If we could only choose one word to describe the term “the pharmacological management of type 2 diabetes,” that word would likely be “change.” Not just singular change, but change on many fronts, including the introduction of novel agents, new methods of delivery, new treatment goals, and new means of monitoring effectiveness.
As Winston Churchill once said, “There is nothing wrong with change if it is in the right direction.” From this perspective, an honest assessment would lead us to the conclusion that in this arena, some of the changes that have occurred in the past three or four decades have been positive, whereas others have been negative.
A dramatic change in the incidence and prevalence of type 2 diabetes has led to the use of the term “epidemic” when referring to the change in frequency of type 2 diabetes.1 There has also been an impressive change in the pharmacological agents used in the management of type 2 diabetes since the 1970s; many novel compounds and new insulin formulations have been brought to market.2 This obviously has been a positive change. Additionally, the treatment goals for those with type 2 diabetes have evolved with the increased use of blood glucose monitoring (both fasting and postprandial), A1C testing, and recognition of the importance of controlling comorbidities such as hypertension and hyperlipidemia. Still, there is not complete consensus regarding these goals, which can sometimes cause confusion.
Time has also witnessed a change in the method of health care delivery in the United States. Our system has evolved from a basic “fee-for-service” model to an administrative quagmire of myriad third-party payers, with many uninsured patients existing on the fringes and lacking access to adequate health care. Although our pharmacological methods of treatment have become more sophisticated and efficacious, they have also become much more costly and are not always available to patients who could benefit from them. This increase in the complexity and sophistication of therapeutic plans also goes hand in hand with the potential for a reduction in adherence to medical care regimens.
In short, we have more patients with type 2 diabetes and more choice in types of antihyperglycemic medications, but potential problems with availability of and adherence to these therapy regimens. This From Research to Practice section will provide insight into these challenges. The articles included address the very real and perplexing problem of patients foregoing prescribed treatments because they cannot afford them; discuss the challenges of poor patient adherence to prescribed regimens and possible methods of improving adherence; offer an overview of available insulin products and suggestions for initiation, titration, and optimization of insulin therapy in type 2 diabetic patients; and describe novel pharmacological agents now in development that will bring further change to the way we treat type 2 diabetes.
When it comes to the topic of compliance or adherence, health care providers often prefer to categorize patients into discreet types or groupings such as an “adherent patient” or a “nonadherent patient.” Most of us have had conversations with other health care providers in which we have described patients in these or similar terms. Although clearly there are situations in which this type of absolute descriptor is warranted, in many cases, patients may be both adherent and nonadherent depending on their current situation, economic and otherwise. The article written by John D. Piette, PhD (p. 77), elucidates this often unrecognized problem. Piette points out, for example, that in one study, 27% of patients taking medication for both diabetes and depression reported cost-related underuse of one of the treatments (either diabetes or depression).3 We, as health care providers, tend to feel comfortable placing patients into convenient clusters and sometimes may fail to recognize that even our “adherent patients” may occasionally undergo periods during which they are unable to remain adherent to prescribed regimens.
Our first response to this quandary could be, “Yes, but patients would let us know that they were having a problem taking their medication as prescribed.” But although this seems a reasonable assumption, it is usually incorrect. Piette tells us that in a national study, ~ 66% of patients did not inform their clinicians that they were going to be unable to follow their regimens, and about one-third of patients never even discussed medication costs with their prescribers.4
Given the toxicity of hyperglycemia, one must wonder about the potential consequences of periodically discontinuing these medications. Additionally, many of the medications we prescribe for the management of hyperglycemia in patients with type 2 diabetes, such as biguanides and thiazolidinediones, need to be taken chronically and over a relatively long period of time to be effective.
Piette also demonstrates that, although nonadherence is sometimes caused by monetary issues, it is in reality much more complex and influenced by manifold other factors. To complicate matters further, a patient's perception of cost may be influenced by hir or her race, age, and psychiatric conditions; not only actual costs, then, but also perceived costs may be a factor as well. Aside from cost, patients may not adhere to their prescribed medication regimen because they have the erroneous belief that the medications do more harm than good, they may think that generic medications do not work, or they may simply not understand the importance of taking their medications. Piette provides a succinct but comprehensive overview of these problems.
