Each and every June, the field of endocrinology celebrates breakthroughs and updates with the prospect of influencing the care of millions with diabetes and other endocrine disorders. This year, the 84th American Diabetes Association Scientific Sessions offered the field another chance to celebrate the advances that could shape the future of their field for years to come. However, the updates were not limited only to ADA 2024, but also expanded beyond to the therapeutic pipeline and more.

In the Endocrinology Month in Review for June 2024, we acknowledge the breakthroughs and innovations that came to define ADA 2024 and also spotlight other top news, including results of the GRACE trial and the first generic GLP-1 receptor agonist.

FDA and Pipeline News in Endocrinology

Generic Liraglutide (Victoza) Becomes First Generic GLP-1 Receptor Agonist

Few pharmacotherapies have captured the public consciousness in the same fashion as GLP-1 receptor agonists. However, accompanying discussions of their profound benefits on weight loss, glycemic control, cardiovascular risk, and kidney disease has been a focus on access issues, including but not limited to the price of these medications.

On June 24, 2024, Teva Pharmaceuticals announced the launch of an authorized generic of liraglutide (Victoza)—the first ever generic GLP-1 receptor agonist in the US.

Full GRACE Results Shed Further Light on Effects of Relacorilant in Hypercortisolism

Final results of the GRACE trial presented at The Metabolic Institute of America’s 8th Heart in Diabetes meeting provide the greatest insight yet into the effects of relacorilant on blood pressure control among patients with hypercortisolism.

Results indicated loss of blood pressure control was 83% less likely to occur among patients relieving relacorilant compared to placebo (OR, 0.17; P = .02). Further analysis revealed similar blood pressure trends favoring use of relacorilant over placebo therapy were observed for 24-hour systolic and diastolic blood pressure, daytime systolic and diastolic blood pressure, and nighttime systolic and diastolic blood pressure.

Top Content Recap of ADA 2024

CATALYST Proves Hypercortisolism More Common than Previously Known in Type 2 Diabetes

Results from the first half of the CATLAYST trial were presented at ADA 2024. Billed as the largest study of its kind, the first half was designed to assess the prevalence of hypercortisolism in people with difficult-to-control type 2 diabetes.

With a population of more than 1000 patients, results presented at ADA demonstrate hypercortisolism was present among 24% of patients. Further analysis revealed these patients were were older, more likely to be on non-Hispanic or Latino ethnicity, more likely to be enrolled based on hypertension or micro/macrovascular complications, be taking newer classes of antihyperglycemic medications, and have greater overall medication burden than those without hypercortisolism. In part 2 of the trial, those with hypercortisolism will be randomized to mifepristone or placebo therapy. Results from part 2 of the trial are expected before the close of 2024.

Related Coverage: CATALYST Raises Red Flag on Hypercortisolism in Type 2 Diabetes, with Ralph DeFronzo, MD

FLOW Analysis Sheds Light on Effects of Combination Therapy with GLP-1 RA and SGLT2 Inhibitor

Less than a month after the landmark trial was debuted at ERA 2024, the community received further insight into the FLOW trial with an ADA 2024 late-breaker shedding light on the effects of combination therapy.

Among those with baseline SGLT2 inhibitor use, investigators found the primary outcome occurred among 41 of the 277 patients receiving semaglutide and 38 of the 273 patients receiving semaglutide (HR, 1.07; 95% CI, 0.69 to 1.67). Among those without baseline SGLT2 inhibitor use, a primary outcome event occurred among 290 of the 1490 patients receiving semaglutide versus 372 of the 1493 participants receiving placebo (HR, 0.73; 95% CI, 0.63 to 0.85; P <.001; P for interaction = .109).

Additional analysis suggested treatment differences for total eGFR of 0.75 ml/min/1.73m2 per year (95% CI, –0.01 to 1.5) in the SGLT2i subgroup and 1.25 ml/min/1.73m2 per year (95% CI, 0.91 to 1.58) in non-SGLT2i-subgroup (P for interaction = .237. Investigators also pointed out the effects of semaglutide on major adverse cardiovascular events (P for interaction =.741) and all-cause mortality (P for interaction =.901) were similar regardless of SGLT2 inhibitor use.

SURMOUNT-OSA: Tirzepatide Cuts Obstructive Sleep Apnea Severity by 30 Events/Hour

Just 2 years after the original SURMOUNT program was presented at ADA 2022, the SURMOUNT-OSA trial headlined ADA 2024. A trial of patients with moderate-to-severe obstructive sleep apnea (OSA),study 1 included patients who were unable or unwilling to use positive airway pressure (PAP) therapy and study 2 included patients who were and planned to stay on PAP therapy during the duration of the trial.

In study 1, for the efficacy estimand, the change in AHI at week 52 was −27.4 events per hour (95% CI, −31.6 to −23.2) with tirzepatide and −4.8 events per hour (95% CI, −9.3 to −0.3) with placebo, which correlates to an estimated treatment difference of −22.5 events per hour (95% CI, −28.7 to −16.4). In study 2, treatment-regimen estimand revealed use of tirzepatide was associated with a mean change of −29.3 events per hour (95% CI, −33.2 to −25.4) in AHI relative to −5.5 events per hour (95% CI, −9.9 to −1.2) with placebo, which correlates to an estimated treatment difference of −23.8 events per hour (95% CI, −29.6 to −17.9) (P <.001).

Related Coverage: Atul Malhotra, MD: Tirzepatide for Obstructive Sleep Apnea and Obesity

Inhaled Insulin Could Improve Glycemic Control, HbA1c Compared to Usual Care in Type 1 Diabetes

Despite being available for a decade, inhaled insulin use has lagged in regard the potential role it could fill in treatment algorithms for type 1 diabetes. This could change as a result of the INHALE-3 trial and the attention it received at ADA 2024.

A phase 4 trial comparing the use of inhaled insulin (Afrezza) against standard care, results demonstrated use of inhaled insulin, in addition to insulin degludec, was associated with improved HbA1c in patients with type 1 diabetes, with an improvement of 0.5% or greater observed among 21% of those on inhaled insulin and 5% of those with usual care.

Diabetes Dialogue at ADA 2024

The Diabetes Dialogue team took to the conference floor at ADA 2024 and produced 5 on-site episodes, focusing on INHALE-3, the ADA’s new Obesity Association, diabetes technology updates, the changing landscape of type 1 diabetes, and more! Below are links and brief descriptions for all 6 on-site episodes and our post-meeting technology recap!

Episodes from ADA:

INHALE-3 and Diabetes Tech Updates, with Grazia Aleppo, MD

ADA Introduces Obesity Association, with Robert Gabbay, MD, PhD

New Early-Stage T1D Monitoring Guidance, with Anastasia Albanese-O'Neill, PhD, APRN

Advances in AID and CGM at ADA 2024, with Davida Kruger, NP

Blue Circle Health, with Monica Gomberg, MD

Patient Considerations for Inhaled Insulin, with Carol Levy, MD

ADA 2024 Diabetes Technology Recap (Preview Below)