Symlin (pramlintide) / AstraZeneca - LARVOL DELTA

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

Development of the novel amylin and calcitonin receptor activators by peptide mutagenesis. (PubMed, Arch Biochem Biophys) - "These mutated peptide activators also showed higher potency for human amylin and calcitonin receptor activation than a clinically available amylin receptor activator pramlintide. These amylin and calcitonin receptor activators developed in this study may be useful as the valuable pharmacological tools that activate amylin receptors in cell-based systems."

Journal • Genetic Disorders • Obesity

A microfluidic in vitro method predicting the fate of peptide drugs after subcutaneous administration. (PubMed, Int J Pharm) - "The results from MIS studies of the peptide drugs exenatide, pramlintide, vancomycin, polymyxin B, lanreotide, MEDI7219 and AZD2820 are compared with results from measurements with the commercially available SCISSOR system and in vivo absorption and bioavailability data from the literature. A correlation is found between the 1st order release rate constant determined with SCISSOR and ka for lanreotide (Autogel), exenatide and AZD2820. A mechanism relating the magnitude of ka to the peptides' charge is proposed."

Journal • Preclinical

Intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions improves cognitive impairments in a mouse model of Alzheimer's disease. (PubMed, Int J Biol Macromol) - "However, Pram treatment did not alter the Aβ1-42-induced anhedonic behavior, oxidative stress parameters, or the pre-synaptic SNAP-25 and post-synaptic PSD-95 levels in the hippocampus and prefrontal cortex. These findings indicate cognitive-enhancing properties of intranasal Pram administration in an animal model of AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

METABOLIC REPROGRAMMING OF THE EWING SARCOMA TUMOR MICROENVIRONMENT USING PRAMLINTIDE (SIOP 2024) - "Pramlintide altered the metabolic capacity of ES cells leading to decreased glucose and oxygen consumption, decreased proliferation, increased apoptosis and inhibited tumor growth. Therefore, Pramlintide has the potential to alter the acidic/hypoxic TME, making it less immunosuppressive."

Biomarker • IO biomarker • Tumor microenvironment • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ANXA5 • CALCR

TOTT: Tailoring Obesity Treatment Trial (clinicaltrials.gov) - P2/3 | N=40 | Not yet recruiting | Sponsor: Esbjerg Hospital - University Hospital of Southern Denmark

New P2/3 trial • Genetic Disorders • Metabolic Disorders • Obesity

Amylin analogs for the treatment of obesity without diabetes: present and future. (PubMed, Expert Rev Clin Pharmacol) - "Amylin analogs (pramlintide and cagrilintide) are emerging as promising anti-obesity agents in non-DM subjects. Amylin analogs will certainly enrich the growing therapeutic armamentarium aimed at tackling obesity. The most exciting future research venue could be development of their combinations with other weight-lowering drugs, especially dual and triple incretin-based co-agonists, thus potentially providing massive weight-loss effects."

Journal • Review • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Oncology

Characterisation of AZD6234, a novel amylin receptor selective agonist peptide, in rodent models of weight loss and aversion (EASD 2024) - "Here we characterize a synthetic long-acting pramlintide analog, that possesses the in vitro amylin/calcitonin receptor selectivity ratio to mimic native amylin. Our data indicate that AZD6234 is a potent AMY3R agonist with selectivity mimicking endogenous amylin. AZD6234 mediated dose-dependent decreases in food intake and body weight. AZD6234 (30 nmol/kg) did not significantly increase GLP-1RA-mediated CTA in rat models."

Preclinical • Metabolic Disorders • Obesity

Managing Post-Transplant Diabetes Mellitus after Kidney Transplantation: Challenges and Advances in Treatment. (PubMed, Pharmaceuticals (Basel)) - "New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients."

Journal • Post-transplantation • Review • Chronic Kidney Disease • Diabetes • Infectious Disease • Metabolic Disorders • Transplant Rejection • Transplantation