Bad News Type 2 Diabetics: The FDA Is Out With Another Warning

Source: Centers for Disease Control and Prevention.

According to the Centers for Disease Control and Prevention, 29.1 million Americans, or 9.3% of the population, have diabetes, an imbalance in the blood sugar that can lead to a bevy of long-term problems if left untreated.

Somewhere between 5% and 10% of diabetics are of the type 1 variety, which is a genetic form of the disease causing an individual to be incapable of producing insulin. The remaining 90% to 95% of cases are of the type 2 variety, which develops over time and is a result of the body not utilizing insulin properly. Per the CDC, about a quarter of these 29.1 million Americans have no clue they have this disease. Furthermore, 86 million Americans, or more than one in three adults, have prediabetes. About 90% of these individuals are unaware they have prediabetes.

Diabetes may not be a swift killer like cancer, but it's nonetheless one of the leading causes of death in the United States. The CDC notes that a patient's risk of death jumps by 50% if they have diabetes. It's also extremely costly, with the tangible cost for medical care, and the intangible factors such as lost work, amounting to $245 billion per year.

This is why early diagnosis and diabetes treatments play such key roles in keeping this disease under control.

DPP-4 inhibitors and SGLT-2 inhibitors square off The diabetes field has two dominating classes of prescription drugs: DPP-4 inhibitors and the relatively new SGLT-2 inhibitors.

Oral DPP-4 inhibitors work by increasing incretin levels in the pancreas, which in turn inhibit the release of glucagon in the liver. Glucagon is responsible for pushing up your blood sugar levels. The best known DPP-4 inhibitor is Merck's Januvia, which is currently on pace to generate about $6 billion in sales in 2015.

The newer class is SGLT-2 inhibitors, which work by blocking the absorption of glucose in the kidneys and allowing a type 2 diabetic to excrete excess glucose through urine. The three best-known SGLT-2 inhibitors to hit pharmacy shelves are Johnson & Johnson'sInvokana, Eli Lilly's and Boehringer Ingelheim's Jardiance, and AstraZeneca'sFarxiga.

The battle for type 2 diabetic customers between these two classes of drugs is expected to be fierce, with each sporting its own advantages.

Source: National Cancer Institute.

In the case of Januvia, Merck has established nine years of rapport with physicians and patients, and a long-term cardiovascular outcomes trial known as TECOS recently demonstrated that Januvia met its primary endpoint of not leading to an increase in cardiovascular-relate death, non-fatal heart attacks, non-fatal strokes, or hospitalization due to heart disease compared to patients not on Januvia.

On the other hand, SGLT-2 inhibitors have a few tricks up their sleeves. SGLT-2 inhibitors were shown in clinical studies to have a welcome side effect of weight loss -- which is good news, since diabetes and obesity are correlated more often than not. For added context, Januvia is considered a weight-neutral therapy.

Even more intriguing, last month Eli Lilly and its partner Boehringer Ingelheim announced positive top-line results for their EMPA-REG OUTCOME study. This long-term trial examined Jardiance's effect on patients' cardiovascular systems, with the results showing that Lilly's and Boehringer's drug was superior to the current standard of care. No previous long-term cardiovascular study has demonstrated a cardiovascular event risk reduction before, meaning Jardiance -- and perhaps other SGLT-2 inhibitors -- could be gaining an upper hand over DPP-4s.

Houston, we have a problemAlthough both drug classes have plenty of sales momentum and an undeniably large group of untreated and undiagnosed patients left to tap, they also share a problem: recent warnings from the Food and Drug Administration.

Source: Merck.

In May the FDA released a safety announcement warning patients taking SGLT-2 inhibitors that they could be at greater risk of ketoacidosis, a condition where high levels of acids build up in the blood, often requiring hospitalization. Between March 2013 and through June 6, 2014, the FDA pointed out that 20 instances of acidosis in patients treated with SGLT-2 inhibitors had been reported, with more cases suspected since then. Though the FDA is not advising patients to stop taking SGLT-2 inhibitors by any means, it is further examining the safety of SGLT-2 inhibitors, and the agency could require a warning label update at some point down the line.

This past week, DPP-4 inhibitors were also in the FDA's sights. According to the FDA, between Oct. 16, 2006 and Dec. 31, 2013, it had identified 33 instances where DPP-4 inhibitors have been linked to severe joint pain. Despite a number of DPP-4 inhibitors being on the market, Januvia was responsible for 28 of those reported cases. As with SGLT-2 inhibitors, the FDA didn't recommend type 2 diabetics cease taking their medication, but encouraged physicians to keep an eye out for joint pain potentially tied to Januvia and other DPP-4 inhibitors (Januvia accounts for about three-quarters of all DPP-4 sales).

Which class of diabetes drug will prevail?FDA warnings are never a particularly good thing, but considering Januvia's long treatment history and successful track record, along with its TECOS trial results, I can't foresee its sales slumping because of the FDA's latest warning.

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The FDA warning for SGLT-2 inhibitors is perhaps a tiny bit more worrisome, only because the incident rate is markedly higher than DPP-4's on an annual basis, and it could lead to an eventual reworking of SGLT-2 inhibitor drug warning labels. Still, neither warning should result in a notable reduction in sales or interest from physicians or consumers -- at least the way I see it.

The big question that's still up in the air is which class of type 2 diabetes drug will be the go-to in the coming years. Januvia has the tenure, but SGLT-2s can offer weight loss (even though they're not indicated for it); and Jardiance can also claim a possible cardiovascular benefit.

Now we play the waiting game. What we really need to see is just how substantial the cardiovascular benefit for Jardiance is compared to the placebo, because that could make a world of difference in terms of whether or not consumers or physicians try to switch off Januvia in favor of an SGLT-2 inhibitor. For what it's worth, I don't see a scenario where Januvia's sales fall off a cliff, even if Jardiance's fully released data is incredibly good -- but I suspect Januvia's best days could be in the rearview mirror, with pricing increases remaining Merck's final resort to growing top-line sales of the drug.

The article Bad News Type 2 Diabetics: The FDA Is Out With Another Warning originally appeared on

Sean Williamshas no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen nameTMFUltraLong, track every pick he makes under the screen nameTrackUltraLong, and check him out on Twitter, where he goes by the handle@TMFUltraLong.The Motley Fool recommends Johnson & Johnson. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

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