Symlin (pramlintide) / AstraZeneca - LARVOL DELTA

Pramlintide‑expressing stem cell‑derived beta cells limit islet amyloid in a transplantation model of type 1 diabetes (TTS 2026) - "Our data suggest pramlintide expression does not adversely impact maturation and function of SC-β cells and may limit amyloid deposition following transplantation in the eye. Future studies will evaluate the impact of transplanting free or encapsulated pramlintide-expressing SC-β cells in alternate sites, in high-fat diet fed immune-deficient and immune-competent diabetic mice."

Diabetes • Inflammation • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Adjunctive Treatments for Patients with Type 1 Diabetes Using Automated Insulin Delivery Systems. A Narrative Review. (PubMed, Diabetes Technol Ther) - "Similarly, adjunctive treatment with empagliflozin resulted in increased TIR without increase in hypoglycemia, reduction in insulin requirements, and increase in the mean plasma ketone value, although DKA remained rare. However, studies of longer duration with more participants are required to establish the long-term safety and efficacy of these interventions in patients with T1D treated with AID."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Amylin Analogs: The Next Major Class of Weight Loss Therapy: A Review of Experimental Data and Early-Phase Clinical Trials. (PubMed, Diabetes Obes Metab) - "Amylin-based therapies represent a promising addition to the evolving treatment landscape of obesity. Their emerging efficacy as both standalone and combination therapies supports a multi pathway approach to addressing the biological complexity and heterogeneity of the disease."

Journal • Genetic Disorders • Obesity

GA-27: Postprandial Regulation of Bone Perfusion in Healthy Individuals (clinicaltrials.gov) - P=N/A | N=15 | Not yet recruiting | Sponsor: University of Copenhagen

New trial

Long-Acting Amylin Analog Petrelintide Does Not Delay Gastric Emptying (ADA 2026) - P1 | "Introduction and Objective: Native amylin, pramlintide (a short-acting amylin analog) and GLP1 based medications have been shown to delay gastric emptying (GE). Petrelintide does not impact GE either after SD or at steady state in doses up to 9.0 mg. Absence of delayed GE and favorable tolerability profile observed in the phase 1 trials potentially represent a clinically relevant benefit of petrelintide. Phase 2 dose finding trial for weight management is ongoing."

Metabolic Disorders

Fully Closed-Loop Delivery of Ultra-Rapid Insulin Lispro and Pramlintide vs. Carbohydrate Counting in Type 1 Diabetes: A Randomized, Crossover, Noninferiority Trial (ADA 2026) - "Fully automated insulin-and-pramlintide delivery achieved similar glycemic outcomes to HCL therapy with carbohydrate counting, though threshold of statistical noninferiority was not met."

Clinical • Head-to-Head • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

TOTT: Tailoring Obesity Treatment Trial (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: Esbjerg Hospital - University Hospital of Southern Denmark | N=40 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Genetic Disorders • Metabolic Disorders • Obesity

APP: Pancreatic Polypeptide as a Modulator of Amylin- Induced Satiety in Healthy Humans (clinicaltrials.gov) - P=N/A | N=18 | Recruiting | Sponsor: University Hospital, Gentofte, Copenhagen

New trial • Genetic Disorders • Obesity

Metal-tuned antimicrobial peptides and zincophore pathways: from coordination chemistry to targeted therapeutics. (PubMed, J Inorg Biochem) - "Pramlintide and shepherins illustrate Zn(II)-driven conformational change and fibril formation associated with antifungal activity...Finally, thermodynamic and structural studies of fungal zincophores and bacterial periplasmic transporters provide a basis for targeted peptide designs that exploit Zn(II) uptake pathways. Together, these case studies outline mechanism-based design principles for future metal-peptide therapeutics."

Journal • Review

Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. (PubMed, Peptides) - "The first therapeutically useful amylin receptor (AMYR) agonist, pramlintide was based upon the structure of non-aggregating rat amylin and found limited application as an adjunct to insulin therapy...Amongst these agents is the dual AMYR/ calcitonin-receptor (CTR) agonist, cagrilintide that has also been co-formulated into a once weekly subcutaneous injection with the long-acting glucagon-like peptide-1receptor (GLP-1R) agonist, semaglutide (CagriSema)...Several recently developed long-acting amylin analogues have shown strong efficacy as monotherapy in clinical trials: these include eloralintide, petrelintide, Met-233 and AZD6234...Gastrointestinal side effects, especially nausea, similar to those reported for GLP-1R agonists are commonplace during initiation and up-titration of amylin analogues but mostly resolve during continued use. Evidence is emerging that long-acting AMYR agonists may show potential therapeutic benefits in treatment of patients with fatty liver..."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Hypertension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

