Clinicians should consider using older insulins in some patients with type 2 diabetes as a cost-saving measure, two endocrinologists suggest in a new opinion piece.

In the article, published in the August 18 issue of the Journal of the American Medical Association, Tracy Tylee, MD, and Irl B Hirsch, MD, both of the University of Washington School of Medicine, Seattle, argue that the old regular and neutral protamine Hagedorn insulins are just as effective as the more expensive analogs for most patients with type 2 diabetes who require insulin and can be used safely as long as steps are taken to avoid hypoglycemia.

"Clinicians will need to make adjustments to their patients' regimens to minimize risk of hypoglycemia, but with some understanding of how to use these insulins properly, clinicians can help patients achieve adequate glycemic control at a more reasonable cost," Tylee and Hirsch write.

The price of insulin analogs have soared in recent years. The cost of lispro, for example, jumped 585% between 2001 and 2015, from $35 to $234 per vial. For human insulin, those cost figures are $20 to $131, respectively. Nonetheless, 96% of type 2 diabetes patients who take insulin in the United States were using analogs, up from just 19% in 2000.

"The affordability of insulin is becoming an important factor in decision making, and clinicians should be aware of the lower-cost options that may be available for their patients," Tylee and Hirsch say.

The newer insulins provide better replication of human physiologic insulin secretion and greater convenience for patients. But, given the lack of data demonstrating a difference in HbA 1c , long-term outcomes, or severe hypoglycemia (Cochrane Database Syst Rev. 2007;2:CD005613) — which is infrequent in type 2 patients generally — physicians really need to pay attention to the price tag, Tylee and Hirsch assert.

"Many patients will have no choice but to use a less expensive alternative, and some patients may stop or ration their insulin because of costs.…The older insulins, while less commonly used, are as effective as the analogs at controlling blood glucose for most patients with type 2 diabetes at a lower price," they write.

Others have been making the same argument recently. The topic was the subject of a debate at the American Diabetes Association's annual Scientific Sessions in June. And in the United Kingdom, a group of prominent physicians has written a strongly worded objection to a draft proposal from that nation's health watchdog agency to recommend older insulins for type 2 diabetes patients, again as a cost-saving measure.

A special article published earlier this year in the New England Journal of Medicine traced the history of insulin's development, explaining why there are no generic insulins even 100 years after its discovery.

Back to the Future?

Now, Tylee and Hirsch go one step further, by providing advice about how to safely switch patients with type 2 diabetes from analogs to older insulins.

Whereas the analog glargine provides all-day basal coverage with one injection, NPH usually must be injected twice a day. To minimize nocturnal hypoglycemia, the dose can be split so that one-third is given at bedtime and the larger dose given in the morning.

To avoid insulin "stacking" leading to afternoon hypoglycemia, the dose of lunchtime premeal insulin should be lowered. When starting this regimen, patients should be encouraged to check their blood glucose levels both in the late morning and early evening and to stick as closely as possible to consistent meal times, Tylee and Hirsch advise.

Clinicians also need to teach patients to resuspend NPH insulin by mixing it gently prior to every use.

While there had been a belief that regular insulin must be taken 20 to 30 minutes prior to a meal, a study of 100 patients with type 2 diabetes found no clinical benefit to doing so (Diabetes Care. 2013;36:1865-1869). Still, the authors note, "given the slow absorption of regular insulin, more data on this topic are needed."

Dr Hirsch has received research grants from Sanofi, Novo Nordisk, and Halozyme. He has consulted with Abbott Diabetes Care, Roche, and Valeritas. Dr Tylee has reported no relevant financial relationships.

JAMA. 2015:314:665-666. Abstract