Initiating and Optimizing Insulin Therapy: Patient Adherence CME

Luigi Meneghini, MD, MBA Authors and Disclosures CME Released: 11/02/2010; Valid for credit through 11/02/2011
Introduction

Type 2 diabetes mellitus (T2DM) is characterized by a number of underlying pathophysiologic defects, including insulin resistance, abnormal insulin secretion, and defects in incretin function that result in elevated plasma glucose concentrations. Although management is often straightforward and responsive to lifestyle modification and oral antiglycemic drugs -specifically with regard to glycemic control -- at the very early stages of disease, over time the loss of endogenous beta-cell function often translates into therapeutic failure and the need to consider alternative strategies. Studies on beta-cell function, which remains our best surrogate marker for beta-cell mass in humans, estimate that at diagnosis of T2DM up to 50%-80% of beta-cell viability has been lost.[1] In addition, evidence points to an acceleration of beta-cell dysfunction following the "conversion" from prediabetes to full-blown disease.[2] Despite the availability of and need for insulin therapy, clinicians are still reluctant to initiate insulin therapy, and patients are equally reluctant to rely on insulin for many reasons. Patients and physicians may have unclear expectations in regard to the effectiveness of insulin replacement, or may have concerns about side effects of therapy, such as weight gain or hypoglycemia. Physicians may lack the time, resources, or skills to effectively convince and teach patients how to initiate insulin therapy. Patients, on the other hand, may perceive the need for insulin therapy as loss of control and disease worsening, as well as personal failure, and they may be anxious about injections. These barriers need to be actively identified and resolved if we are to successfully optimize glycemic control and reduce disease-related complications in patients with worsening beta-cell function.
Initiating Insulin Therapy

Traditionally, our approach to blood glucose management has been the periodic re-evaluation of antiglycemic therapy, with intensification of treatment when glycemic control was deemed inadequate. Unfortunately, substantial evidence in "real-world" situations points to a certain "clinical inertia" in responding appropriately with treatment adjustments,[3] resulting in patients exposed to unacceptable levels of hyperglycemia for prolonged periods of time. In one such example, patients on dual oral antiglycemic drugs remained at glycated hemoglobin (A1c) levels above 8% for over 26 months before the introduction of insulin therapy.[4] Additionally, glycemic targets are increasingly difficult to achieve when appropriate treatment intensification is delayed.[5] Clearly, in the face of endogenous insulin deficiency, insulin replacement is, for the

time being, the only therapy that can effectively achieve and maintain glycemic control over the long term in patients with T2DM.[6] When endogenous insulin secretion fails to maintain glycemic control despite the aid of noninsulin therapies, consideration should be given to replace what is missing. Patients and physicians have several options for how to initiate insulin treatment, from once-daily basal insulin to twice-daily premixed insulin to rapid-acting insulin before meals.[7] The goal of therapy is to reduce the glycemic burden in order to minimize long-term micro- and macrovascular injury, while minimizing the side effects of therapy, such as hypoglycemia and weight gain. In the face of reducing beta-cell function, insulin is the only therapy that can ensure long-term glycemic control. Insulin analogs, compared with their nonanalog (human) counterparts, are associated with better postprandial glucose control (for rapid-acting preparations) and less hypoglycemia (for long-acting basal insulin analogs). A1c goals and their corresponding pre- and postmeal targets should be individualized on the basis of patient characteristics and treatment circumstances. Although an A1c level of < 7% is recommended for the majority of patients with diabetes,[8] a higher A1c target may be appropriate for individuals who are particularly vulnerable to hypoglycemia, have advanced vascular damage, and have short life expectancies or poor responses to increasingly complex therapies.[9] Glycemic monitoring, through A1c testing and daily self-monitoring of blood glucose, provides useful information in determining not only the timing of insulin initiation, but also the most appropriate insulin type(s) and distribution. For example, patients with fasting hyperglycemia and A1c levels under 9% may respond well to basal insulin replacement, whereas a patient with predominantly postprandial glucose elevations or A1c values above 9% may do better with twice-daily premixed insulin. Insulin therapy may also be used as initial therapy at diagnosis of T2DM to rapidly correct hyperglycemia and reverse glucotoxicity, with re-evaluation of treatment options after stabilization of the metabolic status.[10,11] Periodic re-evaluations of treatment efficacy and tolerability, as well as appropriate adjustments to therapy, should be carried out every 2-3 months by the treating health professional.[8,10]
Strategies for Improving Patient Adherence to Insulin Therapy

