Investigational Tube-Free Pump for U-500 Insulin: A Viable Option

Miriam E. Tucker

July 05, 2018

ORLANDO — An investigational tubing-free insulin pump designed specifically to deliver U-500 insulin may help avoid dosing errors in adults with type 2 diabetes who require high insulin doses. 

Results from an open-label randomized trial using an investigational specially designed tubing-free insulin pump (Omnipod U-500, Insulet) delivering U-500 human Regular insulin (Humulin R U-500, Eli Lilly) were presented June 25 here at the American Diabetes Association (ADA) 2018 Scientific Sessions by George Grunberger, MD, medical director of the Grunberger Diabetes Institute, Bloomfield Hills, Michigan.

Currently, Grunberger said, about a quarter of U-500 insulin use is via pumps that were designed to deliver U-100 insulin, resulting in the need for calculations to determine appropriate dosing. In addition to the potential for error, the practice also raises questions about what to record in the notes and how to instruct patients about dosing, as the pump's units don't actually reflect the U-500 doses being given. 

"You have to deal with both the basal and bolus settings. It's very confusing and potentially dangerous," Grunberger said.

On the other hand, "U-500 [insulin] a dedicated pump could be a viable option for patients requiring high doses of insulin."

However, as pump use in the study was associated with more nocturnal hypoglycemia than injected U-500 insulin, he added, "clearly, individualized dose titration will be important to safely achieve HbA1c targets."

Session moderator Elena Toschi, MD, of the Joslin Diabetes Center, Boston, Massachusetts, agrees that use of U-500 in nondedicated devices can be tricky. "As long as you keep in mind that it's U-500 it's not a big challenge, but the problem is it creates a lot of miscommunication between nurses and staff in the hospital" with regard to patient documentation, dosing, and communicating with the pharmacy.

"So, I think having a pump that is specifically designed for U-500 kind of eliminates the questions...That should make the device safer, especially when we transition from one provider to another or from outpatient to inpatient," Toschi told Medscape Medical News.

HbA1c Better With Daily Injections, but Ups Nocturnal Hypoglycemia

The VIVID study involved 420 patients with type 2 diabetes who had HbA1c levels between 7.5% and 12%, a body mass index of 25 to 50 kg/m2, and who required between 200 and 600 units of insulin a day, with or without other glucose-lowering medications.

After a 2-week transition period during which all participants took U-500 insulin injected three-times daily, they were then randomized to continue the regimen or use the U-500 pump for another 24 weeks. In both groups, doses were titrated based on blood glucose readings. 

At 26 weeks, HbA1c reduction from baseline was significantly greater with the pump versus multiple daily injections, by -1.27 versus -0.85 percentage points (P < .001). Fasting plasma glucose levels dropped by 33.9 mg/dL with the pump versus a gain of 1.7 mg/dL with injections (P < .001).

Despite the greater reductions in HbA1c and fasting glucose, total daily insulin doses were reduced slightly in the pump group, by 0.05 units/kg, and rose by 0.42 units/kg with multiple daily injections (P < .001). 

There were no significant differences in rates of documented hypoglycemia of < 54 or ≤ 70 mg/dL, or severe hypoglycemia.

But there was significantly more nocturnal hypoglycemia with the pump, with 18 versus 11 events/patient/year of nighttime hypoglycemia ≤ 70 mg/dL (P < .001) and 7.6 versus 5.1 events/patient/year for < 54 mg/dL (P = .01).  

Grunberger noted that the study pumps were initially set to deliver 10% less basal insulin from 9 PM to 6 AM compared with daytime, and investigators could reduce the rate by another 10% if patients experienced hypoglycemia. And, he added, "there was no obvious trend related to nighttime bolusing."

Similar overall results were seen in a separate analysis that excluded patients taking concomitant sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists. Grunberger presented those data separately at the meeting in a poster on June 23.

Toschi told Medscape Medical News that "more and more we're seeing use of insulin pumps for type 2 diabetes" and at the same time, the rise in obesity and need for higher insulin doses has resulted in greater use of U-500 insulin.

The recent availability of a dedicated insulin pen has, however, made U-500 easier to prescribe, she said. "We can safely dose and be clear in communicating with the patient. I think people are becoming more comfortable prescribing U-500 insulin."

The study was sponsored by Insulet and Lilly. Grunberger has also received research support from Medtronic MiniMed and Novo Nordisk, and is on speakers bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi. Toschi had no relevant disclosures.

American Diabetes Association 2018 Scientific Sessions. June 25, 2018; Orlando, Florida. Abstract 351-OR.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: