Imlifidase (Idefirix) enabled deceased-donor kidney transplantation in highly sensitized patients with a positive crossmatch. Graft failure-free survival was 90% at 1 year in the European post-authorization efficacy and safety (PAES) trial.¹

Oriol Bestard, MD, PhD, head of the Department of Nephrology and Kidney Transplantation at Vall d’Hebron University Hospital in Barcelona, Spain, presented the data at the 

American Society of Nephrology (ASN) Kidney Week 2026

 in Denver, Colorado. In an interview with 

, Bestard said the open-label, nonrandomized trial confirms earlier phase 2 findings. He added that it leaves open questions about antibody rebound and concomitant immunosuppression.

Imlifidase Opens a Transplant Window, With Oriol Bestard, MD, PhD

Highly Sensitized Patients Face Limited Access to Kidney Transplant

Highly sensitized patients carry preformed antibodies against human leukocyte antigens (HLA), which can damage a transplanted organ. These patients make up about 10%–15% of people on transplant waiting lists in the US and Europe. They tend to wait longer for a compatible organ and face a greater risk of dying while waiting.²

“The trial is focusing on a really unmet medical need, which is a subset of patients that are waiting for transplantation, which are called highly sensitized,” Bestard said. “They have developed HLA antibodies in the past for different factors, and they are not capable of being transplanted.”

Imlifidase is an IgG-cleaving enzyme derived from 

. It inactivates all IgG subclasses, including HLA antibodies, within hours of administration.² Bestard explained that the enzyme also depletes IgG on the surface of B cells. Antibodies typically return within about 7 to 8 days.

“It gives a sort of window of opportunity for these patients to be transplanted during that period of time without having donor-specific antibodies,” he said.

Imlifidase received conditional marketing authorization in the European Union in August 2020, contingent on a confirmatory post-authorization study.² In the US, the 

 accepted a biologics license application for imlifidase in February 2026. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of December 19, 2026.²

PAES Trial Design in Crossmatch-Positive Deceased-Donor Transplants

PAES (NCT05369975) was a controlled, nonrandomized, open-label trial requested by the European Medicines Agency (EMA) to support full marketing authorization.¹ The trial ran at 22 transplant centers across 11 countries in the European Union and the United Kingdom.³

Investigators treated 50 highly sensitized patients who received crossmatch-positive deceased-donor kidney offers. All were considered unlikely to be transplanted under available allocation systems, including prioritization programs for highly sensitized patients. Imlifidase was given to convert the positive crossmatch to negative before transplantation.¹

Bestard noted that patients first underwent delisting of selected HLA antibodies according to each transplant program’s local policies. He added that the trial included 2 control groups. One was transplanted concurrently, and the other was a retrospective sensitized group drawn from a large European registry. Neither group had a positive crossmatch.

The primary outcome was graft failure-free survival at 1 year. Secondary outcomes at 1 year included:¹

Kidney function assessed by estimated glomerular filtration rate (eGFR)

Imlifidase Results: Graft Survival, eGFR, and AMR at 12 Months

Graft failure-free survival was 90% at 1 year in patients desensitized with imlifidase (n = 50). Graft survival was 92% and patient survival was 98%. Mean eGFR, calculated by the Modification of Diet in Renal Disease (MDRD) equation, was 51.04 mL/min/1.73 m² (n = 45).¹

Delayed graft function occurred in 40% of patients, with a median duration of 14 days. AMR occurred in 56% of recipients, but no allograft loss was associated with AMR.¹ Bestard said the AMR episodes were managed according to each center’s protocol and did not affect 12-month outcomes.

Investigators reported no new safety signals, and no imlifidase infusions were stopped because of infusion reactions. They concluded that imlifidase enables transplantation with successful kidney function at 1 year, with a safety profile consistent with prior experience.¹

Antibody Rebound and Immunosuppression Remain Open Questions

Bestard said the findings may give patients who have waited for long periods, or indefinitely, a path to transplant. He said key questions remain about which patients rebound and how to pair imlifidase with other therapies.

