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Feature Articles : May 1, 2010 ( )
Treating T2DM with Early Insulin Therapy
Lack of Comprehensive Patient Education Has Stymied Adoption of Beneficial Treatment Option
Traditionally viewed as a primarily Western disease, diabetes is becoming a global threat. While dramatic improvements in emerging economies such as China and India are facilitating middle-class expansion and increasing disposable income, they are also fueling the rapid rise of obesity and, consequently, type 2 diabetes mellitus (T2DM) in these regions. The combined Indian and Chinese diabetic population of over 75 million in 2010 is expected to approach a daunting 120 million by 2025.
Maintaining tight glycemic control is paramount in reducing the risk for long-term complications from diabetes. Patients have several therapeutic options to help maintain healthy glucose levels, insulin is perhaps the most effective option and has been shown to help preserve the viability of insulin-producing, pancreatic b-cells, which weaken and lose functionality over the course of the disease.
Nevertheless, while physicians recognize the benefits of earlier insulin therapy—improved patient outcomes and managed costs—the early administration of insulin for T2DM faces considerable hurdles, including patient resistance to injections and the risk of hypoglycemia with overdose.
We believe that the following factors will facilitate the earlier adoption of insulin in treating T2DM, disrupting the current diabetes treatment paradigm:
Inadequacy of Current Treatments
Following disease diagnosis, physicians typically encourage lifestyle changes first, though these adjustments alone are often insufficient in maintaining normal glucose levels. Metformin is an effective monotherapy in the early stages of the disease and is typically prescribed as a first-line treatment; however, as the patient’s β-cells become progressively weaker, additional oral antidiabetic drugs (OADs) such as sulfonylureas and thiazolidinediones are often needed.
Unfortunately, all of these OADs lose effectiveness over time, necessitating the frequent monitoring of glycemic levels and adjustments of treatment. Eventually, many patients shift to insulin once multiple OADs have failed and after enduring diabetic nephropathy, neuropathy, or cardiovascular concerns.
Insulin therapy offers significant advantages over OADs including the notion of “β-cell rest,” where insulin is believed to decrease the secretory demand for endogenous insulin and preserve β-cell viability. Given the progressive nature of diabetes and the gradual loss of β-cell function, insulin therapy can mitigate the destructive effects of hyperglycemia on these cells. In addition, several studies have illustrated that β-cell dysfunction may be partially reversible when hyperglycemia is corrected via insulin.
Another differentiating benefit of early insulin treatment over OADs is its ability to minimize therapeutic intervention. A recent Chinese study illustrated that in newly diagnosed T2DM patients, short-term, intensive insulin therapy facilitated near-normal glycemic control in a majority of participants, leading to prolonged periods of euglycemia, which could be sustained via diet and exercise alone. These individuals’ β-cell function had largely been preserved and/or restored for up to two years. This phenomenon, as well as insulin’s restorative capabilities on β-cells, may indicate insulin’s ability to attenuate the loss of β-cell function during the course of T2DM, thus slowing the progression of the disease.
Hurdles to Insulin Adoption
Despite the benefits of early insulin therapy in treatment, adoption has thus far been minimal, due to three main hurdles:
1. Patient resistance: The need for injection drives the great majority of patients toward noninvasive oral therapy. Despite modifications like smaller needle sizes, insulin has yet to become desirable for patients, specifically the growing diabetic pediatric population.
2. Risk of inducing hypoglycemia from an insulin overdose: While a serious potential side effect, this risk is arguably less influential on the adoption of early insulin therapy. Fortunately, in the earlier stages of the disease, when glucose responses are still functional, hypoglycemia is less of a concern and can usually be countered with the consumption of a rapidly absorbed carbohydrate.
3. Patient outlook and the negative stigma associated with insulin use: Patients view insulin therapy as permanent and many believe that insulin therapy is addictive, thus making treatment cessation difficult. Numerous studies have shown that not only can insulin therapy be stopped, but in newly diagnosed T2DM patients, near-normal glucose levels could be maintained via only diet and exercise after intensive insulin therapy.
Another common complaint is that insulin encourages weight gain. Although it has certainly been shown to stimulate the appetite, the supplementation of insulin therapy with a healthy diet and regular exercise can help reduce the risk for weight gain.
