Target Audience and Goal Statement: Endocrinologists, cardiologists, nephrologists, and primary care physicians
The goal was to evaluate the association between implementation of a health plan–based intervention of switching patients from analogue to human insulin and glycemic control.
Questions Addressed:
- Is a health plan program that encourages patients to switch from analogue to human insulins associated with a change in glycemic control among older adults with type 2 diabetes?
- Can patients and insurers save money by switching from analogues to human insulins?
Synopsis and Perspective:
Classical paradigms of type 1 and 2 diabetes – diseases that contributed to the
382% increasefrom 1988 to 2014 in diabetes diagnosed in the U.S. – are no longer accurate. The diseases are
heterogeneous in terms of clinical presentation and can occur in children and adults. At least
9.4% of all Americans have diabetes, and nearly
31% of adults with diabetes (≥18 years old) use insulin, either alone or in combination with pills.
Insulin helps blood glucose levels from rising too high (i.e., hyperglycemia). Insulins are
categorized by differences in onset of action, how long it takes to achieve maximum impact, concentration, and route of delivery.
Currently, many Americans with diabetes use
insulin analogues (rapid-acting, short-acting, intermediate-acting, and long-acting) to efficiently, conveniently, and safely control blood glucose levels. Prior studies have also shown that select analogues provided better coverage of the
postprandial glucose surge compared with human insulin.
Synthetic human insulins come in fast-acting (regular) and intermediate-acting (neutral protamine Hagedorn [NPH]) formats. Additionally, premixed, clinically equivalent human insulin includes the fixed 70/30 ratio premix recombinant human insulin formulation, which can be made up of insulin isophane and regular insulin. According to the
Diabetes Teaching Center at the University of California, San Francisco, “regular human insulin has undesirable features, such as a delayed onset of action, variable peak, and duration of action when it is injected under the skin.”
NPH human insulin also has undesirable features such as a suspension of crystals differing in size, which may result in unpredictable absorption, translating into more frequent low and high blood sugars.
Current
debates around human insulins and analogues mainly revolve around the point that the latter drugs are no more effective than human insulins, but are more expensive. In the last 10 years, insulin prices have
tripled in the U.S., while out-of-pocket costs per prescription doubled. Medicare’s outpatient prescription drug program (
Part D) spent more than $4 billion on one long-acting insulin analogue in 2016 alone.
“A vial containing 1,000 U of NPH or regular human insulin can be purchased for $25, whereas the retail price for a vial of analogue insulin ranges between $178 and $320,” according to one
report. Human insulin, when used effectively, may also be a viable initial treatment option for many patients with type 2 diabetes.
Because of the cost implications, one strategy may be to switch patients with type 2 diabetes from analogues to human insulin, and such a strategy formed the basis for the current study by Jing Luo, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
Beginning in 2015, a health plan embarked on an intervention in four states (California, Arizona, Nevada, and Virginia) to shift Medicare beneficiaries with diabetes from insulin analogues to human insulin. Comparisons were also made between 983 participants who did not make the switch and 983 participants who did. The switching protocol involved moving from basal and/or prandial insulins to premixed human 70/30 or NPH insulin.
The researchers reported that 14,635 health plan members (mean [SD] age: 72.5 [9.8] years; 51% women; 93% with type 2 diabetes) filled 221,886 insulin prescriptions over 3 years.
The primary outcome was the change in mean hemoglobin glycated hemoglobin (HbA1c) levels estimated over three 12-month periods:
- Pre-intervention (baseline) in 2014
- Post-intervention in 2016
Secondary outcomes were the rates of serious hypoglycemia or hyperglycemia.
Prior to the intervention, the mean HbA1c was 8.46% (95% CI 8.40%-8.52%). The American Diabetes Association suggests an HbA1c level of
less than 7% for most non-pregnant adults with diabetes. Prior to the intervention switch in the study, HbA1c fell by 0.02% per month: At the beginning of the intervention, HbA1c levels rose by 0.14%, but at study completion, no significant differences were seen in HbA1c changes among all study participants or in the subgroup who made the switch (compared with the 12-month intervention period).
Similarly, there were no significant differences in serious hypoglycemic or serious hyperglycemic events noted among patients who switched medications, the researcher noted.
While the use of insulin analogues dropped from 89% to 30% when comparing the baseline through 2016 time frame, the use of human insulin increased from 11% to 70% during the same period.
Study limitations, Luo and co-authors said, included possible residual confounding and time-related biases and inability to detect small differences in the rates of minor hypoglycemia episodes or nocturnal hypoglycemic events because the outcome definitions relied on claims, and the fact that the results may not be readily generalizable to other healthcare settings with less intensive pharmacy-level support for chronic disease management.
Source Reference: JAMA, Jan. 29, 2019; 321(4): 374-384
Study Highlights: Explanation of Findings
Among more than 14,000 Medicare beneficiaries, most of whom had type 2 diabetes, facilitating an analogue-to-human insulin switch was associated with a small increase in population-level HbA1c, this study showed. In an
accompanying editorial, however, Kasia Lipska, MD, MHS, of the Yale School of Medicine in New Haven, Connecticut, explained that this change was not typically considered clinically meaningful.
Luo and colleagues noted that results from the Action to Control Cardiovascular Risk in Diabetes (
ACCORD) trial, the Action in Diabetes and Vascular Disease (
ADVANCE) trial, and the Veterans Affairs Diabetes Trial (
VADT), suggest that small changes in HbA1c are unlikely to meaningfully affect the rates of macrovascular events or mortality among patients with type 2 diabetes. In addition, “the association with increases in HbA1c reported in this study may reflect underlying changes in clinical practice occurring during 2015 and 2016 as new data counseled against tight glycemic control among older adults with diabetes,” the team said.
This study adds to the literature which suggests that human insulins may result in similar clinical outcomes compared with insulin analogues for many patients with type 2 diabetes, the investigators continued. “Study participants were prevalent insulin users, had better HbA1c control at baseline (7.8%), had lower rates of clinical events, and were part of a health system that did not have a strong preference for human insulin.”
Overall expenditures for insulin were more than halved over 2 years — i.e., from $3.4 million per month in 2014 to $1.4 million in 2016. The 4.5-fold increased cost for human insulin during the same period (from $200,000 to $900,000 per month) was offset by the substantial drop in insulin analogue expenditures (from approximately $3.2 million to $500,000 per month). The proportion of patients who reached the Medicare Part D coverage gap dropped from 20.6% in 2014 to 11.1% in 2016.
Lipska noted that many analogues did not offer “major advantages” over human insulin products for patients with type 2 diabetes. Even clinical trials demonstrating a benefit for insulin analogues in terms of “modestly reducing” self-reported nocturnal hypoglycemia – an important outcome for patients with diabetes — were open-label and therefore a potential area of bias.
Ultimately, the goal of diabetes management is the prevention of
long-term complications. Whether substantial savings in the short-term will translate into cheaper, individualized treatment for a progressive condition with heterogeneous clinical manifestations in the long term, is not clear.
Nevertheless, Luo et al. said, if even a small proportion of Medicare beneficiaries with type 2 diabetes who were prescribed analogues were switched to clinically equivalent human insulin, the resulting savings to the healthcare system would be substantial.
Additional Source
MedPage Today
