bionic pancreas

Bionic pancreas reduces HbA1c, improves time in range in type 1 diabetes: Pivotal data

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 Adults and children with type 1 diabetes who used an insulin-only bionic pancreas had reduced HbA1c without increasing hypoglycemia and other improved metrics compared with standard of care, researchers reported.

The Insulin-Only Bionic Pancreas Pivotal Trial achieved key primary and secondary endpoints in adults and children with type 1 diabetes, according to data presented during a mini-symposium at the American Diabetes Association Scientific Sessions.

Diabetes syringe and stethoscope 2019 adobe
Source: Adobe Stock

The iLet bionic pancreas (Beta Bionics) is a pocket-sized, wearable, investigational device designed to autonomously determine and deliver insulin doses to control blood glucose levels for people with diabetes. It is designed to be worn like an insulin pump; however, users would enter only their body weight to initialize therapy and would not set any insulin parameters. The device is designed to automatically titrate and infuse insulin without requiring the user to count carbohydrates, set insulin-to-carbohydrate ratios, set insulin basal rates, set correction factors or determine bolus insulin for meals or corrections, according to a company release.

This is a “fairly new and different concept in automation,” Greg Forlenza, MD, associate professor of pediatrics at the Barbara Davis Center for Diabetes at the University of Colorado Anschutz Medical Campus, said during a presentation.

Large, diverse trial

The pivotal trial was designed to evaluate safety and efficacy of the iLet bionic pancreas compared with current standard of care for insulin-treated diabetes over 13 weeks.

“This is the largest randomized controlled trial ever conducted to evaluate the safety and efficacy of an automated insulin delivery system,” Steven J. Russell, MD, PhD, associate professor of medicine at Harvard Medical School and Massachusetts General Hospital, said during the presentation.

The study population consisted of 440 adults and children aged 6 years and older with type 1 diabetes at 16 U.S. sites.

“This randomized trial included a more diverse population of adults with type 1 diabetes than previous pivotal studies of hybrid closed-loop systems with respect to minority representation, method of insulin delivery and HbA1c levels,” Davida Kruger, MSN, APN-BC, nurse practitioner at Henry Ford Health System, said here.

Participants were randomly assigned to the bionic pancreas or to continue their standard of care from January to July 2021. Seventy-seven percent of participants were non-Hispanic white, 10% non-Hispanic Black, 9% Hispanic or Latino and 4% other. The standard of care group was comprised of about one-third on automated insulin delivery systems, one-third on insulin pump therapy with continuous glucose monitoring and one-third on multiple daily injection therapy with CGM, Forlenza said.

The primary outcome was HbA1c at 13 weeks.

Primary analysis results

The primary analysis compared outcomes with the bionic pancreas, using insulin lispro (Humalog, Novo Nordisk) or insulin aspart (NovoLog, Novo Nordisk), with standard of care in 326 adults and children. The remaining 114 adults used the bionic pancreas with rapid-acting insulin (Fiasp, Novo Nordisk).

At 13 weeks, the following outcomes were improved over standard of care:

  • Significant reduction in HbA1c: At 13 weeks, mean HbA1c was reduced by 0.5% in the bionic pancreas group vs. standard of care (P < .001). In those with baseline HbA1c higher than 7%, the mean HbA1c reduction was 0.7% for the bionic pancreas group vs. standard of care (P < .001).
  • No increase in hypoglycemia: Those who used the bionic pancreas did not experience any significant increase in average time spent with CGM values less than 54 mg/dL over 13 weeks compared with standard of care (P < .001 for noninferiority).
  • Increased time in range: Those who used the bionic pancreas had an average of 2.6 hours more time in range (70-180 mg/dL) per day over 13 weeks vs. standard of care (P < .001).

Additional analyses

Kruger reported results from 161 adults using insulin aspart or lispro. In this cohort, mean HbA1c decreased from 7.6% at baseline to 7.1% at 13 weeks in the bionic pancreas group vs. 7.5% in the standard of care group (P < .001). Moreover, HbA1c improvement greater than 0.5% at 13 weeks occurred in 43% of the bionic pancreas group vs. 17% of the standard of care group (P < .001) and greater than 1% in 23% vs. 4%, respectively (P < .001). Greater improvements occurred in those with higher baseline HbA1c levels, Kruger said.

