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.

Janani Rangaswami, MD, FAHA, a nephrologist with expertise in cardiovascular- kidney medicine; Professor of Medicine, George Washington University, Washington DC; Co-chair, Scientific Advisory Group of the AHA's presidential advisory on CKM Health.

Holly Kramer, MD, is a nephrologist at Loyola University Medical Center and the editor in chief of 

Vlado Perkovic is Dean and Scientia Professor of Medicine at UNSW Sydney. He is also a Professorial Fellow at The George Institute and a Staff Specialist in Nephrology at the Royal North Shore Hospital in Sydney.

Just 1 year ago, semaglutide (Ozempic) was approved by the 

This approval marked an important milestone as the first GLP-1 receptor agonist to reduce the risk of worsening kidney disease, kidney failure, and death due to cardiovascular disease in these patient populations.

Semaglutide, initially developed by Novo Nordisk, received its first approval from the FDA under the name Ozempic on December 5, 2017. Its first indication was as an injection of 0.5 mg or 1 mg once weekly for glycemic control in patients with type 2 diabetes (T2D) – as an adjunct to diet and exercise.

Since then, semaglutide has exploded into nearly every related field. Glucagon-like peptide-1(GLP-1) receptors were discovered everywhere from the pancreas and the gastrointestinal tract to the heart, kidney, and liver. GLP-1 receptor agonists were quickly introduced into nephrology and cardiology, expanding their indications over the years to meet need in a variety of organs. Semaglutide has been at the forefront of this expansion due to its comparatively superior reductions of A1c, glucose, and overall weight.

In 2020, semaglutide received approval for the reduction of cardiovascular risk in patients with T2D, marking its entry into the cardiology sphere. In January of 2025, semaglutide became the first GLP-1 receptor agonist approved for worsening kidney disease, kidney failure, and death due to cardiovascular disease in patients with T2D and chronic kidney disease (CKD). This approval marked semaglutide’s entry into the full cardio-kidney-metabolic (CKM) disease spectrum, addressing mortality and worsening outcomes for major contributing diseases.

Now, just over a year after semaglutide’s approval for CKD, the editorial team at 

 has gathered insights from key clinicians across the CKM spectrum to discuss how this revolutionary drug overhauled the treatment landscape for kidney disease from all sides.

Semaglutide’s revolutionary impact on the endocrinology field cannot be understated. Despite not being the first, for years, this GLP-1 RA was the best method of reducing 3 major contributing factors to mortality in T2D. A1c reduction, glucose management, and weight loss saw substantial improvements as a result of the drug’s approval. However, semaglutide’s efficacy now extends far beyond T2D.

“I think that, sometimes, there’s hesitancy around starting a new therapy because the clinicians don’t know if other specialties will be on board,” Diana Isaacs, PharmD,

the director of Education and Training in Diabetes Technology and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and a member of 

 in an interview. “Now, we’re seeing through notes that nephrology is saying, ‘Why don’t you consider using semaglutide?’ And when they come to me as part of endocrinology, I see that, and I’m encouraged to use it. I think semaglutide really has enhanced team-based care in that we’re all on board.”

Isaacs went on to describe how semaglutide’s CKD approval provided a major paradigm shift for the American Diabetes Association’s standards of care.

“By showing its positive outcomes, particularly in people with kidney disease, semaglutide was paradigm-changing for the ADA Standards of Care and for our guidelines in that, previously, SGLT2 inhibitors were preferred for people with T2D and CKD,” Isaacs said. “Now, it’s either SGLT2 inhibitors or GLP-1 therapy – in practice, we’re now utilizing both of them.”

The Cardio-Kidney-Metabolic Landscape of Semaglutide

On October 9, 2023, the American Heart Association (AHA) released a presidential advisory regarding CKM syndrome, highlighting the interplay between metabolic risk factors, the cardiovascular system, and CKD. This syndrome has a significant impact on morbidity and mortality – poor CKM health, which is prominent among the American population, is associated with increased incidence of cardiovascular disease events.

