Human and Analogue Insulins Equivalent for Major Outcomes

There was no difference between human and analogue insulin in terms of cardiovascular and mortality outcomes, but cost is another matter, said authors of a large retrospective study.
With data on 127,000 adults with type 2 diabetes who initiated insulin during 2000-2013 and median 2.5 years of follow-up, users of human versus analogue insulin products had similar rates of major cardiovascular events, cardiovascular mortality, and overall mortality, reported Patrick O’Connor, MD, of the HealthPartners Institute in Minneapolis, and colleagues.

More specifically, as they outlined in JAMA Network Open, the study’s five main outcomes had the following adjusted hazard ratios for human versus analogue insulin:

• Overall mortality: HR 1.15 (95% CI 0.97-1.34)

• Cardiovascular mortality: HR 1.26 (95% CI 0.86-1.66)

• Myocardial infarction: HR 1.11 (95% CI 0.77-1.45)

• Cerebrovascular accident: HR 1.30 (95% CI 0.81-1.78)

• Congestive heart failure hospitalization: HR 0.93 (95% CI 0.75-1.11)

“Our results suggest that cardiovascular outcomes and mortality should not be a motivating factor in the decision to start human vs analogue insulin therapy in insulin-naive adults with type 2 diabetes,” the researchers wrote. “Other relevant factors to consider include hypoglycemia, glycemic control, cost, and ease of use. Recent reports have shown similar effects of human and analogue insulins on control of glucose levels and serious hypoglycemic events in primary care practice, which suggest that human and analogue insulins are safe and effective treatments in type 2 diabetes.”
Most insulin users in the U.S. — approximately 90% — use analogue insulins, which were first introduced in 1996. They became widely used despite higher costs, in part because studies indicated lower rates of mild hypoglycemia.
O’Connor and co-authors added that while hypoglycemia rates have been well studied, the effects of human versus analogue insulin on cardiovascular events and mortality have not. Both types of insulin were introduced before 2008 when the FDA mandated cardiovascular outcomes trials for diabetes drugs. Some major clinical trials, such as the Diabetes Control and Complications Trial and the U.K. Prospective Diabetes Study, did not include analogue insulins.
A 10-mL vial of human insulin lists for approximately $25, compared with more than $280 for analogue insulin, O’Connor’s team noted. “The price differential between human and analogue insulins and the lack of significant differences in rates of serious hypoglycemia in recent reports have sparked new interest in the use of human insulin as a way to make health care more affordable to patients with diabetes.”

Previous research on this topic, however, reported mixed results. Those studies also had significant limitations in terms of participant selection, sample size, and analytic details. The current study improved on that research by including a large number of U.S. participants who received care in community-based clinics, by having relatively complete clinical outcome data, and by using machine learning and other advanced statistical methods to analyze the data, O’Connor and co-authors explained.
The 127,600 study participants were treated in four different healthcare systems: HealthPartners in Minnesota, Kaiser Permanente Colorado, Kaiser Permanente Northern California, and Kaiser Permanente Southern California. The mean age of participants was 59, and approximately half were men.
Most participants (85%) used human insulin. Two exposure groups defined by continuous treatment with the same insulin therapy, either human or analogue, were compared. The investigators analyzed medical records for outcomes, controlling for factors that included patient demographics, comorbidities, concomitant medications, and smoking.
Robert Eckel, MD, of the University of Colorado Anschutz Medical Campus in Aurora, who was not involved in the research, said the large number of human insulin users was unusual. Still, “with all of the limitations of retrospective analysis of medical records, the results are not surprising,” he told MedPage Today via email. “However, the discrepancy between clinics in insulin use is of note with three of four locations using mostly human insulin. Moreover, the ongoing use of human insulins 10-15 years after analogue insulins were FDA approved is unexpected based on U.S. data in 2010, and despite the escalating cost of analogues.”
A chief limitation of the study, O’Connor and colleagues said, was its retrospective design. “However, owing to the high cost of conducting large randomized trials in a rapidly evolving insulin market, there is little chance that a large randomized trial will address cardiovascular outcomes of human vs other insulins, although manufacturers have compared newer and older analogue insulins,” the team wrote. “Results show few differences in cardiovascular events, suggesting that newer analogue insulins are unlikely to have better cardiovascular outcomes than the analogue insulins we evaluated.”

The study was supported by the National Institutes of Health (NIH).
O’Connor reported grants from the NIH and the Patient-Centered Outcomes Research Institute; one co-author reported a relationship with a pharmaceutical company (Merck) outside of the study.

• Primary Source

  JAMA Network Open

  Source Reference: Neugebauer R, et al “Comparison of mortality and major cardiovascular events among adults with type 2 diabetes using human vs analog insulins” JAMA Network Open 2020; 3(1): e1918554.

https://www.medpagetoday.com/cardiology/diabetes/84521