The rising prevalence of obesity and increased life expectancy. Initiating Insulin for Type 2 Diabetes: Strategies for Success.

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1 case-based review Initiating Insulin for Type 2 Diabetes: Strategies for Success Anand Vaidya, MD, and Graham T. McMahon, MD, MMSc Abstract Objective: To outline a simple and evidence-based approach for initiating insulin. Methods: Algorithms for considering and approaching insulin initiation were derived from extensive literature searches and author experience. Results: Type 2 diabetes is characterized by progressive loss of beta cell function and peripheral insulin resistance. The initiation of insulin is often a pivotal intervention to avert the exposure to hyperglycemia and prevent diabetic complications. Early use of insulin may mitigate long-term consequences of hyperglycemia and can be done effectively when barriers to initiation are recognized. Conclusion: Successful insulin initiation requires an ability to elicit and navigate common barriers and misperceptions about insulin. Simple algorithms for starting and titrating insulin can be used by primary providers, with ongoing collaboration with diabetes specialists to ensure optimal management. The rising prevalence of obesity and increased life expectancy have together contributed to the epidemic of type 2 diabetes mellitus. The pathophysiology of diabetes is characterized by progressive deterioration of pancreatic beta cell function and concomitant peripheral insulin resistance. Prolonged exposure to hyperglycemia resulting from this pathology increases long-term risk for developing micro- and macrovascular complications. Despite earlier diagnosis and management, beta cell exhaustion and the need for insulin therapy are often inevitable [1]. The conventional approach to treating type 2 diabetes has emphasized a stepwise introduction of lifestyle modifications and oral drugs before recommending insulin. To limit protracted exposure to hyperglycemia, consensus opinion increasingly favors the initiation of insulin earlier in the disease course of diabetes, well before failure with other regimens [2,3]. Early initiation of insulin involves adopting an aggressive strategy towards glucose control and requires health care providers and patients alike to recognize the most appropriate time to start insulin, the barriers impeding early initiation, and feel comfortable with available insulin formulations and starting regimens. CASE STUDY Initial Presentation A 60-year-old man with type 2 diabetes and obesity presents to the primary care office. He was diagnosed with diabetes 6 years ago when fasting blood glucose exceeded 126 mg/dl. Glycosylated hemoglobin (HbA 1c ) at the time of diagnosis was 7.8%. He has no known history of cardiovascular disease, retinopathy, nephropathy, or neuropathy. Despite multiple attempts at losing weight, his body mass index remains unchanged at 35 kg/m 2. He does not routinely exercise and has a sedentary lifestyle. Six months ago, his HbA 1c was 8.7% while on metformin 1000 mg twice daily and glyburide 10 mg twice daily. Pioglitazone 30 mg daily was added to his regimen at that time. He now reports morning fasting glucoses using a glucometer between 145 and 185 mg/dl. HbA 1c today is 8.5%. When should insulin be initiated in patients with type 2 diabetes? When to Initiate Insulin Since its initial discovery in the early 20th century, insulin has been a lifesaving treatment for diabetes. In type 1 diabetes, it serves as vital replacement treatment from the time of diagnosis; however, since insulin deficiency occurs gradually in patients with type 2 diabetes, the optimal time to begin insulin therapy for these patients is not clearly defined or easily recognized. Nevertheless, support for earlier introduction is growing [2,3]. The traditional management paradigm for type 2 diabetes includes a stepwise approach, beginning with lifestyle modifications such as physical activity and dietary education Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital, Harvard Medical School, Boston, MA. Vol. 16, No. 3 March 2009 JCOM 127

2 initiating insulin [4]. For many patients like the case patient, these lifestyle amendments are often challenging and rarely result in sustained normalization of glucose. Oral antidiabetic drug (OAD) monotherapy is generally introduced when lifestyle changes are unable to maintain normoglycemia, followed by combinations of OADs prior to commencing insulin therapy [4 6]. Recently, incretin analogues, such as exenatide, have emerged as additional therapeutic options that can precede insulin in particular circumstances. Despite an extensive track record of efficacy and safety, insulin has generally been reserved as a final armament in the arsenal of antidiabetes therapies [4]. While many other medications are viable alternatives to the early use of insulin, most of these options rely on endogenous insulin production to exert their effect. Consequently, as the natural history of type 2 diabetes progresses and insulin deficiency supervenes, combinations of noninsulin therapies become increasingly less likely to lower HbA 1c and can be very costly [7 11]. Emerging evidence