Diana Isaacs, PharmD, is an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic.

 requiring very high mealtime doses have long lacked a concentrated insulin with a rapid onset, forcing clinicians to choose between large injection volumes and sluggish pharmacokinetics. A newly published pharmacokinetic and pharmacodynamic study on AT278, an investigational insulin aspart formulated at 500 units/mL, suggests this gap may be closing.

Ultra-Rapid U500 Aspart AT278 Aids High-Dose T2D Therapy

, co-hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, discussed the findings and their potential effect on insulin delivery for patients with high insulin requirements.

The single-center, randomized, double-blind, crossover study used a 12-hour euglycemic clamp to compare AT278 against standard-concentration insulin aspart (U100) and regular human U500 insulin in adults with type 2 diabetes and body mass index ranging from 25 to 38 kg/m². Each participant received a single subcutaneous dose of one formulation. AT278 produced significantly faster insulin absorption than both comparators, translating into a significantly greater glucose-lowering effect within the first hour.

This ultra-rapid profile held consistently across the full body mass index range studied, addressing a longstanding limitation of regular U500 insulin, which behaves more like an intermediate-acting agent despite its labeling. Regular U500 requires dosing roughly 30 minutes before meals while also serving a basal function, complicating use in patients who skip or delay meals. Because concentrated insulin volume, not units, is often the limiting factor in insulin pump selection, an ultra-rapid U500 option could allow more patients on high daily doses to use smaller, more desirable devices.

Current concentrated-insulin practice often involves off-label use of U200 insulin in pumps or manual U500 injections, both of which carry meaningful hypoglycemia risk and dosing complexity. An ultra-rapid, high-concentration analog designed for prandial dosing would represent the first option of its kind for insulin-resistant patients with type 2 diabetes on high-dose therapy. If confirmed in larger trials, AT278 could reshape how clinicians manage insulin delivery in this population, including expanding candidacy for automated insulin delivery systems currently considered unsuitable for regular U500 insulin.

Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.

Svehlikova E, Gatschelhofer C, Lackner B, et al. A new highly concentrated insulin aspart at278 (500 u/ ML ) demonstrates Ultra‐rapid pharmacokinetic and pharmacodynamic properties in type 2 diabetes regardless of bmi. Diabetes, Obesity and Metabolism. Published online July 30, 2026. 

Videos

In this segment from the latest episode of Diabetes Dialogue, Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the recent clinical successes of ultra-fast-acting insulin AT278.

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Type 2 Diabetes

Dana Rizk, MD, is a professor of medicine in the division of nephrology at the University of Alabama at Birmingham.

The Phase 3 VISIONARY trial enrolled 510 patients with biopsy-proven, high-risk IgA nephropathy (IgAN), making it the largest IgAN trial to date. The global, randomized, double-blind, placebo-controlled study was built to test whether selectively blocking APRIL, a cytokine central to the disease's underlying immune biology, could change the course of a condition typically defined by relentless kidney function decline.

“The VISIONARY trial was a phase three trial. It's a global study that enrolled patients with biopsy-proven IgA nephropathy, primary IgA nephropathy, really from all around the world, so very good representation,” Dana Rizk, MD, professor of medicine in the Division of Nephrology at the University of Alabama at Birmingham, said in an interview with HCPLive.

How VISIONARY's Design Targets APRIL in IgA Nephropathy, With Dana Rizk, MD

A High-Risk, Globally Representative IgAN Population

To enroll in VISIONARY, patients needed a biopsy confirming primary IgAN and an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m². Rizk noted the trial built in a timing requirement tied to how preserved a patient's kidney function was at screening.

“They had to have a GFR over 30, and it might be worth mentioning that if their GFR was between 30 and 44, they had to have a biopsy within three years. If it was over 45, so, you know, pretty good preserved GFR, they could have had a biopsy at any point in time,” Rizk said.

Patients also had to meet a proteinuria threshold to qualify as high-risk: > 1 g/day of protein, or a urine protein-to-creatinine ratio > 0.75 g/g, based on a 24-hour collection.

