Robert A. Gabbay, MD, PhD, FACP, is chief medical officer and senior vice president at Joslin Diabetes Center, and an associate professor at Harvard Medical School. His research focuses on innovative models of diabetes care to enhance outcomes and patients’ experiences.
An editor from The American Journal of Managed Care® recently conducted a question-and-answer session with Gabbay to discuss recent developments in the treatment of type 2 diabetes and innovative ways to improve care for patients with the condition.
The American Journal of Managed Care®
(AJMC®): Along with lifestyle interventions such as diet and exercise, pharmacotherapy is a cornerstone of care for patients with type 2 diabetes (T2D). What are some of the barriers to meeting glycemic targets through the use of medication? For example, we know that adherence can be a concern.
Robert A. Gabbay, MD, PhD, FACP: Adherence is very much a concern, we see that with our patients. In the literature, one sees that adherence, depending on the study, is between 60% [to] 70%, maybe as high as 80% in some studies.1 But that still leaves a significant gap in terms of patients who are not adherent to their medications. And obviously, if you don’t take the medicine it’s not going to work.
Also, depending where you are in the country and the patient population, cost of medication has become a barrier. High-deductible plans are part of the issue here but cost clearly is another challenge.
: Does pill burden play a role in nonadherence, in your experience?
Gabbay: Absolutely. Where that plays an even greater role is when one wants to advance therapy and deal with this issue of therapeutic inertia, [meaning] that a patient can have a high A1c [glycated hemoglobin level], not be at goal, see their provider, and, at least from the outside, nothing seems to change. And one of the big barriers there is often the conversation where patients say, ‘Well, I don’t really want to take another tablet, or take another medicine.’ So that clearly is an issue.
: In your opinion, what is the role of combination therapy in patients with T2D? Is combination therapy appropriate in patients with a new diagnosis, for example? Can it help with the issue of therapeutic inertia?
Gabbay: Yes, combination therapy has a role in both of those situations. With newly diagnosed patients, I think there are 2 sorts of scenarios. If you imagine that any agent is likely, on average, to lower A1c [by] 1 or at best 2 A1c points, if the patient is further from goal from that amount, they are likely going to need 2 medications to get them to goal. And that is where combination therapy could be the right thing early on even in newly diagnosed patients.
The other thing I want to mention about newly diagnosed patients is, there are studies going on to be able to evaluate whether we should change the paradigm of treatment for diabetes. And what I mean by that is, our traditional approach is, some would say, treat to failure. We treat patients [with monotherapy], their A1c comes down, they ultimately have failure of that monotherapy. Their A1c goes up, we then treat them with a second drug, they improve, but again they fail. [Then we try a] third drug, et cetera. So the question is, if you treated the patient with multiple mechanistic approaches, and therefore multiple medications, early on, right after diagnosis, could you prevent that rise in A1c that typically happens over time? That rise in A1c takes some time to address with additional medications, so patients live outside of goal for a longer period of time.
The other [situation involves] therapeutic inertia. As I mentioned, I do think there’s a role for combination therapy in that case, to reduce the pill burden, increase adherence, and ultimately have better glucose control for a longer period of time, which is our goal to prevent complications.
: It will be interesting to see what the results of those trials show, whether mechanistically hitting multiple targets early on really makes a difference.
Gabbay: Very much so. Some of the thinking on that has been a translation of the cancer world, where really, at diagnosis, one does everything at once, as opposed to treating the cancer with 1 drug, seeing how it responds, then giving a second drug, then giving a third drug. That paradigm might really be the way to attack diabetes.
: The FDA has approved a number of fixed-dose combinations that have 2 medications for the treatment of T2D. Recently, they approved 2 fixed-dose combinations with 3 medications, including a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, and metformin: Trijardy XR (empagliflozin, linagliptin, and metformin) was approved on January 27, 2020, and Qternmet XR (dapagliflozin, saxagliptin, and metformin) on May 2, 2019. What value do these combinations add, compared with previously available treatment options? What are some of the benefits to patients?
Gabbay: I like the idea that these are now available. The easiest role, one could imagine, is for a patient on 2 of these drugs [who] needs to intensify [treatment] further with an additional drug. But they may either be resistant to taking more tablets or perhaps they have a more complex regimen and there is a concern that more tablets will lead to less adherence. That’s where these drugs can really be quite effective. They both use metformin as 1 of the agents, which is in most cases going to be a first-line drug. Although I would say for patients with cardiovascular disease, we are often thinking of adding and using cardioprotective drugs as first-line drugs in that patient population. So yes, I like the combinations. I think it’s particularly important that they have SGLT-2 drugs associated with them. The 2 examples that you gave are particularly nice in that [with] those 3 drugs, or 3 classes of drugs, one does not need to worry about hypoglycemia. They are 3 drugs that are generally pretty well tolerated, so these combinations can really be a nice choice for patients.