“We really need to understand much more about the biology now of how and why some of these patients do show this very severe rebound of antibodies after imlifidase, why some others do not, and what type of immunosuppressive therapies should we concomitantly use together with imlifidase,” Bestard said.

Editors’ Note: Disclosures for Bestard include Hansa Biopharma.

Bestard O, et al. Post-Authorization Efficacy and Safety (PAES): An Open-Label Post-Authorization Trial of 50 Imlifidase Crossmatch-Positive Deceased-Donor Kidney Transplants in Europe. Abstract FR-OR103 presented at: American Society of Nephrology Kidney Week 2026; October 22–25, 2026; Denver, CO.

Hansa Biopharma announces positive Idefirix PAES results presented in the High-Impact Clinical Trials session at ASN Kidney Week. News release. Hansa Biopharma. Published October 23, 2026. Accessed October 28, 2026.

Hansa Biopharma reports positive efficacy and safety results from Idefirix European post authorization study in kidney transplantation. News release. Hansa Biopharma. Published May 27, 2026. Accessed October 28, 2026.

Videos

PAES data from ASN Kidney Week 2026 show graft, patient, and kidney function outcomes at 1 year in crossmatch-positive transplants.


SCENARIO was a multicenter, randomized, single-blind trial of 200 patients with obesity who had a minor ischemic stroke or TIA. It compared a 15-week structured weight reduction program with a 1-hour nutrition education session.


At 24 months, the weight reduction program lowered the risk of recurrent stroke or TIA, myocardial infarction, death or hospitalization for unstable angina by 67% compared with the control group (relative risk, 0.33).

Which patients benefited most from weight reduction after stroke?


Patients younger than 65 years, those with an mRS score of 0 to 2 and those with metabolic syndrome showed the greatest benefit.

A structured weight-loss program lowered the rate of recurrent vascular events in patients with obesity who had a minor ischemic stroke or transient ischemic attack (TIA). The findings come from the SCENARIO analysis, a trial which was presented during the 

Obesity is a known risk factor for cerebrovascular disease, but there is little evidence on whether deliberate weight loss improves outcomes after a first event. Yaroslav Winter, MD, MSc, head of Mainz Comprehensive Epilepsy and Sleep Medicine Center at Johannes Gutenberg University, presented the multicenter results, which address this gap in secondary prevention.¹

The randomized, single-blind, controlled trial enrolled 200 adults with obesity who had a TIA or a minor ischemic stroke, defined as a modified Rankin Scale (mRS) score of 3 or lower.¹˒² Participants were randomly assigned to a 15-week structured weight reduction program or a single 1-hour nutrition education session.¹ The primary composite end point included recurrent stroke or TIA, myocardial infarction, death and hospitalization for unstable angina.

Did Weight Loss Reduce Recurrent Vascular Events?

At 24 months, patients in the weight reduction arm had a significantly lower risk of the composite end point than the control group (relative risk, 0.33; 95% CI, 0.13-0.83; 

 = .02).¹ Investigators also reported significant improvements in functional outcomes, body measurements, blood pressure and lipid levels with the intervention.¹

The benefit was greatest in 3 subgroups: patients younger than 65 years, those with an mRS score of 0 to 2 and those with metabolic syndrome.¹ Winter and colleagues concluded that structured weight management may help prevent secondary stroke in this population. They added that an individualized approach is needed to get the best results.¹

What Do the Findings Mean for Secondary Stroke Prevention?

Clinicians now have more options for weight management, and these results suggest structured lifestyle programs may deserve a place alongside medications for controlling risk factors after a minor stroke or TIA. The full results, including absolute event rates and details of the intervention, have not yet been published.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

Winter Y. Secondary prevention of stroke or transient ischemic attack by means of a weight reduction programme (SCENARIO trial). Presented at: 2026 World Stroke Congress; October 21-23, 2026; Seoul, South Korea. Accessed October 28, 2026. 

https://cslide.ctimeetingtech.com/wsc26/attendee/confcal/session/calendar/2026-10-21#presentation-abstract-2598553795606

Secondary prevention of stroke or TIA by means of a weight reduction programme (SCENARIO). ClinicalTrials.gov identifier: NCT01721538. Accessed October 28, 2026. 

https://clinicaltrials.gov/study/NCT01721538

Articles

In the SCENARIO trial, a 15-week weight-loss program cut recurrent vascular events by 67% in patients with obesity after minor ischemic stroke or TIA.

