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JAOASupplement 5 • Vol 111 • No 7 • July 2011 • S13 Barag • Insulin Therapy for Type 2 Diabetes Mellitus

T

he prevalence of type 2 diabetes mellitus (T2DM) in the US popula-tion has reached epidemic proporpopula-tions. Sedentary lifestyles, poor diets, an aging population, and the associated explo-sion in rates of obesity all contribute to the increasing burden of T2DM.1

The American Diabetes Association (ADA) recommends a target glycosylated hemoglobin (HbA1c) level of 7% or less to achieve glycemic control in most patients with T2DM.2The importance of effective

glycemic control in patients with diabetes

mellitus is well established. In the seminal United Kingdom Prospective Diabetes Study (UKPDS),3which helped

deter-mine current targets for HbA1c, lowering glycemic levels reduced the incidence of long-term microvascular and neuropathic complications. Evidence suggests that the relative risk of retinopathy declines by an estimated 24% with each 10% decrease in HbA1clevel.4

In the early stages of T2DM, disease management focuses on dietary and lifestyle changes and oral hypoglycemic agents. Such medications are generally initiated as monotherapy before being used in combination therapy with 2 or more other drugs as the disease pro-gresses. Unfortunately, increasing the dose of an individual medication often increases adverse effects in the patient. The resulting decrease in adherence to the prescribed treatment can disrupt

con-tinuity of care and increase the likelihood that the patient will be lost to follow-up.

The progressive nature of T2DM is such that b-cell function and physiologic insulin response continue to deteriorate over time, even in the presence of good glycemic management. Therefore, despite escalating regimens of oral medications, many patients eventually require insulin therapy to achieve adequate glycemic control. Up to 60% of patients will require insulin within 6 to 10 years of initial diag-nosis—and even sooner if they have had long-standing undetected disease.5,6

The role of primary care physicians in managing T2DM continues to expand. Primary care physicians are more likely to manage T2DM than are specialists, and they are increasingly responsible for the initiation and management of insulin therapy in patients.5Primary care

physi-cians’ confidence in introducing

treat-Steven H. Barag, DO

Effective glycemic control is essential to minimize the long-term com-plications of type 2 diabetes mellitus (T2DM). However, it is well docu-mented that many patients spend prolonged periods outside of the optimal glycemic range. The use of insulin is important to effectively con-trol the disease process in patients with T2DM. Even so, resistance to insulin use among patients and healthcare providers often limits initi-ation and intensificiniti-ation of insulin therapy. With the increasing preva-lence of T2DM across all socioeconomic strata, an expanded viewpoint of early and sustained insulin use is crucial to enhance glycemic control in patients. To manage the effects of T2DM on cardiovascular disease in the aging population, physicians can promote insulin therapy as an affordable and effective treatment option. The author reviews beliefs and myths about the use of insulin in the management of T2DM and dis-cusses strategies to overcome barriers to initiation of insulin therapy in the primary care setting.

J Am Osteopath Assoc. 2011;111(7 suppl 5):S13-S16

Dr Barag is the medical director at Aureus Medical Group Inc and the principal investigator at Rancho Cucamonga Clinical Trials Inc, both in Rancho Cucamonga, California.

This article was developed with assistance from Global Directions in Medicine, Inc. The author approved the article and all of its contents.

Financial Disclosures:None reported. Address correspondence to Steven H. Barag, DO, 7974 Haven Ave, Suite 250, Rancho Cuca-monga, CA 91730-34063.

E-mail: drbarag@keyway.net

This supplement is supported by an independent educational grant from Novo Nordisk Inc.

Insulin Therapy for Management

of Type 2 Diabetes Mellitus: Strategies for Initiation

and Long-term Patient Adherence

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ment with insulin can be instrumental in improving the long-term health of their patients.

Barriers to Initiation of Insulin Therapy Patients

Patient resistance to insulin therapy is common, and this attitude often causes delays in initiation of the therapy.7,8As

many as one-quarter of insulin-naïve patients express unwillingness to take insulin if prescribed, and another 25% are only slightly willing to take insulin.8

Survey results of insulin-naïve patients with T2DM reveal that attitudinal reluc-tance to take insulin—which has been termed psychological insulin resistance— derives from multiple physical concerns, including fear of injections and worries about potential weight gain and risk of hypoglycemia (Table).8In addition,

psy-chosocial causes of patient resistance include a sense of personal failure and discomfort about administering insulin in public.8Psychological insulin

resis-tance may manifest as resisresis-tance to initi-ation of insulin therapy and to escaliniti-ation of the insulin regimen as the disease pro-gresses.8

A sense of personal failure repre-sents one of the strongest obstacles to patient acceptance of insulin.9From the

patient’s perspective, the need for insulin indicates that his or her inability to control diabetes mellitus through lifestyle changes, weight loss, or adherence to oral therapy has led to a more serious and invasive form of therapy. In the survey by Polonsky et al,8the negative attitude that

most strongly distinguished unwilling from willing insulin-naïve patients was the sense that they had failed to properly manage their disease (Table).

