Peptide Clinical Trial News

A case report published in Nature Communications suggests that the peptide derivative acetyl-DL-leucine (ADLL) may modify the progression of prodromal Parkinson's disease. In two patients with isolated REM sleep behavior disorder (iRBD), long-term treatment with ADLL not only reduced sleep symptoms but also appeared to reverse the loss of dopamine transporter binding in the brain. These findings indicate that ADLL could potentially slow or stabilize neurodegeneration associated with Parkinson's.

Data from the INHALE-1 trial presented at the American Diabetes Association Scientific Sessions indicates that MannKind’s Technosphere insulin (Afrezza) is a safe and effective alternative to injected rapid-acting analogs for children and adolescents with diabetes. The study found that the inhaled formulation achieved similar HbA1c reductions to standard care while resulting in less weight gain and higher patient satisfaction scores.

A new Lancet commission report proposes reframing obesity as a distinct disease spectrum divided into 'preclinical' and 'clinical' stages, moving beyond reliance on BMI. This diagnostic shift aligns with recent FDA guidance prioritizing pharmacological treatments, such as GLP-1 receptor agonists, over lifestyle changes alone. The reclassification aims to improve clinical decision-making regarding which patients require medical intervention for organ dysfunction caused by excess adiposity.

STAT columnist Adam Feuerstein analyzes new clinical data for ImmunityBio's cancer drug Anktiva, arguing that the results contradict founder Patrick Soon-Shiong's claims of survival benefits in advanced lung cancer patients. The article highlights the drug's modest commercial performance for bladder cancer and notes the recent approval of a superior competitor by Johnson & Johnson.

Opus Genetics is advancing clinical programs for inherited retinal diseases, specifically targeting LCA5 and BEST1 mutations. The company recently announced FDA alignment on a Phase 3 trial design for OPGx-LCA5 and provided a timeline for OPGx-BEST1 results. These gene therapy programs aim to address the underlying genetic causes of rare vision loss.

A secondary analysis of a long-term clinical trial published in the Annals of Internal Medicine indicates that bariatric surgery outperforms medical therapy, including GLP-1 drugs, for treating type 2 diabetes and obesity across diverse income levels. The research found that surgery led to superior outcomes in blood glucose control, weight loss, and diabetes remission regardless of social determinants of health. While acknowledging the rapid evolution of more potent obesity medications, the authors maintain that metabolic surgery remains an effective and underutilized durable solution.

Eli Lilly announced that its obesity drug Zepbound (tirzepatide) significantly reduced the risk of heart complications and improved symptoms in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. In a Phase 3 trial, the drug lowered the risk of hospitalization or worsening heart failure by 38% over two years compared to a placebo. These results position Zepbound as the second GLP-1-based therapy to demonstrate cardiovascular benefits in this specific patient population.

Doctors in Brazil are utilizing sterilized tilapia skin as a biological bandage for second- and third-degree burns. The treatment was developed to address a shortage of human and pig skin banks in the country. Analysis revealed that tilapia skin contains high levels of collagen types 1 and 3, proteins essential for scarring, which exist in greater quantities in the fish skin than in human skin.

Pharmability has received regulatory approval from the Swedish Medical Products Agency to initiate a Phase Ib clinical trial for its lead candidate, TIR-C, targeting atopic dermatitis. This first-in-human study, to be conducted in Sweden, is designed to evaluate the safety and tolerability of the peptide drug while also exploring early efficacy signals. The transition to clinical testing marks a significant milestone for the company after several years of preclinical development.

Eli Lilly reported that combining Zepbound (tirzepatide) with the immunology drug Taltz improved symptoms in obese patients with psoriatic arthritis compared to Taltz alone. The findings suggest the GLP-1 drug may have benefits beyond weight loss, potentially aiding those with autoimmune joint pain. Despite the positive data, the drug's prescribing patterns are likely to remain driven by its primary weight loss indications.

Pfizer has advanced its obesity strategy by reporting positive mid-stage clinical results for a long-acting version of the oral peptide danuglipron. Acquired through the purchase of biotech firm Metsera, the therapy is being developed as a once-monthly injection to help patients maintain weight loss. Despite the clinical milestone, investor sentiment cooled as the market awaits detailed comparisons to current market leaders.

