Early Intensive Insulin in Type 2 Diabetes

Gayle Nicholas Scott, PharmD | Disclosures | January 12, 2017
Question
Can the use of early intensive insulin cause remission of type 2 diabetes?
Response from Gayle Nicholas Scott, PharmDAssistant 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. 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. 
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.
The importance of prompt normalization of blood glucose after
diagnosis of T2D was established by the United Kingdom Prospective
Diabetes Study (UKPDS). 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. 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. 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. Early intervention
within the first 2 years after T2D diagnosis appears to be key in the
effectiveness of intensive insulin treatment.
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.
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. 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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