The fire intensifies

The fire intensifies

Yesterday the FDA issued the following safety announcement;

“The U.S. Food and Drug Administration (FDA) has strengthened the warning for the type 2 diabetes medicine canagliflozin (Invokana, Invokamet) related to the increased risk of bone fractures and added new information about decreased bone mineral density. Bone mineral density relates to the strength of a person’s bones. To address these safety concerns, we added a new Warning and Precaution and revised the Adverse Reactions section of the Invokana and Invokamet drug labels.”

Yet Invokana is not the only drug that has come under fire by the agency as they also added a joint-pain warning to the official labeling on the entire DPP-4 class. In this class is Januvia from Merck (NYSE:MRK) which is a mega-blockbuster.

The question now is how or whether these labels changes will have a material impact on the sales of DPP4’s and SGLT2’s. With $596 million in sales for first half of the year Invokana was on track to reach blockbuster status this year. Over the same time frame the Januvia franchise has racked up nearly $3 billion in sales. Needless to say with this type of money at stake there is cause for concern.

Yet on the flip side of this bad news Lilly (NYSE:LLY) received some good news for their SGLT2 Jardiance which last month was able to claim to be the first diabetes drug to show that it can lower the risk of heart attack, stroke and death from cardiovascular causes. Although the FDA safety announcement was aimed at Invokana it did contain the following statement; “We are continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empagliflozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed.”

So on the one hand it may appear that Jardiance has a leg up on other SGLT2’s based on the cardiovascular data, it may also have the same bone fracture issues which are currently plaguing Invokana. The simple fact is until the agency evaluates the risk for other SGLT2’s we just don’t know.

Now here is where things get interesting, let’s assume for a moment that Invokana has the same cardiovascular benefits as Jardiance and Jardiance turns out to have the same bone fracture risks as Invokana. What then? What’s more important the cardiovascular benefits or the bone fracture risks? Considering diabetes can increase the risk of heart disease and strokes, having a drug that can treat the disease and a side effect of the disease would seem to be a big claim to be made. Yet given that the FDA felt it necessary to issue a safety alert for the bone fracture risk this issue cannot be dismissed as unimportant.

But wait it gets even crazier what about combination meds which combine a DPP4 and SGLT2 into one pill, Merck among others is working on just such a pill. What happens then? Even without such a pill this combination is already being used today as physicians have become more aggressive when treating their patients.

We can’t help but wonder how our good friend that crusading cardiologist Dr. Steven Nissen fells today. As thanks to the good doctor cardiovascular issues with diabetes meds has become an obsession. On the one hand the good doctor must be thrilled with the Jardiance cardiovascular data, yet being a physician the bone fracture risk may dampen his enthusiasm. Talk about irony.

Yes we’ve said it before but the real losers here are physicians and the patients they treat. Patients who want a simple answer to what seems like a simple question; “Are the drugs I am taking to treat my diabetes safe?” Does the physician take patients off these drugs due to the risk? Or do they feel that the risk of poorly controlled diabetes outweighs the risks of these drugs? As we witnessed during the Avandia controversy many patients stopped taking all of their diabetes meds altogether and not just Avandia.

Not like the situation needs to be more complicated but just which drug or drugs would a physician use should they determine there is an unacceptable level risk with DPP4’s or SGLT2’s. Sure they could move these patients to insulin or a GLP-1 but these drugs also carry their own risk profile.

We hate to keep repeating ourselves but the fact is there is no such thing as a completely safe drug. This is pure fantasy. The reality is patients need to be made aware of risks but also informed of the risk of poorly controlled diabetes. Some perspective and balance must be factored into the equation. Diabetes management is complex enough as it is and it frankly it doesn’t get easier when it seems like every drug on the market used in treating diabetes carries with it an unfavorable risk profile. When the reality is the complications from poorly controlled diabetes are worse than the risk associated with these drugs.

Let’s not lose sight of that.