Vertex Pharmaceuticals has released clinical data for suzetrigine (VX-548), a novel non-opioid pain treatment. The drug met primary endpoints in acute pain trials but failed to outperform placebo in a study for sciatica. Despite the mixed results, Vertex is moving forward with regulatory submissions, positioning the molecule as a potential alternative to opioids.

Elicio Therapeutics announced that the Phase 2 AMPLIFY-7P study of ELI-002 7P in adjuvant pancreatic cancer did not meet its primary endpoint of disease-free survival (DFS) in the overall intent-to-treat population. However, the company attributes this failure to an imbalance in high-risk patients with residual disease (R1 resection) in the treatment arm. In a post-hoc analysis of patients with complete tumor resection (R0), the peptide vaccine demonstrated a statistically significant improvement in DFS and a strong correlation between mutant KRAS-specific T cell responses and survival.

Preliminary results from a Phase 1/2 study presented at ESMO GI 2026 evaluate the safety and efficacy of zoldonrasib (RMC-9805) combined with chemotherapy for first-line treatment of RAS G12D-mutated metastatic pancreatic adenocarcinoma. Zoldonrasib is an oral, selective inhibitor designed to target the RAS G12D mutation, which occurs in approximately 40% of pancreatic cancer cases and currently lacks approved targeted therapies. The study assesses the drug in combination with standard regimens like mFOLFIRINOX or gemcitabine/nab-paclitaxel.

OS Animal Health is developing OST-HER2, an immunotherapy for canine osteosarcoma that utilizes a bioengineered Listeria vector to target the HER2 protein. In a Phase 2 trial, the combination of OST-HER2 and radiation significantly improved survival rates compared to radiation alone, with a 2-year survival rate of 20% versus 1%. The company is currently engaging in a 'test the waters' campaign under Regulation Crowdfunding to gauge investor interest.

The FLOW trial (Perkovic et al., NEJM 2024) established that once-weekly semaglutide significantly reduces the risk of clinically important kidney outcomes and cardiovascular death in adults with type 2 diabetes and chronic kidney disease (CKD) - the first GLP-1 receptor agonist to demonstrate dedicated renal-protection benefit at this scale. The trial was stopped early for efficacy because the benefit crossed pre-specified thresholds. The results have driven updates to kidney-disease treatment guidelines and expanded the cardiometabolic case for GLP-1 peptide therapy well beyond weight and glycemic control.

Boehringer Ingelheim and Zealand Pharma's survodutide - a dual glucagon/GLP-1 receptor agonist - produced up to 16.6% mean weight loss at 76 weeks in the phase 3 SYNCHRONIZE-1 obesity trial, with a striking 34% reduction in visceral fat and a 63% reduction in liver fat versus 25% on placebo. Roughly 85% of treated patients achieved at least 5% weight loss. Published in Diabetes, Obesity and Metabolism (Wharton et al., 2025), the data differentiate survodutide on body-composition and MASLD (fatty liver) benefits rather than raw weight-loss magnitude, where it trails the triple-agonist retatrutide.

Amgen's MariTide (maridebart cafraglutide) - a peptide that both activates GLP-1 and blocks GIP receptors, designed for once-monthly dosing - produced up to roughly 20% average weight loss at 52 weeks in a phase 2 trial in adults with obesity, with or without type 2 diabetes, results published in the New England Journal of Medicine (Jastreboff et al., 2025). Notably, weight reduction had not plateaued at 52 weeks, implying further loss with continued treatment. The novel mechanism (GLP-1 agonism plus GIP antagonism, rather than dual agonism) and monthly schedule differentiate MariTide in a crowded obesity pipeline; phase 3 MARITIME studies are now underway.

