Combination Therapy for the Treatment of Diabetes

APRIL 26, 2018


Troy Trygstad, PharmD, MBA, PhD; Tripp Logan, PharmD; Dhiren Patel, PharmD; and Javier Morales, MD, FACP, FACE, highlight the appeal in using combination therapy in the management of diabetes.

Troy Trygstad, PharmD, MBA, PhD: Tripp, when we talk about barriers for patients, I always think about combination therapy. Traditionally, we think about it as, “If they’re on combination therapy or it’s simpler to administer, there’s probably better adherence.” Do you see that? Is it mostly the appeal, that patients are more likely to be adherent and it’s simplified? Or is it that it makes sense to give these therapies together (administer them together), from a mechanism-of-action perspective? What is the appeal to you, as a community pharmacist, for combination therapy?

Tripp Logan, PharmD: I’m not a big fan of over-the-counter combination therapy. Many times, there’s not enough of any one thing that the person needs. Typically, there’s something that they don’t need in the combination therapy. So, I’ve got a negative step-back reaction to combination therapy.

Troy Trygstad, PharmD, MBA, PhD: Right, it’s not a magic bullet.

Tripp Logan, PharmD: Absolutely not. Now, in this situation, especially in the diabetes space, I’ve seen a lot of benefits. When you think of somebody who is on a brand name medication with a flat co-pay, and they use that plus metformin, that combination therapy makes sense. It only makes sense. We see that a lot, especially in the same product. And then if somebody is on the exact same thing that’s available in combination, but they’re on it separately, and there are 2 co-pays or 2 different administrations, maybe taken at 2 different times a day, where they can consolidate and improve adherence, then it makes sense. I wouldn’t say that it always makes sense, across the board, with the patients we’re working with. There’s always a little bit of variability. Everybody’s got their own unique reason for what they want to do.

Troy Trygstad, PharmD, MBA, PhD: Do you find that you assess patients for this need? For the average patient, are there any indications in which you might say, “You know, for this person, in particular, combination therapy really works. It makes sense.”

Dhiren Patel, PharmD: I agree with Tripp. Let’s, for example, look at the 2 classes that we talked about: the DPP-4 inhibitors and the SGLT2 inhibitors. They’re 2 branded drug classes, right? We’re talking about a combination with metformin, which we see a lot. And that is providing a very big benefit to that patient. You have 2 branded medications. They consolidate to 1 co-pay or they may include a savings card. And so, the out-of-pocket costs could go down by $50 if they’re on 2 branded medications. If they’re thinking of advancing to the third, but they don’t want to incur that additional co-pay, going to something like this, and explaining why to the patient becomes a little bit more attractive. Again, it is still once a day. Sometimes you don’t know what is causing an issue. But here, you have 2 unique mechanisms of action with unique adverse events. So, it’s easy to pick up on any issues that are happening. Let’s say you see a urinary tract infection. You’re going to know it’s from the SGLT2 inhibitor and not the DPP-4 inhibitor. So, sometimes that combination, again, makes more sense. It becomes much more attractive.

Troy Trygstad, PharmD, MBA, PhD: What about the evidence for combination therapy? Are the results different, the same, better, or worse? Dr. Morales, where are you at, from a clinical assessment perspective, with the data on combination therapies?

Javier Morales, MD, FACP, FACE: When we look at these combination therapies, because they mechanistically work differently, they offer a collaborative effect toward targeting the reduction of that hyperglycemia. Looking at these combination products, when studied against each other, the efficacy of the combination product wound up needing statistical significance in favor of the combination rather than each individual component. So, for those patients who might not be at their hemoglobin A1C target, and you need to intensify with something, maybe the combination therapy increases the likelihood of achieving that ascribed A1C target rather than using a single agent and then intensifying later?

Troy Trygstad, PharmD, MBA, PhD: If I’m hearing you correctly, on some level of what we’re talking about here, 1 drug for 1 purpose and one drug for another, with separate mechanisms, is convention? The whole idea is to put them together for an ease of administration? But the potential exists for one drug to have a mechanism of action that works together with another drug with a mechanism of action. And actually, they’re complementary and conjoined.

Dhiren Patel, PharmD: Earlier, we talked about the different core defects that we look at. With this combination, you’re hitting 4 to 5 of those different core defects. So, you’re getting that complementary mechanism of action, and I think that becomes really valuable for patients.