WAYS TO OVERCOME CHALLENGES IN GLP USE IN TYPE 1 DIABETES (ATTD 2026) - "These include: Metformin,Coleselvelam, Dipeptidyl Peptidase-4 Inhibitors (DPP-IVinhibitors), Sodium-Glucose Cotransporter 2 inhibitors(SGLT-2is), daily or weekly Glucagon-Like Polypeptides(GLPs), with or without Glucose-Dependent InsulinotropicPolypeptide (GIPs)-dual incretin.(11-15) These medicationshave benefits beyond glucose control that include: weightloss, protections from cardiovascular disease (CVD), and diabetickidney disease (DKD)...The only other medication that wasapproved by the Food and Drug Administration (FDA) waspramlintide (Symlin®), which is hardly used in clinical practicebecause of the gastrointestinal (GI) side-effects, frequencyof injections per day and the increased risk of severehypoglycemia and ketosis...Both semaglutide(Ozempic®/Wegovy®, Copenhagen, Denmark) and tirzepatide(Mounjaro®/Zepbound®, Indianapolis, IN) weekly GLPanalogs are the preferred options for use in patients withT1D...There was recent FDA approval..."

Cardiovascular • Chronic Kidney Disease • Constipation • Diabetes • Diabetic Nephropathy • Diabetic Retinopathy • Fibrosis • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Pancreatitis • Renal Disease • Retinal Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • TINCR

The story of amylin: from physiology to therapy. (PubMed, Nat Metab) - "Almost 20 years later, pramlintide, a human amylin analogue, emerged as the first amylin-based drug, approved as an adjunct treatment to insulin for type 1 diabetes (T1D) and type 2 diabetes (T2D)...This Review contextualizes the evolving therapeutic potential of amylin, focusing on recent preclinical and clinical data, amylin receptor pharmacology and its broader biological effects. We discuss the potential and challenges of developing amylin-based treatments for cardiometabolic disease, including milestones in drug development of amylin, and its combination with additional molecules as part of the future landscape of therapies for patients with diabetes or obesity."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

In vitro metabolic profiling of weight-loss-inducing amylin receptor agonists in the context of preventive doping research. (PubMed, J Pharm Biomed Anal) - "This study provides the first systematic metabolic characterization of pramlintide, cagrilintide and KBP-066. The identified metabolites and LC-MS/MS detection approach offer a foundation for future monitoring of emerging weight-loss peptide hormone analogues in anti-doping contexts."

Journal • Preclinical

Systemic Pharmacokinetic Principles of Therapeutic Peptides. (PubMed, Clin Pharmacokinet) - "In summary, our results underscore that the systemic pharmacokinetics of peptide drugs generally follow size-related physiological scaling patterns and provide quantitative tools to facilitate translational assessments in the drug discovery process."

Journal • PK/PD data

Amylin Revisited: A 5-Year Perspective on Its Emerging Role in the Treatment of Diabesity. (PubMed, J Obes Metab Syndr) - "Clinically, the synthetic analog pramlintide has been shown to modestly improve glycemic control and induce weight loss in patients with diabetes. More recently, cagrilintide, a long-acting analog, has produced substantial weight reduction in individuals with obesity. Combination therapy with glucagon like peptide-1 receptor agonists has achieved synergistic effects, with weight loss exceeding 15%, positioning amylin analogs as a promising approach for treatment of diabesity-the co-existence of diabetes and obesity. This review summarizes recent advancements and discusses their implications for future therapeutic applications in diabesity management."

Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Amylin-Induced Migraine Attacks Without Aura (clinicaltrials.gov) - P=N/A | N=21 | Not yet recruiting | Sponsor: Danish Headache Center

New trial • CNS Disorders • Migraine • Pain

Hypersensitivity to Amylin in Post-Traumatic Headache (clinicaltrials.gov) - P=N/A | N=21 | Not yet recruiting | Sponsor: Danish Headache Center

New trial • CNS Disorders • Immunology • Migraine • Pain

Comparison of functional responses to CGRP and related peptides in human middle meningeal and superficial temporal arteries (EHF-EHC 2025) - "Our aim was to compare the vasodilatory responses of extracranial human superficial temporal arteries (HSTA) and intracranial middle meningeal arteries (HMMA) to CGRP, the amylin analogue pramlintide, and adrenomedullin 2 (AM2), as well as the inhibition induced by the CGRP receptor-binding monoclonal antibody erenumab and the CGRP receptor antagonist olcegepant. The comparable responses of HSTA (innervated by V3) and HMMA (innervated by V1) to CGRP, pramlintide and AM2 do not challenge the potential role of extracranial arteries in the pathophysiology of migraine. Similar CGRP inhibition in both arteries may contribute to the antimigraine effects of CGRP receptor-targeting medications at either location. Finally, these results may also suggest that pain pathways relevant to migraine may overlap with those implicated in temporomandibular disorders."