“CKM syndrome encompasses the entire spectrum of risk, starting from people who have no risk factors or cardiovascular disease, going all the way through 

, vascular risk factors, subclinical disease, and clinical cardiovascular disease,” Janani Rangaswami, MD, professor of medicine at George Washington University and co-chair of the Scientific Advisory Group of the AHA’s presidential advisory on CKM Health, told 

 in an exclusive interview. “In any healthcare setting, the interplay between cardiology, nephrology, and endocrinology is the bulk of practice. In my practice, when I see individuals with kidney disease, diabetes alone is responsible for close to 50% of the cause of that kidney disease. When you add in obesity, metabolic dysfunction, and hypertension, all of these come together very heavily.”

Semaglutide’s approval for CKD effectively provided a bridge between all 3 specialties. When coupled with its initial diabetes indications and its cardioprotective effect, the drug was approved to tackle CKM syndrome on all fronts. Additionally, semaglutide’s efficacy when combined with SGLT2 inhibitors and RAAS blockade in patients with both CKD and high cardiovascular risk made it an effective tool for bolstering the protective effects of existing therapies. In this collaborative space between cardiology and nephrology, semaglutide became something of a miracle drug.

“While GLPs like semaglutide are very effective for A1c management and weight management, the FLOW trial really showed that this therapy saved lives, hearts, and kidneys,” Rangaswami said. “So now these therapies do multiple things; they’re addressing everything from improving lifespan to improving health outcomes, heart and kidney, and even beyond.”

The Bilateral Relationship Of CKD and Obesity

CKD remains one of the most common and serious complications of T2D, with obesity increasingly shaping disease trajectory, transplant eligibility, and therapeutic decision-making.

As global rates of obesity and CKD continue to climb, clinicians are paying closer attention to how excess adiposity directly affects renal physiology, independent of diabetes and hypertension.

“In obesity, metabolic demands increase, so the kidneys have to increase glomerular filtration rate and renal plasma flow to meet those demands. If nephron number is already reduced, the remaining nephrons have to work even harder. That leads to increased pressure inside each nephron, which causes barotrauma, scarring, and increased urine protein excretion,” explained Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of 

. “Severe obesity can also directly contribute to nephron loss through inflammatory effects. Often, obesity is accompanied by diabetes and hypertension, which further accelerate kidney disease progression.”

At BMI levels >40, systemic inflammation rises, adipokine signaling alters renal hemodynamics, and insulin resistance further increases glomerular stress. These processes frequently coexist with hypertension and T2D, amplifying cumulative kidney injury.

Despite this convergence of risk factors, CKD is often managed reactively rather than proactively. By the time patients reach end-stage kidney disease (ESKD) and require maintenance dialysis, obesity can create additional barriers to transplantation because of higher perioperative and postoperative complication risks. Increasingly, clinicians are focused on intervening earlier in the disease course.

In this landscape, GLP-1 agonists have emerged as a treatment strategy for patients with CKD and T2D, especially as a anti-imflammatory marker.

Subsequent research has shown an association of persistent low‑grade inflammation with worsened clinical outcomes in CKD, including faster eGFR decline, higher cardiovascular risk, and increased all‑cause mortality. Additionally, inflammation is a driving factor in the development and progression of T2D and its complications.

The reduction of inflammatory markers, such as CRP, has been highlighted as a potential clinical strategy to protect kidney function. In turn, semaglutide has been associated with reductions in CRP and other inflammatory markers independent of glycemic effects.

“GLP-1 receptor agonists have become another pillar we can use for people with chronic kidney disease. I see them being used as an adjunct to other medications, such as SGLT2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists. Especially when used in conjunction with those therapies, I think they have kidney benefits,” said Kramer. “They reduce urine albumin-to-creatinine ratios. If patients lose weight, we improve blood pressure control. If they have type 2 diabetes, glucose control improves. All of those factors help slow kidney disease progression, so I think GLP-1 receptor agonists are a great addition to our existing armamentarium.”