Several approaches may be useful in addressing, or even averting, such a poor self-image among patients. It remains common clinical practice to use insulin therapy as the proverbial stick. Many practitioners hold the “threat” of insulin over patients to compel better adherence to early-stage interventions.10

However, it can be useful at the outset of the patient-physician relationship— well before insulin is needed—to explain to the patient that insulin is part of the normal continuum of care as a patient’s

disease progresses.7When patients

under-stand that the need for insulin represents not a drastic or punitive measure but rather an expected step stemming from the progressive nature of the disease itself, the stigma of insulin therapy fades.5

Healthcare Providers

Research shows that nearly all primary care physicians are aware of appropriate goals for glycemic control in patients with T2DM.10Nevertheless, many of these

physicians tend to adopt treatment approaches that are inconsistent, or at least inadequate, to achieve glycemic tar-gets. Notable among these approaches is resistance to initiate insulin.7,10

The Diabetes Attitudes, Wishes, and Needs (DAWN) study7found that many

US physicians, especially those in pri-mary care, are inclined to delay initiation of insulin therapy. In fact, US physicians ranked lowest among physicians in all nations except Japan and India in their disposition to initiate insulin.7Evidence

suggests that, in a typical US primary care practice, insulin initiation is not trig-gered until a patient’s HbA1clevel has reached 9% or greater.11Some authors

have even characterized the current state of T2DM management as collusion between physicians and patients, proposing that there is a dynamic of “implicit and unspoken contracts to con-tinue oral agents for as long as possible.”12

Physician resistance to prescribing insulin may originate from either physi-ologic or practical concerns. Physiphysi-ologic concerns include apprehension about hypoglycemia or weight gain and the belief that insulin causes adverse metabolic effects. Examples of practical concerns about insulin initiation include patient anxiety, complexity in training patients, and demands on the physician or the physician’s practice to manage the patient’s use of insulin.13These concerns,

however, are often unfounded or exag-gerated. For example, evidence suggests that insulin is actually associated with Table.

Results of Survey of Insulin-Naïve Subjects With Type 2 Diabetes Mellitus Who Were Unwilling and Willing to Take Insulin if Prescribed (N=708)*

Survey Respondents, % Survey Item Unwilling Willing Total PValue†

Expected harm: Insulin therapy can 16.7 8.0 10.1 0.005 cause problems, such as blindness

Illness severity: Taking insulin means my 46.7 35.4 38.1 0.000 diabetes will become a more serious disease

Restrictiveness: Insulin therapy would restrict 56.1 41.6 44.8 0.000 my life; it would be harder to travel, eat out, etc

Lack of fairness: I’ve done everything I was 41.5 21.9 26.8 0.000 supposed to; if I had to do insulin therapy,

it just wouldn’t be fair

Anticipated pain: I couldn’t take the needle 50.8 30.2 34.7 0.000 every day; it would be just too painful

Problematic hypoglycemia: Insulin therapy 49.3 37.9 40.6 0.021 might cause serious problems with low

blood sugar

Low self-efficacy: I’m not confident I could 58.1 39.7 43.9 0.000 handle the demands of insulin therapy

Personal failure: Insulin therapy would mean 55.0 33.6 38.4 0.000 I had failed, that I hadn’t done a good enough

job taking care of my diabetes

Permanence: Once you start insulin, you can 53.1 42.6 44.9 0.000 never quit

* Data are percentages of subjects who agree (either mildly, moderately, or strongly) with each barrier. † Pvalues compare differences between willing and unwilling subjects.