Weight-Loss Program Cuts Vascular Events by 67% After Minor Stroke, TIA

 care, and phosphodiesterase 4 (PDE4) inhibitors now offer a once-daily option capable of reaching optimal targets for skin and itch.

In this episode of ABCs in Dermatology, hosts Lindsay Ackerman, MD, and Chris Bunick, MD, PhD, examined where topical PDE4 inhibitors fit and how to measure meaningful response.

On this episode of ABCs in Dermatology, Lindsay Ackerman, MD, and Chris Bunick, MD, PhD, talk through the growing role of nonsteroidal topical therapy in eczema care and how they set treatment goals with patients.

ABCs in Dermatology: Understanding PDE4 Inhibition in Atopic Dermatitis

PDE4 hydrolyzes cyclic adenosine monophosphate (cAMP), a second messenger driving anti-inflammatory programming. Because inhibition acts upstream of the Janus kinase (JAK)-STAT pathway, it dampens Th1, Th2, Th17, and Th22 signaling. Roflumilast (Zoryve) more closely mimics cAMP than crisaborole (Eucrisa) or apremilast (Otezla), with roughly 25-fold to more than 300-fold greater in vitro potency.

In the phase 3 INTEGUMENT-1 and INTEGUMENT-2 trials, 1337 patients aged 6 years or older applied roflumilast cream 0.15% or vehicle once daily for 4 weeks.

 Validated Investigator Global Assessment success reached 32.0% vs 15.2% and 28.9% vs 12.0%, respectively, with 75.8% entering with moderate disease.

 Itch improved within 24 hours of the first application.

Application-site pain occurred in 0.9% and 2.1% of roflumilast-treated patients, and none of 47 patients who previously stopped crisaborole for stinging or burning developed application-site adverse events.

 One hypothesis attributes part of crisaborole's irritation to its boron-containing structure. Nausea affected 2.0% or fewer of treated patients,

 and moderate to severe hepatic impairment remains the key contraindication.

In the INTEGUMENT open-label extension, patients reaching clear skin switched to twice-weekly proactive application and maintained clear or almost clear skin for a median of 281 days.

 The regimen mirrors proactive corticosteroid maintenance without cumulative steroid exposure, useful on the face, eyelids, and skin folds. In children aged 2 to 5 years, roflumilast cream 0.05% likewise improved pruritus within 24 hours.

Unlike ruxolitinib cream (Opzelura), limited to short-term use on 20% or less of body surface area, roflumilast carries no duration or surface area cap. Clinicians increasingly pair it off label with biologics or oral JAK inhibitors for residual disease, often persistent itch.

Treat-to-target goals now define minimal disease activity as clear or almost clear skin plus an itch score of 0 or 1 on a 0-to-10 scale. Reduction of 4 or more points on the Worst Itch Numeric Rating Scale marks a moderate target, signaling response while deeper improvement accrues.

Collectively, once-daily topical PDE4 inhibition positions nonsteroidal therapy as a credible route to minimal disease activity in atopic dermatitis. The data reinforce corticosteroid stewardship for long-term and sensitive-site use.

Relevant disclosures for Bunick include AbbVie, South Beach Symposium, Almirall, Apogee Therapeutics, Arcutis Biotherapeutics, Daiichi Sankyo, Eli Lilly, LEO Pharma, US, Novan, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Timber Pharmaceuticals, and UCB. Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

Simpson EL, Eichenfield LF, Alonso-Llamazares J, et al. Roflumilast cream, 0.15%, for atopic dermatitis in adults and children: INTEGUMENT-1 and INTEGUMENT-2 randomized clinical trials. 