Troy Trygstad, PharmD, MBA, PhD; Tripp Logan, PharmD; Dhiren Patel, PharmD; and Javier Morales, MD, FACP, FACE, highlight the appeal in using combination therapy in the management of diabetes.

Troy Trygstad, PharmD, MBA, PhD: Tripp, when we talk about barriers for patients, I always think about combination therapy. Traditionally, we think about it as, “If they’re on combination therapy or it’s simpler to administer, there’s probably better adherence.” Do you see that? Is it mostly the appeal, that patients are more likely to be adherent and it’s simplified? Or is it that it makes sense to give these therapies together (administer them together), from a mechanism-of-action perspective? What is the appeal to you, as a community pharmacist, for combination therapy?

Tripp Logan, PharmD: I’m not a big fan of over-the-counter combination therapy. Many times, there’s not enough of any one thing that the person needs. Typically, there’s something that they don’t need in the combination therapy. So, I’ve got a negative step-back reaction to combination therapy.

Troy Trygstad, PharmD, MBA, PhD: Right, it’s not a magic bullet.

Tripp Logan, PharmD: Absolutely not. Now, in this situation, especially in the diabetes space, I’ve seen a lot of benefits. When you think of somebody who is on a brand name medication with a flat co-pay, and they use that plus metformin, that combination therapy makes sense. It only makes sense. We see that a lot, especially in the same product. And then if somebody is on the exact same thing that’s available in combination, but they’re on it separately, and there are 2 co-pays or 2 different administrations, maybe taken at 2 different times a day, where they can consolidate and improve adherence, then it makes sense. I wouldn’t say that it always makes sense, across the board, with the patients we’re working with. There’s always a little bit of variability. Everybody’s got their own unique reason for what they want to do.

Troy Trygstad, PharmD, MBA, PhD: Do you find that you assess patients for this need? For the average patient, are there any indications in which you might say, “You know, for this person, in particular, combination therapy really works. It makes sense.”

Dhiren Patel, PharmD: I agree with Tripp. Let’s, for example, look at the 2 classes that we talked about: the DPP-4 inhibitors and the SGLT2 inhibitors. They’re 2 branded drug classes, right? We’re talking about a combination with metformin, which we see a lot. And that is providing a very big benefit to that patient. You have 2 branded medications. They consolidate to 1 co-pay or they may include a savings card. And so, the out-of-pocket costs could go down by $50 if they’re on 2 branded medications. If they’re thinking of advancing to the third, but they don’t want to incur that additional co-pay, going to something like this, and explaining why to the patient becomes a little bit more attractive. Again, it is still once a day. Sometimes you don’t know what is causing an issue. But here, you have 2 unique mechanisms of action with unique adverse events. So, it’s easy to pick up on any issues that are happening. Let’s say you see a urinary tract infection. You’re going to know it’s from the SGLT2 inhibitor and not the DPP-4 inhibitor. So, sometimes that combination, again, makes more sense. It becomes much more attractive.

Troy Trygstad, PharmD, MBA, PhD: What about the evidence for combination therapy? Are the results different, the same, better, or worse? Dr. Morales, where are you at, from a clinical assessment perspective, with the data on combination therapies?

Javier Morales, MD, FACP, FACE: When we look at these combination therapies, because they mechanistically work differently, they offer a collaborative effect toward targeting the reduction of that hyperglycemia. Looking at these combination products, when studied against each other, the efficacy of the combination product wound up needing statistical significance in favor of the combination rather than each individual component. So, for those patients who might not be at their hemoglobin A1C target, and you need to intensify with something, maybe the combination therapy increases the likelihood of achieving that ascribed A1C target rather than using a single agent and then intensifying later?

Troy Trygstad, PharmD, MBA, PhD: If I’m hearing you correctly, on some level of what we’re talking about here, 1 drug for 1 purpose and one drug for another, with separate mechanisms, is convention? The whole idea is to put them together for an ease of administration? But the potential exists for one drug to have a mechanism of action that works together with another drug with a mechanism of action. And actually, they’re complementary and conjoined.

Dhiren Patel, PharmD: Earlier, we talked about the different core defects that we look at. With this combination, you’re hitting 4 to 5 of those different core defects. So, you’re getting that complementary mechanism of action, and I think that becomes really valuable for patients.
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