ADA 2023 Top News Recap

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A recap of the top news from the 83rd Scientific Sessions of the American Diabetes Association, including data related to retatrutide, tirzepatide, oral semaglutide, and more!

To celebrate the advances and breakthroughs showcased at the 83rd Scientific Sessions of the American Diabetes Association, the editorial team of HCPLive Endocrinology has compiled a review to highlight our most popular from ADA 2023. The list of the most popular stories features clinical trial data for novel agents, episodes of our flagship podcast Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, and more.

Editor’s note: For continuity, stories have been grouped together according to theme and content area. This list does not reflect an exact ranking of popularity.

Incretin Therapies

On June 23, 2023, the opening day of the meeting, the ADA hosted a session of oral presentations on incretin therapies, which opened the flood gates of pipeline data that would continue through the scientific sessions. IN this session were presentations related to a pair of novel agents in orforglipron, an oral non peptide GLP-1 receptor agonist from Eli Lilly and Company, and survodutide, a glucagon/GLP-1 receptor agonist from Boehringer Ingelheim formerly known as BI 456906.

Although not included in the aforementioned oral presentations, new data related to a pair of other, already approved, incretin therapies were presented at ADA, with new trial phase 3 trial data from oral semaglutide and tirzepatide. On the final day of ADA 2023, the historic debut of retatrutide stole headlines with weight loss rivaling that of bariatric and metabolic surgery and a phase 2 trial in type 2 diabetes purporting significant benefits in glycemic control.

Orforglipron Shows Promise as Weight Loss, Diabetes Agent in Phase 2 Trials

A pair of phase 2 trials from Eli Lilly and Company gave the community its most comprehensive look yet into the effects of their nonpeptide, oral GLP-1 receptor agonist, orforglipron, as an agent for use in chronic weight management and type 2 diabetes. In the obesity trial, use of orforglipron was associated with a mean reduction in body weight up to 14.7% at 26 weeks and, in the type 2 diabetes trial, use of orforglipron was association with a mean reduction in HbA1c of 2.1% at 16 weeks.

Survodutide, Formerly BI 456906, Impresses in Phase 2 Dose-Finding Trial

Boehringer Ingelheim and Zealand Pharma shared phase 2 data detailing the effects of their glucagon/GLP-1 receptor dual agonist survodutide, formerly BI 456906, at ADA 2023. Also, under investigation for use in NASH and liver fibrosis, the phase 2 obesity trial concluded use was associated with a mean body weight reduction of 14.9%, with more than 65% of those receiving the 4.8 mg dose experiencing body weight reductions of 15% or greater.

SURMOUNT-2: Tirzepatide Demonstrates Body Weight-Lowering Effects in T2D

Presented just a year after SURMOUNT-1 results stole headlines at ADA 2022, results of the phase 3 SURMOUNT-2 trial provide further insight into the effects of GIP/GLP-1 receptor agonist in people with overweight and obesity, with results confirming the benefit seen in SURMOUNT-1 also translates to populations with type 2 diabetes. Results of the trial, which randomized 938 participants, indicate use of tirzepatide was associated with an overall mean weight reduction of 33 pounds, with 49% of participants receiving tirzepatide achieving a normal HbA1c below 5.7% without signs of severe hypoglycemia.

Check out a clip from an interview with study presenter W. Timothy Garvey on Diabetes Dialogue.

Additional Content: Breaking Down Tirzepatide and SURMOUNT-2 Data, with W. Timothy Garvey, MD

Increased Doses of Oral Semaglutide Can Induce Pronounced Weight Loss, Improve Glycemic Control

The demand for subcutaneous semaglutide in the US has ballooned in recent years as the agent has gained prominence for its body weight-lowering effects. Now, data from the phase 3 OASIS-1 and phase 3b PIONEER PLUS trials suggest a chronic weight management indication could be on the way for semaglutide 25 and 50 mg. In OASIS-1, which examined oral semaglutide 50 mg against placebo in patients with overweight or obesity without type 2 diabetes, results suggested use of oral semaglutide was associated with an estimated mean change in body weight of -15.1% (SE, 0.5) from baseline to week 68 compared to -2.4%(SE, 0.5) with placebo therapy (estimated treatment difference [ETD], -12.7 percentage points; 95% Confidence interval [CI], -14.2 to -11.3; P < .0001). In PIONEER PLUS, which examined oral semaglutide 25 and 50 mg against oral semaglutide 14 mg, the mean changes in HbA1c at week 52 were -1.5 (SE, 0.05) percentage points with oral semaglutide 14 mg, -1.8 percentage points (SE, 0.06) with oral semaglutide 25 mg (ETD, -0.27; 95% CI, -0.42 to -0.12; P =.0006), and -2.0 percentage points (SE, 0.06) with oral semaglutide 50 mg (ETD, -0.53; 95% CI, -0.68 to -0.38; P < .0001).

