Top Highlights: Day 1 of ADA Scientific Sessions 2021
By Eliza Skoler, Matthew Garza, Arvind Sommi, and Andrew Briskin
We bring you the most exciting news from day one of the 81st ADA Scientific sessions, including updates on inhaled insulin, digital diabetes management programs, automated insulin delivery, beta cell replacement therapies, and more.
In two small studies, the ultra-rapid acting insulin Afrezza – the only inhalable insulin currently available in the US – was found to be safe in children and adults with type 2 diabetes.
In a phase 2 clinical trial, Afrezza was tested in 30 children ages 8 to 17 years with type 1 diabetes. The goal of the trial was to observe the pharmacokinetics (how a drug moves into, through, and out of the body) and the safety of Afrezza in this population, given that inhalable insulin is currently only approved for adults.
The study showed that serum insulin (the insulin found in the blood) reached its peak around 10 to 15 minutes after inhalation and returned to normal after about two hours. The peak decrease in post-meal glucose levels was observed 30 to 60 minutes after inhalation. This is similar to how Afrezza works in adults.
The only side effect observed was a cough in the early stages of inhalation. There was no severe hypoglycemia observed. When diaTribe founder Kelly Close first began using Afrezza she also experienced a cough, but it went away after she tried drinking water.
Researchers determined Afrezza was safe in this group and that a phase 3 clinical trial could be initiated.
In another study, of 20 adults with type 2 diabetes who have highly variable glucose levels, the use of Afrezza was shown to greatly improve Time in Range during the day (between 6am until midnight).
Time in Range increased from 39% at baseline to 62% (that’s more than four additional hours spent in range each day!).
Time above Range decreased from just over 60% (at baseline) to 31%.
Time below Range increased slightly from 0.8% (at baseline) to 2.3%.
It’s good to see that the drug works similarly in adults and children, and that it helps improve Time in Range. Since insulin injections are a challenge for people with diabetes – and especially for children and parents – it is exciting that a way to reduce the number of daily insulin injections may eventually be available for more families (though basal insulin injections will still be necessary).
New data from Onduo, a digital diabetes management service, shows that people in its type 2 diabetes program reduced their A1C levels after six months and kept those reductions at one year. The type 2 diabetes program gives participants access to a mobile app, remote personal coaching, telemedicine visits with endocrinologists, and intermittent use of continuous glucose monitors (CGM) for people meeting certain A1C or medication criteria. The A1C reductions were seen among participants with or without CGM access, though there was greater A1C improvement in the CGM group.
The analysis included 772 participants – 46% of this group (354 people) used a Dexcom G6 CGM and 54% (418 people) did not. At baseline, CGM users were younger, had a higher A1C level (7.9% versus 7.6%), and used more insulin compared to the non-CGM group. After one year, among the 772 participants:
Overall, CGM users saw a 0.7 percentage point decrease in A1C (to 7.2%), while non-CGM users saw a 0.2 percentage point reduction (to 7.4%). The 0.7 percentage point reduction is impressive given this relatively low baseline.
People with a starting A1C above 9.0% – 69 people in the CGM group and 62 people in the non-CGM group – experienced a 2.8 percentage point average A1C reduction in the CGM group, and a 1.8 percentage point decrease in the non-CGM group.
A smaller study of participants in Onduo’s type 2 diabetes program found that the A1C improvements were maintained even after people stopped using the service (for any reason). Among 52 people that used the service for four months, participants saw a 1.5 percentage point A1C reduction at one year (from a baseline of 7.4%). This suggests that even short-term participation in digital diabetes management programs like OnDuo’s could be helpful for people.
Real-world data on Medtronic’s MiniMed 770G system showed promising Time in Range results. MiniMed 770G launched in the US last November and was the first system to make automated insulin delivery (AID) technology available to children between the ages of two and six. Here’s new data from 11,909 people with diabetes, over the age of two:
Time in Range was 70.8% while mean glucose was 156 mg/dL. (This translates to a glucose management indicator, GMI, of 7.0%.)
The majority of users (56%) achieved the recommended goal of 70% Time in Range.
The average Time in Range was slightly better overnight (77.4%) than during the day (68.6%) – expected since people are not physically active or eating during the night.
Time below Range was very low. On average users spent just 1.8% of time below 70 mg/dL and only 0.4% of time below 54 mg/dL.
Users spent about 27% of time above 180 mg/dL and about 6% of time above 250 mg/dL (close to the targets of less than 25% and 5%, respectively).
MiniMed 770G is the same system as MiniMed 670G, but with the addition of Bluetooth connectivity for sharing and viewing data. The MiniMed 780G system is an exciting new system – it includes a new algorithm, but is currently only approved in Europe. Medtronic has stated that people who purchase MiniMed 770G system will be able to upgrade to the 780G system when it becomes available.
Two speakers discussed the latest developments in research on replacing pancreatic beta cells (these are the cells that produce insulin) in people with type 1 diabetes.
JDRF's renowned Dr. Esther Latres presented updates on manufacturing beta cells from stem cells (these are a special type of cell that can develop into many different cell types), and encouraged involvement in and acceleration of research and clinical trials to test beta cell therapy. Progress in beta cell replacement therapy is quite encouraging – early studies in humans have shown promising results that will lead to improve diabetes management. Dr. Latres has focused specifically on protecting beta cells from being destroyed by the immune system without the need for broad immunosuppressing drugs. As background, immunosupression refers to taking medications that limit or shut off your immune system so that your body’s infection-fighting cells do not harm the transplanted cells. Some strategies to avoid this include enclosing the new beta cells within a physical barrier in the pancreas (protecting them from being attacked by the immune system cells) and ensuring that newly implanted cells have sufficient oxygen to survive.
Dr. Quinn Peterson shared the latest from his own research at the Mayo Clinic on growing stem cell-derived pancreatic islets. Pancreatic islets are a collection of cells in the pancreas that contain insulin-producing beta cells, glucagon-producing alpha cells, and other cell types that are critical for the function of the islet as a whole. Dr. Peterson’s approach has been to grow both alpha and beta cells from stem cells and then combine the components to form a functional pancreatic islet. In a study conducted in his lab, Dr. Peterson demonstrated that significant improvements in insulin production occurred when beta cells were grouped together with alpha cells.
Both speakers advocated for further research on increasing the beta cell lifespan through methods (such as encapsulation) that avoid immunosuppression. This will enable further advances in research on beta cell replacement therapies for type 1 diabetes.
A clinical trial tested AstraZeneca’s GLP-1 agonist medication – exenatide, also known by brand names Bydureon and Byetta – in youth with type two diabetes between the ages of 10 to 18 years old, with starting A1C levels between 6.5% to 12%. Participants taking insulin or sulfonylureas continued those treatments. After 24 weeks, the 58 adolescents treated with once-weekly exenatide had an average 0.4 percentage point decrease in individual A1C levels from baseline, compared to an increase (of 0.5 percentage points) in A1C among the 24 youth in the placebo group. Exenatide treatment was also associated with positive changes in fasting glucose, systolic blood pressure, and body weight – though these changes were not statistically significant. In terms of side effects, the treatment group did see higher rates of hypoglycemia (14% versus 4% in the placebo group) and upper respiratory infections, but no difference in gastrointestinal events.
About 5,000 people under the age of 18 are diagnosed with type 2 diabetes in the US each year – so there is a growing need for emerging treatments for this population that can help them manage their glucose levels more easily. The exenatide results are similar to those found for GLP-1 Victoza in children and teens, and Victoza is currently available for people with type 2 diabetes over the age of ten in the US.
Tami Sadusky, who lives with type 1 diabetes and chronic kidney disease (CKD), shared her experiences to highlight the importance of chronic kidney disease prevention and management for people with diabetes. Diagnosed with type 1 diabetes at age 13 in rural Alaska, Sadusky had limited access to proper healthcare. Without information on how she could prevent long-term complications, she developed retinopathy, neuropathy, gastroparesis, and eventually chronic kidney disease. After two life-saving kidney transplants and one pancreas transplant, Sadusky has benefitted from team-based care, diabetes education, and improved self-management. Inspired by her own experiences, she founded an endowment to help fund research on curing diabetes and improving the lives of transplant recipients. The experience of living with CKD can be very difficult, but it’s important to remember that you don’t have to fight this disease alone – you can find information on the National Kidney Foundation’s Peers program here.
In the wake of the very personal story from Sadusky, Dr. Luiza Caramori and Dr. John Buse provided an update to healthcare professionals on some of the guidelines that they should use to treat diabetes and CKD:
Treatments should focus on the person.
Proper diet and exercise remain the foundation of care plans.
Glucose targets should be tailored to the individual, since some people may have increased risk of hypoglycemia as a result of their declining kidney function.
For people with type 2 diabetes and CKD, metformin and SGLT-2 inhibitors remain the first line of treatment, followed by GLP-1s for additional blood glucose management.
To learn more about preventing kidney disease, read diaTribe's “Chronic Kidney Disease and Diabetes – What You Should Know."