Simpson EL, Eichenfield LF, Papp KA, et al. Long-term safety and efficacy with roflumilast cream 0.15% in patients aged ≥6 years with atopic dermatitis: a phase 3 open-label extension trial. 

Eichenfield LF, Serrao R, Prajapati VH, et al. Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients aged 2-5 years with mild-to-moderate atopic dermatitis (INTEGUMENT-PED): a phase 3 randomized controlled trial. 

Podcasts

Lindsay Ackerman, MD, and Chris Bunick, MD, PhD, discuss where topical PDE4 inhibitors fit in atopic dermatitis and how to measure skin and itch response.

ABCs in Dermatology: Topical PDE4 Inhibition in Atopic Dermatitis

Physicians often find it easier to discuss clinical failures than personal exhaustion.

People-pleasing and fear of lost opportunities can push women physicians toward burnout.

Women in medicine can be excellent clinicians while still exhausted or imperfect.

, host Mona Shahriari, MD, associate clinical professor of 

 at Yale University and a practicing dermatologist in Connecticut, is joined by Shannon C. Trotter, DO. Trotter is a dermatologist from Springfield, Ohio, a speaker and educator, and host of the ‘

This podcast episode is a sequel to Shahriari’s appearance on Trotter’s own show. It explores the gap between the polished podium version of physicians and the real-life version that emerges over coffee, in hotel lobbies, and in group chats with trusted colleagues.

The Medical Sisterhood: How to Approach Burnout, Boundaries, and Authenticity in Medicine

Shahriari opens with a series of candid statements for Trotter to react to. The first is that expertise alone does not earn someone a microphone. Trotter agrees that research or clinical expertise and the ability to communicate it are separate skill sets, and that only some clinicians have both. The two discuss the challenge of co-presenting with colleagues whose energy and style differ from their own. Trotter describes how a spontaneous live demonstration with a more reserved co-presenter became one of the session’s strongest moments.

Why Do Physicians Hide Exhaustion More Than Clinical Failures?

Trotter suggests physicians find clinical failures easier to discuss because they can be explained by outside factors, such as incomplete patient histories, adherence issues, or a trial that missed its end point. Personal exhaustion, by contrast, tends to be seen as a flaw in oneself. Both clinicians note that women in medicine often hold themselves to especially high standards, a pattern reinforced by curated social media feeds.

Shahriari describes canceling a lunch meeting after a cross-country lecture schedule left her running on minimal sleep, and notes how long she hesitated before admitting she was tired. Trotter links this hesitation to people-pleasing and to fear that declining a commitment could cost future opportunities. That cycle, she says, can push clinicians toward burnout. Survey data continue to show higher rates of burnout among women physicians than among men.

How Can Physicians Handle Missteps When Speaking in Public?

Trotter emphasizes the power of pausing before speaking and asking whether a comment adds value. Criticism of a colleague’s presentation, she notes, belongs in a private conversation rather than a public chat. She acknowledges that jokes sometimes fall flat on stage and that constant recording makes such moments feel more permanent, but encourages speakers to keep going and accept imperfection. Both agree that speakers are usually their own harshest critics, and Shahriari has stopped listening to recordings of herself for that reason. Trotter adds that learning not to take rejection personally is especially hard for younger clinicians.

What Should More Women in Medicine Say Out Loud?

Trotter describes herself as a serious physician who is not always a serious person. She uses humor to build rapport with patients while reading each room to decide how far to take it. The two share lighthearted confessions about conference life, including pretending to recognize colleagues, slipping out of events unnoticed, and the effort behind polished social media photos. Trotter also recounts responding to emergencies outside the clinic, including a stroke on an airplane, as an example of physicians’ innate drive to help others. She closes by urging women physicians to acknowledge that they can be excellent clinicians while still feeling exhausted or disorganized. She also encourages them to promote themselves without making themselves smaller for others’ comfort.

