Symlin (pramlintide) / AstraZeneca - LARVOL DELTA

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

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. 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

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

DTAD: Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease (clinicaltrials.gov) - P1 | N=57 | Active, not recruiting | Sponsor: Boston University | Trial primary completion date: Jun 2025 ➔ Nov 2026

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Characterisation of peptide agonists' binding affinity and kinetics at amylin receptors (ECO 2025) - "The binding parameters of Cy5–labelled salmon calcitonin (Cy5– sCT) were established in a BRET–based saturation assay; subsequently, the displacement of Cy5–sCT by increasing concentrations of non– fluorescent ligands was used to calculate their affinities and on–/off–rates...Residues responsible for CTR vs. AMYR selectivity, or bias towards individual AMYR subtypes, were identified by analysing the binding profiles of pramlintide Ala scan peptides. The use of a NanoBiT split luciferase system in conjunction with a BRET–based binding assay enabled a comprehensive characterisation of peptides' binding to AMYRs, revealing differences in both selectivities and kinetic parameters. Further research should look at the intracellular signalling downstream of the ligand/receptor interaction, as well as examine whether the binding kinetics of an agonist and its physiological actions (e.g. appetite suppression or weight loss) are correlated."

Genetic Disorders • Obesity

Amylin: emergent therapeutic opportunities in overweight, obesity and diabetes mellitus. (PubMed, Nat Rev Endocrinol) - "The identification of amylin as a glucoregulatory peptide hormone with roles in meal-ending satiation sparked a surge of experimental development, which culminated in the amylin mimetic drug pramlintide...The widespread pharmacotherapy of otherwise healthy populations with overweight or obesity with the goal of improving future health requires further regulatory and ethical consideration. This Review describes how amylin controls energy homeostasis and provides a current overview of amylin-based therapeutic development."

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

Amylin and the amylin receptors in migraine: Is there another pathway to target? (PubMed, Cephalalgia) - "Comprehending the distinct and overlapping mechanisms between amylin and CGRP signalling could develop further our understanding of migraine pathophysiology. In summary, this review reveals, through initial studies, that targeting the amylin pathway may have a potential role as a novel treatment option for those who may not respond to other treatments, or as a better alternative."

Journal • Review • CNS Disorders • Migraine • Pain

Amylin: From Mode of Action to Future Clinical Potential in Diabetes and Obesity. (PubMed, Diabetes Ther) - "In individuals with advanced β-cell dysfunction, supplementing insulin therapy with pramlintide, the first and currently only approved injectable short-acting selective analog of amylin, has demonstrated efficacy in enhancing both postprandial and overall glycemic control in both type 2 diabetes (T2D) and type 1 diabetes (T1D) without increasing the risk of hypoglycemia or weight gain...As such, amylin agonists (combined with other members of the incretin class) could represent the elusive drug candidate to address the multi-hormonal dysregulations of diabetes subtypes and qualify as a precision medicine approach that surpasses the long overdue division into T1DM and T2DM. Further development of amylin-based therapies or delivery systems is crucial to fully unlock the therapeutic potential of this intriguing hormone.Graphical abstract available for this article."

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

DTAD: Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease (clinicaltrials.gov) - P1 | N=57 | Active, not recruiting | Sponsor: Boston University | Recruiting ➔ Active, not recruiting | N=240 ➔ 57

Enrollment change • Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Intranasal pramlintide matches intraperitoneal effects on food intake and gastric emptying in mice. (PubMed, Endocrine) - "Although intranasal pramlintide is not comparable in magnitude to intraperitoneal administration at an equivalent administered dose, our evidence corroborates the development of novel intranasal formulations destined to overpass the bioavailability issue and potentially serve as an alternative route."

Journal • Preclinical • Diabetes • Metabolic Disorders

From the pancreas to the amygdala: New brain area critical for ingestive and motivated behavior control exerted by amylin. (PubMed, iScience) - "Clinically used amylin analogue, pramlintide, reduced meal size and frequency by acting on the CeA...Importantly, CeA amylin signaling was required for appetite suppression induced by peripherally applied amylin, highlighting translational relevance of this brain site. Our data indicate the CeA is a critical neural substrate for amylin signaling."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

Newer GLP analogs for treatment of obesity in type 1 diabetes (ATTD 2025) - "These medications include using Glucagon like Polypeptide (GLP like semaglutide) analogs or Glucose-dependent insulinotropic polypeptide (GIP+ GLP like tirzepatide) and or Sodium-dependent Glucose Cotransporter inhibitors (SGLT 2 is like empagliflozin) etc. The current recommendations (by American Diabetes Association {ADA} and European Association for Study of Diabetes {EASD}) for initiating treatment for patients with T2D should be based on associated co-morbidities...The other pharmacological agent approved by the FDA as adjunctive therapy for patients with T1D is pramlintide which is rarely used due to gastrointestinal (GI) side effects, risk of severe hypoglycemia and need for multiple injections a day...Although Randomized Control Trials (RCTs) would be ideal to show the safety and efficacy of GLP analogs in patients with T1D, manufacturers of these medications have not indicated any desire (for now) to do RCTs studies in patients with T1D. Clinical experience is..."

Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Gout • Hepatology • Inflammatory Arthritis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Oncology • Pancreatitis • Renal Disease • Rheumatology • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

AID with drugs: semaglutide, empagliflozin, and pramlintide (ATTD 2025) - No abstract available

Diabetes • Diabetic Nephropathy • Metabolic Disorders • Type 1 Diabetes Mellitus

IN SILICO EVALUATION OF PRAMLINTIDE DOSING ALGORITHMS IN ARTIFICIAL PANCREAS SYSTEMS (ATTD 2025) - "Funding: This work was supported by PID2019-107722RB-C21 funded by MCIN/AEI/10.13039/501100011033, grant CIPROM/2021/012 funded by Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital from Generalitat Valenciana and Plan de ayudas a la I+D+i del Instituto AI2, Convocatoria 2022. Corresponding author: jbondia@isa.upv.es"

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus