Symlin (pramlintide) / AstraZeneca - LARVOL DELTA

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) - "Available on Friday, May 29, 2026 at 12:00am CDT."

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

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

Acute i.v. infusion of the amylin analogue pramlintide does not affect glucagon levels in individuals with type 1 diabetes or in healthy controls (EASD 2025) - P=N/A | "A 3-hour i.v. infusion of the amylin analogue pramlintide did not affect glucagon levels in individuals with type 1 diabetes or healthy controls compared to placebo. However, pramlintide appeared to reduce glucose levels in individuals with type 1, which may suggest a differential glucose-lowering effect between groups."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

The amylin analogue pramlintide suppresses bone resorption without affecting bone formation in individuals with type 1 diabetes and in healthy controls (EASD 2025) - P=N/A | "We demonstrate that a continuous i.v. infusion of the amylin analogue pramlintide potently reduces bone resorption without affecting bone formation in individuals with type 1 diabetes as well as in healthy controls."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Case Series of Nizon-Isidor Syndrome by Heterozygous Variants in MED12L With Further Evidence of Mitotic Instability in One Case With Diploid-Triploid Mosaicism. (PubMed, Am J Med Genet A) - "In Proband 1, caloric restriction and semaglutide-pramlintide combination therapy were started at age eight and were effective in weight reduction. Overall, this report expands the phenotypic spectrum of Nizon-Isidor syndrome, highlights a potential link between MED12L and cytogenetic abnormalities, and demonstrates a case of weight loss through GLP-1 therapy in a child with a genetic obesity syndrome."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Gastrointestinal Disorder • Genetic Disorders • Obesity • Rare Diseases • Strabismus

Non-insulin therapies in management of type 1 diabetes. (PubMed, Endocr Pract) - "Using a PubMed literature search, we identified 51 randomized clinical trials investigating sodium glucose co-transporter inhibitors (SGLTi :9), glucagon like peptide 1 receptor agonist (GLP1RA: 13), metformin (13), dipeptidyl peptidase-4 inhibitor (DPP-4i: 9), pramlintide (4), bromocriptine (1) and combination therapies (2) in T1D. SGLTi could be another beneficial therapy in T1D, however, more research is needed to improve DKA risk with this therapy. Efficacy trials of weekly GLP-1RA and its potential cardio-renal benefits in T1D are much needed."

Clinical • Journal • Review • Cardiovascular • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

AI-Based Meal Detection Enables Fully-Automated Pramlintide and Insulin Closed-Loop System to Improve Postmeal Glucose in Type 1 Diabetes (T1D) (ADA 2025) - "An AI-enabled meal detection algorithm performed well in automated meal insulin and pramlintide dosing, contributing to achieving a TIR of 74% in the 6 hours after a large meal."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

In silico evaluation of pramlintide dosing algorithms in artificial pancreas systems. (PubMed, Comput Biol Med) - "The results of the insulin-pramlintide algorithms are compared against their insulin-alone counterparts, showing an improvement in the time in range between 3.00% and 10.53%, consistent with results reported in clinical trials in the literature. Future work will focus on individualizing the pramlintide model to the patients' characteristics and evaluating the implemented strategies under more challenging scenarios."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Generating Amyloid Resistant Stem Cell-Derived Beta Cells to Improve Islet Transplant Outcomes in Type 1 Diabetes (IPITA 2025) - "Pramlintide-expressing SC-β cells do not form amyloid following transplantation and have potential as an improved SC-β cell source for transplantation in T1D."

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