Patient education is essential to the successful implementation of medical treatment, particularly with regard to insulin replacement therapy. Patients need to understand that, despite their best efforts to control diabetes through lifestyle modification and medication adherence, beta-cell function wanes over time and insulin replacement is an expected and effective intervention to correct hyperglycemia and prevent "disease" progression, specifically end-organ damage from chronic hyperglycemia.[12,13] Although busy practitioners might not have the time or resources to appropriately educate and inform their patients, they can arrange consultations with certified diabetes educators who are trained to address many of the issues and concerns in regard to insulin therapy initiation. Patients who are apprehensive about the use of needles benefit from current insulin delivery technologies, which through the use of disposable insulin pens and finegauge needles can reduce some of the discomfort of prior approaches, possibly leading to increased patient acceptance and adherence.[14] Health professionals should also address issues in regard to the side effects of therapy, such as weight gain and hypoglycemia risk, or the common misconception that insulin actually causes some of the end-organ damage that they are trying to

avoid.[15] These concerns need to be openly discussed and actively addressed if patients are to feel comfortable accepting insulin as a beneficial therapy. The negative perception of insulin as a treatment option could be reinforced further by physicians who might view insulin replacement as an intervention of last resort, or even use insulin as a threat to ensure patient compliance with prescribed lifestyle interventions and medications.[16] The Diabetes Attitudes, Wishes, and Needs (DAWN) study, which examined patient and provider attitudes toward insulin therapy in 13 countries, offers a number of useful insights in regard to some of the barriers to timely initiation of insulin replacement.[17] For example, in the United States both physicians and nurses were more likely to delay starting insulin therapy than providers in most other countries. Delay in initiating insulin was, however, less among specialists and providers who believed that insulin was efficacious. Of interest, failure to intensify oral antiglycemic drug treatment was the strongest predictor of delay in introducing insulin therapy, pointing to clinical inertia as a possible contributor. Clearly, the opportunity exists to increase provider awareness of the many strategies for insulin initiation that have been shown to be effective, safe, user-friendly, well tolerated, and accepted by patients. Patient resistance to insulin therapy was also greater for individuals who did not believe that insulin was going to help them control their blood glucose.[17] On the other hand, younger patients, those with worse blood glucose control, and those who tested their glucose level more often were more likely to believe that insulin could be of benefit in their treatment paradigms. Reflecting the historical approach of the medical establishment in putting the responsibility for failed glycemic control on the patient, those surveyed also reported more self-blame for having to start insulin therapy. Providers need to be prepared to identify and address barriers to appropriate self-care behaviors in patients struggling to control their diabetes, by implementing practical behavioral interventions within the limits of a short clinic visit. Peyrot and Rubin have proposed a simplified conceptual approach that addresses self-care issues, such as regimen acceptance and adherence, which lend themselves to problem-focused strategies that can directly remedy a deficiency.[18] They propose to divide the conceptual approach to behavior change in 4 categories: motivators; inhibitors/facilitators; intentions; and triggers (Table 1). Table 1. Behavior Change Categories and Interventions
Categories Motivators Definition Factors that predispose to action Examples Perceived susceptibility and severity of illness; perceived need and benefit of treatment; consequences; rewards; incentives Absence of resources (funds, Intervention Information; motivational interviewing; behavior contracting

Inhibitors/Facilitators Barriers to or

Training in problem

resources for action skills, support); presence of obstacles vs enabling factors

solving and coping skills; environmental change; self-monitoring Goal setting

Intentions

Proximal cause of behavior change

Intention and readiness to change with specific goal(s) to accomplish Precipitating factors or cues to action

Triggers

Events that shift one from predisposition to action

Environmental change; self-monitoring; behavior contracting

Data from Peyrot M, et al. Diabetes Care. 2007;30:2433-2440. Within this framework they propose a practical and readily applicable step-by-step approach divided into 5 major sequential steps, the "5C intervention" (Table 2). These steps include: (1) constructing a problem definition; (2) collaborative goal setting; (3) collaborative problem solving; (4) contracting for change; and (5) continuing support. This patient-centered approach begins by having providers understand what patients identify as the most pressing or difficult issue with regard to managing their disease, and assists patients in specifying concrete issues rather than general problems. Subsequently, providers need to assist patients in transforming an intention into a goal that is specific, measurable, action oriented, and realistic (but challenging enough). Collaborative problem solving, which is the next step, focuses on identifying current and potential barriers to goal attainment and devises strategies to overcome or address these identified barriers. The fourth step requires patients under guidance from providers to commit, through a "behavior contract," to specific goals and strategies. It is essential that patients track, in writing, both successes and lapses in achieving their objectives as well as the reasons for achievement or not. Continuing support of patients' efforts is essential, especially with regard to preventing, recognizing, and managing relapses toward less healthy behaviors. Although these strategies require a certain skill set on the part of health providers, they are simple enough to be approachable for any motivated physician managing patients with diabetes. Table 2. Practical Approach to Behavioral and Psychosocial Interventions on the Basis of the 5C Intervention
Intervention Constructing a problem Components 1. Start with the patient's own Example Questions 1. What is the most difficult aspect about controlling Example Answers 1. Exercising 2. No time or schedule to be

