has proved to be tricky.

While I'm not sold on the long-term potential for publicly traded diet companies, I do think investors should spend a little due diligence on the drug side of the equation. Remember, though, to evaluate the entire company -- not just its prospects in the obesity market. Given the miserable track record of pharmaceutical candidates for obesity, any investor willing to bet the farm on a single drug in early-stage clinical trials is taking an outsized risk.

For more on this topic, look for Part 2 of this commentary tomorrow.

For a head start in getting up to speed on some of these ideas, take a look at these other Foolish thoughts:

Merck is a Motley Fool Income Investor recommendation. For other income-generating ideas, consider taking a free, no-obligation trial today.

Fool contributor Stephen Simpson owns shares of Sanofi-Aventis, Amylin Pharmaceuticals, and Johnson & Johnson. The Motley Fool is investors writing for investors .