suggests that despite the improvements in diabetes regimens over the last decade, delaying the introduction of insulin subjects patients to years of avoidable hyperglycemia [11,12]. In a large prospective evaluation of diabetes treatment strategies, the average patient incurred 3 years of HbA 1c levels greater than 8% and 5 years of HbA 1c levels greater than 7% before insulin therapy was begun [12].Conversely, the early and prompt administration of insulin to newly diagnosed patients with type 2 diabetes has been shown to facilitate more effective glycemic control, improve beta cell survival and function, and potentially delay disease progression [13 15]. The Epidemiology of Diabetes Interventions and Complications (EDIC) study group showed that long-term benefits on vascular health are achieved when intensive insulin therapy was instituted early in the cohort of patients from the Diabetes Control and Complications Trial (DCCT) [16,17]. Cumulative evidence supports the need for more intensive approaches to the management of type 2 diabetes and has demonstrated the efficacy of early introduction of insulin. Proactive counseling on the benefits of insulin therapy to patients in the nascency of their disease course can mitigate culturally prevalent fears and misconceptions about impending insulin use. Additionally, health care providers need to be willing to introduce insulin at lower glycemic thresholds. Traditionally, insulin has been initiated in subspecialty clinics dedicated to diabetes care rather than in the primary care setting. However, recent trends suggest that introduction of insulin by primary care providers is associated with improved resource and clinical outcome effectiveness, supporting the case for extending the role of primary providers to include early insulin initiation [18 20]. Successful establishment of insulin early in the pathophysiology of type 2 diabetes will rely on assertive action and community-based care. Most guidelines recommend that insulin should be prescribed when a patient continues to have elevated glucose levels despite attempts at treatment with oral hypoglycemic drugs; others have recommended insulin initiation as early as the time type 2 diabetes is diagnosed [9,13 15,21]. The introduction of insulin to patients already at their goal HbA 1c should also be considered, especially when the pace of disease progression is fast and long-term insulin independence is deemed unlikely. The American Diabetes Association recommends the earliest consideration of insulin when lifestyle modifications with metformin fail to lower HbA 1c below a threshold of 7%, and reconsideration when HbA 1c remains greater than 7% despite 2 or 3 OADs [22]. Starting insulin when dual-oral therapy has failed is cost-effective and offers benefits on weight, lipid profile, and peripheral edema [23 26]. Adding a third oral hypoglycemic drug is rarely effective, since additional drugs provide diminishing levels of efficacy. Alternative therapies such as incretin agonists or inhibitors of dipeptidyl-peptidase-4 inhibitors are only appropriate if the patient s HbA 1c is very close to goal, since both of these drugs have limited efficacy. In the case patient, insulin therapy could have been discussed when it became clear that lifestyle modification was unlikely to normalize his glucose (Figure 1). Starting insulin when metformin failed to bring HbA 1c below the 7% threshold, rather than treatment with pioglitazone, would have been an effective approach. Case Continued The patient had expressed concern that administering insulin would unnecessarily complicate his life and commit him to a lifetime of painful daily injections. His mother died 6 months after starting insulin treatment. He is anxious to avoid insulin treatment by being compliant with any other oral treatments and feels that his diabetes is not so bad that it warrants treatment with insulin. What are barriers to insulin initiation? Overcoming Barriers to Insulin Initiation Although the early commencement of insulin is associated with significant clinical benefits, several physical and psychological obstacles constrain both patients and providers from advancing therapy (Table 1 and Table 2). The Diabetes Attitudes, Wishes, and Needs (DAWN) study employed survey assessment to understand patient reticence for beginning insulin injection administration and provider reluctance in prescribing insulin [27]. The DAWN analysis revealed that within the global community, general physicians in the United States were among the most likely to delay insulin 128 JCOM March 2009 Vol. 16, No. 3