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beneficial effects on cardiovascular status, particularly on levels of triglycerides and high-density lipoprotein cholesterol.10,14

Similarly, although patients do gain weight after insulin initiation, the gain is relatively modest, ranging from 4.4 lb to 8.8 lb (2 kg to 4 kg). Furthermore, weight gain is inversely proportional to body mass index, so that patients who weigh more at the outset of insulin therapy gain less weight as a result of the therapy.14

With regard to practical concerns, initiation of insulin will likely impose additional time demands on the cian or practice. However, many physi-cians report that these additional demands are not excessive10and can be

addressed with small steps in patient edu-cation. Although some patients initially experience anxiety about insulin, this atti-tude often reverses after they begin using insulin. Many patients report less fatigue and an improved sense of well-being, as well as high levels of treatment satisfac-tion, after beginning insulin therapy.15

Thus, early education of patients about the benefits of insulin can reduce bur-dens on the physician and practice. Adherence to Insulin Therapy Rates of adherence to insulin therapy among patients with T2DM range from 63% to 77%.16,17Demographic factors

associated with poorer adherence include younger age at presentation, younger age at diagnosis, greater social deprivation, higher body mass index, and higher HbA1clevel.17Not surprisingly, more

complex insulin regimens and higher doses of insulin are also associated with poorer rates of adherence. In addition, ethnicity has been linked to differences in insulin adherence, with African Amer-icans demonstrating lower adherence than all other ethnic groups.16

Recognition by medical staff of the high rate of patient nonadherence is important for obvious reasons. Rather than routinely changing a patient’s reg-imen in response to elevated blood glu-cose or HbA1clevels, physicians should consider that the patient is simply not adhering to the prescribed regimen.

Good patient-physician communi-cation remains a cornerstone of improving insulin acceptance and adher-ence by patients.18Achieving such

effec-tive communication includes efforts by physicians to explore reasons for patients’ resistance.9For example, patients who

are fearful of needles may be unaware of improvements in dosing and injection devices that make insulin administration easier and less painful. A simple, in-office demonstration that includes the first injec-tion may be all that is needed to reassure the patient. For patients concerned about the risks of weight gain, providing accu-rate information about these risks while emphasizing that most patients feel sub-stantially better when using insulin can alleviate their anxiety.

Because patients often take cues from physicians, greater engagement of the patient in disease management can yield considerable improvement in insulin adherence.16Certain novel approaches

may help physicians better engage patients. For example, findings from one study16suggest that discussions about

prescription refill rates may stimulate dia-logue between patients and healthcare providers about conscientious adherence to insulin regimens. For patients who are anxious about the lifelong need for insulin, the use of insulin therapy can be suggested as only a trial intervention lasting several months. After patients begin using insulin and start to feel better, they are likely to continue the therapy.19

Empowering patients with an algo-rithm to self-titrate their insulin therapy

(Figure 1) is another way to improve

adherence and, thereby, help patients achieve and maintain glycemic control.20

Results from multiple studies—including A Trial Comparing Lantus Algorithms to Achieve Normal Blood Glucose Tar-gets in Subjects With Uncontrolled Blood Sugar (AT.LANTUS)21; the Glycemic

Optimization with Algorithms and Labs at Point of Care (GOAL A1C) study22;

and the Predictable Results and Experi-ence in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVE 303) trial23,24—show that good glycemic

control with a low incidence of hypo-glycemia (ie, <1%) were achieved with both patient-driven and clinic-directed algorithms.20

Tighter glycemic control yields a longer life expectancy as well as reduced vascular and neuropathic complications

of T2DM.25-27Many patients have

expe-rienced the ravages of these complica-tions and want desperately to avoid them. Physicians should recommend that patients “parent” themselves. A physi-cian can note, for example, that a patient would never allow his or her child to stray far from adherence to treatment, so why would the patient allow himself or herself to do so by not following an insulin regimen? Physicians should also stress that a patient has many people relying on his or her health and well-being, and these people would suffer if the patient became ill from not adhering to the insulin regimen.

Recommendations for Earlier Implementation of Insulin Therapy Clinical practice has long focused on man-aging T2DM first with lifestyle changes and later with addition of an oral hyper-glycemic agent. Early guidelines recom-mended delaying insulin therapy for as long as possible.10However, such an

approach leaves many patients with inad-equate long-term glycemic control. Research has shown that by the time insulin therapy is initiated, many patients have lived 5 years with an HbA1clevel greater than 8% and 10 years with an HbA1c level greater than 7%.11

This realization has led to revised thinking about treatment. The most recent standard-of-care guidelines by the ADA2

and the European Association for the Study of Diabetes (EASD)14 recommend

earlier initiation of insulin in patients for whom glycemic targets are not being achieved. Although an HbA1clevel of less than 7% is recommended for most patients with T2DM,2,14treatment goals

should be individualized based on patient status and medical history. Higher HbA1c levels may be appropriate for some patients, including those who are espe-cially vulnerable to hypoglycemia, those who have severe microvascular compli-cations or comorbid conditions, and those who have short life expectancies.2