Time in range improved after just 1 day of use of the bionic pancreas, Kruger said. At 13 weeks, those assigned the bionic pancreas spent 11% more time in range (2.6 hours per day) compared with standard of care (P < .001). The researchers reported no difference in time spent below 54 mg/dL.

Seven severe hypoglycemia events were reported in the bionic pancreas group (25.5 per 100 person-years) and two in the standard of care group (14.2 per 100 person-years). No diabetic ketoacidosis events occurred. Thirty hyperglycemia adverse events associated with infusion set failures occurred in the bionic pancreas group (failure rate = 0.9 for 3,203 infusion sets), according to the presentation.

Laurel H. Messer, PhD, presented results from 165 children using insulin aspart or lispro. In the pediatric cohort, mean HbA1c decreased from 8.1% at baseline to 7.5% at 13 weeks in the bionic pancreas group and remained steady at 7.8% in the standard of care group (P < .001). HbA1c improvement greater than 0.5% at 13 weeks occurred in 51% of the bionic pancreas group vs. 17% of the standard of care group (P < .001) and greater than 1% in 29% vs. 6%, respectively (P < .001). As in adults, greater improvements in HbA1c occurred in those with higher levels at baseline.

At 13 weeks, those assigned the bionic pancreas spent 10% more time in range (2.4 hours per day) compared with standard of care (P < .001). Again, there was no difference in time spent with glucose below 54 mg/dL, Messer said.

Laurel H. Messer

Three severe hypoglycemia events were reported in the bionic pancreas group (10.4 per 100 person-years) and one in the standard of care group (7.3 per 100 person-years). No DKA events occurred. There were 30 hyperglycemia adverse events associated with infusion set failures in the bionic pancreas group (failure rate = 3% for 3,420 infusion sets), according to the presentation.

In these analyses, Kruger said the benefits of the bionic pancreas were “more prominent in multiple daily injection users without having a pre-randomization run-in period to initiate pump use, and the benefit was seen across race/ethnicity and socioeconomic status subgroups.”

In another analysis, Russell highlighted a comparison of the bionic pancreas using rapid-acting insulin aspart (n = 114 adults) compared with standard of care (n = 54 adults) and compared with the bionic pancreas using insulin aspart or insulin lispro (n = 107 adults).

“Compared with standard care, HbA1c was improved with the bionic pancreas using fast-acting insulin aspart without increasing CGM-measured hypoglycemia,” Russell said.

At 13 weeks, mean HbA1c decreased from 7.8% to 7.1% in the rapid-acting insulin aspart group and from 7.6% to 7.1% in the insulin aspart/lispro group (P < .001 for both).

“Compared with the bionic pancreas using insulin aspart or lispro, there was no difference in HbA1c, no difference in mean glucose, a 2% difference in mean time in range due to differences during the daytime, an increase in the proportion with time in range greater than 70% and no significant difference in the proportion with an increase in time in range by 5% or more or 10% or more,” Russell said.

In other results, there were no differences between the groups across nine patient-reported outcome surveys, according to Russell.

Jill Weissberg-Benchell, PhD, CDCES, with Ann and Robert H. Lurie Children’s Hospital of Chicago, reported additional patient-reported outcomes. Adults using the bionic pancreas cited reduced diabetes distress, improved fear of hypoglycemia and improved well-being. Among pediatric patients using the device, distress at baseline was associated with a steeper decrease in HbA1c compared with the standard of care group, Weissberg-Benchell said. Parents of the children in the study also reported satisfaction and acceptability of the bionic pancreas, she said.

Taken together, “Compared to a challenging standard of care, the bionic pancreas reduced HbA1c by a clinically significant margin (0.5%) overall and in subgroups; did not increase hypoglycemia; increased time in range by 2.4 to 3.1 hours per day; decreased mean glucose, time above 180 mg/dL and above 250 mg/dL; gave reasonable control of glycemia without CGM input; and autonomously produced and updated an open-loop regimen that gave reasonable control of glycemia,” Russell said.

Reference:

Bionic pancreas effective in home setting for reducing glucose, hypoglycemia

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Use of a bionic pancreas was associated with reductions in mean glucose and hypoglycemia compared with conventional insulin pump therapy, when used in the home setting by adults with type 1 diabetes.

