ADA Scientific Sessions Address the Old and the New

Miriam E. Tucker

June 22, 2021

Long-awaited twincretin data, a study to inform prescribing in type 2 diabetes, COVID-19 and diabetes, and new guidance for treating type 1 diabetes in adults will be among the hot topics at the American Diabetes Association (ADA) 81st Scientific Sessions.

The meeting, to be held virtually for a second year, will take place June 25-29. As usual, the sessions will cover a wide range of basic, translational, and clinical material pertaining to type 1 and type 2 diabetes, complications, related subjects such as obesity and cardiovascular disease, and healthcare delivery.

New to this year's agenda is COVID-19 and the many ways it has affected people with diabetes and healthcare delivery. And, more than in the past, the meeting will focus on ethnic and racial disparities in the delivery of care to people with diabetes.

And of course, there will be a tribute to another special aspect of 2021: the 100th anniversary of the discovery of insulin.

"I think there will undoubtedly be several things that will come out of this meeting that will change practice, and it will be important for clinicians to be aware of those, whether that's ground-breaking trials or interpretation of data that will help us understand the interrelation between diabetes and COVID-19, which is still with us," ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, told Medscape Medical News.

And ADA President of Medicine and Science Ruth S. Weinstock, MD, PhD, told Medscape Medical News: "I think there are many exciting sessions at this year's meeting...I hope that it will help [clinicians] take better care of their patients with diabetes."

Will the Twincretin Tirzepatide Live Up to the Hype?

Between December 2020 and May 2021, Eli Lilly issued a series of four press releases touting positive top-line results from a series of phase 3 studies on its novel agent tirzepatide, dubbed a twincretin for its dual actions as an agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors.  

Detailed results from those four trials, SURPASS-1, -2, -3, and -5, will be presented in a symposium on Tuesday, June 29. Results from SURPASS-4 will be presented at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting in September.

According to the company, the drug met its phase 3 primary efficacy endpoints for both A1c reduction and weight loss.

"At least the buzz on it has been good, but now we want to see the real data," Gabbay said, noting that "the early data on weight loss in particular were quite good. So then the question would be: Do you go to a GLP-1 [agonist] or a dual agonist? There will be studies to tease that out."   

Regarding tirzepatide, Weinstock said: "Hopefully, more people with type 2 diabetes could achieve their glycemic goals, and those who would benefit from weight loss could have better weight loss. I haven't seen the data, but if the addition of GIP can further improve glucose lowering as well as weight loss that would be great."

How Far Will GRADE Go in Answering the Second-Drug Question?

On Monday, June 28, results will be presented from the long-awaited Glycemia Reduction Approaches in Diabetes — A Comparative Effectiveness (GRADE) study.

Launched in 2013, the trial is funded by the National Institutes of Health and several pharmaceutical company partners. Over 5000 patients diagnosed with type 2 diabetes within the prior 10 years and already taking metformin were randomized to one of four commonly used second-line glucose-lowering agents: glimepiride, sitagliptin, liraglutide, and basal insulin glargine. The aim was to determine which combination produced the best glycemic control with the fewest side effects.

Weinstock said, "Clinicians now have increasing numbers of medications to choose from when treating hyperglycemia in type 2 diabetes, and a common dilemma is which one to select. The results of GRADE should be informative for people taking care of type 2 diabetes in different populations."

However, she also pointed out that GRADE does not include a group with a sodium-glucose transporter 2 (SGLT2) inhibitor, as the trial was designed prior to the availability of the drug class. Now, SGLT2 inhibitors are widely used and recommended for cardiovascular and kidney benefit as well as glucose-lowering.   

"I believe the future is really precision medicine where we individualize treatment. So, for someone with heart failure you might choose an SGLT2 inhibitor, but there are plenty of other subpopulations. They are going to be looking at different subpopulations. I think we're all very interested in seeing what the results are, but it's not the end of the story. We will still have to individualize therapy and keep in mind their kidney, heart, heart failure status, and other factors," she said.

Gabbay pointed out that GRADE is important because it's one of the few comparative effectiveness trials conducted in diabetes. "I think it will be very rich [data] that will impact practice in a variety of ways. On the one hand, it doesn't do everything we'd want it to do, but on the other hand, if you think of the number of comparative effectiveness trials in diabetes, there are not a lot...I think it will be big."

COVID-19 and Diabetes: A Lot to Discuss  

In contrast to the ADA 80th Scientific Sessions in 2020, which took place too soon after the start of the COVID-19 pandemic to include much material about it, this year's meeting will address many different aspects of the novel coronavirus.

Sessions will cover minimizing risk in people with diabetes during the pandemic, the latest data on whether COVID-19 triggers diabetes, and if so, by what mechanism, mental health issues related to COVID-19, as well as the management of foot care, pregnancy, and the pediatric population during the pandemic.

On Sunday, June 27, a symposium will be devoted to results of the DARE-19 trial, which explored the effects of the SGLT2 inhibitor dapagliflozin in more than 1200 patients hospitalized with COVID-19. The overall results, presented in May at the American College of Cardiology (ACC) 2021 Scientific Session, showed a nonsignificant trend for benefit in time to organ failure or death compared with placebo. At ADA, separate efficacy and safety results for patients with and without diabetes will be presented.

According to Weinstock, "We know that in nonhospitalized patients with type 2 diabetes the SGLT2 inhibitors can help preserve kidney function and reduce heart failure. But we also know there can be diabetic ketoacidosis and genital infections and other side effects, so it's been unclear up till now in type 2 diabetes whether they are safe and effective in people hospitalized in respiratory failure with COVID-19. And, given that people with type 2 diabetes and COVID-19 are more likely to require mechanical ventilation and are at greater risk of mortality, we're anxious to see what these results are."

Gabbay commented that when the DARE study was initiated in April 2020, there were concerns about whether it was safe. And even now, "we're still not sure about whether SGLT2 inhibitors should be stopped in hospitalized patients. The recommendations say to stop. I think this will be interesting."  

Also to be addressed in several meeting sessions are related issues the pandemic has brought forth, such as the use of telehealth for routine diabetes management, inpatient use of continuous glucose monitoring, and of course, healthcare disparities.

"A lot of important issues related to COVID-19 of great interest will be discussed in a variety of sessions," Weinstock said.

Type 1 Diabetes in Adults: It's Not Just a Pediatric Disease  

On Monday, June 28, a draft of the first-ever ADA/EASD consensus report on the management of type 1 diabetes in adults will be presented, with the final version slated for the virtual EASD 2021 Annual Meeting in September.

A previous ADA position statement had addressed management of type 1 diabetes across all age groups, but this will be the first to focus on adults. This is important, given that type 1 diabetes was formerly called juvenile diabetes and is still often perceived as a childhood disease. Adults who develop it are commonly misdiagnosed as having type 2 diabetes, Gabbay noted.

"A big-time issue is recognition of type 1 in adults. We often see patients come in who were misdiagnosed, on metformin, and not given insulin. Often they go for a while and get sicker and sicker." Or, he said, sometimes they're prescribed insulin but not the intensive regimens that are required for adequate glycemic control in type 1 diabetes. "They can be suboptimally treated and it can take years to get the right therapy...It's unfortunate that they have to experience that."

Weinstock, one of the authors of the statement, said it will cover a range of issues, including care schedules, therapies, psychosocial issues, and social determinants of health. "We tried to be comprehensive in this in terms of glycemic management. It doesn't include a discussion of complications or their management. It really focuses on diagnosis and glycemic management."

Dealing With Disparities: ADA Has Taken Several Steps

A priority of ADA is addressing disparities in the delivery of healthcare to people with diabetes, both Weinstock and Gabbay stressed. Quite a few sessions at the meeting will touch on various aspects, including sessions on Friday afternoon on "Health Care as a Social Justice Issue in the Diagnosis and Management of Diabetes," and separate sessions on "Challenges and Successes With Health Inequities and Health Disparities in Diabetes" in adult and pediatric populations.

"For us at ADA, addressing health disparities is extremely important and we have a number of new programs this year to address this very important issue," Weinstock said.

In August 2020, ADA issued a Health Equity Bill of Rights, which includes access to insulin and other medications, affordable healthcare, and freedom from stigma and discrimination. The Association has also requested applications from researchers studying disparities in diabetes care.

Celebrating 100 Years of Lifesaving Medication

Of course, ADA will be celebrating the 100th anniversary of the discovery of insulin. A session on Saturday afternoon, entitled, "Insulin at Its 100th Birthday," will cover the history of the landmark discovery, as well as insulin biosynthesis and mechanisms of action, and "the future of insulin as a therapy."

Weinstock noted, "The discovery of insulin was an incredible achievement that, of course, saved the lives of many millions of children and adults. Before insulin became available, children and adults only survived for days or at most a few years after diagnosis. We will commemorate this anniversary."

The Virtual Platform: Like Last Year, Only Better

Gabbay told Medscape Medical News that the virtual setup will be similar to last year's in that talks will be prerecorded to ensure there are no technical glitches, but for many, presenters will be available afterward for live question and answers.

This year, though, the chat functionality will be enhanced to allow for discussion during the presentation, separate from the scientific question and answers. And, he noted, the virtual exhibit hall will be "bigger and better."

Despite these improvements, Gabbay said, the plan is to go back to an in-person meeting in 2022, in New Orleans.

Weinstock's institution receives research grants from Medtronic, Insulet, Lilly, Novo Nordisk, and Boehringer Ingelheim. Gabbay has reported no relevant financial relationships.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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