John Buse, MD, PhD 

HCPLive Five at ADA Scientific Sessions 2025

2025 American Diabetes Association (ADA) Scientific Sessions, held June 20–23 in Chicago

, reflected a shifting paradigm in diabetes care prioritizing comprehensive approaches to glucose management, cardiometabolic health, and patient-centered outcomes. This year’s meeting featured a diverse slate of groundbreaking research spanning automated insulin delivery, weekly insulin alternatives, and novel interventions tackling unique drivers of glycemic dysregulation.

Among the most talked-about data were CIRCUIT trial findings on automated insulin delivery systems improving time-in-range during pregnancy; the QWINT program’s demonstration that once-weekly insulin efsitora alfa can effectively replace daily basal insulin; and evidence supporting prediabetes remission as a superior goal to weight loss for type 2 diabetes prevention. Additional highlights included the CATALYST trial’s success with mifepristone in hypercortisolism-related diabetes and the STRIDE trial’s new insights into semaglutide’s effects on walking capacity and disease progression in patients with type 2 diabetes and peripheral artery disease.

Hybrid Closed Loop Insulin Improves Time in Range for T1D During Pregnancy, with Lois Donovan, MD, and Denice Feig, MD, MSc

The CIRCUIT trial compared an automated insulin delivery (AID) system using Control-IQ technology to standard care in pregnant women with type 1 diabetes, presented at ADA 2025 by Lois Donovan, MD, and Denice Feig, MD. Participants using the hybrid closed-loop system achieved a 12.6% (95% CI, 9.9–15.2; 

<.001) higher time in range during pregnancy (TIRp) compared with standard care (65.4% vs. 50.3%). Additionally, the AID group had 11.4% (95% CI, 8.6–14.2; 

<.001) less time above range, 1.04% (95% CI, 0.6–1.48; 

<.001) less time below 63 mg/dL, and a mean glucose 11.2 mg/dL lower than standard care (95% CI, 7.2–16.2; 

Once-Weekly Insulin Efsitora a Practical Option for Type 2 Diabetes, with Athena Philis-Tsimikas, MD

The QWINT-3 phase 3 trial investigated weekly insulin efsitora alfa versus daily insulin degludec in patients with type 2 diabetes switching from basal insulin, presented at ADA 2025 by Athena Philis-Tsimikas, MD. Weekly efsitora injections were non-inferior to daily degludec for glycemic control, supporting its potential as a practical alternative. Philis-Tsimikas noted the findings suggest switching to weekly insulin could substantially reduce treatment burden for patients.

Glycemic Control Trumps Weight Loss for Type 2 Diabetes Prevention, with Arvid Sandforth, MD

A prediabetes lifestyle intervention study presented by Arvid Sandforth, MD, at ADA 2025 showed achieving normal glycemia, regardless of weight change, provided the same protective effect against developing type 2 diabetes. Participants achieving glycemic remission experienced significantly reduced T2D incidence even if they maintained or gained weight, compared to those who did not normalize glycemia. The multicenter German study highlighted that while weight loss remains a powerful tool, achieving glycemic control should be prioritized as the primary prevention target.

Diabetes Dialogue: CATALYST Trial, Mifepristone, and Hypercortisolism in T2D, with John Buse, MD, PhD

The phase 4 CATALYST trial enrolled 1055 adults with type 2 diabetes and HbA1c >7.5% despite optimized therapy, screening for hypercortisolism using dexamethasone suppression testing, which identified a 24% prevalence (95% CI, 21.4–26.7%). In part 2, 136 patients with confirmed hypercortisolism were randomized 2:1 to mifepristone or placebo for 24 weeks, with mifepristone reducing HbA1c by 1.3 percentage points versus placebo (95% CI, –1.81 to –0.83; 

 <.001). Secondary outcomes showed reductions of 5.12 kg in body weight (95% CI, –8.20 to –2.03) and 5.1 cm in waist circumference (95% CI, –8.23 to –1.99) relative to placebo.

New Data Supports Protective Vascular Effects of Semaglutide in T2D and PAD, with Subodh Verma, MD, PhD

The STRIDE trial randomized 792 adults with T2D and PAD to semaglutide (n=396) or placebo (n=396) for 52 weeks, presented by Subodh Verma, MD, PhD, at ADA 2025. Patients receiving semaglutide showed a median baseline-adjusted maximum walking distance ratio of 1.21 compared with 1.08 for placebo. Semaglutide also reduced the risk of a composite disease progression endpoint—including death, major adverse limb events, or rescue medication use—by 54% relative to placebo.

These 5 represent only some of the data the 

 team covered at this year's meeting! Check out more KOL insight and our full conference coverage on our 

Videos

From uncovering new benefits of semaglutide to targeting hypercortisolism in people with type 2 diabetes, here are 5 key updates from the annual meeting.

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives

, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, speak with John Buse, MD, PhD, of the University of North Carolina School of Medicine, about the treatment phase of the CATALYST trial.

Findings from the phase 4 CATALYST trial suggest that mifepristone (Korlym), a glucocorticoid receptor antagonist, significantly improves glycemic control, reduces body weight, and lowers waist circumference in patients with hypercortisolism and difficult-to-control type 2 diabetes—offering a promising therapeutic option for a population with limited treatment success.

The two-part, multicenter study enrolled 1055 adults with type 2 diabetes and HbA1c >7.5% despite optimized therapy. In part 1, participants underwent dexamethasone suppression testing to identify hypercortisolism, defined by post-test cortisol levels >1.8 µg/dL and dexamethasone >140 ng/dL. Results revealed a 24% prevalence of hypercortisolism in this population (95% CI, 21.4–26.7%).

Part 2 randomized 136 patients with confirmed hypercortisolism in a 2:1 ratio to receive mifepristone or placebo for 24 weeks. The primary endpoint was change in HbA1c. Mifepristone treatment led to a least squares mean HbA1c reduction of 1.3 percentage points compared to placebo (95% CI, –1.81 to –0.83; 

Secondary endpoints also favored mifepristone: body weight decreased by 5.12 kg (95% CI, –8.20 to –2.03), and waist circumference dropped by 5.1 cm (95% CI, –8.23 to –1.99) relative to placebo.

Despite its efficacy, 49% of mifepristone-treated patients discontinued therapy, compared to 18% on placebo. Adverse events included hypokalemia, fatigue, nausea, vomiting, and elevated blood pressure, consistent with the drug’s known safety profile.

During the episode, which was recorded during the 

85th Scientific Sessions of the American Diabetes Association (ADA 2025)

, Buse provides hosts with a deep dive into the background of the trial, prevalence of hypercortisolism in difficult-to-control type 2 diabetes, and the historic relevance of the CATALYST results. Buse also discusses how the trial offers insight into dosing approaches with mifepristone and advocates for broader cortisol screening in patients with complex type 2 diabetes—suggesting that ADA Standards of Care should reflect these findings.

Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others. Relevant disclosures for Buse include Altimmune, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept Therapeutics, Eli Lilly, embecta, Moderna, Novo Nordisk, Tandem, Vertex, and others.

Podcasts

Discover how the CATALYST trial reveals mifepristone's potential to enhance glycemic control and weight loss in challenging type 2 diabetes cases.

Addressing Potential Barriers to Implementing Hypercortisolism Screening in Practice

Video content above is prompted by the following:

What are some potential barriers to screening for hypercortisolism in primary and specialty care settings?

What are some ways to address and overcome these barriers?

When should a patient be referred to endocrinology after hypercortisolism screening?

How can primary care clinicians and specialists collaborate effectively to identify, screen, and refer patients with hypercortisolism in a timely manner to optimize patient care?

Experts discuss potential barriers to screening for hypercortisolism in primary care and specialty settings, ways to address these barriers, when a patient should be referred to endocrinology after screening, and how primary care clinicians and specialists can collaborate effectively to identify, screen, and refer patients with hypercortisolism to optimize patient care.

Importance of Multispecialty Communication in Hypercortisolism Management and Referrals

What is the role of primary care clinicians in identifying and screening patients for hypercortisolism?

How does hypercortisolism affect mental health? How can primary care clinicians help identify patients with mental health conditions who might be at risk for hypercortisolism?

How does hypercortisolism contribute to osteoporosis and an increased risk of fractures?

Experts discuss the role of primary care clinicians in identifying and screening patients for hypercortisolism, how hypercortisolism affects mental health and how primary care clinicians can identify at-risk patients, and how hypercortisolism contributes to osteoporosis and an increased risk of fractures.

John Buse, MD, PhD

Articles