Where Obesity, CKD, and T2D Intersect with Semaglutide: The FLOW Trial

The approval for semaglutide for patients with T2D and CKD was based on data from FLOW, a phase 3b, multinational, parallel-group, double-blind, randomized, placebo-controlled trial investigating the effects of 1.0 mg once weekly semaglutide, a once-weekly GLP-1RA, on kidney outcomes in participants with CKD and T2D.

“I think it has largely removed the uncertainty that once existed around the effects of GLP-1 receptor agonists on kidney function and has clearly demonstrated that these agents are kidney-protective,” FLOW study investigator, Vlado Perkovic, MBBS, PhD, and provost at the University of New South Wales, told 

 “That, in turn, has informed guideline updates and helped the clinical community accept GLP-1 receptor agonists as a fourth pillar of care for people with diabetic kidney disease. That is a major advance.”

FLOW included 3533 participants with T2D and CKD, with the composite primary endpoint being time to first kidney failure, defined as persistent eGFR <15 ml/min/1.73 m2 or initiation of chronic kidney replacement therapy, persistent ≥50% reduction in eGFR, or death from kidney or cardiovascular causes.

Over a median follow-up of 3.4 years, semaglutide reduced the risk of a primary outcome event by 24% compared with placebo (331 vs 410 first events; HR, 0.76; 95% CI, 0.66-0.88; P = .0003). Similar reductions were observed for the kidney-specific composite (HR, 0.79; 95% CI, 0.66-0.94) and cardiovascular death (HR, 0.71; 95% CI, 0.56-0.89).

All confirmatory secondary outcomes favored semaglutide, including a slower annual decline in eGFR (difference, 1.16 mL/min/1.73 m²; P <.001), an 18% reduction in major cardiovascular events (HR, 0.82; 95% CI, 0.68-0.98; P = .029), and a 20% lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.67-0.95; P = .01). Serious adverse events occurred in 49.6% of the semaglutide group versus 53.8% with placebo.

Beyond Weight Loss: Inflammation and Future Directions of Semaglutide

Perkovic emphasized that FLOW was not intended to be a weight-loss trial, with a broad range of BMIs among participants, including 25% with BMI <27. While GLP-1 receptor agonists, especially semaglutide and emerging combination therapies, present efficacy regarding weight loss, FLOW indicated semaglutide’s specific kidney benefits not simply attributable to obesity treatment.

However, Perkovic also remarked on patterns from the FLOW trial’s participant population, where the mean BMI was 32. Additionally, in the CREDENCE trial, which also evaluated patients with T2D and CKD, the mean BMI was 31. This highlights obesity as a prevalent, rather than incidental, comorbidity in contemporary CKD populations. Taken together, these findings underscore the importance of considering body weight as a core component of CKD risk assessment, rather than a secondary concern.

“What that tells us is that people with diabetes and kidney disease are, on average, significantly overweight and often fall into the obese category. Many of these patients are therefore likely to benefit from weight loss as well,” explained Perkovic. “These therapies address multiple, parallel pathologies that commonly coexist in our patients, which makes them particularly exciting. It also raises the question of whether more potent agents that induce greater weight loss might confer additional kidney benefits, something that still needs to be tested.”

As obesity, T2D, and CKD increasingly converge in clinical practice, therapies capable of targeting overlapping metabolic, hemodynamic, and inflammatory pathways may redefine standard care. For clinicians managing complex kidney disease populations, GLP-1 receptor agonists now represent not simply a metabolic adjunct, but a foundational component of comprehensive CKD risk reduction.

Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others.

Rangaswami reports relevant disclosures with the Veterans Health Administration, Boehringer Ingelheim, Bayer, Procyrion, and the American Heart Association.

Kramer reports relevant disclosures with Bayer, Alexion, American Journal of Kidney Disease, National Kidney Foundation, and others.

Perkovic reports relevant disclosures with AstraZeneca, Bayer, Boehringer Ingelheim, and others.

Novo Nordisk. Novo Nordisk Receives FDA Approval of OZEMPIC (semaglutide) Injection For the Treatment of Adults with Type 2 Diabetes. 