All of these treatment hurdles stem from an overall lack of patient education. Indeed, insulin treatment continues to improve through the emergence of novel insulin analogs including slow-acting basal insulins, long-acting insulins for postprandial use, and premixes of the two types. Additionally, certain categories of insulins, primarily the basal insulin analogs, may have a very promising future in the early management of T2DM, particularly in emerging economies as they can offer a more cost-effective form of treatment through the delay, or possible prevention, of therapy via multiple OADs.
Insulin in Emerging Economies
Diabetes will continue to have a severely negative economic impact on healthcare in India and China. Obesity-related health expenses in China are expected to grow from $50 billion in 2000 to over $110 billion by 2025. In India, the total cost of diet-related, noncommunicable diseases (NCDs) is nearly $3.4 billion, or roughly 1.1% of India’s GDP. Even more troubling is that mortality due to diet-related NCDs in India is expected to account for over 43% of all deaths by 2020, where T2DM is a major contributor.
Although the monetary and human costs associated with T2DM’s proliferation will continue to devastate these countries if the status quo is maintained, significant opportunities exist for cost-effective therapies. To be successful, these therapies must be coupled with far-reaching educational programs to foster the two-pronged effect of decreasing disease incidence and treating those already living with the disease.
In India, the launch of large-scale health-intervention programs encouraging increased physical activity and healthier eating habits are working to slow the T2DM growth rate, with the latter program aiming to reach over 500,000 children in northern India alone. These programs are limited to reducing the number of new diabetics in these countries, therefore, modifications to the treatment paradigm should be considered to reduce disease mortality while controlling costs.
Not all insulin types will achieve widespread success, especially in the early stages of T2DM treatment. Significant adoption will be limited to those specific subcategories of insulins that require the least amount of patient education, have support from leading diabetic organizations like the American Diabetes Association, and provide cost advantages over other treatments.
Insulin determir (Levemir, Novo Nordisk) and insulin glargine (Lantus, Sanofi-Aventis) are best positioned to capitalize on the need for early, more effective treatments due to their ease of use and existing endorsements. Unfortunately, these products do not offer much of a cost advantage until later in the progression of the disease when several OADs are prescribed concomitantly. For example, treatment via generic metformin and sulfonylurea can cost as little as $10 per month, whereas one 10 mL vial of Lantus, which lasts for 30–45 days, typically costs over $100, as much as ten times that of treatment via these generic OADs. However, when drugs like metformin are combined with OADs in emerging classes (e.g., GLP-1 agonists and DPP-IVs), which themselves can cost over $200 per month, the cost advantages of these basal insulin analogs become more apparent.
Although the worldwide market for long-acting insulins is likely to grow from $2.5 billion in 2007 to $4.6 billion in 2012, a reduction in the cost of these drugs will likely accelerate growth beyond these initial projections. The introduction of effective, low-cost insulin analogs to populations in India and China is occurring.
Biocon launched its version of insulin glargine, Basalog, in India earlier this year at a 40% discount compared to its peers, a considerable difference that may facilitate its adoption earlier in the treatment paradigm, encourage its coverage by the state, and accelerate access. Biocon also plans to introduce Basalog outside India.
Although in no way localized to emerging economies, countries such as India and China are positioned to suffer from the epidemic growth of T2DM more severely than most developed countries due to greater cost sensitivity, inconsistent patient access to adequate healthcare, and insufficient—or nonexistent—educational programs encouraging healthy lifestyles aiming to deter the onset of the disease.
Early insulin use has the potential to greatly improve patient outcomes in the form of sustained prevention of hyperglycemic episodes and, with newly diagnosed patients, to foster euglycemia for extended periods via intensive administration without therapeutic intervention.
Furthermore, long-acting insulins may see less patient resistance than other forms of insulin, which require more closely monitored blood glucose levels and a greater degree of patient education. In developing countries, the emergence of less costly basal insulin analogs like Basalog is critical to facilitating earlier use of insulin.
Thus, we believe that the emergence of novel, low-cost insulins, combined with more widespread patient information regarding diabetes, will not only temper the devastating effects of T2DM on developing countries, but also usher in a hugely disruptive force in the treatment algorithm for the disease, one of which marketers of OADs must remain highly alert.
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