Glycosylated hemoglobin is an index of glycemic control during the preceding 2 to 3 months. To achieve an HbA1clevel of less than 7%, targets for fasting plasma glucose (FPG) and peak postprandial glu-cose (PPG) are, respectively, 70 mg/dL to 130 mg/dL and less than 180 mg/dL

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Start with bedtime intermediate-acting insulin or bedtime or morning long-acting insulin (can initiate

with 10 units or 0.2 units per kg)

HbA1c⩾7% after 3 months Check fasting glucose (fingerstick) usually daily and increase dose, typically by 2 units every 3 days until fasting levels are consistently in target range (3.9-7.2 mmol/L [70-130 mg/dL]). Can increase dose in larger increments, eg, by 4 units every 3 days, if fasting glucose

>10 mmol/L (180 mg/dL)

If hypoglycaemia occurs, or fasting glucose level <3.9 mmol/L (70 mg/dL), reduce bedtime dose by 4 units or 10%, whichever is greater

If fasting bg in target range (3.9-7.2 mmol/L [70-130 mg/dL]),

check bg before lunch, dinner, and bed. Depending on bg results, add second injection as

below. Can usually begin with ~4 units and adjust by 2 units every 3 days until bg in range Continue regimen.

Check HbA1c

Pre-lunch bg out of range. Add

rapid-acting insulin at breakfasta Pre-dinner bg out of range. Add NPH insulin at breakfast or rapid-acting at lunch Pre-bed bg out of range. Add rapid-acting insulin at

dinnera

No Yes

No

Yes HbA1c⩾7% after 2-3 months

Recheck pre-meal bg levels and if out of range, may need

to add another injection. If HbA1ccontinues to be out of range, check 2 h postprandial levels and adjust preprandial

rapid-acting insulin

Figure 1.Algorithm for initiation and adjustment of insulin therapy. Insulin regimens should take a patient’s lifestyle and meal schedule into account. aAlthough premixed insulins are not recommended during dose adjustment, they can be used conveniently—usually before break-fast or dinner—if the proportion of rapid-acting and intermediate-acting insulins is similar to the fixed proportions available. Abbreviations:

bg, blood glucose; HbA1c, glycosylated hemoglobin; NPH, neutral protamine Hagedorn. With kind permission from Springer Science+Business Media: Diabetologia, Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of betes, Vol 52, 2009, 17-30, Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for the Study of Dia-betes, Figure 1.

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(which, for self-monitoring patients, cor-responds to a value of <140 mg/dL 2 hours after beginning a meal).14

Newly Diagnosed T2DM Cases In recent years, short-term intensive insulin therapy in patients newly diag-nosed as having T2DM has drawn increasing attention. Ryan et al28reported

that in patients newly diagnosed as having T2DM, a 2-week to 3-week course of intensive insulin therapy, including multiple daily injections, could success-fully lay a foundation for prolonged good glycemic control.28More recently,

inves-tigators have reported that early inten-sive insulin therapy in patients newly diagnosed as having T2DM could con-tribute to improved recovery and main-tenance of b-cell function, protracted glycemic remission, and improved glycemic control, compared with oral antihyperglycemic treatment.29,30

Insulin Preparations

Numerous insulin preparations, with a range of pharmacodynamic properties, are available (Figure 2).31These

prepara-tions include insulin analogs that offer certain advantages over nonanalog (ie, human insulin) alternatives. Among these advantages are improved physiologic time-action profiles and lower incidence of hypoglycemia.32Insulin analogs

include rapid-acting analogs (for pran-dial insulin coverage), long-acting analogs (for basal coverage), and premixed insulin analogs (which combine both a rapid-acting and an extended-duration com-ponent in a single formulation).33

Insulin Regimens

Strategies for initiating insulin therapy have been widely studied, with the goal of determining the relative safety and effectiveness of basal, bolus, or basal-bolus regimens.34,35The APOLLO (A

Par-allel design comparing an Oral antidia-betic drug combination therapy with either Lantus once daily or Lispro at meal-time in type 2 diabetes patients failing Oral treatment) trial34was designed to

compare basal insulin vs prandial insulin administration in patients with T2DM inadequately controlled by oral therapy. Patients were randomly assigned to receive either basal insulin glargine once

daily at the same time each day or insulin lispro 3 times daily at mealtimes. At 44 weeks, the basal regimen was found to be as effective as prandial administration with regard to controlling glycemic levels. The basal regimen was also associated with lower risk of hypoglycemia and greater treatment satisfaction.34