Before randomization, all participants were optimized on background therapy reflecting current standard of care. Patients were maintained on maximum tolerated renin-angiotensin system (RAS) inhibition, and those on sodium-glucose cotransporter-2 (SGLT2) inhibitors had to be on a stable dose for at least 3 months prior to enrollment. Concomitant immunosuppressive medications were not permitted leading up to the study.

Once patients cleared screening, they were randomized to receive sibeprenlimab, 400 mg subcutaneously every 4 weeks, or placebo.

How Anti-APRIL Therapy Targets IgA Nephropathy

Sibeprenlimab is an anti-APRIL therapy, and Rizk walked through why that mechanism was chosen to target IgAN at its immunologic root.

“APRIL is a cytokine that is important in allowing B cells to become IgA-secreting cells, and also is important for the survival of B cells,” Rizk said.

IgAN is an immune-mediated disease, and its pathogenesis has been summarized by the four-hit hypothesis: overproduction of galactose-deficient IgA1 (Gd-IgA1) triggers the formation of autoantibodies against it, which in turn form circulating immune complexes. Those complexes ultimately deposit in the kidneys, driving inflammation and, over time, fibrosis.

“Targeting B cells and this immune backbone to the disease is of course important, makes sense, and that was the premise for the anti-APRIL therapy design,” Rizk said.

Sibeprenlimab (marketed as VOYXACT) received accelerated approval from the U.S. Food and Drug Administration (FDA) in November 2025 for reduction of proteinuria in adults with IgAN at risk of disease progression, based on VISIONARY's primary endpoint results. The trial's key secondary endpoint, annualized eGFR slope over 24 months, offers a longer-term view of whether that upstream mechanism translates into preserved kidney function.

include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Disclosures for

include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. Disclosures for

include Novartis Pharmaceuticals, Otsuka Pharmaceutical Inc., Vera Therapeutics, Biogen, Travere Therapeutics, and others.

Perkovic V, Trimarchi H, Tesar V, et al. Sibeprenlimab in IgA nephropathy: interim analysis of a phase 3 trial. 

. 2026;394(7):635-646. doi:10.1056/NEJMoa2512133

Otsuka. Otsuka unveils unprecedented phase 3 VISIONARY two-year eGFR results demonstrating VOYXACT (sibeprenlimab-szsi) stabilizes kidney function decline to baseline physiologic rate, fundamentally altering disease progression in IgA nephropathy (IgAN). News release. August 3, 2026. 

https://www.otsuka-us.com/news/otsuka-unveils-unprecedented-phase-3-visionary-two-year-egfr-results-demonstrating-voyxactr

Rizk DV, Perkovic V, Trimarchi H, et al. Two-year eGFR and safety results from the VISIONARY phase 3 trial of sibeprenlimab in IgA nephropathy. Presented at: GlomCon Hawaii; August 3-7, 2026; Maui, HI.

VISIONARY enrolled 510 high-risk IgAN patients globally. Learn how the trial's design and anti-APRIL mechanism were built to target disease at its root.


Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

Topline results from Part 2 of the phase 3 ABTECT maintenance trial showed obefazimod sustained clinical benefit through week 44 in patients with ulcerative colitis (UC) who had not initially responded to induction therapy, adding to positive Part 1 data released earlier this year. 

With those results in hand, Remo Panaccione, MD, professor of medicine and director of the IBD Clinic at the University of Calgary, spoke with HCPLive about where obefazimod might fit into an increasingly crowded UC treatment landscape.

"You're absolutely right that it's becoming a crowded landscape," Panaccione said.

Where Could Obefazimod Fit in UC Treatment, With Remo Panaccione, MD

How Does Obefazimod's Mechanism Set It Apart?

Obefazimod is a once-daily oral small molecule with a mechanism of action unlike anything currently available in the clinic. Rather than broadly suppressing the immune system, it works by increasing expression of miR-124, a naturally occurring microRNA that helps bring the immune system back into balance. "It's not a true immunosuppressant like some of the therapies we have," Panaccione said.

In Part 1 of the ABTECT maintenance trial, both the 25 mg and 50 mg doses of obefazimod met the primary endpoint of clinical remission at week 44, with remission rates of approximately 51% compared with 10% with placebo. Endoscopic remission, a Mayo endoscopy score of 0 among patients who entered the trial with a score of 2 or 3, was achieved by 41.5% of patients on 25 mg and 47.7% of patients on 50 mg, versus 10% on placebo. Part 2 data, released in June, showed continued benefit among patients who had not initially responded to induction therapy, with no new safety signals through 44 weeks.