. December 5, 2017. Accessed February 19, 2026. 

https://www.prnewswire.com/news-releases/novo-nordisk-receives-fda-approval-of-ozempic-semaglutide-injection-for-the-treatment-of-adults-with-type-2-diabetes-300567052.html

Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. 

Novo Nordisk. FDA approves Ozempic for cardiovascular risk reduction in adults with type 2 diabetes and known heart disease, updates Rybelsus label. 

. January 16, 2020. Accessed February 19, 2026. 

https://www.prnewswire.com/news-releases/fda-approves-ozempic-for-cardiovascular-risk-reduction-in-adults-with-type-2-diabetes-and-known-heart-disease-updates-rybelsus-label-300988672.html

Anderer S. FDA approves semaglutide to reduce risk of kidney disease progression. 

Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: A presidential advisory from the American Heart Association. 

Furth SL, Colhoun HM, Kanbay M, et al. The relationship between obesity and chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. 

. Published online September 2025:S0085-2538(25)007744. doi:

https://doi.org/10.1016/j.kint.2025.09.019

Good PI, Li L, Hurst HA, et al. Low nephron endowment increases susceptibility to renal stress and chronic kidney disease. 

https://doi.org/10.1172/jci.insight.161316

Wang H, Fan K, Ning Y, et al. Hypertension and BMI as Mediators of Type 2 Diabetes-Induced CKD: Insights from an Integrative Multi-Database Study. 

Perkovic V. Inflammation Emerges as Promising CKD Treatment Target, With Vlado Perkovic, MBBS, PhD. HCPLive. Published February 9, 2026. Accessed February 20, 2026. 

https://www.hcplive.com/view/inflammation-emerges-as-promising-ckd-treatment-target

Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. 

Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. 

Pruijm M, Belmar N, Bjornstad P, et al. REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. 

https://doi.org/10.1016/j.kint.2025.10.005

Articles

Semaglutide has expanded from a T2D glycemic agent to a cardio-kidney-metabolic therapy, culminating in FDA approval for reducing CKD progression, kidney failure, and CV death in T2D with CKD. Cross-specialty adoption is accelerating, reshaping guideline positioning alongside SGLT2 inhibitors and enabling combination strategies with RAAS blockade and nsMRAs. Obesity is increasingly recognized as a direct mediator of renal injury via hyperfiltration, inflammation, and nephron stress, influencing progression and transplant candidacy. FLOW established kidney and survival benefits beyond weight loss.

1 year into real-world use, 4 clinicians discuss how semaglutide is transforming the endocrinology, nephrology, and cardiology landscape.


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Type 2 Diabetes

Strategic Alliance Partnership

1 Year After CKD Approval, Semaglutide Transforms Diabetes, Kidney, and Heart Care

Ron Vender, MD, is a dermatologist in Hamilton, Ontario, and is the founder and director of Dermatrials Research Incorporated and Venderm Consulting Inc. He is also an associate clinical professor at McMaster University in the Department of Medicine, Division of Dermatology.

3-Year Patient-Reported Psoriasis Outcomes for Bimekizumab, With Ron Vender, MD

 emphasizing that its design reflects the types of patients dermatologists see in everyday clinical practice.

In this interview, Vender noted that the study’s head-to-head comparison of bimekizumab, a dual interleukin (IL)-17A and IL-17F inhibitor, with secukinumab, an established IL-17A inhibitor, provides meaningful informtion beyond traditional efficacy endpoints.

“This paper in particular was looking at patient reported outcomes in that and not necessarily efficacy in terms of [body surface area] or [Psoriasis Area and Severity Index], but we, of course, we did look at that as well,” Vender explained.

While PASI and body surface area (BSA) outcomes remain important, Vender stressed that the most compelling aspect of this analysis was its focus on patient-reported outcomes (PROs). According to Vender, rapid relief of symptoms is critical in psoriasis management. He pointed to data showing improvements in itch, skin pain, and scaling as early as the 4-week mark with bimekizumab use.