3 case-based review Diagnosis of type 2 diabetes Education on the progressive nature of type 2 diabetes and counseling on the benefits of insulin use. Consider immediate initiation of insulin and referral to diabetes educator and nutritionist Lifestyle modifications and metformin HbA 1c 7% after 3 mo YES NO Reiterate benefits of early insulin. Strongly consider insulin initiation and referral to diabetes educator Continue regimen, recheck HbA 1c every 3 mo Addition of second OAD and/or incretin analogue HbA 1c 7% after 3 mo YES NO Continue regimen, recheck HbA 1c every 3 mo. Consider starting insulin if prolonged maintenance of HbA 1c < 7% on OADs seems unlikely INITIATE INSULIN THERAPY Figure 1. When to start insulin. HbA 1c = glycosylated hemoglobin; OAD = oral antidiabetic drug. therapy until absolutely needed, while patients in the United States tended to hold a very negative view towards insulin [27]. The perceptions highlighted by the DAWN study group play a considerable role in the underutilization of insulin in the treatment of type 2 diabetes. Data from the Third National Health and Nutrition Examination Survey (NHANES III) reveal that the last decade has witnessed a significant decline in the use of insulin in the United States, with concomitant decreases in achievement of glycemic targets [28]. Fear of insulin is very common. Supportive feedback, sincere empathy, and guided education to empower selfmanagement can help overcome this apprehension [27,29]. Fear of needles and injections is a concern shared by patients with and without diabetes. Some have genuine trepidation regarding the prospect of pain, while others may focus on the perceived stigma of publicly carrying and using a needle [30]. Modern day technology has facilitated the design of needles with very fine gauges (31 32G) and shortened lengths (0.5 in), which minimize pain. Additionally, in-office demonstration of self-injection with sample equipment can reassure patients by illustrating that self-injection is not only minimally invasive but also not as daunting as perceived. For some, the standard vial and syringe can be cumbersome and associated with significant social stigma. Insulin pens can be easily concealed and carried at room temperature and are therefore preferred by a growing number of patients for their ease of use [31,32]. Concerns about weight gain, hypoglycemia, and the relative efficacy of insulin over other therapies is commonly encountered. Since patients with type 2 diabetes, unlike many patients with type 1 diabetes, retain a normal glucagon response to hypoglycemia, severe insulin-induced hypoglycemia is rare [33,34]. Disciplined physical activity and dietary education should be reinforced when starting insulin, as these interventions have been shown to abrogate weight gain [35 37]. Additionally, continuing the use of insulin sensitizers such as metformin following insulin initiation has also been shown to maintain weight neutrality [38]. As expressed by the case patient, initiation of insulin can be interpreted as a personal failure of disease management; this concept is widely endorsed by many patients and Vol. 16, No. 3 March 2009 JCOM 129

4 initiating insulin Table 1. Health Care Provider Barriers to Initiating Insulin Barrier Perceived risk of causing hypoglycemia Reinforcing feelings of failure Competing array of treatment choices Resource limitations Solutions Risk of insulin-induced hypoglycemia in type 2 diabetes is very low and comparable with that induced by oral insulin secretagogues (< 3% per patient-year) Long-acting insulin analogues provide even lower rates of hypoglycemia than traditional basal insulins Help patients disconnect individual behaviors from the natural progression of disease Gradual beta cell loss is inevitable, but early insulin use can mitigate unnecessary exposure to hyperglycemia Studies continue to support the association between early initiation of insulin and improved glycemic control and costeffectiveness The American Association of Diabetes Educators provide information for locating local diabetes educators at educator.org Patients can be instructed to titrate their insulin doses themselves using simple available algorithms contributes to the avoidance of insulin. This phenomenon of self-blame and psychological insulin resistance is most typical among older U.S. patients [27,39 41]. Clinicians can reinforce this perception if insulin treatment is used as a threat to encourage patients to engage in lifestyle modification. Such threats reinforce the stigma associated with insulin use and make adoption of insulin even more challenging when it becomes necessary. Early advocacy for insulin therapy well before it is prescribed can mitigate and minimize insulin resistance. Cultivating the understanding that progressive beta cell loss and peripheral insulin resistance may occur even with diligent adherence to therapy can help make insulin more acceptable in future discussions [42]. Clinicians can help patients understand that insulin therapy may improve a patient s sense of well-being if the alternative is prolonged hyperglycemia: use of insulin and subsequent attainment of glycemic control can increase patients physical and mental well-being. Direct empathy followed by a structured discussion regarding the realistic needs for insulin help vitalize patient-physician trust and can galvanize patients to approach insulin therapy as a boon rather than penalty. When available, a diabetes educator or other dedicated health care professional can maximize the efficiency of insulin initiation in a busy practice. The availability of ancillary Table 2. Patient Barriers to Initiating Insulin Barrier Fear of selfinjection Social stigma Weight gain Hypoglycemia Efficacy Misperceptions linking insulin with poor prognosis Feelings of