Diabetes Forecast

New Combo Drugs Control Diabetes

Two-for-one diabetes medications may help you take pills as directed for better control

By Allison Tsai , ,
illustration of blue pills

Chad Baker/Thinkstock

Taking multiple pills a day is complicated. And it’s all too easy to miss doses and skip refills. Combination glucose-lowering drugs, which combine two medications in a single pill, have become a viable alternative, says endocrinologist Yehuda Handelsman, MD, FACP, FACE, FNLA, medical director and principal investigator of the Metabolic Institute of America, and president of the American College of Endocrinology.

Treating Aggressively

As type 2 diabetes progresses, people taking only one diabetes medication will often need to add another drug in order to control their blood glucose. The first drug may not work as well over a period of time, and a drug that lowers blood glucose in a different way may become necessary.

In addition, treating high blood glucose early and aggressively with medication may keep a person’s A1C controlled for longer periods of time than a single drug would, but that hasn’t been studied in a clinical trial, says John Buse, MD, professor of medicine and division chief of endocrinology at the University of North Carolina School of Medicine.

Another potential advantage of combination therapy is that each drug works in a different way to lower blood glucose. For example, one drug may reduce insulin resistance, and another may reduce the release of glucose by the liver. By taking the two drugs together, you can gain added glucose-lowering benefits.

Taking as Directed

Combining two medications into a single pill decreases the number of pills that need to be taken every day and may make it easier to stick with a treatment plan, a behavior known as “medication adherence.”

“There is a theoretical advantage with regard to adherence,” says Buse. “It’s easier to take one pill than two pills.” There also may be a cost advantage.

Cost Effective

In some cases, taking a combination pill will result in less out-of-pocket costs for the patient, says Buse, and sometimes there will be less cost to the pharmacy and insurer. “Now the patient is only making one copayment, and often the pricing structure is such that the generic half of the combination therapy is basically thrown in there for free,” he says. Almost all combo drugs have at least one generic medication.

Handelsman warns, however, that not all insurance companies cover every available combination medication. That’s because pharmaceutical companies tend to charge a premium for two-in-one pills, and insurers aren’t keen on the extra cost. If combination medications aren’t covered by insurance, a person with diabetes will need to purchase each drug separately—with two different copays. Depending on the copay, it may be cheaper to buy the generic part of the combo out of pocket. Before purchasing, it’s a smart idea to compare the cost and availability of the drug at different pharmacies.

The cost of these drugs may change as new combinations become available. Buse says that raises an important question: How will companies price a pill that includes two already expensive brand-name medications?

If cost or insurance is an issue, manufacturer prescription assistance programs may be a short-term option for people who qualify. “There is [the] advantage of getting patients free medications that are brand names, and we can get them in combination therapy as a good option,” says Judy Chen, PharmD, BCPS, CDE, FNAP, clinical associate professor of pharmacy practice at Purdue University.

Dose Limitations

A major drawback to combination pills? If you can’t tolerate metformin, which most of the drugs contain, two-in-one formulations may not be an option.

There’s also the lack of flexibility when it comes to the strength of the medications. For example, Buse says combination pills almost all contain either once-a-day or twice-a-day formulations of metformin—not both. There are differences between the two formulations in terms of how well a person tolerates the drug, with the once-a-day (extended release) pill being better tolerated by some people. So if you take the twice-a-day version because it lessens gastrointestinal side effects but the combo pill you want only has once-daily metformin, the medication may not be right for you.

But Handelsman doesn’t consider this a major roadblock—there are plenty of combo options.

Side Effect Sense

To gauge how you may tolerate combo medications, consider trying each drug individually at first. “Before we consider combination pills, I like to make sure that the patient is tolerating the one ingredient of the pill,” says Chen. “Then we try the next ingredient.” It’s important for people to stick with individual pills for several months to make sure they have no issues.

New Combinations

Several new diabetes combination drugs are on the market, including pairings of SGLT-2 inhibitors and metformin, such as dapagliflozin and metformin hydrochloride extended release (Xigduo XR) and canagliflozin and metformin hydrochloride (Invokamet). SGLT-2 inhibitors block some glucose from being absorbed by the kidneys and flush it out through the urine.

The most recent combination drug to be approved for the treatment of type 2 diabetes (Glyxambi) is the first to pair an SGLT-2 inhibitor with a DPP-4 inhibitor. DPP-4 inhibitors increase insulin production and decrease glucose stored in the liver. Also under review by the Food and Drug Administration: newer combinations that involve other drug classes, such as DPP-4 inhibitors and thiazolidinediones. Thiazolidinediones increase the body’s insulin sensitivity.

Handelsman says he’d like to see a triple combination drug, including metformin, a thiazolidinedione, and a DPP-4 inhibitor or an SGLT-2 inhibitor, but he doesn’t see that on the horizon any time soon.

In the meantime, he says it’s generally easier for people to stick with a medication regimen for combination drugs than follow a pill schedule for different drugs with different doses. “I think that it simplifies management and keeps patients on the two drugs longer term,” Handelsman says.

NOTES: Yehuda Handelsman, MD, works as a researcher, consultant, and educator on behalf of AstraZeneca (Xigduo), Novo Nordisk (PrandiMet), Boehringer Ingelheim (Jentadueto), Janssen (Invokamet), and Takeda (Actoplus Met, Duetact, Kazano, and Oseni). John Buse, MD, has no direct financial disclosures, but works as a consultant for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Takeda, Bristol-Myers Squibb (Glucovance and Metaglip), Merck (Janumet), and GlaxoSmithKline (Avandamet and Avandaryl) through the University of North Carolina.

More on Combo Meds

To see a list of new diabetes combo meds, visit diabetesforecast.org/combomeds.



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