Vender underscored early attainment of PASI 0 alongside a Dermatology Life Quality Index (DLQI) score of 0 or 1 reflects not just clearance of skin, but meaningful quality-of-life improvement. At a single year and extending through 3 years, Vender emphasized the durability of patients’ responses. He acknowledged clinicians often express concern about loss of efficacy over time with biologic therapies, but the sustained symptom resolution and maintained low DLQI scores observed with continued bimekizumab therapy address that concern.

Importantly, he also discussed the subgroup of patients who switched from secukinumab to bimekizumab during the open-label extension. These patients experienced additional improvements after switching, suggesting that dual IL-17A/F inhibition may provide incremental benefit for certain individuals. However, Vender was careful to note that secukinumab remains an effective and widely used therapy; the findings represent comparative gains rather than shortcomings.

Overall, Vender framed the data as reinforcing the importance of considering both rapidity and durability of patient-centered outcomes when selecting biologic therapy for moderate to severe plaque psoriasis.

The quotes used in this summary were edited for clarity.

Vender reported support from AbbVie, Alumis, Amgen, Arcutis, Bausch, Bristol Myers Squibb, Celltrion, JAMP, Janssen, Leo, Lilly, Meiji, Novartis, Organon, Orka, Sandoz, Sun, Takeda, and UCB.

Augustin M, Feldman SR, Warren RB, et al. Three-Year Patient-Reported Outcomes From Bimekizumab for Plaque Psoriasis: The BE RADIANT Randomized Clinical Trial With Open-Label Extension. JAMA Dermatol. Published online February 18, 2026. 

Smith T. BE RADIANT Trial: Bimekizumab Effective for Psoriasis After 3 Years of Use. HCPLive. February 19, 2026. Accessed February 20, 2026. 

https://www.hcplive.com/view/be-radiant-trial-bimekizumab-effective-psoriasis-after-3-years-use

Videos

This interview with Vender highlights recent findings on patient-reported outcomes (PROs) in patients in the BE RADIANT trial with psoriasis.

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

Real-World Upadacitinib Results in Ulcerative Colitis

New interim data from the ongoing PROFUNDUS study, presented at the European Crohn’s and Colitis Organisation Congress, provide important real-world insight into the effectiveness and safety of upadacitinib (Rinvoq) in patients with moderate-to-severe ulcerative colitis (UC).

While randomized controlled trials established the drug’s efficacy under tightly controlled conditions, the PROFUNDUS findings help clarify how those results translate into everyday clinical practice.

, Remo Panaccione, MD, director of the inflammatory bowel disease unit at the University of Calgary, explained that randomized controlled trials rely on strict inclusion and exclusion criteria, often excluding the complex patients physicians routinely encounter. Real-world studies like PROFUNDUS, by contrast, include patients with diverse comorbidities, varied steroid tapering approaches, and heterogeneous prior treatment histories.

“When we complement those findings from the randomized controlled trials with real world evidence, if we see that the response rates and remission rates that we're seeing in the clinical trials hold up in the real world in these complex settings, it gives us a lot more confidence that the trial results are valid and that they can be translated into our clinical practice,” Panaccione explained. “Plus, it gives us that experience in those patients that are not necessarily included in the clinical trials.”

The interim analysis evaluated 494 of the first 500 eligible adult patients (aged 18-79 years) with moderate-to-severe UC who initiated once-daily upadacitinib across 16 countries, per investigator discretion and according to the local label. Induction was initiated with the first dose of upadacitinib 45 mg at the beginning of the study. Maintenance was initiated with the start of upadacitinib 15 mg or upadacitinib 30 mg after completion of the induction phase.

Assessed endpoints included clinical response per Partial Adapted Mayo Score (PAMS), corticosteroid (CS)-free response per PAMS, clinical remission per Partial Mayo Score (PMS), absence of abdominal pain, and absence of bowel urgency at week 26.

Among the overall population at week 26, with any upadacitinib dose, 81.8% of patients achieved clinical response, 72.4% clinical remission, 66.3% no abdominal pain, and 71.9% no bowel urgency. Among those on baseline CS, 64.4% attained CS-free response. Of note, similar results were observed for all endpoints, regardless of advanced therapy status.

