Patients may see a bump in HbA1c levels when switching to human insulin from an analogue product for type 2 diabetes, but probably not enough to make a clinical difference, researchers reported.
In a retrospective study looking at Medicare beneficiaries with type 2 diabetes, patients who switched from analogue to human insulin saw a small (0.14%) but statistically significant increase in mean HbA1c levels over the course of a year (95% CI 0.05%-0.23%, P=0.003), reported Jing Luo, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
Twelve months after this switch, mean HbA1c levels stabilized as there were no significant changes among patients that made the switch (0.08%, 95% CI -0.01% to 0.17%), they wrote in JAMA.
In the year prior to the switch, there was a slight, yet statistically significant decrease in mean HbA1c levels while patients were on analogue insulin — dropping at a rate of -0.02% each month (95% CI -0.03% to -0.01%, P<0.001), although the average baseline A1c was generally high at 8.46%. Switching to human insulin also appeared to be generally safe, with no significant changes in the rates of serious hypoglycemic and hyperglycemic events, which was maintained through the following year.
“Although it was significant … the observed increase in population-level HbA1c may not be clinically important because the value (0.14%) falls within the biological within-patient variation of modern HbA1c assays,” the researchers stated, adding that findings from the ACCORD, ADVANCE, and VADT trials all “suggest that small changes in HbA1c are unlikely to meaningfully affect rates of macrovascular events or mortality among patients with type 2 diabetes.”
They also noted that “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.”
In an accompanying editorial, Kasia Lipska, MD, MHS, of the Yale School of Medicine in New Haven, Connecticut, explained that, besides cost, the choice between an insulin analogue and human insulin likely would have “little clinical consequence for most patients.”
“For example, a vial containing 1000 U of NPH [neutral protamine Hagedorn] or regular human insulin can be purchased for $25, whereas the retail price for a vial of analogue insulin ranges between $178 and $320,” she explained, also noting how these steep prices are only increasing as of late.
Why have insulin analogues become so popular over human insulin? Lipska suggested that “may have the appeal of novelty” due to the fact they’re newer versions of insulin. Also, many of the post-marketing studies of insulin analogues may have been a way to “encourage” providers to prescribe the newer products when paired with “successful” marketing, she stated.
The analysis included 3-year data on nearly 2,500 Medicare beneficiaries who switched from analogue insulin (glargine, detemir, aspart, and lispro) to human insulin products, such as NPH and regular human insulin, as part of a cost-savings program initiated in February 2015 across four states. These patients were compared with over 2,100 patients who remained on analogue insulin.
In order to qualify to be switched to human insulin, patients included in the study had to be on more than two injections a day or were receiving basal and prandial insulin analogues, taking more than 50 U of insulin per day, had a history of non-adherence, and had no history of recurrent hypoglycemia.
In the year prior to the switch, about 89% of prescriptions for analogue insulin products were filled by Medicare Advantage Plan beneficiaries. During the year immediately following the switch (2015), there was a drop down to 53% in the percentage of filled analogue insulin prescriptions, while there was an increase from 11% up to 47% in the percentage of filled human insulin products. By 2016, the percentage of filled analogue insulin prescriptions continued to drop, while filled prescriptions for human insulin products continued to rise, accounting for 70% of these insulin prescriptions.
A study limitation was the inability to detect differences in rates of minor hypoglycemia episodes or nocturnal hypoglycemic events because the outcome definitions relied on claims, the authors explained. They recommended longer follow-up of these patients on human insulin to see if there are any clinically relevant changes in HbA1c.
Lipska suggested healthcare providers note that “Human insulin may not be the optimal choice for everyone, but it could be a solution for many patients with diabetes. On the individual patient level, use of human insulin may minimize out-of-pocket spending, and, on the health care system level, it may allow insurers to maximize the value of diabetes care.”
The study was funded by the Laura and John Arnold Foundation with additional support from the Engelberg Foundation, the Harvard-MIT Center for Regulatory Science, and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital.
Luo disclosed relevant relationships with Alosa Health and Health Action International. Co-authors disclosed multiple relevant relationships with industry.
Lipska disclosed a relevant relationship with the Centers for Medicare & Medicaid Services and support from the National Institute on Aging and the American Federation of Aging Research through the Paul Beeson Career Development Award.