In today's matchup, we have two drugmakers both waiting for decisions from the Food and Drug Administration about their diabetes drugs: Amylin Pharmaceuticals (Nasdaq: AMLN) and MannKind (Nasdaq: MNKD).

Which one's the better buy? Let's take a closer look.

A little background
Amylin's Bydureon and MannKind's Afrezza won't actually compete with each other, as they're used by diabetics during different stages of their disease development.

Bydureon is a long-lasting version of Amylin's Byetta, which is typically prescribed after oral medications are no longer effective at keeping blood glucose levels down in type 2 diabetics. Unlike Byetta, which has to be injected twice a day, Bydureon only has to be injected once a week, thanks to an extended release technology developed by Alkermes (Nasdaq: ALKS).

Afrezza is an inhaled insulin product that would compete with injected insulin given to type 2 diabetics after their disease has progressed substantially, as well as type 1 diabetics. The drug has passed multiple phase 3 trials.

Market
On the surface, Afrezza looks to have the upper hand here. If the drug works as well as or better than injected insulin, who wouldn't want to give up syringes and pumps for an inhaler?

Apparently, diabetics. Exubera, an inhaled insulin product developed by Pfizer (NYSE: PFE) and Nektar Therapeutics (Nasdaq: NKTR), was a marketing flop. Afrezza has a lot more going for it than Exubera, including having a much smaller delivery device, but I think adoption is likely to be slow as doctors warm to the idea of a different mode for taking insulin.

Bydureon needs to do a lot more than just replace Byetta to be successful. Victoza, Novo Nordisk's once-daily drug in the same class, should be fairly easy to pick off -- one shot a week is still better than seven -- but Amylin and marketing partner Eli Lilly (NYSE: LLY) really need to get Bydureon prescribed earlier in diabetics' disease development. Investors should keep an eye on how well the duo are doing at taking away patients from oral medications such as GlaxoSmithKline's Avandia, Merck's (NYSE: MRK) Januvia, and Takeda's Actos. If they can make a substantial push into the multi-billion market, Bydureon will be a success.

Approvability
Both drugs are awaiting their second attempt at approval by the FDA, but Bydureon has a greater likelihood of approval.

When Bydureon was turned down by the FDA back in March, shares in Amylin and Alkermes, which will get royalties from the drug, both shot up by double digits. The FDA response, while not exactly what investors were looking for, made it clear that the drug was approvable as soon as the drugmakers cleared up a couple of minor issues.

The FDA's response to MannKind, on the other hand, was rather baffling. MannKind has responded to the issues, but investors still remain rightfully skeptical; shares are still well below where they were in March after the first response.

Backing
Amylin has the clear advantage here, too. In addition to a major marketing partner in Eli Lilly, Carl Icahn is also a major shareholder.

MannKind owns the full rights to its drug, which is good in the sense that it doesn't have to share revenue with anyone. But it's somewhat disconcerting that no pharmaceutical company has stepped up to license the drug. Yet.

Upside potential
With all its negatives, MannKind is clearly the winner here. At a market cap of about $800 million, there's plenty of upside. There are multiple catalysts to push the stock higher: a partnership, FDA approval, and proving skeptical investors -- and Foolish analysts -- wrong about sales.

For Amylin, an FDA approval is somewhat priced into the stock; I'd expect it to go up a little on an approval, but not nearly as much as MannKind. Purchasing Amylin is basically a bet on Bydureon being more successful than Byetta.

Different strokes for different folks
The companies are so different, I'm not sure there's a good answer to which one is best. Both could potentially fill a spot in your portfolio. MannKind is a high-risk, high-reward prospect, while Amylin is less risky but doesn't offer the same kind of potential returns in the mid-term. Determining which one (or neither) you buy is largely dependent on your risk tolerance.

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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 and has a disclosure policy.