Dual-hormone artificial pancreas ‘next logical treatment’ for type 1 diabetes
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Adults with type 1 diabetes may be able to maintain their glucose levels in target range longer, particularly during the day, by using an artificial pancreas with rapid-acting insulin and pramlintide, according to findings published in Diabetes Care.
“The novel dual hormone system that we developed has a significant potential, but we still need to confirm the finding in outpatients,” Ahmad Haidar, PhD, assistant professor in the department of biomedical engineering and an association member of the department of medicine and division of experimental medicine at McGill University in Montreal, told Healio. “We still need to have a coformulation of insulin/pramlintide to translate this into clinical practice.”
Haidar and colleagues assessed how frequently a cohort of 28 adults with type 1 diabetes (mean age, 25 years; 43% women) were able to maintain blood glucose levels between 3.9 mmol/L and 10 mmol/L during 24 hours using artificial pancreas systems that delivered either rapid insulin plus pramlintide (Symlin, AstraZeneca), regular insulin plus pramlintide, or rapid insulin alone. Blood glucose was measured at 10- to 30-minute intervals, according to the researchers, who noted that there was a roughly 2-week “optimization period” prior to each study visit depending on the system to be used, with the researchers randomly assigning the order in which participants used each system.
“To initialize the dual-hormone systems properly, we need parameters that result from a prolonged use of insulin and pramlintide concomitantly, and this requires a run-in period,” the researchers wrote. “Without a run-in period, the gastrointestinal outcomes during the dual-hormone artificial pancreas interventions would reflect the acute effect of pramlintide.”
The researchers also noted that the artificial pancreas using rapid insulin plus pramlintide “spread the delivery of pramlintide over 20 [minutes]” and was “mimicking a dual-wave bolus.”
Participants maintained glucose levels between 3.9 mmol/L and 10 mmol/L, or in range, 84% of the time while using the rapid insulin plus pramlintide system and 74% of the time while using rapid insulin alone (P = .0014). The researchers also found that participants using rapid insulin plus pramlintide achieved mean glucose of 7.4 mmol/L and participants using rapid insulin alone achieved mean glucose of 7.9 mmol/L (P = .0053). However, “there were no benefits associated with the regular insulin-and-pramlintide artificial pancreas,” the researchers wrote.
Participants maintained glucose levels in range 78% of the time while using rapid insulin plus pramlintide and 63% of the time while using rapid insulin alone between 8 a.m. and 11 p.m. Participants achieved 7.9 mmol/L in mean glucose when rapid insulin plus pramlintide was used and 8.7 mmol/L in mean glucose when rapid insulin alone was used between 8 a.m. and 11 p.m. (P = .0011).
According to the researchers, hypoglycemia occurred in 12 instances when rapid insulin plus pramlintide was used, in 18 instances when regular insulin plus pramlintide was used and in 11 instances when rapid insulin alone was used. The researchers also noted that gastrointestinal adverse effects, such as nausea or heartburn, occurred six times when rapid insulin plus pramlintide was used and 11 times when regular insulin plus pramlintide was used, and not at all when rapid insulin alone was used.
“We did better than conventional pump therapy … so it’s a great intervention, but we still have a long way to go before everyone gets normal control. This is why this work is important,” Haidar told Healio. “It’s one of the interventions that’s shown the most promise.” – by Phil Neuffer
For more information:
Ahmad Haidar, PhD, can be reached at ahmad.haidar@mcgill.ca.
Disclosures: Haidar reports he has received research support and consultant fees from AgaMatrix, Dexcom, Eli Lilly and Medtronic.
Perspective
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Joseph Aloi, MD
Current hybrid closed-loop systems improve blood glucose time in range compared with traditional insulin pump therapy and multiple daily insulin injections while minimizing glucose variability and hypoglycemia. Predictably, more blood glucose variability and relatively less time in range is seen during the awake hours — fed state — compared with overnight hours. Large postprandial blood glucose excursions challenge current closed-loop insulin dosing algorithms contributing to the increases in glucose variability and less time in range experienced during the daytime hours.
The researchers pose an interesting hypothesis to improve overall time in range by adding pramlintide administered by a second infusion pump to conventional insulin pump therapy using either a rapid insulin analogue or regular insulin.
Pramlintide is an analogue of amylin, which in normal physiology is co-secreted with insulin and suppresses glucagon and delays gastric emptying — all factors that can help mitigate large postprandial glucose excursions. Pramlintide has been available for use in augmenting insulin action in minimizing post-prandial glucose excursions for some time. Historically, the need for a separate injection at mealtime, dose titration and nausea limits patient acceptance.
Participants using pramlintide experienced an improvement in time in range when used with rapid insulin analogue infusion and had no significant increase in gastrointestinal complaints. In the dual-hormone therapy group, no negative effects on blood glucose or hypoglycemia were seen overnight. The study is limited by a 1-day inpatient study interval but does provide promising insights into the potential use of amylin analogues. We would expect that if a rapid insulin plus amylin combination became available, this could enhance blood glucose control in patients using insulin pump therapy. Also, long-term addition of amylin analogues to insulin therapy is associated with modest to moderate weight loss, which is another potential advantage to systems employing dual-hormone therapy.
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