failure Complexity of treatment regimen Cost Solutions Ultrafine (31 32G) and ultrashort (0.5 in) needles provide little to no pain In-office injection demonstrations can overcome initial apprehension Insulin pens provide more discretion and ease of use than vials and syringes The use of insulin is more common in the community than perceived by most patients Dietary counseling at initiation of insulin helps mitigate weight gain Concurrent use of metformin protects against weight gain Hypoglycemia in type 2 diabetes is an uncommon adverse event The use of insulin does not increase this risk significantly more than the use of sulfonylureas Long-acting insulins impart very low risk of hypoglycemia Insulin is the most studied and most potent glucose-lowering medication available Insulin actually improves prognosis. Poor outcomes usually occur when insulin therapy is delayed or avoided Type 2 diabetes pathophysiology is progressive, typically irrespective of personal behavior Addition of insulin can impart significant success in achieving glucose goals Insulin regimens can be tailored to patient needs Use of insulin pens can simplify administration Long-acting insulins and premixed insulin can minimize daily injections Insulin preparations are available at lower cost than many oral agents staff in the fields of diabetes education and nutrition has been associated with improved adherence to insulin use and glycemic control [43,44]. When such support is absent and the clinician has limited resources to effectively engage his/ her patients with insulin, referral to a local diabetes educator or subspecialty diabetes practice with sufficient resources is appropriate [45]. To actively engage the case patient in the insulin initiation plan that he needs, his fears must be acknowledged and misperceptions clarified. Firm reiteration that his prolonged hyperglycemia will contribute to microvascular and macrovascular disease is a reasonable prologue to recommending insulin initiation at this time. He should be reminded of the 130 JCOM March 2009 Vol. 16, No. 3

5 case-based review safety, history, and reliability of insulin, with a demonstration of insulin use offered to illustrate its feasibility. Case Continued The patient is counseled on the adverse effects of prolonged hyperglycemia and reminded that insulin is a safe and effective agent, capable of decreasing complications akin to those his mother suffered. He is reassured that injections with ultrafine needles elicit very little pain, and an in-office demonstration with insulin pens reinforces this discussion. He is amenable to start treatment with insulin but still apprehensive that this new therapy will be too complex. Which insulin regimen should be selected? Selecting the Appropriate Insulin Regimen When agreement to begin insulin has been reached, selecting the most appropriate insulin type and schedule becomes the next priority. The goal is to mimic normal physiology while maintaining patient compliance with an administration protocol that can be realistically maintained. Fortunately, insulin regimens can be more flexible now that clinicians have an ever-expanding array of insulin formulations available. Newer long-acting insulin analogues such as glargine and detemir provide basal insulin needs for up to 24 hours and are therefore used commonly as once daily basal formulations [46,47]. Neutral protamine Hagedorn (NPH) is a well-known intermediate-acting insulin used to provide basal coverage with either once- or twice-daily administration. To date, newer long-acting analogues have not shown greater HbA 1c -lowering effects when compared with established intermediate insulins such as NPH but are associated with less weight gain and nocturnal hypoglycemia [48 51]. The addition of prandial rapid-acting insulin (lispro, aspart, or glulisine) to a basal insulin regimen is the foundation of basal-bolus therapy. While this approach is tailored to replicate physiologic pancreatic action, it is generally too complex to be used at the time of insulin initiation. Although several reasonable permutations to begin insulin exist, the general consensus still favors initiating once-daily basal insulin therapy, with either a long-acting analogue or NPH once nightly before bed (Figure 2). This approach targets elevated fasting blood glucose, and with the addition of a single injection, can provide significant reductions in HbA 1c [51,52]. This strategy allows providers to recommend a simple and effective insulin regimen and sets the stage for future modifications that will likely be less challenging to implement. Commencing with 10 units per day as an initial insulin dose is generally safe. In heavier patients, this can be preferentially tailored by using a starting dose of roughly 0.2 units per kg. This injection can be given in the evening if using NPH or either evening or morning when using long-acting analogues. Patients should be instructed to record morning fasting blood glucose, as future titrations to basal insulin will rely on these values as a proxy for insulin action. Several major studies have demonstrated the achievement of HbA 1c of less than 7% when patients are given algorithms and appropriate