Among patients treated with upadacitinib induction/maintenance) at either 45/15 mg, 45/30 mg, or any upadacitinib dose, adverse event (AE) were 66.0%, 50.8%, and 51.4%, respectively. Serious AEs were 3.8%, 4.6%, and 5.7%, and severe AEs were 5.7%, 4.0%, and 5.5%. Within the subgroup of patients who experienced TEAEs potentially related to upadacitinib, as assessed by the study investigator, exhibited serious and severe AEs at 3.6%, 6.3%, 6.9%, and 7.1%, 5.4%, 6.9%, respectively.

Panaccione called attention to the consistency of the results across advanced therapy–naïve and experienced populations. Of note, in October 2025, the US Food and Drug Administration approved an updated indication statement for upadacitinib for the treatment of adults with moderately to severely active UC and moderately to severely active Crohn's disease (CD), allowing the use of upadacitinib for patients with moderately to severely active UC or CD after they have received ≥ 1 approved systemic therapy in the event tumor necrosis factor (TNF) blockers are clinically inadvisable. Previously upadacitinib was only indicated for adults who had an inadequate response or intolerance to ≥ 1 blockers.

“This data from the real world studies allows physicians to feel very confident that they can position upadacidinib in different patient populations,” Panaccione said.

Editors’ Note: Panaccione reports relevant disclosures with Abbott, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Janssen, Lilly, Novartis, Takeda, and others.

R Panaccione, M Fumery, D Bettenworth, S Danese, P Morisset, M Mallick, S H Chen, J Kim, S Suravaram, G Parkes, P1073 Real-World Effectiveness, Symptomatic Improvement, and Safety of Upadacitinib in Patients With Moderate-to-Severe Ulcerative Colitis: Interim Findings From the PROFUNDUS Study, 

, Volume 20, Issue Supplement_1, January 2026, jjaf231.1254, 

https://doi.org/10.1093/ecco-jcc/jjaf231.1254

Brooks A. FDA Approves Updated Indication for Upadacitinib (Rinvoq) in IBD. HCPLive. October 13, 2025. Accessed February 20, 2026. 

https://www.hcplive.com/view/fda-approves-updated-indication-for-upadacitinib-rinvoq-in-ibd

Panaccione recaps interim PROFUNDUS data showing real-world efficacy and safety of upadacitinib (Rinvoq) for ulcerative colitis.

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PROFUNDUS: Real-World Outcomes With Upadacitinib in Ulcerative Colitis, With Remo Panaccione, MD

Chelsie Derman is an associate editor for 

who covers psychiatry, sleep medicine, geriatrics, migraine, and allergy. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

A randomized, placebo-controlled phase 2a trial evaluating SPL026, an intravenous formulation of dimethyltryptamine (DMT), met its primary endpoint in adults with moderate-to-severe 

, demonstrating a statistically significant reduction in depressive symptoms at 2 weeks compared with placebo. The findings represent one of the first controlled trials of a short-acting psychedelic in MDD.

 SPL026 (intravenous dimethyltryptamine, DMT)

 Short-acting serotonergic agonist; 5-HT2A receptor agonist

 Moderate-to-severe major depressive disorder

 –7.35 MADRS point difference vs placebo at Week 2 (

 (≥50% MADRS reduction at Week 2): 35% vs 12%

 No treatment-related serious adverse events reported

 SPL026 not advancing; informing HLP004 Phase 2 GAD program

“We have shown that a single dose of SPL026 is safe, effective and durable, with treatment effects comparable to other promising interventional treatments often requiring much longer treatment sessions,” lead investigator David Erritzoe, MD, PhD, from Imperial’s Department of Brain Sciences, said in a statement, “Although such early trial results should always be interpreted with some caution, these data show the promise of DMT as a potentially more cost-effective treatment for clinical depression than related serotonergic agonists with longer psychoactive action due to the shorter dosing sessions.”