Could Obefazimod Work Across Multiple Lines of Therapy?

Panaccione said the combination of oral dosing, once-daily administration, and strong efficacy makes obefazimod attractive across a range of patient populations, not just one line of therapy. "That combination of oral, once daily, is attractive from a patient perspective," he said. "And if you combine that with the efficacy we just discussed, which, without a direct comparison, is some of the strongest efficacy we've seen, and no safety signal in an expanding, large safety database, I can see this being used across multiple different patient populations."

He described a dual role: as a strong first advanced therapy option for patients who need to start one, and as a viable option later in the treatment course given the refractory population studied in ABTECT. "This can easily be slotted as a first advanced therapy in patients who need to go onto an advanced therapy," Panaccione said. "But also, because of the patient population that was studied here, in particular the patients who are refractory to other advanced therapies and JAK inhibitors, it could also slot in as a second line and or a third line therapy."

Panaccione also pointed to an early durability signal from the phase 2 program, where patients who achieved a response tended to maintain it over time. He said that pattern could reflect the drug's efficacy, its non-immunogenic profile as an oral small molecule, or its underlying mechanism of restoring immune balance.

What Should Clinicians Watch For Ahead of FDA Review?

Abivax has said it plans to submit a new drug application (NDA) to the US Food and Drug Administration (FDA) in late fourth quarter 2026. Asked what clinicians should keep in mind as that submission approaches, Panaccione encouraged a close, independent read of the data once it's published rather than taking topline figures at face value.

He said clinicians should evaluate the published data against the phase 3 evidence that has already supported regulatory approvals for other UC therapies, paying particular attention to both absolute and placebo-adjusted efficacy numbers. "They should think about those absolute numbers and those placebo-adjusted numbers and what that's going to mean not only for their own practice, but for their patients," Panaccione said.

Editors' note: Panaccione has relevant disclosures with Abbott, AbbVie, Abivax, Alimentiv, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Janssen, Merck, Novartis, Pfizer, Takeda, and others.

Abivax announces landmark Phase 3 ABTECT maintenance trial results evaluating obefazimod in moderately to severely active ulcerative colitis. News release. Abivax. June 1, 2026. Accessed August 19, 2026. 

https://www.globenewswire.com/news-release/2026/06/01/3304711/0/en/abivax-announces-landmark-phase-3-abtect-maintenance-trial-results-evaluating-obefazimod-in-moderately-to-severely-active-ulcerative-colitis.html

Abivax reports positive ABTECT maintenance Part 2 results for obefazimod, demonstrating meaningful clinical benefit in refractory ulcerative colitis patients and strengthening the Phase 3 maintenance safety database. News release. Abivax. June 29, 2026. Accessed August 19, 2026. 

https://ir.abivax.com/news-releases/news-release-details/abivax-reports-positive-abtect-maintenance-part-2-results/

Obefazimod could work as first, second, or third line therapy in ulcerative colitis ahead of a planned FDA submission this year.

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Jessica Mercer, MD, serves as co-managing owner of Georgia Dermatology Partners near Atlanta, Georgia.

Some of the most valuable lessons in medicine happen outside scheduled clinical hours, according to a discussion between Andrew Alexis, MD, MPH, professor of clinical 

 at Weill Cornell Medicine in New York City, and host Jessica Mercer, MD, co-managing owner of Georgia Dermatology Partners near Atlanta, Georgia, on the 

Does Mentorship Improve Outcomes for Patients of Color?

How Should Mentees Make the Most of a Mentorship Experience?

Alexis advised mentees to treat mentorship as more than a scheduled 9-to-5 obligation, encouraging trainees to stay engaged during informal moments after the last patient leaves, such as when a mentor reviews charts, checks labs, or handles administrative tasks. He said these unstructured windows often create space for more relaxed conversation, reflection, and questions that may not arise inside the exam room.