: In your clinical practice, what types of support have you received from health insurance plans, employers, and health systems for patients with T2D—–for example, case management programs? Have these programs helped improve patient outcomes? If yes, what has been helpful, and if no, what more can be done?
Gabbay: That’s a good question. On the health-system side, that’s where one sees the greatest benefit in that the health system often has access to clinical data to be able to identify a high-risk group. The challenge with insurance company and payer intervention is that typically the only data they have access to [are] claims data and sometimes they don’t have enough clinical information to be able to provide reminders or other things that could be useful for the healthcare provider. Within the health system, the data [are] more likely to be accurate.
The most helpful service is really around care management for high-risk patients. I think that works generally well or is helpful in health systems. It is most helpful when it is not centralized but embedded into practice. Particularly in the primary care world, there’s a lot of literature stating that an embedded care manager is more effective than a centralized one, that is to say, someone who calls and says, ‘I’m calling from your doctor’s office and I’ve noticed A, B, C, D,’ as opposed to someone who says, ‘I’m calling from your health plan.’
What would make these programs better? Having that [program] more embedded or with better communication with the practice is number 1. Number 2 is more accurately identifying patients. And then number 3, I would say that for programs offered by health insurance plans, it tends to be very challenging for healthcare providers to understand the different resources available from the different payers, because providers typically have a payer mix. Therefore, it is often quite challenging to make a referral, to know how to do that and who to call. Easing that morass, making that kind of information more easily accessible would be helpful. Really, it all boils down to better communication.
: Given some of the support that health plans, employers, and health systems have provided, what could endocrinologists do better or differently at the clinician level to improve quality of care for patients with diabetes?
Gabbay: I do think there is a role for us as endocrinologists in the diabetes world to more broadly engage with population management around diabetes. We’ve really been underutilized, and you know that’s probably a 2-way street. We maybe have not been engaged [at] and/or invited to the table. But we have a lot of tricks of the trade that could be shared more broadly, and again this really would involve engaging at the health system level with those who are designing programs, because most places have some initiatives around diabetes. The endocrinologists’ input and engagement around that and how they influence primary care really varies significantly. There is a real opportunity there.
: There is probably an opportunity to work with the cardiology community as well, given some of the cardioprotective benefits that we are seeing with “diabetes medications.”
Gabbay: Absolutely. We have a program here where we work with a neighboring hospital, Beth Israel Deaconess’s cardiology department, to facilitate starting patients on SGLT-2 and GLP-1 [glucagon-like peptide-1 receptor agonist] drugs because of their cardioprotective [benefits]. And interestingly, we’ve seen this in a number of places around the country, where the cardiologists are interested in their patients being on these drugs, because they’re quite efficacious, but [the cardiologists] feel a little nervous about managing the diabetes. Better collaboration is needed where endocrinologists can initially put these patients on the drugs but ultimately guide cardiologists to make that the protocol.
: Are you optimistic about the future of diabetes care? What can we look forward to in the next 5 to 10 years?
Gabbay: I am very optimistic, and today we have better tools than we have ever had before. One could argue that we already have the tools, in large part, to be able to get most patients to goal. Yet, if you look over the last decade, with a plethora of new treatments and technologies becoming available, quality of care has not really changed much. Arguably, the answer is not just coming up with new treatments, though new treatments will be helpful. What’s needed is better implementation of existing treatments and better engagement of providers and patients in using the things that work.
Another area is digital health. There’s a huge opportunity for digital health to be another member of the diabetes team and I have enjoyed being an advisor to a number of efforts in this realm. I think where they have the greatest potential impact is in an area where we in the healthcare system do a very poor job, and that is the care between visits. We generally do very little between visits but do a lot at each visit, and obviously most patients are living their lives between visits. That is where digital health has a huge opportunity. And finally, if we take that horizon of 5 to 10 years, the opportunities for curing diabetes are better than ever, and that’s also incredibly exciting.
1. Krass I, Schieback P, Dhippayom T. Adherence to diabetes medication: a systematic review. Diabet Med. 2015;32(6):725-737. doi: 10.1111/dme.12651.