SPL026 is an intravenous formulation of DMT, a short-acting serotonergic psychedelic that acts primarily as a 5-HT2A receptor agonist. Unlike psilocybin, which typically produces psychoactive effects lasting 4 to 6 hours, intravenous DMT has a substantially shorter duration of acute subjective effects, often less than 30 minutes.

In the double-blind stage of the study, a single 21.5-mg intravenous infusion of SPL026 administered over 10 minutes resulted in a mean difference of –7.35 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) at week 2 compared with placebo (95% CI, –13.62 to –1.08; 

=.023). Treatment effects were detectable as early as week 1, with a mean difference of –10.75 points (95% CI, –16.95 to –4.55; 

 =.002). Response rates, defined as ≥5 0% reduction in MADRS score at week 2, were 35% in the SPL026 arm versus 12% with placebo. Remission rates (MADRS ≤ 10) were 29% vs12%, respectively.

The study enrolled 34 participants (mean age 32.8 years; 29.4% female; predominantly White) with a mean depression duration of 10.5 years. Participants were randomized 1:1 to receive SPL026 (n = 17) or placebo (n = 17) in conjunction with supportive psychotherapy that included preparation and integration sessions. The primary endpoint was the change in MADRS score from baseline to week 2.

In an open-label extension, all participants were eligible to receive SPL026 2 weeks after the initial dose, with antidepressant effects reported as persisting up to 3 months post–first dose. Some participants reportedly maintained benefits up to 6 months, although detailed long-term subgroup data were not announced. The therapy was generally well tolerated, with no reports of treatment-related serious adverse events.

Although SPL026 demonstrated proof-of-concept efficacy, Helus Pharma indicated it is not advancing the intravenous formulation in its current form. Instead, mechanistic and clinical insights from the trial are informing the development of HLP004, a proprietary novel serotonergic agonist under investigation for generalized anxiety disorder (GAD), with phase 2 topline data anticipated in the first quarter of 2026. The company is also advancing HLP003 in phase 3 development as adjunctive therapy for MDD; that program has received Breakthrough Therapy designation from the FDA.

“This publication represents an important validation of short-acting serotonergic agonists as a clinically meaningful approach in mental health treatments,” said Michael Cola, chief executive officer of Helus Pharma, in a statement. “The findings provide clinical proof-of-concept for short-acting serotonergic modulation and further support our conviction that our novel serotonergic agonist molecules, such as HLP004, can potentially deliver meaningful outcomes with greater consistency and commercial feasibility. We look forward to reporting topline data from our Phase 2 study of HLP004 in generalized anxiety disorder later this quarter.”

Nature Medicine Publishes Helus Pharma’s Randomized, Placebo-Controlled Phase 2a Trial of SPL026 in Major Depressive Disorder. Helus Phama. Published on February 17, 2026. Accessed on February 19, 2026. 

https://www.globenewswire.com/news-release/2026/02/17/3239141/0/en/Nature-Medicine-Publishes-Helus-Pharma-s-Randomized-Placebo-Controlled-Phase-2a-Trial-of-SPL026-in-Major-Depressive-Disorder.html

A single 21.5-mg IV infusion of SPL026 (DMT) plus supportive psychotherapy produced a statistically significant and clinically meaningful MADRS reduction versus placebo in moderate-to-severe MDD, with separation by week 1 and sustained benefit at week 2. Acute psychoactive effects were brief (<30 minutes), supporting a shorter-session psychedelic model. In 34 participants, response and remission rates favored SPL026, and tolerability was acceptable without treatment-related serious adverse events. Despite proof-of-concept efficacy, development is shifting toward next-generation serotonergic agonists.

A phase 2a randomized, placebo-controlled study shows –7.35 MADRS difference at 2 weeks with SPL026 compared with placebo. However, the study is not advancing.


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Intravenous DMT (SPL026) Demonstrates Significant MDD Reduction in Phase 2a Trial

Andres Hurtado-Lorenzo, PhD, is VP of IBD Ventures and Translational Research at the Crohn’s & Colitis Foundation.