Alexis noted mentees who take this approach tend to build stronger, longer-lasting relationships with their mentors. Mercer agreed, noting these moments give trainees a fuller picture of dermatology beyond the patient encounter itself, including the preparation and follow-up work that happens before and after every visit.

Does Mentorship Improve Outcomes for Patients With Skin of Color?

Alexis said mentorship can directly benefit patients with skin of color, since training exposure to conditions such as pigmentary disorders, keloids, and hair and scalp disorders varies widely across geographic locations and training programs. He noted mentees who pursue away electives or shadowing opportunities with mentors experienced in these areas gain exposure to patient populations they might not otherwise encounter, allowing them to supplement textbook knowledge with real-world clinical experience and expert best practices.

Mercer added that dermatologic disease often presents differently across Fitzpatrick skin types, making varied training experiences essential to building the breadth of knowledge needed to earn patient trust and deliver expert, well-rounded care.

To learn more about SOCS’s programs and initiatives, visit 

Editor’s note: This episode was summarized with the help of AI tools. Alexis and Mercer had no relevant disclosures of note.

Perlman KL, Williams NM, Park JH, et al. Skin of color lacks representation in medical student resources: A cross-sectional study. Int J Womens Dermatol. 2021 Jan 8;7(2):195-196. 

Andrew Alexis, MD, MPH, and Jessica Mercer, MD, discuss how informal mentorship moments improve training and care for skin of color.

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

Insulin-resistant patients with type 2 diabetes who require high-dose therapy have long lacked a rapid-acting option concentrated enough for compact insulin pumps. New pharmacokinetic data on an ultra-rapid U-500 insulin aspart, alongside additional phase 3 results for a combined once-weekly insulin icodec-semaglutide regimen, both aim to close persistent gaps in insulin delivery for this population.

On a recent episode of Diabetes Dialogue, co-hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, reviewed two studies addressing unmet needs in insulin therapy for type 2 diabetes.

Diabetes Dialogue: Ultra-Rapid Insulin, IcoSema Advance in Type 2 Diabetes

The investigational agent AT278 is a highly concentrated insulin aspart formulated at 500 units/mL, distinct from existing U-500 regular human insulin, which behaves more like an intermediate-acting product. In a single-center, randomized, double-blind, crossover euglycemic clamp study spanning body mass index from 25 to 38 kg/m², AT278 produced significantly faster absorption and a greater glucose-lowering effect within the first hour versus both standard U-100 insulin aspart and U-500 regular human insulin. The ultra-rapid pharmacokinetic and pharmacodynamic profile held consistent across the BMI range studied.

Current U-500 regular insulin requires dosing 30 minutes before meals while simultaneously serving as basal and prandial coverage, complicating use in automated insulin delivery systems and limiting compatibility with smaller-volume pumps. A concentrated, rapid-onset formulation could allow patients with high insulin requirements to use compact pumps and extended-wear infusion sets without the absorption problems tied to large-volume subcutaneous depots. Drawn from an early-phase study, the findings position AT278 as a potential first ultra-rapid option for prandial dosing in this population, though regulatory approval for pump use remains undefined.

Separately, the phase 3 COMBINE 4 trial evaluated a fixed combination of once-weekly insulin icodec (Awiqli) and semaglutide, known as IcoSema, against once-daily insulin glargine U-100 in 485 adults with type 2 diabetes and baseline A1C above 8%. Over 40 weeks, IcoSema reduced A1C by 3.32 percentage points versus 2.44 points with glargine, a between-group difference of 0.88 percentage points, while producing a 0.79 kg weight reduction compared with a 3.81 kg gain with glargine. Time in range reached 79.8% with IcoSema versus 64.5% with glargine, consistent with the mechanistic rationale of pairing glucagon-like peptide-1 receptor agonism with basal insulin to limit postprandial excursions.

These results build on earlier COMBINE 1 through 3 data, which showed IcoSema achieving noninferior or superior A1C reduction, superior weight outcomes, and lower hypoglycemia rates versus comparators. A single weekly injection combining basal insulin with a GLP-1 receptor agonist could reduce treatment burden and consolidate pharmacy copays, though semaglutide exposure remains capped by concurrent insulin titration, averaging 0.66 mg in COMBINE 4. Whether either agent reaches United States practice, including reported uncertainty around a domestic IcoSema launch, will determine their eventual role in managing insulin-resistant type 2 diabetes.

