Dual-hormone systems: Extra benefit worth it?
Dr. Russell, who is an investigator in multicenter pivotal studies of both insulin-only and bihormonal configurations of the Beta Bionics iLet bionic pancreas, began his debate presentation by endorsing the effectiveness of insulin-only hybrid systems and stating that he encourages his patients with type 1 diabetes to use them.
Michele G. Sullivan/MDedge News
Dr. Steven J. Russell
But, he said, adding glucagon can allow for better automation of hypoglycemia prevention and treatment in situations such as exercise.
“A bihormonal system achieves lower glucose, higher time-in-range, and less hypoglycemia than a well-functioning insulin-only system.”
Moreover, Dr. Russell said, “Glucagon reduces the need for medicinal carbohydrates, promotes satiety, and increases energy expenditure. ... Combined, these three factors may oppose weight gain or encourage weight loss as opposed to a system that uses insulin only.”
He pointed to a 2017 meta-analysis that showed improved time-in-range and greater reductions in hypoglycemia with dual- versus single-hormone systems.
And, in unpublished data from a randomized random-order crossover study of 23 patients with type 1 diabetes who each spent a week with usual care (insulin pump with or without CGM), insulin-only iLet, and bihormonal iLet, mean glucose levels were 165, 148, and 139 mg/dL, respectively. Time-in-range was 60%, 72%, and 79%, and median time with glucose below 54 mg/dL was 0.6%, 0.6%, and 0.2%, respectively.
Dr. Russell also addressed each of the arguments made by Dr. Hovorka and others against glucagon use.
Regarding the need for a stable glucagon formulation, he said that the analogue being developed for the iLet, dasiglucagon (Zealand pharma), is stable for more than a month at 40º C, with higher bioavailability and slightly slower absorption than glucagon.
And while he acknowledged the need for two separate hormone cartridges, Dr. Russell said that the Gen4 version of the iLet is fairly simple and intuitive, and the device itself is about the same size as the Tandem t:slim.
Use of glucagon didn’t increase insulin use in iLet trials, nor was it associated with increased reported nausea or liver glycogen depletion.
And users universally reported preferring the bihormonal system.
Long-term safety of chronic glucagon exposure has yet to be addressed, but animal data are reassuring, Dr. Russell said.
Regarding increased cost, he pointed to 2018 data showing that the incremental improvement in glycemic control from no automation to single-hormone automation is the same as from single to dual (mean glucose reductions of 7.4 and 13.6 mg/dL, respectively, and decreases in time spent in hypoglycemia of 1.28% vs. 2.95%).
“I would argue that, if one can justify adding automation, one could justify some additional expense to add the cost of glucagon.” And, he said, the cost would likely be based on a negotiation around the extra value offered by the dual-hormone system.
“The addition of glucagon, I believe, will be justified by the improved outcomes and improved quality of life,” he concluded.
Dr. Hovorka has reported receiving research support from MiniMed Medtronic, Abbott Diabetes Care, and Dexcom; being a speaker for Novo Nordisk, Eli Lilly, and Dexcom; holding license fees from B. Braun and Medtronic; and being director of CamDiab. Dr. Russell has reported holding patents on aspects of the bionic pancreas; receiving honoraria, travel expenses, and/or research support from Dexcom, Eli Lilly, Tandem Diabetes, Sanofi, Novo Nordisk, Roche, Ascensia, Zealand Pharma, and Beta Bionics; being a consultant for Flexion Therapeutics, Senseonics, and Beta Bionics; and participating in scientific advisory boards for Companion Medical, Tandem Diabetes, and Unomedical.
A version of this article originally appeared on Medscape.com.