The Treating to Target in Type 2 Dia-betes (4-T) study35examined the

ques-tion slightly differently but reached sim-ilar conclusions. In the 4-T study, patients who had failed to reach glycemic targets with combination therapy of metformin and a sulfonylurea were randomly assigned to 1 of 3 insulin regimens: biphasic insulin aspart twice daily, pran-dial insulin aspart 3 times daily, or basal insulin detemir 1 to 2 times daily.35At 3

years, glycemic efficacy was similar across the 3 groups, but the basal insulin group experienced statistically significant fewer hypoglycemic events and less weight gain than the other groups (P<.001). These and other data form the basis for present recommendations that the initial insulin regimen for patients with T2DM should consist of basal administration.14

Although initial therapy seeks to raise levels of basal insulin, patients may eventually require prandial therapy with short-acting or rapid-acting insulin.14This

requirement develops because the relative roles of FPG and PPG change as the level of HbA1cdecreases. At an HbA1clevel of approximately 10% or greater, FPG con-tributes approximately 70% to overall glycemic burden. Below an HbA1clevel of approximately 7.5%, the contribution reverses, with PPG being responsible for 70% of glycemic burden.14At an HbA

1c

level of approximately 7.5% to 8.5%, the contributions of FPG and PPG are approximately equal. Once the FPG level is well controlled, any escalation in the basal dose of insulin will not address the postprandial component. At this point, a regimen that includes both basal and bolus insulin dosing is required.5

Insulin Dose

Various algorithms are available to guide insulin initiation,36,37and physicians are

encouraged to choose 1 algorithm with which they are comfortable. Furthermore, no single approach should be used. Drug

Barag • Insulin Therapy for Type 2 Diabetes Mellitus JAOASupplement 5 • Vol 111 • No 7 • July 2011 • S17

Time of Action, h*

Agent Onset Peak Duration

Insulin ◽Short-acting – RHI 30-60 min 2-4 5-8 ◽Intermediate-acting – NPH 1-3 8 12-16 ◾Insulin Analog ◽Long-acting – Detemir 1 peakless 20-26 – Glargine 1 peakless 22-26

◽Rapid-acting, mealtime bolus

– Aspart 15 min 30-90 min 3-5

– Glulisine 15 min 30-90 min 3-5

– Lispro 15 min 30-90 min 3-5

◾Premixed

◽NPH/RHI 70/30 30-60 min varies 10-16

◽NPR/RHI 50/50 30 min 1.5-2 ⩽24

◽Insulin aspart protamine/ 5-15 min varies 10-16 insulin aspart 70/30

◽Insulin lispro protamine/ 10-15 min varies 10-16 insulin lispro 75/25

◽Insulin lispro protamine/ 10-15 min varies 10-16 insulin lispro 50/50

Figure 2.Time action profiles of insulins and insulin analogs. *Units are in hours unless otherwise indicated. Abbreviations:NPH, neutral protamine Hagedorn; RHI, regular human insulin. Adapted from the National Diabetes Information Clearinghouse.31

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therapy should be tailored to the needs of individual patients based on such factors as age, concomitant disorders, and ability to adhere to medical instructions.14

A common starting dose of insulin in patients with T2DM is either 10 U daily or 0.2 U/kg daily of an intermediate-acting or long-acting insulin.5 However, because

more than 90% of patients with T2DM are resistant to insulin, higher doses are often required to achieve adequate glycemic control.5Many patients with

T2DM may require relatively large doses of insulin compared to patients with type 1 diabetes mellitus—sometimes exceeding 1 U/kg daily—to bring their HbA1clevels into the target range.14

A patient-driven algorithm devel-oped by the ADA and the EASD (Figure 1) is widely used because it is relatively simple and can be applied to initiating, titrating, and intensifying insulin therapy.14This algorithm recommends

increasing the basal insulin dose by 2 U every 3 days until the FPG target is achieved, or by 4 U every 3 days if the FPG level remains above 180 mg/dL. If hypoglycemia occurs or if FPG falls below 70 mg/dL, the basal dose should be reduced by either 4 U or by 10% of the dose, whichever is greater.14

Regardless of the dosing approach used, timely assessment and adjustment of insulin is crucial. As they do with oral medications, physicians often wait too long before intensifying insulin therapy, leaving patients exposed to excessive glycemia and at increased risk of long-term complications.5Another reason that

delay in using insulin is detrimental is that glycemic control becomes more dif-ficult to achieve with increasing delays in intensification of treatment.38

Patient Self-Monitoring

Self-monitoring of blood glucose (SMBG) is an important component of successful use of insulin in patients with T2DM. Education of patients is essential to stress the importance of SMBG in avoiding hyperglycemia or hypoglycemia and to ensure that patients understand proper techniques and timing for self-monitoring.

At initiation of insulin therapy (assuming that basal therapy is pre-scribed), once-daily SMBG may be ade-quate. If patients are engaged in self-adjustment of insulin doses, SMBG should always be performed before administering the daily dose, and the results should be used to increase or decrease the dose as necessary. Approaches in Primary Care As primary care physicians assume a greater role in managing insulin therapy, it is important to identify particular prac-tices that can be effectively implemented in such settings. One trend in this regard is a shift toward more patient-centered insulin management.

Recent research has examined if patients can safely and effectively self-titrate insulin levels by following easy-to-use dosing guidelines.23,39-41One such

study is the PREDICTIVE 303 trial,23,24

which prospectively evaluated the use of insulin detemir in primary care practices in the United States. This study sought to determine the feasibility and utility of simple, patient-directed insulin guide-lines (ie, the “303 Algorithm,” shown in

Figure 3) for administration of insulin

detemir, compared with the standard practice of physician monitoring and dose adjustment.24The PREDICTIVE 303

trial23,24 showed that the patient-directed

intervention was at least as effective as standard clinical management. The HbA1c levels decreased from a baseline of 8.5% in both groups to 7.9% in the algorithm group and 8.0% in the standard man-agement group (P<.001). The mean reduction in FPG level was 1.8 mmol/L in the algorithm group and 1.2 mmol/L in the standard management group (P<.001). No increased risk of hypo-glycemia was observed in the patient-directed group compared to the physi-cian-directed group.23,24

The PREDICTIVE 30323,24 findings

suggest that a patient-driven approach to insulin dose adjustment is a safe and effective alternative to physician-directed management. The implications for such a patient-centered model may extend even further. When involved and empowered to play a greater role in their own care, patients may take more personal respon-sibility for their health, achieving results that meet or exceed those observed in physician-directed situations.24,39

Conclusion

Despite vast expenditures of healthcare resources, management of T2DM remains woefully inadequate, and many patients spend a long time well outside the rec-ommended glycemic range. New stan-dard-of-care practice guidelines entail ini-tiating insulin therapy much earlier in the treatment continuum than did pre-vious guidelines. However, resistance to initiation of insulin therapy, both from patients and physicians, is widespread. Furthermore, as much as one-third of patients who use insulin therapy do not adhere to their prescribed regimen.

For patients with deteriorating phys-iologic function, the importance of insulin therapy in controlling glycemia and min-imizing diabetes-related complications cannot be overstated. As the principal responsibility for managing T2DM con-tinues to shift to the primary care setting, primary care physicians must rise to the challenge of overcoming their own resis-tance and that of their patients to effec-tively implement insulin therapy. References

1.Diabetes Action Online-About diabetes. World Health Organization Web site. http://www.who.int /diabetesactiononline/diabetes/basics/en/index1 .html. Accessed June 14, 2011.

Fasting Plasma Glucose,

mean, mg/dL (mmol/L) Dosing

<80 (<4.4) Decrease by 3 units

80–100 (4.4-6.1) No change

>100 (>6.1) Increase by 3 units

Figure 3.Simplified, patient-directed insulin guidelines (ie, the “303 Algorithm”) used in the Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVE 303) trial.24The algorithm was used for basal insulin analog (insulin detemir) dosing, based on the mean of 3 fasting plasma glu-cose levels self-measured for 3 consecutive days.

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2.American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care. 2011;34(suppl 1):S11-S61.

3.UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphony-lureas or insulin compared with conventional treat-ment and risk of complications in patients with type 2 diabetes (UKPDS 33) [published correction appears in Lancet.1999;354(9178):602]. Lancet. 1998;352(9131):837-853.

4.Molyneaux LM, Constantino MI, McGill M, Zilkens R, Yue DK. Better glycemic control and risk reduc-tion of diabetic complicareduc-tions in type 2 diabetes: comparison with the DCCT. Diabetes Res Clin Pract. 1998;42(2):77-83.

5.Hirsch IB, Bergenstal RM, Parkin CG, et al. A real-world approach to insulin therapy in primary care practice. Clin Diabetes.2005;23(2):78-86.

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References

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