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.