Eli Lilly's orforglipron - a once-daily, small-molecule oral GLP-1 receptor agonist (no injection, no peptide backbone) - met its primary endpoint in the phase 3 ATTAIN-1 obesity trial, with the 36 mg dose producing 12.4% mean weight loss (~27 lb) at 72 weeks in 3,127 adults. Nearly 60% of participants on that dose lost at least 10% of body weight and ~40% lost at least 15%, with cardiometabolic improvements, results published in the New England Journal of Medicine. A parallel type-2-diabetes trial (ATTAIN-2, Lancet) confirmed statistically superior weight reduction versus placebo. While the magnitude trails injectable leaders tirzepatide and retatrutide, orforglipron is the first oral GLP-1 with phase 3 efficacy approaching the injectable class.

The amylin/GLP-1 combination CagriSema - Novo Nordisk's cagrilintide paired with semaglutide - achieved 22.7% mean weight loss at 68 weeks in the phase 3a REDEFINE 1 trial in adults with overweight or obesity, published in the New England Journal of Medicine (Davies et al., 2025). Roughly 40% of CagriSema-treated participants lost at least 25% of body weight, and the combination beat both semaglutide and cagrilintide alone. In REDEFINE 2 (type 2 diabetes) the regimen delivered up to a 1.91 percentage-point HbA1c reduction. A head-to-head (REDEFINE 4) showed CagriSema (23.0%) slightly trailing tirzepatide (25.5%), clarifying the competitive ordering at the top of the obesity market.

Eli Lilly's retatrutide - a first-in-class triple GLP-1/GIP/glucagon receptor agonist - delivered bariatric-surgery-level weight loss across its phase 3 TRIUMPH program in obesity and type 2 diabetes, with the 12 mg dose achieving roughly 28.7% mean weight reduction at 68 weeks and about 30.3% (~85 lb) in a pre-specified 104-week extension with no plateau. In TRANSCEND-T2D-1, retatrutide cut HbA1c by 1.7-2.0 percentage points at 40 weeks, and up to 68% of participants hit the composite of A1c <=6.5% plus >=10% weight loss. The data position retatrutide at the top of the obesity efficacy ladder, ahead of tirzepatide and semaglutide, pending regulatory filings.

Novo Nordisk's experimental combination therapy CagriSema demonstrated superior weight loss and blood sugar control compared to semaglutide alone in a Phase 3 trial. The drug combines the GLP-1 agonist semaglutide with cagrilintide, an amylin receptor agonist, resulting in a 14.2% reduction in body weight over 68 weeks. These results suggest a potential new standard for treating type 2 diabetes and obesity.

Novo Nordisk's amycretin, a long-acting GLP-1 and amylin receptor agonist, demonstrated significant weight loss and a tolerable safety profile in a Phase 1b/2a trial. The study tested both single and multiple ascending doses, with the highest dose cohort achieving substantial reductions in body weight over 36 weeks. Gastrointestinal issues were the most common side effects, but no unexpected safety concerns were reported.

Eli Lilly's investigational amylin receptor agonist, eloralintide, demonstrated 'clinically meaningful' weight loss in a phase 2 trial. The highest dose achieved up to 20.1% weight reduction at 48 weeks. The drug showed an acceptable tolerability profile, particularly when using dose escalation to mitigate gastrointestinal side effects.

Eli Lilly announced positive Phase 2 results for eloralintide, a selective amylin receptor agonist, showing placebo-adjusted weight loss ranging from 9.1% to 19.7% over 48 weeks. The drug demonstrated a favorable tolerability profile and improvements in cardiometabolic markers. Based on these data, Lilly plans to initiate Phase 3 trials for obesity treatment next month.

A randomized controlled trial of 44 males with abdominal obesity found that a six-week intervention of aerobic-resistance exercise combined with a high-protein, low-glycemic diet significantly reduced levels of the adipokines asprosin and leptin. While exercise alone lowered asprosin concentrations, the addition of the specific diet was required to achieve a statistically significant decrease in leptin and improvements in overall body composition.

Pelage Pharmaceuticals secured $16.75 million in Series A funding to advance PP405, a topical treatment designed to reactivate dormant hair follicle stem cells for androgenetic alopecia. The company reported successful Phase 1 results where the drug met safety endpoints and demonstrated statistically significant stem cell activation after one week of dosing. Pelage plans to initiate a Phase 2a trial in mid-2024 to further evaluate the regenerative therapy.

