The American Diabetes Association annual meeting wraps up today, with a few companies making a splash -- both the perfect-10-entry kinds, as well as a few belly flops.

Diabesity: Half diabetes, half obesity
Perhaps the biggest winner from the ADA meeting wasn't even a diabetes drug at all, but  Orexigen Therapeutics' (Nasdaq: OREX) obesity drug Contrave. Given the linkage between the two -- obesity is a risk factor for developing type 2 diabetes -- that shouldn't be much of a surprise.

Orexigen shot up 18% yesterday, after the company presented data showing that roughly 44% of obese patients taking Contrave hit the target for healthy blood glucose levels, compared to 26% of patients taking placebo.

Contrave doesn't have the most stellar weight-loss data, and it has plenty of potential competition, but the diabetes angle could be enough to give the drug some added heft (sorry).

At the very least, it's a potential backup plan.

Avandia: Take number 237
Believe it or not, we're still talking about GlaxoSmithKline's (NYSE: GSK) Avandia, some three years after Dr. Steven Nissen presented his meta-analysis linking Avandia to heart problems. Sales have dropped substantially, but Glaxo still managed to sell $1.2 billion worth of Avandia-containing drugs last year.

Two more studies focused on heart issues were published in conjunction with the ADA meeting this week. The first was an update to Nissen's original analysis, pooling data from 56 different studies. The bad news for Glaxo is that the new analysis showed a 28% increase in the risk of heart attacks for patients on Avandia. But there's good news: That's down from the original study of 42 clinical trials, which said there was a 43% increase in the risk of heart attacks. A second study showed an 18% increase in heart attacks when Avandia was compared to Takeda's Actos.

The renewed debate comes just before next month's two-day advisory committee meeting by the Food and Drug Administration, which could set the stage for the FDA to consider pulling Avandia off the market.

At this point, losing the drug isn't as big a loss for Glaxo, but it would still be a 2.7% hit to the company's total revenue. Actos and Merck's (NYSE: MRK) Januvia would be the clear beneficiaries if the FDA took such a drastic step.

Innovation is the key
The diabetes space is a crowded field; there are oral compounds like Actos and Januvia, and injectable drugs like Eli Lilly (NYSE: LLY) and Amylin Pharmaceuticals' Byetta and Novo Nordisk's Victoza. And those are just the compounds used before diabetics transition to insulin.

For a drug to break into this tightly packed space, it needs to be innovative. Bristol-Myers Squibb (NYSE: BMY) and AstraZeneca have learned the hard way with Onglyza, a copycat that has started out with lackluster sales. The drug acts under the same mechanism as Januvia, and it doesn't seem to offer any material benefits.

The duo is out with a new offering, dapagliflozin, which works under a different mechanism. Dapagliflozin looked good in the phase 3 trial presented at the ADA, although it was tested as an add-on therapy against placebo. The real money lies in first-line therapies.

Johnson & Johnson (NYSE: JNJ) also has a similar drug, canagliflozin, which it tested against Januvia. Canagliflozin lowered glucose levels more than Januvia, but the trial wasn't big enough to prove that the difference was statistically significant.

Mannkind (Nasdaq: MNKD) got a nice boost going into the meeting, where it presented more data supporting its case for approval of its inhaled insulin Afrezza. But data isn't the missing ingredient in Mannkind's success; it's whether a novel drug delivery system will convince doctors to prescribe inhaled insulin, when the injectable kind works reasonably well. The marketplace, not the ADA meeting, will decide Mannkind's long-term future.

We're not getting any thinner
Diabetes is an epidemic, and where there's growth in the number of potential patients, there's money to be made. Analysts predict that two of the top 10 drugs in 2014 will treat diabetes; this year, none cracked the top 10.

Investors would be smart to pop open a can of diet soda, drop a few pounds, and keep an eye on the space. There's bound to be a few more pops and drops.

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Fool contributor Brian Orelli, Ph.D., doesn't own shares of any company mentioned in this article. The Fool owns shares of GlaxoSmithKline. The Fool has a disclosure policy.