- |||||||||| Symlin (pramlintide) / AstraZeneca
Preclinical, Journal: Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats. (Pubmed Central) - Mar 3, 2022
Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co-formulation will be well preserved in future translation to humans. Together these results suggest that the co-formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.
- |||||||||| Symlin (pramlintide) / AstraZeneca
From barnyard to bedside: Using interspecies variants to inform the rational design of novel analogs of islet amyloid polypeptide (Sapphire I/J (Hilton San Diego Bayfront)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_5878;
Rat IAPP, a highly studied sequence, has previously been used in the development of an FDA-approved amylin analog pramlintide (Symlin), used in hormone replacement therapy...The present work includes the characterization of a novel variant, sheep IAPP, and incorporation of key moieties found in sheep, bovine, and other sequences in the design and characterization of novel analogs. These analogs are non-amyloidogenic, activate human amylin receptors, non-toxic, exhibit enhanced solubility, and represent a promising adjunct to insulin therapy in the treatment of diabetes mellitus.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Thermodynamic surprises of Cu(II)-amylin analogue complexes in membrane mimicking solutions. (Pubmed Central) - Jan 12, 2022
Complex stabilities are comparable, with the exception of the very stable Cu(II)-amylin, which proves that the presence of the amylin C-terminus lowers its affinity for copper(II); although not directly involved, its appropriate arrangement sterically prevents early metal binding. Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment closed: Alleviating Carbohydrate Counting for Patients With Type 1 Diabetes Using a Novel Insulin-plus-pramlintide Artificial Pancreas (clinicaltrials.gov) - Jan 11, 2022
P=N/A, N=36, Active, not recruiting,
Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix. Recruiting --> Active, not recruiting
- |||||||||| Symlin (pramlintide) / AstraZeneca, Fiasp (fast-acting insulin aspart) / Novo Nordisk
Clinical, Journal, Head-to-Head: A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. (Pubmed Central) - Jan 7, 2022
P2
However, participants still spent a high percentage of time within the target range with the fully-closed loop system. Outpatient studies comparing the fully closed-loop hybrid systems with patient-estimated, rather than precise, carbohydrate counting are warranted.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Review, Journal: Dual-hormone artificial pancreas for management of type 1 diabetes: Recent progress and future directions. (Pubmed Central) - Jan 5, 2022
In addition, novel ultra-rapid-acting insulin analogs with a more physiological time-action profile are currently under investigation for use in artificial pancreas devices, aiming to address the unmet need for further improvements in postprandial glucose control. This review article aims to discuss the current progress and future outlook in the development of novel ultra-rapid insulin analogs and dual-hormone closed-loop systems, which offer the next steps to fully closing the loop in the artificial pancreas.
- |||||||||| cagrilintide (AM833) / Novo Nordisk
Journal: AM833 is a novel agonist of calcitonin family G protein-coupled receptors: pharmacological comparison to six selective and non-selective agonists. (Pubmed Central) - Dec 25, 2021
In the current study, we have investigated the pharmacology of AM833 across 25 endpoints and compared this peptide with AMYR selective and nonselective lipidated analogs (AM1213 and AM1784), and the clinically used peptide agonists pramlintide (AMYR selective) and salmon CT (nonselective)...In this study we demonstrate that AM833 has a unique pharmacological profile across diverse measures of receptor binding, activation and regulation, when compared to other selective and non-selective calcitonin receptor and amylin receptor agonists. Our data provide mechanistic insight into the actions of AM833.