CNS Disorders • Giant Cell Arteritis • Migraine • Musculoskeletal Diseases • ADM

Basic Science and Pathogenesis. (PubMed, Alzheimers Dement) - "Prediabetic amylin hypersecretion increases brain amylin level and exacerbates amylin receptor signaling controlling glycolysis, leading to impairments of glycolytic flux and memory."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus

Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies. (PubMed, Vascul Pharmacol) - "The article is a review of the emerging preclinical and clinical data regarding the application of peptide-based amylin receptor agonists (AMYRAs), including pramlintide and cagrilintide, KBP-series DACRAs, and investigational drugs, including ZP8396 and amycretin. Of particular interest, amylin-derived medications can have advantages over weight loss but definite disease-modifying action remains to be determined. Taken together, AMYRAs represent a potential category of therapeutics with promising disease-modifying effects that goes beyond weight loss, providing fresh perspectives for precision obesity management by 2030."

Journal • Review • Genetic Disorders • Metabolic Disorders • Obesity • CALCR

Amylin and the renin-angiotensin system: risk or opportunity in amylin-based therapy? (PubMed, Lancet) - "We hypothesise that amylin receptor agonists (eg, pramlintide) and dual amylin and calcitonin-receptor agonists (eg, cagrilintide), which are emerging treatments for obesity and type 2 diabetes, can activate the renin-angiotensin system (RAS) and potentially undermine the cardiorenal benefits of these therapies...To test this, we propose: (1) preclinical studies investigating amylin-RAS interactions with or without RAS blockade; (2) post-hoc analyses of phase 2/3 trials stratified by RAS inhibitor use; (3) biomarker studies monitoring renin, aldosterone, angiotensin-(1-7), and ACE2; and (4) mechanistic human studies prospectively assessing cardiovascular-kidney metabolic effects by RAS inhibitor status. These suggestions aim to determine whether RAS inhibition enhances the overall efficacy of amylin-based therapies, and whether RAS blockers should be strongly recommended in patients receiving them."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Use Of Glucagon Like Peptide 1 Receptor Agonists In Non Diabetic Patients With Dilated Cardiomyopathy (AHA 2025) - "Patients were stratified based on GLP-1 receptor agonist use (liraglutide, semaglutide, dulaglutide, lixisenatide, tirzepatide, pramlintide)...In this real-world, propensity-matched study of non-diabetic patients with DCM, GLP-1 receptor agonists were associated with substantial reductions in 1-year mortality, hospitalization, MI, and HF exacerbation. Although a 3-year follow-up window was available, median follow-up (~11 months) supported 1 year as the most reliable endpoint. Limitations include lack of LVEF or biomarker data, unmeasured confounding, and inability to confirm long-term medication adherence or persistence."

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Myocardial Infarction

A Pilot Outpatient Assessment of a Fully Closed-Loop Insulin and Pramlintide System. (PubMed, J Diabetes Sci Technol) - "This study suggests that automated insulin and pramlintide systems have the potential to alleviate carbohydrate counting without degrading time in range. A longer and larger study is underway."

Clinical • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Multi-Omics discovery and clinical validation of IGFBP2, B2M, and CST3 as a serum biomarker panel for diabetic kidney disease progression. (PubMed, Gene) - "Through a multi-omics approach, we identified IGFBP2/B2M/CST3 as a non-invasive biomarker panel for DKD progression, highlighting their roles as both diagnostic markers and therapeutic targets."

Biomarker • Journal • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • B2M • CST3 • IGFBP2

Central pramlintide administration potently suppresses operant responding for sucrose and locomotor activity in male rats. (PubMed, Physiol Behav) - "To test whether central pramlintide impacted locomotor activity, we conducted an open field study and found that ICV pramlintide significantly reduced distance traveled at several timepoints, suggesting suppressed locomotor activity. Overall, our results suggest that peripheral pramlintide does not affect motivation for sucrose, and that although central pramlintide does reduce outcomes assessing motivation, this may be confounded by a concurrent reduction in locomotor activity."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders