Q4 2025 Recap: Endocrinology News and Updates

The fourth and final quarter was somewhat quieter for endocrinology, but no less impactful for it. Although there were fewer regulatory updates from the US Food and Drug Administration (FDA), they carried substantial weight in the past 3 months. Between the acceptance of inhaled insulin for type 1 (T1D) and type 2 diabetes (T2D) and the approval of oral semaglutide for cardiovascular risk in T2D, the pipeline of diabetes care is promising as we enter 2026. Additionally, the American Diabetes Association released its 2026 Standards of Care, providing new guidelines for everything from GLP-1 usage to insulin pump access.

The editorial team at HCPLive has collected some of the most impactful headlines from Q4 of 2025 – check them out below:

FDA News

FDA Accepts Inhaled Insulin (Afrezza) sBLA for Pediatric Diabetes

On October 13, 2025, the MannKind Corporation announced the FDA’s acceptance of their supplemental biologics license application (sBLA) for human insulin inhalation powder (Afrezza) in children and adolescents living with type 1 diabetes (T1D) or type 2 diabetes (T2D). The submission was based on positive data from the phase 3 open-label INHALE-1 study, which showed the drug’s noninferiority to standard-of-care, which was multiple daily injections with basal insulin. The FDA has assigned the application a Prescription Drug User Fee Act (PDUFA) target action date of May 29, 2026.

FDA Approves Oral Semaglutide (Rybelsus) for CV Risk Reduction in Type 2 Diabetes

On October 17, 2025, the FDA approved oral semaglutide 7 mg and 14 mg (Rybelsus) for cardiovascular risk reduction in patients with T2D, irrespective of prior cardiovascular events. The approval was based on positive data from the SOUL trial, during which oral semaglutide 14 mg displayed a 14% relative reduction in major adverse cardiovascular event risk after 4 years, with a 2% reduction after 3 years, compared to placebo. The approval makes oral semaglutide the first GLP-1 to receive FDA approval in pill form.

FDA Issues Complete Response Letter for Relacorilant for Hypercortisolism

On December 31, 2025, the FDA announced their issuance of a Complete Response Letter (CRL) in response to Corcept Therapeutics’ New Drug Application of relacorilant for hypercortisolism. Although they acknowledged that the phase 3 GRACE trial successfully met its primary endpoint, and that the subsequent GRADIENT trial provided confirming evidence, the FDA determined that it was unable to establish a favorable risk-benefit assessment without further evidence of effectiveness. According to a press release from the company, Corcept plans to meet with the FDA as soon as possible to work out a path forward.

Trial Results

Orforglipron Maintains Weight Loss in Patients Switching from Semaglutide or Tirzepatide

The phase 3 ATTAIN-MAINTAIN trial, the results of which were announced on December 18, 2025, saw orforglipron provide superior weight maintenance compared to placebo. A total of 376 participants who had completed the prior SURMOUNT-5 trial were enrolled and randomly assigned in a 3:2 ratio to either orforglipron maximum tolerated dose or placebo, as an adjunct to healthy diet and physical activity. Ultimately, patients switched from semaglutide to orforglipron maintained their achieved weight loss, with an average difference of 0.9 kg; those switching from tirzepatide also maintained their weight loss, with an average difference of 5 kg.

Mazdutide Demonstrates Superiority to Semaglutide in Type 2 Diabetes and Obesity

DREAMS-3, the fourth in a series of phase 3 clinical trials investigating mazdutide, proved the drug’s superiority to semaglutide in HbA1c and body weight reduction in patients with T2D and comorbid obesity, according to an October 26, 2025 announcement from parent company Innovent Biologics. A total of 349 patients were enrolled in the study and randomly assigned in a 1:1 ratio to either mazdutide 6 mg or semaglutide 1 mg for 32 weeks. Ultimately, investigators recorded a -2.03% mean HbA1c change in the mazdutide arm, versus a -1.84% reduction in the semaglutide arm. Mean percentage weight reduction was logged as 10.29% in the mazdutide arm and 6% in the semaglutide arm.

SELECT: Semaglutide Indicates Possible Cardiovascular Disease-Modifying Effect

Data from the recent SELECT trial, investigating patients with atherosclerotic cardiovascular disease, suggest that semaglutide’s cardioprotective effects may be totally independent of baseline adiposity and weight loss. During the trial, semaglutide reduced major adverse cardiovascular event incidence across all baseline weight and waist circumference categories among 8803 patients in that arm. These data support the recontextualization and reconceptualization of GLP-1 receptor agonists as cardiovascular disease-modifying drugs, expanding beyond endocrinology.

Regulatory Updates

Diabetes Dialogue: Therapeutic Updates from the ADA 2026 Standards of Care

In this episode of Diabetes Dialogue, cohosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the therapeutic side of the 2026 American Diabetes Association Standards of Care. Between new inclusion in the heart failure treatment algorithm and the first-ever recommendation for consideration in T1D and obesity, GLP-1s are still dominating the news. Expanded guidance on metabolic dysfunction-associated steatotic liver disease (MASLD/MASH) and kidney protection strategies, as well as updates to glycemic targets to normalize continuous glucose monitor usage, round out the discussion as Isaacs and Bellini encourage clinicians to engage with the guidelines and to view them as a living framework supporting comprehensive and proactive diabetes care.

Diabetes Dialogue: 2026 Technology Updates and American Diabetes Association Standards of Care

In this episode of Diabetes Dialogue, Isaacs and Bellini discuss updates from the 2026 American Diabetes Association Standards of Care, including the removal of C-peptide and autoantibody requirements as barriers to insulin pump and automated insulin delivery access. The guidelines now include a Level A recommendation for the use of automated insulin delivery in T2D, as well as updates to expand support for continuous glucose monitor usage during pregnancy beyond T1D and to reduce reliance on confirmatory fingerstick language.