This retrospective cohort study analyzed electronic health records from UK primary care to compare cardiovascular outcomes in type 2 diabetic patients adding DPP-4 inhibitors to metformin versus those adding sulphonylureas. The research found that the incidence of major adverse cardiovascular events (MACE) and all-cause mortality was statistically similar between the two treatment groups, even after adjusting for various comorbidities. While a potential protective effect was observed for DPP-4 inhibitors in elderly patients with low BMI, the overall data suggests that cardiovascular prognosis should not be the deciding factor when choosing between these two add-on therapies.

A small clinical trial led by Steve Horvath and Greg Fahy demonstrated that a combination of growth hormone, DHEA, and metformin could significantly reverse the epigenetic clock in humans. The treatment reduced the participants' biological age by an average of 2.5 years over a one-year period, marking the first time such a reversal has been shown in a randomized controlled human study.

A clinical trial involving 20 men with erectile dysfunction found that the synthetic peptide Melanotan II, a melanocortin receptor agonist, significantly induced penile erections and increased sexual desire compared to a placebo. While the peptide demonstrated efficacy in initiating erections even without sexual stimulation, treatment was associated with a high frequency of side effects, specifically nausea and yawning.

A speaker at the Heart in Diabetes CME Conference presented evidence that combining GLP-1 receptor agonists with SGLT2 inhibitors may provide additive cardiovascular and renal benefits in type 2 diabetes. A 2025 meta-analysis of 18 cohort studies found lower risks of major adverse cardiovascular events and all-cause mortality with combination therapy versus monotherapy. No formal outcome trial of the combination is expected, so observational data inform current guidance.

A retrospective cohort study presented at ENDO 2026 found adults with type 2 diabetes taking semaglutide had about 15% lower fracture risk than those using other diabetes or weight-loss medications. Researchers, led by Stanford's Sun H. Kim, aimed to determine whether the effect was unique to semaglutide or related to weight-loss differences. The findings follow earlier data showing semaglutide linked to 26% lower fracture risk than sleeve gastrectomy. More research is needed to assess whether other incretin medications confer similar benefits.

Topline results from the STEP Young trial show once-weekly injectable semaglutide (Wegovy) produced greater BMI reductions than placebo in children aged 6 to 11 with obesity. Of children receiving semaglutide, 40.4% were no longer classified as having obesity after 68 weeks, while all placebo participants still met obesity criteria. Safety and tolerability were consistent with prior semaglutide studies.

This article examines the expanding role of GLP-1 receptor agonists in treating metabolic dysfunction-associated steatohepatitis (MASH), particularly in patients with comorbid obesity and type 2 diabetes. Despite the recent FDA approval of a dedicated MASH therapy (resmetirom), experts predict that GLP-1s will inevitably be used in hepatology due to their metabolic benefits. Clinicians emphasize the need for more specific data on liver outcomes, the potential for combination therapies, and the continued importance of lifestyle interventions.

New real-world evidence indicates that tirzepatide significantly reduces the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease. The study, utilizing U.S. claims databases, compared tirzepatide against sitagliptin and found the GLP-1 agonist offered superior protection for heart health. Additionally, the data suggested a decrease in infection-related hospitalizations for patients taking the medication.

A meta-analysis of eight cardiovascular outcomes trials indicates that adults with type 2 diabetes derive cardiovascular benefit from SGLT2 inhibitors and GLP-1 receptor agonists regardless of concurrent insulin use. Researchers found that while baseline insulin use was associated with a higher likelihood of major adverse CV events, the protective effects of these newer drug classes remained significant. Consequently, experts recommend prescribing these therapies as early as possible in the disease course to maximize cardiac protection.

A 12-week randomized clinical trial investigated the effects of 250 mg/day oral nicotinamide mononucleotide (NMN) supplementation on NAD+ metabolism and arterial stiffness in 36 healthy middle-aged adults. Results showed that NMN intake significantly elevated serum nicotinamide levels, indicating increased NAD+ metabolism, and was well tolerated without adverse events. While pulse wave velocity measurements suggested a trend toward reduced arterial stiffness in the NMN group, the difference compared to the placebo group was not statistically significant.