Intermittent Fasting for Crohn’s Disease? New Clinical Trial Explained

Interest in dietary management of Crohn’s disease has long focused on identifying specific foods that trigger symptoms or promote remission, but a growing body of research is expanding that conversation beyond food composition alone. Increasingly, investigators are examining whether meal timing may influence inflammation, metabolic health, and the gut microbiome in patients with inflammatory bowel disease.

In a recent randomized clinical trial published in 

, researchers evaluated time-restricted feeding as a complementary strategy in adults with Crohn’s disease, adding new rigor to a field eager for validated lifestyle interventions.

In discussing the findings, Andres Hurtado-Lorenzo, PhD, VP of IBD Ventures and Translational Research at the Crohn’s & Colitis Foundation, emphasized that traditional dietary strategies in Crohn’s disease have largely focused on what patients should eat. While he says that food quality remains central, emerging science now suggests that when people eat may be equally important.

“Multiple studies in the context of other diseases have shown that meal timing can independently influence circadian regulated immune and metabolic pathways, microbial balance and adipose tissue biology, even without changes in calorie intake or nutrient composition,” Hurtado-Lorenzo explained. “In Crohn's disease, the intersection of chronic immune dysregulation, disturbances in gut microbiota, and high prevalence of overweight and obesity establishes a strong case for examining time based dietary interventions such as intermittent fasting.”

The 12-week randomized controlled trial evaluated the effects of a 16:8 time-restricted feeding protocol, in which participants fasted for 16 hours and consumed all meals within an 8-hour window. Investigators assessed the impact on clinical disease activity, body composition, and systemic inflammation in adults with Crohn’s in clinical remission and overweight or obesity.

Results showed that over 12 weeks, BMI decreased significantly in the time-restricted feeding group compared with controls (Δ –0.9 ± 0.03 kg/m2 vs +0.6 ± 0.3 kg/m2; 

 <.001). Energy intake and diet quality (Mediterranean Diet Index) did not differ between groups or across time, suggesting BMI reduction occurred independent of caloric restriction and diet quality.

Clinical disease activity as measured by the Harvey–Bradshaw Index also improved significantly in the time-restricted feeding group (Δ –2 ± 4 vs –0.5 ± 2; 

 = .02), with a 40% decrease in stool frequency and 50% reduction in abdominal discomfort, which was not observed in controls.

Additionally, compared with controls, the time-restricted feeding group exhibited significant reductions in serum adipokines, including leptin, plasminogen activator inhibitor-1, and adipsin (all, 

 < .05). Further analysis revealed ​​greater BMI loss correlated positively with both anti-inflammatory cytokines (interleukin [IL]1RA, IL4; 

 = 0.78) and pro-inflammatory cytokines (IL2, IL12p40, IL12p70; 

Hurtado-Lorenzo pointed to the magnitude and speed of change as being among the most striking findings from the study. From a mechanistic standpoint, he outlined 2 primary processes underlying these effects, metabolic remodeling and autophagy, and further hypothesized that fasting-induced autophagy could play a therapeutic role in Crohn’s due to its potential contribution to disease pathogenesis.

“Importantly, this is the first randomized clinical trial to demonstrate a benefit of intermittent fasting in patients with Crohn's disease, providing rigorous evidence in the field that is hungry for validated lifestyle strategies,” Hurtado-Lorenzo said. “In my opinion, this approach meets a real clinical need of sustaining remission by offering a practical solution in synergy with pharmacological treatment strategies for Crohn's disease.”

Crohn’s & Colitis Foundation of America. Intermittent fasting cut Crohn’s disease activity by 40% and halved inflammation in randomized clinical trial. February 9, 2026. Accessed February 19, 2026. 

https://www.eurekalert.org/news-releases/1114988

Haskey N, Ye J, Lewis A, Yousuf M, Reimer RA, Raman M. Time-Restricted Feeding Reduces Body Mass Index, Visceral Adiposity, Systemic Inflammation, and Clinical Disease Activity in Adults With Crohn's Disease: A Randomized Controlled Study. 

. Published online February 9, 2026. doi:10.1053/j.gastro.2025.11.008

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