“This was our first true home-study,” Edward R. Damiano, PhD, professor of biomedical engineering at Boston University, said during a presentation at the American Diabetes Association Scientific Sessions. “All participants lived at home and went to work, and there were no restrictions on diet or exercise.”

Edward Damiano

Edward R. Damiano

Damiano and colleagues sought to determine the efficacy of continuous, multi-day, automated glycemic control using a bihormonal bionic pancreascompared with conventional insulin pump therapy in adults with type 1 diabetes living at home and performing normal activities. Glycemic regulation was compared between the bionic pancreas and insulin pump over 11 days each in all participants. During the bionic pancreas period, continuous glucose monitor (CGM) data were used by an autonomous adaptive algorithm to control subcutaneous insulin and glucagon delivery. During the pump period, patients managed their own conventional insulin pump therapy.

The mean reduction in glucose level was 162 mg/dL with the bionic pancreas compared with 141 mg/dL with the insulin pump (P < .0001). The bionic pancreas was also associated with greater reductions in time less than 60 mg/dL by CGM (1.9% vs. 0.6%; P < .0001).

In other results, the mean number of symptomatic hypoglycemia events was lower with the bionic pancreas: 0.59 events per day compared with 0.6 events per day (P = .023). The mean total daily dose of insulin was 6% greater with the bionic pancreas compared with the insulin pump (P = .01). – by Amber Cox

Bionic pancreas effective in home setting for reducing glucose, hypoglycemia

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Use of a bionic pancreas was associated with reductions in mean glucose and hypoglycemia compared with conventional insulin pump therapy, when used in the home setting by adults with type 1 diabetes.

“This was our first true home-study,” Edward R. Damiano, PhD, professor of biomedical engineering at Boston University, said during a presentation at the American Diabetes Association Scientific Sessions. “All participants lived at home and went to work, and there were no restrictions on diet or exercise.”

Edward Damiano

Edward R. Damiano

Damiano and colleagues sought to determine the efficacy of continuous, multi-day, automated glycemic control using a bihormonal bionic pancreascompared with conventional insulin pump therapy in adults with type 1 diabetes living at home and performing normal activities. Glycemic regulation was compared between the bionic pancreas and insulin pump over 11 days each in all participants. During the bionic pancreas period, continuous glucose monitor (CGM) data were used by an autonomous adaptive algorithm to control subcutaneous insulin and glucagon delivery. During the pump period, patients managed their own conventional insulin pump therapy.

The mean reduction in glucose level was 162 mg/dL with the bionic pancreas compared with 141 mg/dL with the insulin pump (P < .0001). The bionic pancreas was also associated with greater reductions in time less than 60 mg/dL by CGM (1.9% vs. 0.6%; P < .0001).

In other results, the mean number of symptomatic hypoglycemia events was lower with the bionic pancreas: 0.59 events per day compared with 0.6 events per day (P = .023). The mean total daily dose of insulin was 6% greater with the bionic pancreas compared with the insulin pump (P = .01). – by Amber Cox

Type 1 Diabetes BioHub Trial Patient is Living “Insulin-Free”

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On August 18th, 2015, Wendy Peacock underwent the first-ever BioHub transplant–a minimally invasive procedure to place a “bioengineered mini-organ that mimics the native pancreas to restore natural insulin production” in people with type 1 diabetes.

biohub

Wendy Peacock, now age 43, has lived with type 1 diabetes since she was 17 years old–andshe is now living “insulin-free” with perfect non-diabetic blood sugar levels nearly two months since the procedure.

The Diabetes Research Institute (DRI), a Center of Excellence at the University of Miami Miller School of Medicine, launched this pilot study, to test their transplant technique for insulin-producing cells–islet cells–after decades of research and development on clinical islet transplantation. This first-ever human trial is a tremendous leap forward in the development of the DRI BioHub.

“The first subject in our Phase I/II pilot BioHub trial is now completely off insulin with an excellent glucose profile. These are the best post-transplant results we’ve seen in an islet recipient,” said Camillo Ricordi, MD, director of the DRI and the Stacy Joy Goodman Professor of Surgery, Distinguished Professor of Medicine, Professor of Biomedical Engineering, Microbiology and Immunology at the University of Miami Miller School. Dr. Ricordi also serves as director of the DRI’s Cell Transplant Center.