instructions to titrate doses of their basal injections themselves [33,51 55]. This strategy is valuable because it empowers patients to take control of their disease, while decreasing a portion of management burden from primary health care providers. The Treat-to-Target study demonstrated the efficacy of a strategy that initiated glargine or NPH at 10 units before sleep, with patient instructions to increase their dose by 2 units every 3 days until a target fasting glucose of 70 to 130 mg/dl was achieved; up-titration was temporarily halted with any hypoglycemic readings [51]. Using this approach, more than half of the treated patients achieved a HbA 1c of less than 7% within 24 weeks. Depending on the comfort level of the patient and provider, more conservative or aggressive algorithms can also be used. If HbA 1c has not declined below 7% after 2 to 3 months of titrating basal insulin to target fasting glucose, the addition of prandial insulin should be considered. Although some advocates support starting with basalbolus treatment rather than single injection when baseline HbA 1c is higher than 8.5%, we prefer starting with a single daily injection, with subsequent alterations to the number of injections as insulin-naive patients acclimatize to their regimen [56]. The use of premixed insulin may provide an alternative solution as an initial regimen when starting HbA 1c levels are greater than 8.5%. Premixed formulations are available in a variety of compositions containing part intermediate-acting insulin and part rapid-acting insulin, often in a ratio of 70:30 [57]. These preparations meet basal insulin requirements in addition to mitigating postprandial glucose excursions and have been shown to be superior at lowering HbA 1c when compared with long-acting analogues in some studies [58,59]. While the postprandial action of premixed insulins is theoretically advantageous, because their formulations are restricted to fixed ratios of short- and long-acting insulin and contain only NPH as the basal formulation, the incidence of hypoglycemia and erratic glucose levels can limit their effectiveness [60]. Premixed insulins can serve as effective and uncomplicated initial regimens for patients with markedly dysregulated glycemic control; however, achievement of long-term fasting and postprandial glucose control will frequently require gradual transition to a basal-bolus strategy. Vol. 16, No. 3 March 2009 JCOM 131

6 initiating insulin INITIATE INSULIN THERAPY Provide reassurance directed at individual barriers to insulin therapy (see Table 1 and Table 2). Demonstrate in-office injection and offer use of insulin pens. Refer to local diabetes educator Start bedtime NPH insulin or morning or bedtime long-acting insulin analogue. Begin with either 10 units, or 0.2 units per kg for heavier patients Continue metformin; stop sulfonylureas and other antidiabetes drugs Instruct to record fasting blood glucose every morning. Encourage selftitration of insulin based on simple dosing algorithms (ie, increase dose by 2 units every 3 5 days until fasting blood glucose is mg/dl). If symptomatic hypoglycemia or fasting blood glucose < 70 mg/dl, decrease dose by 10%, or 4 units, whichever is greater Yes YES HbA 1c 7% after 3 mo NO Fasting blood glucose > 130 mg/dl? No Continue regimen, recheck HbA 1c every 3 mo ADD PRANDIAL INSULIN Figure 2. Initiating insulin. HbA 1c = glycosylated hemoglobin; NPH = neutral protamine Hagedorn. Case Continued Glargine insulin is started at a conservative dose of 20 units before sleep, and the patient is advised to discontinue glyburide. A glucometer is provided, and he is instructed to measure fasting blood glucose daily and to increase his daily glargine dose by 2 units every 3 days until fasting glucose declines below 130 mg/dl. He is advised to call the office to relay his morning glucose values weekly to ensure safety and answer questions. A prescription for a glucagon home injection kit is provided for safety, with instructions on recognizing and treating hypoglycemia and a recommendation to obtain a medical alert bracelet or pendant. Two months later, he returns to the office. He is currently taking glargine 34 units nightly, and fasting blood glucose measurement have consistently been between 105 and 130 mg/dl. He reports periodic measurements of preprandial glucose values through the day ranging from 110 to 230 mg/dl. His HbA 1c at this visit has declined from 8.5% to 7.4%. How should the insulin regimen be modified if glycemic targets are not being met? Intensification of Insulin Regimens When goal HbA 1c is not achieved with adjustment of oncedaily injections, attention should be directed to controlling postprandial glucose variations. Intensification of insulin regimens to control postprandial glucose excursions has been shown to improve glucose control and has been associated with a reduction in markers of atherosclerosis [61 66]. Postprandial hyperglycemia contributes fractionally more 132 JCOM March 2009 Vol. 16, No. 3

