Sometimes you don't have to look very hard for an investment idea. Pardon the pun, but obesity is a pretty big problem in the U.S. You certainly don't need to work at Weight Watchers or a gym to see that Americans are overweight.

While gyms and diets are certainly one way to fix the problem, they don't seem to be doing a whole lot of good; Americans have become more overweight with each passing year. Ultimately, Americans might get out of this mess the same way we got fat in the first place -- a lazy fix, in the form of a drug.

Unfilled market
You'd think that weight-loss drugs would create a multibillion-dollar market, but that hasn't happened yet.

Part of the problem is that the drugs just don't work terribly well. In clinical trials supporting Abbott Laboratories' (NYSE: ABT) Meridia, for instance, obese patients lost just 10-15 pounds more than patients not taking the drug. While every little pound helps, drugs like Meridia don't seem to be the magic bullet that people are looking for.

The other problem is that the current drugs have side effects that drive prospective patients away. For example, GlaxoSmithKline's (NYSE: GSK) Alli can cause gas and other unpleasant bowel changes. And while you might think that'd provide extra incentive to people taking the drug to stay away from fatty foods, those consequences are more than some people are willing to take.

In the works
The FDA's refusal to approve Sanofi-Aventis' Acomplia for marketing in the U.S. broke the field wide open. The first company to gain approval could open up the market, although me-too drugs that work better or have better side-effect profiles could easily overcome the first mover's initial advantage.

Merck's (NYSE: MRK) Taranabant and Pfizer's (NYSE: PFE) CP-945598 both work by blocking the cannabinoid receptors in the brain. While stimulating the receptors (sometimes by smoking marijuana) gives you the munchies, blocking them causes you to lose your desire to eat. But like Acomplia, which also blocks the same receptor, the drugs can cause side effects like depression and even suicidal thoughts. Investors will get a closer look at Merck's phase 3 data later this month, but early indications suggest that the drug isn't as promising as Merck had hoped.

Arena (Nasdaq: ARNA) is targeting a different receptor, but it too could potentially have issues with side effects. Its phase 3 drug candidate, Lorcaserin, targets the same receptor as American Home Products' (now Wyeth (NYSE: WYE)) fen-phen. One-year safety data from its two-year trial is due out this month, which should give insight into whether the drug causes the same heart-valve issues fen-phen did.

Farther behind in the pack, Amylin Pharmaceuticals (Nasdaq: AMLN) is testing a combination of its diabetes drug Symlin and an analog of leptin, a signaling molecule that regulates energy metabolism and body weight. The combination showed promising results in its phase 2 trial, but we'll need a longer phase 3 trial to know for sure whether the drug combination really works. Like Novo Nordisk's liraglutide, Amylin's only downfall might be that its drug is injected, which could potentially scare off some patients if it doesn't produce stellar results.

Risk vs. reward
The biggest problem for obesity-drug makers might not be the amount of pounds the drugs shed, but their safety in doing so.

All drugs have some side effects, but the acceptable level of side effects is generally tied to how likely one is to die of the disease. Thus, anti-cancer drugs can gain FDA approval with horrible side effects -- think hair loss and nausea -- but drugs that treat less severe diseases aren't as liberally approved.

Given the history of side effects for weight-reducing drugs, investors should be cautious about the value they ascribe to drugs in the pipeline until all the long-term safety data is in. Waiting to invest might not fatten up your wallet as much, but it'll sure keep you from losing your shirt -- a side effect of failed phase 3 trials.

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Fool contributor Brian Orelli, Ph.D., wouldn't mind losing a few pounds. He doesn't own shares of any company mentioned in this article. Even when printed on 60 lb paper, the Fool's disclosure policy is lightweight.