“This was the first tissue engineered islet transplant using a ‘biodegradable scaffold’ implanted on the surface of the omentum,” explains Dr. Ricordi. “The technique has been designed to minimize the inflammatory reaction that is normally observed when islets are implanted in the liver or in other sites with immediate contact to the blood. If these results can be confirmed, this can be the beginning of a new era in islet transplantation. Our ultimate goal is to include additional technologies to prevent the need for life-long anti-rejection therapy.”

The omentum, explains the press release, is a “highly vascularized tissue covering your abdominal organs.

“The donor islets were implanted within a biodegradable scaffold, one of the platforms for a DRI BioHub, made by combining the patient’s own blood plasma with thrombin, a commonly used, clinical-grade enzyme,” explains the press release. “Together, these substances create a gel-like material that sticks to the omentum and holds the islets in place. The omentum is then folded over around the biodegradable scaffold mixture. Over time, the body will absorb the gel, leaving the islets intact, while new blood vessels are formed to provide critical oxygen and other nutrients that support the cells’ survival.”

One of the hardest parts of any type of transplant is suppressing the recipient’s body natural protective response from attacking the transplanted organ, or in this case, incredible man-made organ. For the BioHub, immunosuppressive therapy will be used in the study, but not all of the patients involved will receive immunosuppressants.

“As any type 1 knows,” says Wendy Peacock, groundbreaking BioHub recipient, “you live on a very structured schedule. I do a mental checklist every day in my head…glucose tabs, food, glucometer, etc., and then I stop and say, ‘WOW! I don’t have to plan that anymore.’ Laying down at night and going to sleep and not having to worry about lows is something that is so foreign to me. It’s surreal to me…I’m still processing the fact that I’m not taking insulin anymore.”

Peacock became a potential candidate for the DRI’s clinical trial because ofsevere hypoglycemia unawareness–“a complication of diabetes in which patients are unable to sense that their blood glucose is dropping to dangerously low levels,” explains the press release.

“We’re quite excited. This has been the best outcome we have seen at this stage. It’s a unique site, the surgery is very simple and the patient recovers very quickly. We will continue until our final goal–islet transplantation without immunosuppression,” says Rodolfo Alejandro, MD, Professor of Medicine and director of the DRI Clinical Cell Transplant Program.

In people with type 1 diabetes, islet cells are produced by the pancreas and continuously destroyed by the immune system. While islet cell transplantation is not a new approach to curing type 1 diabetes, it has yet to become an approach that could truly be applied to the larger population of people with type 1 diabetes.

“Islet transplantation has allowed some patients to live without the need for insulin injections after receiving a transplant of donor cells. Some patients who have received islet transplants at the DRI have been insulin independent for more than a decade,” explains the press release.

Another reason past approaches to islet cell transplantation has been unsuccessful is become they have always been “infused into the liver,” despite the fact that many of the cells are unable to survive in that location.

“The liver is a very simple site to access, but we have known for years that it’s not the ideal site. And the liver will not accommodate a device for housing the islets,” explained Dr. Alejandro.

The DRI continues to lead the way in cure-focused research as the largest and most comprehensive research center completely dedicated to curing diabetes. “The DRI is aggressively working to develop a biological cure by restoring natural insulin production and normalizing blood sugar levels without imposing other risks,” explains the press release.

“Researchers have already shown that transplanted islet cells allow patients to live without the need for insulin therapy. The DRI is now building upon these promising outcomes by developing the DRI BioHub and is testing various BioHub platforms in preclinical and clinical studies.”

For those who were diagnosed with type 1 diabetes even just a decade or two ago, the idea of a biological cure seemed like a distant dream. Today, that possibility grows more and more real by the day.

Bionic Pancreas Gets Prime Time Slot at AACE

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  • A year-long trial is the next test for the device, developer says.

The developer of a bionic pancreas came here to deliver good — if early — news, and he did just that before a rapt audience.

Edward Damiano, PhD, of Boston University, revealed the partial results at the annual meeting of the the American Academy of Clinical Endocrinologists and said that his team is planning a large, year-long, randomized trial of the device.