- |||||||||| Symlin (pramlintide) / AstraZeneca, cagrilintide (AM833) / Novo Nordisk
Review, Journal: Amylin as a Future Obesity Treatment. (Pubmed Central) - Dec 21, 2021
AM833 (cagrilintide), an investigational novel long-acting acylated amylin analogue, acts as a non-selective amylin receptor. This calcitonin G protein-coupled receptor agonist can serve as an attractive novel treatment for obesity, resulting in reduction of food intake and significant weight loss in a dose-dependent manner.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Review, Journal: Adjunct Therapies in Treatment of Type 1 Diabetes. (Pubmed Central) - Dec 16, 2021
Global trials have been conducted with liraglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and sotagliflozin, an inhibitor of both SGLT1 and SGLT2 transporters...Liraglutide, on the other hand, induced a smaller reduction in HbA1c and thus, was not considered for a license. However, further trials are currently being conducted with a combination of semaglutide, the most potent GLP-1RA and dapagliflozin to determine whether this approach would yield better outcomes.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Amyloidogenesis of feline amylin and plasma levels in cats with diabetes mellitus or pancreatitis. (Pubmed Central) - Dec 16, 2021
We compared 4 amylin analogues and found cat amylin to be more prone to amyloid fibrillation than human amylin, the triple-proline analogue pramlintide and rat amylin...These data support evidence of feline amylin being more prone to aggregation than human amylin in vitro, which may influence diabetes mellitus progression and β-cell failure in vivo. Furthermore, our data show an increase in amylin levels during feline pancreatitis and the need for future research on the role of this hormone in the pathogenesis of pancreatic inflammation associated to feline diabetes mellitus.
- |||||||||| Review, Journal: Amyloidogenicity of peptides targeting diabetes and obesity. (Pubmed Central) - Dec 16, 2021
Proper formulation, storage, manipulation and usage by professionals and patients are required in order to avoid agglomeration into high molecular weight products (HMWP), either amorphous or amyloid, which could result in potential loss of biological activity and short- or long-term immune reaction and silent inactivation. In this narrative review, we present perspective of the aggregation of therapeutic polypeptides used in diabetes and other metabolic diseases, covering the nature and mechanisms, analytical techniques, physical and chemical stability, strategies aimed to hamper the formation of HMWP, and perspectives on future biopharmaceutical developments.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment open, Trial completion date, Trial primary completion date: Co-administration of Pramlintide and Insulin Via an Automated Dual-hormone Artificial Pancreas System in Adults With Type 1 Diabetes (clinicaltrials.gov) - Dec 10, 2021
P=N/A, N=26, Recruiting,
In this narrative review, we present perspective of the aggregation of therapeutic polypeptides used in diabetes and other metabolic diseases, covering the nature and mechanisms, analytical techniques, physical and chemical stability, strategies aimed to hamper the formation of HMWP, and perspectives on future biopharmaceutical developments. Not yet recruiting --> Recruiting | Trial completion date: Apr 2022 --> Nov 2022 | Trial primary completion date: Apr 2022 --> Nov 2022
- |||||||||| Symlin (pramlintide) / AstraZeneca
Clinical, Review, Journal: A review of the Efficacy and Cardiovascular Safety of Amylin Analogues. (Pubmed Central) - Oct 27, 2021
Other medications with similar properties are glucagon-like peptide-1 receptor agonists (GLP-1 RAs). In this article we will review the efficacy of pramlintide when given with insulin in improving HbA1c, weight, and cognition with/without GLP-1 RAs as well as its cardiovascular (CV) safety.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Preclinical, Journal: Effects of pramlintide on energy intake and food preference in rats given a choice diet. (Pubmed Central) - Oct 27, 2021
The same intracerebroventricular doses of pramlintide did not induce pica, suggesting that pramlintide-mediated reductions in feeding are not due to nausea/malaise. Our results suggest that pramlintide reduces food intake in rats largely via reductions in intake of HFD versus chow, supporting the idea that the potent effects of pramlintide on palatable food intake may have utility in the treatment of obesity.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Symlin (pramlintide) / AstraZeneca, Qsymia (topiramate/phentermine) / IEH Biopharma, Alvogen
Retrospective data, Review, Journal: The best drug supplement for obesity treatment: a systematic review and network meta-analysis. (Pubmed Central) - Oct 22, 2021
The most effective drugs for weight loss were phentermine and topiramate, pramlintide, naltrexone, bupropion, and liraglutide compared to placebo treatment, respectively. This study provides new insights into anti-obesity drugs and hopes to shed new light on future research to manage and treat obesity.