7 case-based review ADD PRANDIAL INSULIN Add 4 6 units of preprandial, rapid-acting insulin before the largest meal of the day Gradually increase dose until postprandial (2 4 hr) blood glucose < 130 mg/dl HbA 1c 7% after 3 mo YES NO Continue regimen, recheck HbA 1c every 3 mo Instruct to check preprandial blood glucose at every meal and at bedtime Give additional mealtime injections and/or adjust current doses as needed Consider referral to endocrinologist Figure 3. Intensifying insulin therapy. to the HbA 1c at lower HbA 1c concentrations, thus control of postprandial glucose is necessary if recommended glycemic targets are to be attained. For patients on a once-daily basal injection, the addition of a rapid-acting insulin with 1 meal a day (usually the largest meal) is a reasonable start, as introducing 3 rapid injections at once can overwhelm many patients (Figure 3). A prandial rapid-acting insulin dose of roughly 4 to 6 units is a good initial approximation (or approximately 30% of the total basal dose at the time of initiation), and this can be increased by titrating to either a 2-hour postprandial glucose of less than 140 to 180 mg/dl or the next preprandial glucose less than 130 mg/dl. The dose of basal insulin does not generally need to be reduced when starting a prandial insulin for the first time in a patient who is not at his/her goal HbA 1c. Gradually, prandial injections can be added to other meals as needed. Fixed doses of mealtime insulin can be prescribed, but carbohydrate-adjusted prandial insulin regimens can also be developed with the assistance of dietary specialists. Theoretically, carbohydrate counting provides a more physiologic approach than fixed basal-bolus injections; however, both fixed dosing and carbohydrate counting approaches have been shown to be equally effective in patients with type 2 diabetes when practiced correctly and can be safely managed by patients with home adjustment algorithms based on their preference [67]. When the addition of individual mealtime injections is perceived as overly complex, an intensive regimen of premixed insulin can provide modest coverage of both basal and prandial insulin needs, with fewer injections. Individuals on once-daily dosing of premixed insulin can be escalated to twice or even thrice daily, with significant HbA 1c -lowering effects, but this can be associated with a higher hypoglycemia risk than basal-bolus strategies [59,68]. As with basal-bolus therapies, simple titration algorithms for intensification exist for premixed insulins [60]. Because premixed insulins contain fixed ratio of both basal and short-acting insulin, as additional premixed injections are added, each individual dose may need to be reduced to prevent hypoglycemia. While the transition from OAD therapy to initiating single injection insulin treatment can be simple, coordinating the addition of multiple injections based on basal and prandial needs can be daunting, both for provider and patient. In these situations, referral to a local diabetes educator or endocrine specialist can help foster multidisciplinary care and safely steward intensive insulin management. Case Continued The patient is advised to check his preprandial and bedtime glucose values in addition to fasting levels. His bedtime glucose levels are routinely greater than 200 mg/dl, consistent with his dietary habit of eating a large dinner. Five units of aspart insulin to be taken with dinner is added to his regimen. In the subsequent months, his home measurements show prelunch and predinner glucose levels greater than 140 mg/dl, prompting the addition of breakfast Vol. 16, No. 3 March 2009 JCOM 133

8 initiating insulin and lunchtime aspart insulin as well. He initially gains 5 lb after starting prandial insulin, but returns to his baseline weight with dietary management. He reports no glucose readings below 60 mg/dl. Most recently, his regimen has consisted of glargine 35 units at bedtime, 8 units of aspart with breakfast and lunch, and 12 units of aspart with dinner. His HbA 1c is now 6.8%. CONCLUSION Insulin replacement therapy is ultimately necessary in most patients with type 2 diabetes. The initiation of insulin represents a pivotal intervention to avert the exposure to hyperglycemia and prevent diabetic complications. Earlier introduction of insulin is steadily gaining credence, usually in combination with continued use of metformin. Successful insulin initiation requires an ability to elicit and navigate common barriers and misperceptions about insulin. A myriad of insulin formulations capable of meeting the needs of almost any patient are available, accompanied by advances in administration modalities addressing comfort, discretion, and simplicity. Home titration of a basal insulin formulation followed by addition of prandial insulin before the largest meal is an effective evidence-based approach. Collaboration with diabetes educators, nutritionists, and endocrinologists can help ensure success but should not delay therapy. Most importantly, ongoing collaboration with patients can ensure they achieve the best possible health and enjoy the benefits of the most effective diabetes treatment available. Corresponding author: Anand Vaidya, MD, Brigham and Women s Hospital, Div. of Endocrinology, 221 Longwood Ave., Boston, MA 02115, avaidya1@partners.org. Financial disclosures: None. 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