Our next article reminds us of the obvious but frequently disregarded idea that medications only work for the patients who take them. Following our motif of change, this article, by Barbara Kocurek, BS, PharmD, BCPS, CDE (p.80), provides a roadmap to the implementation of enhanced adherence initiatives.
I believe that most of us, as health care providers, operate with the basic assumption that most patients are adherent to their medication regimens. After all, as Kocurek points out, “Taking medications as directed seems like such an easy thing.” Unfortunately, studies cited in her article suggest that adherence rates in patients with diabetes are not as acceptable as we might believe and have been reported to be as low as 53% in prospective studies and 31% in retrospective trials.5
Given the amount of money spent on medications annually in the United States—$286.5 million in 2007—along with the dire consequences associated with noncompliance, it is painfully obvious that this is a major problem that requires investigation. One study6 cited by Kocurek demonstrates a correlation between nonadherence and a reduction in positive outcomes in patients with diabetes.
Kocurek's article reviews the impact of nonadherence and outlines the patient, provider, and pharmacy factors contributing to this problem. It goes on to provide strategies for improving medication adherence in individual patients, as well as in society at large.
After decades of use, the development of new analogs and formulations, and a plethora of clinical trials, the debate continues regarding when and how insulin should be used in patients with type 2 diabetes. Our third article (p. 85) delves into these important questions. This article, written by Joshua J. Neumiller, PharmD, CDE, CGP, FASCP, Peggy Soule Odegard, BS, PharmD, BCPS, CDE, FASCP, and Carol H. Wysham, MD, offers a well-written overview of the initiation, titration, and optimization of insulin therapy in patients with type 2 diabetes. The authors tackle several difficult questions such as “Should insulin be used early on in the course of the disease or reserved as a ‘lastditch’ effort?” They also review factors that differentiate insulin products and discuss the pros and cons of available formulations.
Continuing with our theme of change and medication use, our final article (p. 92) offers a review of one of the most exciting topics in the pharmacological management of diabetes—the future. Terri L. Levien, PharmD, and Danial E. Baker, PharmD, FASHP, FASCP, provide thumbnail sketches of the more salient medications that are currently under development. The authors include reviews of five new dipeptidyl peptidase-4 inhibitors (alogliptin, dutogliptin, linagliptin, saxagliptin, and vildagliptin); four new glucagon-like peptide 1 analogs or new analog formulations (AVE0010/ZP-10, exenatide LAR, liraglutide, and tasoglutide) along with mention of a fifth; two new peroxisome proliferator-activated receptor-Γ agonists (balaglitazone and rivoglitazone); one new glinide (mitiglinide); several new insulin formulations; and dapagliflazin, the flagship of a new category of oral agents called selective sodium glucose cotransporter 2 inhibitors. Additionally, the authors describe several other medications currently in development. Clearly, the dramatic changes we have experienced in the field of diabetes pharmacotherapy during the past few decades are destined to continue.
In summary, we will face many hurdles and growing challenges in dealing with the type 2 diabetes epidemic in the coming years. The challenges seem quite daunting just considering the increase in the slope of either type 2 diabetes incidence or prevalence curves.
From an optimistic standpoint, better understanding of the physiological processes underlying fat deposition and the progression of insulin resistance, along with increased public awareness of and personal responsibility for our diets and physical activity, may result in a blunting of the aforementioned curves. However, even under the most optimistic of circumstances, changes are and will be needed in the pharmacological management of type 2 diabetes. These changes will include but not be limited to changes in our level of awareness of and response to the many problems associated with patient adherence to regimens, changes in our use of insulin, and the incorporation of new, more effective pharmacological agents into our patients' regimens. Meeting the challenges posed by type 2 diabetes at the individual and societal levels will require changes on the part of patients, providers, and the health care delivery system.