Editor’s note: This summary was edited for the purposes of grammar and clarity using AI tools. Shahriari and Trotter highlighted no relevant financial disclosures of note. 

Want to join The Medical Sisterhood community? Click here to join our LinkedIn Group!

Berg S. What’s behind the persistent gender gap in physician burnout. American Medical Association. Published April 30, 2026. Accessed October 28, 2026. 

https://www.ama-assn.org/practice-management/physician-health/what-s-behind-persistent-gender-gap-physician-burnout

Ortega MV, Hidrue MK, Lehrhoff SR, et al. Patterns in physician burnout in a stable-linked cohort. 

. 2023;6(10):e2336745. doi:10.1001/jamanetworkopen.2023.36745.

Shannon C. Trotter, DO, and Mona Shahriari, MD, discuss burnout, people-pleasing, public speaking, and the real life behind physicians’ polished personas.

With no antidepressant or talk therapy yet shown to outperform control in 

, clinicians are left weighing whether and how to treat 

, which affects about 1 in 5 of these patients.² The latest negative trial, CONCORD, tested bupropion and behavioral activation therapy (BAT) and found neither superior to control at 16 weeks.¹

Susan Hedayati, MD, MHSc, vice dean for research and professor of medicine in nephrology at Stony Brook University Renaissance School of Medicine, led CONCORD and presented it at the American Society of Nephrology (ASN) 

, she outlined how clinicians can approach treatment until better evidence arrives.

Treating Depression in CKD After CONCORD, With Susan Hedayati, MD, MHSc

Why Depression Treatments May Work Differently in CKD

“So that tells me that maybe the pathophysiological factors that lead to these symptoms in the general population may not be the same as they are in people with CKD or with other chronic diseases,” Hedayati said.

Her group’s earlier Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) found sertraline no better than placebo in 201 patients with CKD who were not receiving dialysis. It also found that sertraline caused more gastrointestinal adverse effects.³ In CONCORD, an early advantage for BAT at 8 weeks did not persist, and bupropion was associated with more insomnia and confusion than BAT.¹

Hedayati said the pattern extends beyond depression. Trials of interventions for other CKD symptoms, including sleep problems and fatigue, have generally been negative or lacked a control arm or a clinically meaningful difference. Depression trials in heart failure, asthma, and coronary artery disease have also come up negative.

Shared Decision Making and a 4 to 6 Week Treatment Trial

“I think we should use a shared decision making approach with the patient, and if they do want to try treatment, offer them one of these medications that we tried before, like sertraline or bupropion, or talk therapy,” Hedayati said. “But the thing to keep in mind is try it for a short duration period, like 4 to 6 weeks, and if the patient doesn’t respond, don’t continue it, because it’s just a treatment burden.”

Talk therapy options include cognitive behavioral therapy or BAT, a shorter form that requires fewer sessions. Hedayati emphasized that the goal of a defined trial period is to avoid keeping patients on a therapy that isn’t helping them.

Starting Sertraline at a Low Dose in Patients With CKD

“Reassess the patient for tolerability and safety,” Hedayati said. “And again, if it’s not working, stop the intervention.”

For SSRIs, she advised starting sertraline at 50 mg daily and increasing gradually, which she described as doubling the dose every 2 weeks, up to a maximum of 200 mg daily. That range mirrors the flexible dosing used in CAST, which started at 50 mg daily and escalated to a maximum of 200 mg daily based on tolerability and response.³

Biomarkers May Identify Who Responds to Depression Treatment in CKD

Hedayati believes the next step is understanding what drives depressive symptoms in CKD, and whether a prediction model can identify subgroups of patients likely to respond to existing treatments. With an NIH R01 supplement to CONCORD, her team is studying circulating serum and inflammatory biomarkers using whole genome profiling, RNA sequencing, and proteomics. The goal is to determine which patients will and will not respond to treatment.

Editors’ Note: Hedayati reports no relevant disclosures with industry.