Svehlikova E, Gatschelhofer C, Lackner B, et al. A new highly concentrated insulin aspart at278 (500 u/ ML ) demonstrates Ultra‐rapid pharmacokinetic and pharmacodynamic properties in type 2 diabetes regardless of bmi. 

Ji L, Benamar M, Mohan V, et al. Once-weekly ICOSEMA versus once-daily insulin glargine U100 in type 2 diabetes management (Combine 4): An open-label, multicentre, treat-to-target, randomised, phase 3B trial. 

This episode discusses the recent results from trials of IcoSema and a new highly concentrated insulin aspart.

Diabetes Dialogue

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives is a podcast hosted by Diana Isaacs, PharmD, and Natalie Bellini, DNP, aimed at providing a regular roundup of the latest clinically applicable insights across diabetes and metabolic diseases, with a focus on leveraging technology to improve care.

Strategic Alliance Partnership

One year after FDA approval, Basavaraj discusses NTM overlap, geographic variation, and real-world access in bronchiectasis care.

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Brensocatib and NTM Overlap in Bronchiectasis, With Ashwin Basavaraj, MD

Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

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United Therapeutics' ralinepag NDA rests on phase 3 ADVANCE OUTCOMES data showing a 55% reduction in clinical worsening versus placebo.

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FDA Accepts NDA for Ralinepag in Pulmonary Arterial Hypertension

Saakshi Khattri, MD, is a board certified Dermatologist, Rheumatologist and Internist and one of only a handful of triple board-certified physicians across the US.

In "Real-World Evidence and Systemic Inflammation in Psoriasis," our experts scrutinize the evidence behind popular claims about disease progression.

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Real-World Evidence and Systemic Inflammation in Psoriasis

This episode, "IL-17 Inhibitor Safety in Psoriasis: Candidiasis, IBD, and Mental Health," features the panel putting the class's safety signals in context.

IL-17 Inhibitor Safety in Psoriasis: Candidiasis, IBD, and Mental Health

Victoria Johnson joined MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and is now an assistant managing editor for HCPLive and RheumatologyLive. She doesn’t have enough time for her numerous hobbies. You can reach her at vjohnson@mjhlifesciences.com.

Dallas allergist-immunologists discuss real-world use of non-steroidal topicals in AD, steroid phobia, and the nematode story.

Atopic Dermatitis

Atopic Dermatitis condition center page, audiences can find a variety of coverage mediums for medical news and updates, including articles, video interviews, podcasts, and breaking news on dermatitis research, treatment, and drug development.

Allergists Debate: Which Nonsteroidal to Use for Atopic Dermatitis?

Andrew Alexis, MD, MPH, and Jessica Mercer, MD, discuss how mentorship shapes dermatology careers and supplements trainee education.

Why Mentorship Matters Most for Dermatology Trainees

A new study from the AHA has indicated the real prevalence of CKM syndrome stages 0-3 in young adults in their 20s.

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Chronic Kidney Disease

CKM Syndrome, Artery Damage Prevalence Higher in Young Adults than Previously Believed

One year after FDA approval, Mark Metersky, MD, discusses which bronchiectasis patients benefit most from brensocatib and its safety profile.

Pulmonary Fibrosis

Brensocatib Patient Selection Evolves 1 Year After FDA Approval

Stay updated with the latest healthcare breakthroughs, including a new lerodalcibep FDA approval and phase 3 avexitide data in post-bariatric hypoglycemia.

The HCPFive: Top News for Healthcare Providers from the Week of 08/16

A recent study has shown that a significantly greater proportion of patients with HF were correctly identified when testing NT-proBNP levels.

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Latest News

Ultra-Rapid U500 Aspart AT278 Aids High-Dose T2D Therapy

How VISIONARY's Design Targets APRIL in IgA Nephropathy, With Dana Rizk, MD

Where Could Obefazimod Fit in UC Treatment, With Remo Panaccione, MD

Does Mentorship Improve Outcomes for Patients of Color?

Diabetes Dialogue: Ultra-Rapid Insulin, IcoSema Advance in Type 2 Diabetes