Early Intensive Insulin in Type 2 Diabetes

Gayle Nicholas Scott, PharmD


January 12, 2017


Can the use of early intensive insulin cause remission of type 2 diabetes?

Response from Gayle Nicholas Scott, PharmD
Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia

Type 2 diabetes (T2D) is a progressive condition of glucose toxicity and insulin insufficiency caused by insulin resistance and beta cell dysfunction.

Current guidelines advocate metformin or another oral antihyperglycemic as the initial medication treatment with the addition of other medications, including insulin, as the disease progresses.[1] Insulin is not recommended as a first-line agent and is often regarded by clinicians and patients as a last resort option to control rising hemoglobin A1c levels.

In patients with T2D, beta cell dysfunction could begin 15 years before becoming clinically apparent.[2] Obesity and a sedentary lifestyle, especially in the setting of a family history of T2D, increase the demand for insulin, leading to a vicious cycle of decreased insulin secretion, increased glucose production by the liver, and insulin resistance (Figure).[3,4]

Figure. The vicious cycle of type 2 diabetes.[3,4]

Some research suggests that intensive insulin treatment administered in newly or recently diagnosed T2D could interrupt glucose toxicity or delay disease progression. Interruption of the cycle of decreased insulin secretion, increased glucose production, and insulin resistance may preserve remaining beta cell function and induce a remission of hyperglycemia, possibly altering normal disease progression.[3,4]

The importance of prompt normalization of blood glucose after diagnosis of T2D was established by the United Kingdom Prospective Diabetes Study (UKPDS).[5] The Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial prospectively assessed adding, vs not adding, basal insulin glargine (at a dose targeting fasting normal blood glucose) to the therapeutic regimen of participants with prediabetes for a median period of 6.2 years.[6] A total of 1456 participants had prediabetes but not T2D at randomization. Although insulin glargine increased the risk for hypoglycemia and modestly increased weight, participants without T2D in the insulin glargine group were 28% less likely to develop diabetes than patients in the standard care group.

Studies over several decades, many conducted in Asian populations, suggest that short-term intensive insulin treatment for patients with recently diagnosed T2D can "give the pancreas a rest" with exogenous insulin and may effectively delay or prevent the need for antidiabetic medications.[7,8,9,10,11,12,13,14,15,16,17,18,19,20] Most studies used insulin pumps to deliver basal insulin (some used multiple daily subcutaneous injections), and some added preprandial insulin. Treatment durations have varied in most studies from 2 to 4 weeks; some studies had longer treatment durations. In a meta-analysis of studies evaluating early intensive insulin therapy in T2D, the percentage of participants in drug-free remission was about 66% after 3 months of follow-up, about 60% after 6 months, about 46% after 12 months, and about 42% after 24 months.[21] Early intervention within the first 2 years after T2D diagnosis appears to be key in the effectiveness of intensive insulin treatment.[22,23]

The idea of inducing remission of hyperglycemia and maintaining normal blood glucose without antidiabetic medication is a tantalizing outcome for patients with T2D. Although researchers have suggested the benefits of early intervention with insulin for T2D for more than 3 decades, current guidelines do not endorse or mention this approach.[1] Economic data from the ORIGIN trial suggest that the high cost of insulin glargine, which was used in early insulin treatment in this trial, may be offset in the long term by the lower use of oral medications in patients with newly diagnosed T2D.[24] The authors speculated that the cost of insulin glargine could be offset with reduced medication and medical costs in patients with prediabetes, but the actual cost impact is unknown.

Early intensive insulin treatment in patients with prediabetes and newly diagnosed T2D appears to have merit; however, insulin treatment is time-consuming and expensive to implement. Third-party payers would likely deem early intensive insulin investigational and refuse coverage of insulin and associated costs. Patient acceptance of administering insulin, as well as the intensive educational requirement (eg, use of an insulin pump or multiple daily injections, continuous or frequent glucose monitoring, diet), presently limit the practicality of early intensive insulin therapy in all but the most motivated patients and physicians. Early intensive insulin therapy continues to be an area of active research.


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