Hedayati S, Zhang X, Tuttle KR, et al. CONCORD: a randomized controlled trial of novel therapies for depression in patients with CKD. Abstract FR-OR110. Presented at: American Society of Nephrology Kidney Week 2026; October 21-25, 2026; Denver, CO.

Palmer S, Vecchio M, Craig JC, et al. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. 

Hedayati SS, Gregg LP, Carmody T, et al. Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: the CAST randomized clinical trial. 

. 2017;318(19):1876-1890. doi:10.1001/jama.2017.17131

Hedayati recommends shared decision making and a 4 to 6 week treatment trial, stopping therapy when patients don’t respond.

Neither behavioral activation therapy (BAT) nor bupropion, started alone and escalated to combination therapy when needed, improved depressive symptoms more than control at 16 weeks in patients with 

 and major depressive disorder (MDD).¹ The findings from the randomized, double-blind CONCORD trial add to a series of negative depression trials in this population.

Susan Hedayati, MD, MHSc, vice dean for research and professor of medicine in nephrology at Stony Brook University Renaissance School of Medicine, presented the data at the American Society of Nephrology (ASN) 

 in Denver, Colorado, and discussed the trial in an interview with 

. In her view, the results send investigators back to the drawing board on treating depression in CKD.

CONCORD Trial Results in CKD Depression, With Susan Hedayati, MD, MHSc

Why CONCORD Moved Beyond Sertraline for Depression in CKD

“We saw that not only did sertraline not improve depressive symptoms in that patient population, but it actually led to more GI adverse effects like nausea and vomiting, which is really problematic, especially in our patients as they get closer to stage 5 CKD and develop uremia,” Hedayati said.

That earlier trial, the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), randomized 201 patients with CKD who were not receiving dialysis to sertraline or placebo. It found no significant benefit with sertraline.³ CAST was an exception: 

 diagnosed by clinical interview affects about 1 in 5 patients with CKD,² yet these patients have largely been excluded from large antidepressant trials because of safety concerns at low glomerular filtration rate (GFR).

For CONCORD, the investigators turned to bupropion, a non-SSRI antidepressant that Hedayati said has shown efficacy comparable to SSRIs in the general population with fewer adverse effects. They paired it with BAT, a form of cognitive behavioral therapy that requires fewer sessions and places less burden on patients with CKD.

“We noticed that patients with advanced CKD, some of them prefer talk therapy, and some of them prefer, ‘Just give me another medication for my depression,’” Hedayati said. “So we thought if either arm was more efficacious than control, then the patients can choose which one they wanted to try first before having to do the combination therapy.”

Because monotherapy alone often fails to bring depression into remission, patients who had not responded by the midpoint of the trial received both treatments.

CONCORD Trial Design: BAT, Bupropion, and Attention Control

The multicenter, 16 week trial screened 4360 people with CKD stages G3b to G5D using the Quick Inventory of Depressive Symptomatology (QIDS). It randomized 202 patients with MDD to 1 of 3 arms:

 bupropion XL 150 mg daily plus clinical management.

Clinical management served as an attention control. Patients in either active arm who had not reached remission at 8 weeks went on to receive both bupropion and BAT.

Hedayati said the 150 mg bupropion dose is the one recommended for patients with GFR <45. Clinical management sessions were delivered by video at the same weekly frequency as BAT so that patient contact was matched between arms. The primary outcome was the change in QIDS score from baseline to week 16. Secondary outcomes were the change at week 8 and safety.

The intention-to-treat analysis included 201 patients. Of these, 36% had stage G3b disease, 43% had G4, 11% had G5 not on dialysis, and 10% were receiving dialysis. Mean baseline QIDS scores were similar across arms:

Mean participation time was 15.2 weeks and did not differ between arms.