perceived problem 2. Specify the problem Collaborative goal setting Set goals that are: 1. Specific 2. Measurable 3. Action oriented 4. Realistic, but challenging

your diabetes? 2. Give me an example. 1. What activity would you feel comfortable starting? 2. How much and how often?

physically active; afraid of starting 1. Start a walking program 2. 30 min 5 days per week

Collaborative 1. Identify barriers problem solving (cognitive, emotional, resources, environment) 2. Formulate strategies

1. What could prevent you from starting or continuing your walking? 2. Might there be 30 minutes at the end of the day, and are you ever in a safe environment? 1. What do you consider success, and would you sign a "behavior contract"? 2. How will you track your efforts? 3. What reward would you like for reaching stated goal? 1. How will you deal with lapses? 2. How can your medical team help you?

1. Lack of time and dangerous neighborhood 2. Put on sneakers after work and stop at the mall to walk on the way home

Contracting for change

1. Document explicit agreement 2. Track outcomes 3. Reward success

1. 20 min 3 days a week 2. Block time on weekly schedule for walking days, and keep log of successes and lapses and reasons 3. New pair of walking shoes

Continuing support

1. Plan for relapse prevention and management

1. Not get discouraged and understand reason for lapse 2. Schedule more frequent follow-ups

Providers should screen for patients with depression who experience unexpected deterioration in diabetes control or obvious loss of adherence to prescribed treatments. Patients with diabetes carry a lifetime risk for mental illness of around 30%, with depression and anxiety disorders being the most common disturbances.[19] Depression has been associated with treatment nonadherence[20] as well as hyperglycemia[21] and diabetes complications.[22] Health professionals can quickly screen for depression in their patients with a number of validated tools, including the Patient Health Questionnaire-9 (PHQ-9), a 9-item self-reporting instrument that evaluates the major symptoms of major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This tool can be used to identify depression and

monitor symptom severity and clinical impact of any subsequent intervention.[23,24] An even quicker initial screen using the 2 first questions of the PHQ-9 can be used (Table 3), leading to a more careful assessment of the patient's mental health. Table 3. Quick Patient Health Questionnaire-9 Screen
Over the past 2 weeks how often have you been bothered by: Little interest or pleasure in doing things Feeling down, depressed, or hopeless Not at All 0 0 Several Days 1 1 Over Half the Days 2 2 Nearly Every Day 3 3

A total score of 3 optimally balances sensitivity and specificity for diagnosis of depression.
Effective Clinician/Patient Communication

Communication between the clinician and patient is important for effectively educating patients about and initiating insulin therapy. The first step is to discuss with patients the natural progression of beta-cell failure and the eventual need for insulin replacement to prevent disease progression (vascular damage). This dialogue needs to take place early in the disease process and well before insulin replacement is actually needed. As the dialogue continues, ask patients about their greatest fear/anxiety with regard to insulin therapy, and either address these concerns directly or refer the patient to a diabetes educator who can carefully address these issues. Once the need for insulin therapy has been established, demonstrate to patients how an insulin pen works and have them do a first insulin injection, with a nominal dose of 1 U, in the office -- or delegate this task to an appropriate staff member. This allows patients to quickly realize the simplicity and ease of insulin dosing and comfort of smallgauge (31-32G) pen needles. If some patients are still resistant or express concern about the chronicity of insulin therapy ("Will I have to be on it for the rest of my life?"), negotiate an agreement with those patients so that they accept a 2- to 3-month trial on insulin, after which time you will both re-evaluate how they are doing and decide whether they want to continue with this treatment regimen. On the basis of clinical experience, most patients will realize the ease and benefits of insulin therapy, while still feeling in charge of their "destiny."
Summary

Addressing treatment barriers to the initiation and intensification of diabetes therapy, particularly insulin replacement, can be a challenging task for healthcare providers. The importance of appropriate insulin replacement in the face of beta-cell failure with the goal of controlling glycemia and minimizing diabetes-related complications cannot be understated. A number of

tools and strategies are available for practicing physicians to effectively introduce and implement appropriate treatments and optimize patient understanding of and adherence to effective interventions.