The artificial pancreas — which automatically regulates insulin levels and dispenses glucagon and insulin according to an algorithm — improved glycemic control and led to less hypoglycemia in a small, short-term trial of adults and in a separate trial of pre-teens.

“We want a technology that adapts to the spontaneity of life,” said Damiano, who added that the device could change the way type 1 diabetes patients care for themselves until a cure is found. “It does this while simultaneously unburdening people from management decisions and worrying about being wrong.”

The Study

Damiano was the first speaker at this year’s AACE conference — probably the first biomedical engineer to lead an AACE conference — said Mack Harrell, MD, the president of AACE.

And he played that novel role well: dressed in black shirt and jeans, he paced the stage, liberally using terms like “synergy” and “integration” and topping his presentation with a high-production-value marketing video that touted the bionic pancreas. He also shared pictures of his son — who at 11 months was diagnosed with type 1 diabetes.

 Damiano was channeling Steve Jobs, not Arnold A. Berthold.

But he also had results from two trials to report. In the first trial, 19 pre-teens at a summer camp in 2014 wore either the device or had normal care for 5 days. In the control group, the mean continuous glucose monitor (CGM) was 168 ± 30 mg/dL; for the group with the device, the mean CGM was 137 ± 11 mg/dL.

The time spent under 60 mg/dL was 2.8% of the time for the control group, and 1.2% for the intervention group. Time over 180 mg/dL was 36% versus 17%.

In the separate trial, Damiano and his colleagues enrolled a group of 38 adults, seven of them in the control group, for 11 days. The patients were at four different medical centers around the country. Those in the control group had a mean CGM of 162 ± 29 mg/dL versus 141 ± 10 mg/dL for the group with the device. Time spent under 60 mg/dL was 1.9% versus 0.6%, and 34% above 180 mg/dL versus 20%.

In both of the studies, the same amount of insulin was used.

The device is an amalgam of several different parts: a Dexcom monitor, two Tandem infusion pumps, and an iPhone accessible algorithm — the user carries the phone. Damiano said he tested kids at summer camp because their active lifestyle would test not only the algorithm, but the durability of the device itself.

“They’re not exactly showing proper respect to this device,” he said.

But Is It Safe?

“You have to realize that there are circumstances in which things can really go wrong,” said Damiano, speaking of the safety and security of the device. “And that you’re dealing with a very vulnerable population.”

In addition to the possibility of glitches or malfunction, app-based medical devices must also worry about cybersecurity. A recent study found that the majority of insulin dosing apps are unreliable and put patients at risk. Nearly a quarter of these apps crashed. Two-thirds carried a risk of giving the wrong dosage recommendations, and there was a lack of transparency with most of the apps. The software on a fully automated bionic pancreas would have to be much more reliable.

And a study by Yogish Kudva, MD, from the Mayo Clinic, and colleagues, found thatcybersecurity is not where it should be for artificial pancreases. “We suggest that, to date, the essential concept of cybersecurity has not been adequately addressed in this field,” concluded the authors of that paper.

Damiano said he agreed. “I don’t think in the med device industry that has been handled particularly well,” he said during a press conference here. “We have a lot of strategies for that, but I think we’re really going to have as cybersecure a system as we can hope to have with the technology that there is now.”

He added that they’ve hired a security expert to help them.

Upcoming Study

The next step is a longer, randomized trial, said Damiano. They are working on a proposal for a year-long study of 480 participants, 160 of whom will belong to a control of usual care. There will be no remote monitoring of the patients, and the primary outcomes will be HbA1c levels and mean CGM levels.

The current plan is to include patients more than 10 years old, said Damiano, though he would like it to be for ages 6 and above. “The FDA is really encouraging us to push that number down,” he said. “They want to test it with as many people as possible. If we do a trial with 2- and 3-year-olds, that’s going to give them peace of mind.”

He said the FDA has been cooperative, contradicting their image that the agency is slow to react.

“They’re taking a very different attitude from what people have expected them to do,” he said. Damiano and his team must build a single device in which all of the components come together in order to move forward. He said that they are working with industry to design the device.

He added that it will be at least 3 years before the device is available. When asked to speculate about the cost, he said it would be slightly more expensive than current devices because it needs two chambers — one for insulin and one for glucagon — at around $8,000 to $9,000.

The Bionic Pancreas: Safe & Effective?

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As more and more stories are popping up from those who have been part of the “Artificial Pancreas” closed-loop study, the rest of us are getting really curious: is it really as safe and effective as they say…to let a machine do all the thinking and all the decision-making for your type 1 diabetes?

For many of us, the idea of letting a computer decide how much insulin we’re going to take is nerve-wracking! We know how many variables go into every insulin dose we take…can a machine really take care of all those variables?

A very recent study, published in Diabetes Care concluded: yes! It is safe and effective! Even for adolescents at home!

Details of the latest Bionic or Artificial Pancreas technology include:

Trial results of 16 pump-treated adolescents with type 1 diabetes aged 12 to 18 years showed that the systems improved glucose control during the day and night with reduced nocturnal hypoglycemia.

…evaluated insulin delivery directed by a closed-loop system for 3 weeks, with sensor-augmented therapy applied for another 3 weeks. The order of interventions was random. Closed loop was applied continuously for a minimum of 4 hours on 269 nights (80%). Sensor data were collected for at least 4 hours on 282 control nights (84%). The primary endpoint was the time when adjusted sensor glucose registered 3.9 mmol/L to 8 mmol/L during the night, specifically between 11 p.m. and 7 a.m.

“The artificial pancreas can be safely used to improve overnight glucose control, providing a stepping stone for longer and larger clinical studies,” Roman Hovorka, PhD, of the Wellcome Trust-Medical Research Council Institute of Metabolic Science at the University of Cambridge, United Kingdom.

“Without supervision, adolescents with type 1 diabetes started and stopped closed loop by their own volition over multiple nights and without real-time monitoring or redundant sensor, which will accelerate cost-effective transition into routine clinical care,” the researchers wrote.

So, when will this technology make its way to the masses? The next step in their patient trials will begin in 2016, and then eventually, finding its way to the FDA for approval. But Hovorka says it will certainly be within our near future when patients with type 1 diabetes will have access to their own artificial pancreas: “The artificial pancreas is likely to become an important treatment option in the next decade.”

 Other articles on the Bionic/Artificial Pancreas:

  • Kerri Sparling at SixUntilMe shares thoughts from teen campers on the Artificial Pancreas
  • Bill Woods from Glu.org shares his own experience being attached to the Artificial Pancreas
  • More articles from Bill at Glu.org on his bionic experience!

What do YOU think of this awesomely evolving technology? Would you love to try it?

Scientists have created a bionic pancreas that outperforms insulin pumps .

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Clinical trials show that a smartphone-linked artificial pancreas could help free patients with type 1 diabetes from needing to regulate their blood glucose levels.

shutterstock_128572523small.jpg

The results showed that type 1 diabetics who used the bionic pancreas were more likely to have blood glucose levels consistently within the normal range than those who used fingerstick tests and then manually injected insulin.

While these traditional methods can help type 1 diabetics to live normally with their disease, they require constant attention and can often result in dangerous glucose highs and lows.

The new bionic pancreas, created by a team from Boston University, has a tiny removable sensor located in a thin needle, which is inserted under the skin of a patient and beams their glucose levels in real time to a smartphone app.

The app calculates the levels of insulin or glucagon needed to balance blood sugar, and tells an implanted pump to administer the required dose automatically.

Before eating, patients can simply input data about their meal to have the app factor it in. Other than that, the patients don’t need to think about their levels.

The researchers tested the device on 20 adults staying in a hotel for five days, free to live, eat and exercise as they pleased. They also monitored it on 32 adolescents who were at a summer camp for kids with diabetes. The results were compared with participants who had used traditional methods of controlling the disease.

The findings, published in the New England Journal of Medicine, revealed the bionic pancreas was much better at keeping user’s levels stable.

The leader of the project, Ed Damiano, came up with the idea for the device after his son was diagnosed with type 1 diabetes. His aim is to have it ready by the time his son is in college, as Bob Roehr reports in New Scientist.

These results suggest he’s on track for that goal.

“The performance of our system in both adults and adolescents exceeded our expectations under very challenging real-world conditions,” said Damiano in a press release.

Previous research has shown that by keeping blood glucose levels in this normal range, patients can avoid complications such as heart, kidney and eye disease.

The next step is more real-world testing. The scientists hope within the next few years the devices will be available to a broader range of patients.