BAT Edges Out Control at 8 Weeks but Not at 16 Weeks

At 16 weeks, QIDS scores had fallen by almost the same amount in every arm:

Strategy 1: 5.9 points (95% CI, −7.0 to −4.7)

Strategy 2: 5.7 points (95% CI, −6.7 to −4.6)

Control: 5.9 points (95% CI, −6.9 to −4.9)

The BAT strategy did not differ from control (arm effect, 

The picture was different at 8 weeks. Scores had changed by −5.4 (95% CI, −6.6 to −4.3) with BAT, −3.8 (95% CI, −4.7 to −3.0) with bupropion, and −4.9 (95% CI, −5.9 to −4.0) with control. BAT produced greater improvement than control (arm effect, 

 = .01), while bupropion produced less (arm effect, 

 = .02). Remission at 8 weeks was reached by 26% of patients in the BAT arm vs 6% in the bupropion arm (

Hedayati noted that the 8 week BAT difference, although statistically significant, fell short of the 2 point QIDS change the investigators considered clinically meaningful.

Bupropion was also associated with more adverse events than BAT. Insomnia occurred in 13% vs 3% of patients (

 = .03). The investigators concluded that BAT improved MDD symptoms more than control at 8 weeks, but neither strategy was superior to control at 16 weeks.

Editor’s Note: Hedayati reports no relevant disclosures

An early behavioral activation therapy signal at 8 weeks didn’t hold, and bupropion brought more insomnia and confusion.

Retatrutide reduced A1C more and produced more than double the weight loss of semaglutide 2 mg (Ozempic) at 80 weeks in adults with 

 in the phase 3 TRANSCEND-T2D-2 trial, according to topline results from Eli Lilly.

TRANSCEND-T2D-2 is the sixth phase 3 trial of retatrutide to report positive results, according to Lilly.

 Retatrutide is an investigational once-weekly single molecule activating receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon.

 Lilly is also comparing retatrutide with tirzepatide in TRIUMPH-5, an ongoing phase 3 trial in adults with obesity with or without type 2 diabetes.

“In TRANSCEND-T2D-2, the first Phase 3 trial comparing retatrutide with another incretin medicine, retatrutide delivered greater A1C reduction and more than double the weight loss of the highest approved dose of Ozempic for type 2 diabetes,” said Kenneth Custer, PhD, executive vice president and president, Lilly Cardiometabolic Health. “Based on these results and those from across our Phase 3 program, we believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions.”

Retatrutide is an investigational once-weekly injectable agonist of the GIP, GLP-1, and glucagon receptors. It is not approved by the FDA or any regulatory agency.

How did retatrutide compare with semaglutide in TRANSCEND-T2D-2?

At 80 weeks, both retatrutide doses lowered A1C by 2.2% vs 1.8% with semaglutide 2 mg. Weight loss was 19.5% to 20.9% with retatrutide vs 9.4% with semaglutide.

What were the most common adverse events with retatrutide?

Gastrointestinal events, including diarrhea, nausea, constipation, and vomiting, were most common. Discontinuation due to AEs was 4.8% to 7.9% with retatrutide vs 2.7% with semaglutide.

Retatrutide vs Semaglutide: TRANSCEND-T2D-2 Design and A1C Results

The randomized, open-label trial (NCT06260722) enrolled 1,298 adults with type 2 diabetes inadequately controlled on metformin, with or without an SGLT2 inhibitor, and a baseline A1C of 7.0% to 10.5%.

 Participants were randomized 2:2:1 to once-weekly retatrutide 9 mg, retatrutide 12 mg, or semaglutide 2 mg. Retatrutide was started at 2 mg and escalated every 4 weeks to the target dose.

The primary objective was to show noninferiority of retatrutide 12 mg vs semaglutide 2 mg for A1C reduction at 80 weeks.

 From a mean baseline A1C of 8.3%, both retatrutide doses lowered A1C by 2.2% at 80 weeks, compared with 1.8% with semaglutide.

Superiority of retatrutide 12 mg was significant with family-wise type 1 error control (P < .001). The 9 mg dose met noninferiority as a key secondary end point and showed nominal superiority (P < .001).

 All results reflect the efficacy estimand, which assumes participants remained on treatment without additional glucose-lowering medication.

Retatrutide Weight Loss and Safety in Type 2 Diabetes

Mean baseline body weight was 102.4 kg, with a mean BMI of 36.8 kg/m².

