Update on combination pills for people with diabetes

Health Professional

Recently, several more combination diabetes pills have become available, and I think I ought to update my previous essay on "Combination pills for type 2 diabetes" to include the new combo pills. I won't repeat many of the concepts there, so if your physician is discussing possibly prescribing combination diabetes pills with you, please review that article, Combination pills for type 2 diabetes.

Just for clarification, what I am calling "combination pills" are described more precisely by the FDA as "a fixed-dose combination (FDC) prescription medication that contains two previously approved medicines in one tablet for use in adults who need both."

At the time of the previous article (in 2008), there were not yet any combination diabetes pills that included a DPP4-inhibitor as one of the two ingredients. Indeed, at that time there was only one DPP4-inhibitor that was FDA-approved: sitagliptin (Januvia). Now there three in the US, and a fourth in Europe:  saxagliptin (Onglyza), linagliptin (Trajenta), and vildagliptin (Galvus) (the latter is approved in Europe only). With fierce competition between these manufacturers for the biggest possible slice of the pie, several new combo pills using a DPP4-inhibitor plus another diabetes drug was inevitable.

The most recent addition to the combo party is the totally unsurprising combination of a DPP4-inhibitor, sitagliptin (Januvia) plus metformin, in a pill brand-named Janumet XR. The reason it's unsurprising is that this same combination is already on the market from the same company, without the "XR" (extended release) in the name. I can't see any benefit to the manufacturer to selling both the XR version and the twice-daily version, so I'd expect the combo pill Janumet-twice-daily to quietly disappear from the marketplace. In fact, I wouldn't be surprised if the marketing department would encourage physicians and patients to swap from twice-daily Janumet to the once-daily XR version, and I wouldn't be surprised if the XR is more expensive than the twice-daily. A corporate mouthpiece is quoted in the press release as saying "JANUMET XR is a new treatment that adds once-daily convenience to the powerful efficacy of JANUMET for patients with type 2 diabetes... This is important because many patients with type 2 diabetes require treatment with multiple drugs to maintain blood sugar control, and JANUMET XR is a new option to help more patients get to their glucose goals." Well, sorta kinda. Yes, metformin is powerful; most studies show it's the best drug out there for controlling A1C. And yes, adding sitagliptin to metformin would be somewhat more powerful. But is the XR a "new treatment option"? Not exactly; it's just a more convenient way to take exactly the same two drugs as before. And inevitably more expensive: metformin is dirt-cheap, and sometimes free when retail pharmacies use it as a loss leader, so any premium that the company is placing on Janumet prices (compared to Januvia alone) seems likely to be almost pure profit.

Another new combo pill consists of another DPP4-inhibitor, linagliptin plus metformin, sold under the brand name Jentadueto. This combination was approved by the FDA last week, and is simply another DPP4-inhibitor (linagliptin instead of sitagliptin), again combined with metformin. I wonder how long before the Jentadueto marketers plays the same game as the Janumet XR people, and modify Jentadueto and re-release it as "Jentadueto XR"

And of course, expect to see the other DPP4-inhibitor, saxagliptin, combined with metformin in the very near future. It's been repeatedly studied, according to ClinTrials.gov.

Let's switch to some different combination concepts: how about a pill that contains two different drugs to treat what are usually regarded as two different diseases. One example: a pill containing a drug to lower glucose and another drug to lower lipid levels. Such a product is available, with the brand name Juvisync, a combination of the DPP4-inhibitor sitagliptin plus a statin, simvastatin. There's also a combo pill for hypertension and hyperlipidemia: Caduet, which combines Norvasc (amlodipine) and Lipitor (atorvastatin) in a single pill.

The existence of such combinations are fascinating in many ways, but I won't go into speculation as to why they exist, other than the obvious: convenience for the patient who's taking both components, and profit for the manufacturer.

And confusion for the physicians and pharmacists who have to keep them all straight...