Symlin (pramlintide) / AstraZeneca - LARVOL DELTA

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

ADJUNCTIVE THERAPIES AND AUTOMATIC INSULIN DELIVERY IN TYPE 1 DIABETES (ATTD 2025) - "This work reviews which drugs have been tested in clinical trials alongside AID systems, analyzing their contributions and outcomes.Methods A comprehensive search was conducted across multiple databases, including Scopus, Web of Science, and PubMed, to identify clinical trials that used adjunctive therapies with AID systems in T1D.Results Around 15 clinical trials were found in the literature, testing the AID system's performance while using adjunctive therapies, including pramlintide, GLP-1 receptor agonists, SGLT2 inhibitors, and DDP4 inhibitors...Achieving a fully automatic AID system would require tuning the algorithms to adapt more closely to the dynamics introduced by the adjunctive drugs. Work supported by grant CIPROM/2021/012 funded by Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital from Generalitat Valenciana."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Automated multi-hormone delivery approach to manage postprandial glycemic excursion (ATTD 2025) - "Pramlintide is an analogue of amylin that delays gastric emptying and reduces nutrient-derived glucagon secretion, thus improving postprandial glucose levels...In a study with liraglutide subcutaneously daily as an adjunctive to closed-loop without meal announcement a reduction of post prandial glucose excursions was noted, as well as a reduction in prandial insulin delivery and weight loss. Although the effects of GLP-1 RAs as adjunct to automated insulin delivery systems has shown considerable weight loss, reduction of HbA1c and reduction in insulin dose, currently no studies have been conducted with the simultaneous delivery of GLP-1RA and insulin in a multi hormone closed-loop. Further studies are needed to explore the use of this class of agents in a multi hormone automated insulin delivery system to manage postprandial glycemic excursions."

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

Fully closed-loop - Bihormonal approaches (ATTD 2025) - "Glucagon counteracts insulin and pramlintide mitigates postprandial glucose excursions. This lecture will cover recent progress in bihormoal approaches towards the fully closed loop."

AI-enabled meal detection and dosing in automated insulin delivery systems (ATTD 2025) - "An AI-enabled dual-hormone insulin and pramlintide AID can improve postprandial glucose outcomes both in silico and in an in-clinic study. In silico results show that including PK/PD dynamics in the MPC algorithm is helpful."

Diabetes • Infectious Disease • Metabolic Disorders

Fusion Outcomes of GLP-1 Agonist Therapy in Multilevel Cervical Spinal Fusion: A Propensity-Matched Analysis. (PubMed, Clin Spine Surg) - "Our findings demonstrate a statistically significant lower incidence of pseudarthrosis among patients treated with GLP-1 agonist therapy at all timepoints within this study-from 6-months to 2-years postoperatively, suggesting a potentially beneficial effect of GLP-1 agonist therapy in promoting fusion success in multilevel cervical spine surgery. Fundamentally, this aligns with the pharmacodynamic nature of GLP-1 agonists: as compounds that enhance osteoblastic activity and suppress osteoclastic activity, thereby facilitating bone formation and attenuating bone resorption. Further investigation into the mechanistic underpinnings of GLP-1 agonists' effects on bone metabolism may pave the way for enhancing the success of cervical spine surgery."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Nicotine Addiction • Obesity • Orthopedics • Osteoarthritis

TOTT: Tailoring Obesity Treatment Trial (clinicaltrials.gov) - P2/3 | N=40 | Suspended | Sponsor: Esbjerg Hospital - University Hospital of Southern Denmark | Trial completion date: Dec 2025 ➔ Dec 2026 | Initiation date: Oct 2024 ➔ Sep 2025 | Not yet recruiting ➔ Suspended | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial initiation date • Trial primary completion date • Trial suspension • Genetic Disorders • Metabolic Disorders • Obesity

Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance. (PubMed, Endocr Rev) - "Among other concepts, metformin, pioglitazone, incretin-based drugs such as GLP-1 receptor agonists, sodium-glucose cotransporter inhibitors, and pramlintide can improve insulin resistance, either directly or indirectly. However, considering the current issues of high cost, side effects, limited efficacy, and their off-label status, these agents in people with T1D are not widely used in routine clinical care at present."

Journal • Diabetes • Immunology • Inflammation • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Two Way Crossover Closed Loop Study Insulin vs Insulin and Pramlintide (clinicaltrials.gov) - P=N/A | N=33 | Completed | Sponsor: Oregon Health and Science University | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

International Society for Pediatric and Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Insulin and Adjunctive Treatments in Children and Adolescents with Diabetes. (PubMed, Horm Res Paediatr) - "The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and updates recommendations on the principles of intensive insulin regimens, including more intensive forms of multiple daily injections with new-generation faster-acting and ultra-long-acting insulins; a summary of adjunctive medications used alongside insulin treatment that includes details on pramlintide, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and sodium-glucose cotransporter inhibitors; and key considerations with regard to access to insulin and affordability to ensure that all persons with diabetes who need insulin can obtain it without financial hardship."

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

Pramlintide and Tirzepatide Therapy for Weight Loss in Diabetes and ESRD: A Bridge to Transplant (OBESITY WEEK 2024) - "Combining tirzepatide with existing amlylin analog pramlinitide may provide additional benefits for patients with diabetes and obesity. Further studies warrant examining this relationship to explore new avenues of treatment in such cases."

Diabetes • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

Trends in the Prescription of Weight Loss Medications in Patients With Obesity: A Nationwide Cross-Sectional Analysis, 1999-2018 (ACG 2024) - "Prescription medication data included FDA-approved weight-loss drugs such as phentermine, sibutramine, diethylpropion, phentermine/topiramate, orlistat, bupropion/naltrexone, GLP-1 agonist. Weight-loss inducing anti-diabetic drugs included pramlintide, SGLT-2 inhibitors, metformin...The most prescribed FDA-approved medication was phentermine followed by liraglutide and orlistat... The proportion of subjects who met the criteria for receiving weight-loss drugs increased from 42.4% in 1999-2000 to 51.9% in 2017-2018. However, the use of FDA-approved drugs alone remained low ranging from 0.29% in 1999-2000 to 1.12% in 2017-2018. When anti-diabetes drugs with weight-loss effects were included, the proportion of use ranged from 5.16% in 1999-2000 to 14.24% in 2017-2018."

Clinical • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Obesity