Retatrutide Showcases Historic Weight-Lowering, Glycemic Control Benefits in Phase 2 Data

On the final day of the 83rd Scientific Sessions of the ADA, investigator presented a pair of phase 2 trials examining using of Eli Lilly and Company’s novel GIP/GLP-1/glucagon triagonist retatrutide.

The weight management trial, which enrolled 338 people with obesity or overweight, concluded there were least-squares mean percentage changes in body weight at 48 weeks of -8.7% in the retatrutide 1 mg group, -17.1% in the combined retatrutide 4 mg group, -22.8% in the combined retatrutide 8 mg group, -24.2% in the retatrutide 12 mg group, and -2.1% in the placebo group.

The type 2 diabetes, which enrolled 281 patients with type 2 diabetes and an HbA1c of 7.0 to 10.5%, concluded HbA1c reductions achieved with retatrutide were significantly greater than placebo in all but the 0.5 mg group and greater than 1.5 mg dulaglutide in the 8 mg slow escalation group (P = .0019) and retatrutide 12 mg escalation group (= .0002).

Additional Content: Phase 2 Substudy Shows Retatrutide Use Could Contribute to NAFLD Resolution

Other Top Headlines

Guideline Updates Reflects New Emphasis in T1D Screening and NAFLD

The Standard of Care in Diabetes stand apart from guidelines and clinical recommendations of many other professional organizations as a result of the ADA’s commitment to it being a living document. This commitment was showcased at ADA 2023, with the organization releasing updates to the recommendations for 2 areas with evolving data: type 1 diabetes and nonalcoholic fatty liver disease. The updates reflect the approval of teplizumab and need for greater screening. The updates related to NAFLD reflect a need for greater emphasis in screening efforts, particularly among those with additional comorbidities.

Study Suggests Bempedoic Acid Could Find Role in Primary Prevention

New research presented at ADA 2023 suggests bempedoic acid could prove useful in a primary prevention role for people with statin intolerance. A subgroup analysis of a primary prevention cohort within the CLEAR Outcomes trial, results of the study, which come less than 4 months after the initial presentation of the trial ACC 2023, suggest use of bempedoic acid was associated with a 30% reduction in relative risk of a primary endpoint event in adjusted analyses during a median follow-up of 39.9 months (aHR, 0.70; 95% CI, 0.55 to 0.89; P = .002).

Diabetes Dialogue at ADA 2023

Since the podcast was launched in 2022, Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives has sought to bring you clinically applicable insights directly from experts. During their time at the meeting, Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, sat down with 10 special guests to record 9 episodes. Below, we have highlighted a pair of episodes from the meeting.

Diabetes Dialogue: Improving Implementation of New Technology, with Cari Berget, RN, MPH

Isaacs and Bellini engage in an extended discussion around the application of new diabetes technologies with Cari Berget, RN, MPH, a registered nurse and certified diabetes care and education specialist at the Barbara Davis Center for Diabetes within the University of Colorado School of Medicine. In the episode, Berget offers hosts perspective into a symposium she led at ADA 2023 titled "Demystifying Diabetes Device Data” as well as a breakdown of the PANTHER program and the current slate of resource offerings available for clinicians.

Diabetes Dialogue: TRANSITION-T2D

Scaling back insulin therapy was an abstract goal but has since become attainable for many patients as a result of newer antidiabetes medications. Isaacs and Bellini sat down with TRANSITION-T2D investigators, Paloma Rodriguez, MD, and Kevin Pantalone, DO, to learn more about the trial, which concluded more than 95% of those using of semaglutide 1.0 mg were able to fully replace prandial insulin use during the 26-week study and 57.5% of the those receiving semaglutide 1.0 mg reduced their total daily insulin dose by more than 50%.

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