 At 80 weeks, body weight fell 19.5% (20.1 kg) with retatrutide 9 mg and 20.9% (21.5 kg) with retatrutide 12 mg, vs 9.4% (9.5 kg) with semaglutide (P < .001 for both doses).

 Retatrutide also produced greater improvements in non-HDL cholesterol, triglycerides, and systolic blood pressure, according to Lilly.

Gastrointestinal events were the most common adverse events (AEs). Diarrhea occurred in 28.3% and 32.7% of participants receiving retatrutide 9 mg and 12 mg vs 26.4% with semaglutide, and nausea occurred in 21.2% and 23.8% vs 21.3%.

 Vomiting rates were 10.2% and 15.0% vs 13.2%, while constipation was less frequent with retatrutide (14.2% and 13.1% vs 19.8%).

Dysesthesia occurred in 4.8% and 6.5% of retatrutide recipients vs 2.7% with semaglutide.

 Discontinuation due to AEs was 4.8% and 7.9% with retatrutide 9 mg and 12 mg, respectively, vs 2.7% with semaglutide.

 Lilly reported most events were mild to moderate and typically resolved during treatment.

In the phase 3 TRIUMPH-2 trial in adults with obesity and type 2 diabetes, the highest retatrutide dose produced mean weight loss of 20.8%.

 Detailed TRANSCEND-T2D-2 results will be presented at a future medical meeting and published in a peer-reviewed journal.

An extension period will follow approximately 650 participants on retatrutide for an additional 24 weeks.

 Retatrutide remains investigational and is under phase 3 study in obesity, knee osteoarthritis pain, obstructive sleep apnea, cardiovascular outcomes, and metabolic dysfunction-associated steatotic liver disease.

Eli Lilly and Company. Lilly's retatrutide delivered greater A1C reduction and more than double the weight loss of Ozempic's highest approved dose in head-to-head trial. Published October 28, 2026. Accessed October 28, 2026. 

https://investor.lilly.com/news-releases/news-release-details/lillys-retatrutide-delivered-greater-a1c-reduction-and-more

Effect of retatrutide compared with semaglutide in adult participants with type 2 diabetes and inadequate glycemic control with metformin with or without SGLT2 inhibitor (TRANSCEND-T2D-2). ClinicalTrials.gov identifier: NCT06260722. Accessed October 28, 2026. 

https://clinicaltrials.gov/study/NCT06260722

HCPLive. TRIUMPH-2: Retatrutide reduces weight, A1C in patients with obesity. 

https://www.hcplive.com/view/triumph-2-retatrutide-reduces-weight-a1c-in-patients-with-obesity

. Published August 5, 2026. Accessed October 28, 2026.

Retatrutide lowered A1C 2.2% vs 1.8% and cut weight 19.5%-20.9% vs 9.4% with semaglutide 2 mg at 80 weeks in adults with type 2 diabetes.

TRANSCEND-T2D-2: Retatrutide Beats Semaglutide 2 mg on A1C, Weight Loss

Shape-sensing robotic-assisted bronchoscopy (ssRAB) achieved a consensus-defined diagnostic yield of 82.1% and a sensitivity for malignancy of 87.3% in the first 750 patients with 1-year follow-up from the prospective, multicenter Ion Registry.

 Michael Pritchett, DO, MPH, medical director of the Chest Center of the Carolinas and an advanced bronchoscopist with FirstHealth Pulmonology and Pinehurst Medical Clinic, discussed the findings with 

Pritchett presented the late-breaking analysis at the 

, held October 18-21, 2026, in Phoenix, Arizona. The registry enrolled patients undergoing ssRAB biopsy with no prespecified patient or nodule criteria, and this analysis included 750 of 1,301 enrolled patients across 11 sites and 22 proceduralists.

Michael Pritchett, DO, MPH, discusses real-world Ion Registry yield, sensitivity, and safety data for robotic bronchoscopy presented at CHEST 2026.

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