- |||||||||| ZP5461 / Boehringer Ingelheim
Preclinical, Journal: The long-acting amylin/calcitonin receptor agonist ZP5461 suppresses food intake and body weight in male rats. (Pubmed Central) - Oct 9, 2021
Using virally-mediated knockdown of DVC CTRs, the ability of chronic systemic ZP5461 to promote early reductions in intake and body weight gain was determined to be mediated in part by activation of DVC CTRs, implicating the DVC as a central site of action for ZP5461. Future studies should address other dosing regimens of ZP5461 to determine whether an alternative dose/frequency of administration would produce more sustained body weight suppression.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Microcanonical insights into the physicochemical stability of the coformulation of insulin with amylin analogues. (Pubmed Central) - Aug 29, 2021
However, the high amyloidogenicity of hIAPP precluded it as a therapeutics and led to the design of pramlintide (sIAPP), a chimeric analogue with substitutions (A25P, S28P, and S29P) inherited from the aggregation-resistant rat isoform (rIAPP)...These results are then correlated with estimates of solvation free energies, modeled by the Poisson-Boltzmann equation, and structural propensities. Experimental essays are compared to our simulations and support our methodology.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion date, Trial primary completion date, MRI: A Study of the Functional Magnetic Resonance Imaging Response to Leptin and Pramlintide (clinicaltrials.gov) - Aug 18, 2021
P=N/A, N=10, Active, not recruiting,
The substrate uptake and gene expression profiles demonstrate that AAs addition enhances glycerol and lactose assimilation due to overall improvement in their metabolism governed by global regulators of carbon metabolism. Trial completion date: Jul 2020 --> Jul 2022 | Trial primary completion date: Jul 2020 --> Jul 2022
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Amino acid supplementation for enhancing recombinant protein production in E. coli. (Pubmed Central) - Aug 12, 2021
In this study, the effect of amino acid supplementation in a chemically defined medium on cellular growth and recombinant pramlintide production was investigated...Further, transcriptomics data indicated downregulation of several genes associated with global stress response and genes involved in amino acid biosynthesis in test culture, supported by proteomics analysis. These results signify that external supply of critical amino acids decreases the cellular stress during RPP and improves process productivity.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Clinical, Journal: Amylin analog pramlintide induces migraine-like attacks in patients. (Pubmed Central) - Aug 4, 2021
Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Adjunctive therapies in type 1 diabetes mellitus. (Pubmed Central) - Jul 28, 2021
In addition, the risk of hypoglycemia, gastrointestinal side effects and diabetes ketoacidosis may be increased with the use of these adjunctive therapies. Pramlintide is currently the only FDA-approved adjunctive therapy, whereas others require continued research to better understand risk-to-benefit ratio.
- |||||||||| cagrilintide (AM833) / Novo Nordisk
Journal: Development of Cagrilintide, a Long-Acting Amylin Analogue. (Pubmed Central) - Jul 22, 2021
We report here the development of the stable, lipidated long-acting amylin analogue cagrilintide (23) and some of the structure-activity efforts that led to the selection of this analogue for clinical development with obesity as an indication. Cagrilintide is currently in clinical trial and has induced significant weight loss when dosed alone or in combination with the GLP-1 analogue semaglutide.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Clinical, Journal: A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. (Pubmed Central) - Dec 18, 2020
P2
Our data thus far suggests differential effects of peripheral amylin and even AMYR activation or antagonism on cognitive behavior, APP processing enzymes, and soluble amyloid-beta levels when in the presence or absence of receptor antagonism. A novel rapid insulin-and-pramlintide artificial pancreas improves glucose control compared with a rapid insulin-alone artificial pancreas (ClinicalTrials.gov number NCT02814123).
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: The effect of pramlintide, an antidiabetic amylin analogue, on angiogenesis-related markers in vitro. (Pubmed Central) - Dec 17, 2020
However, there was not any significant change in VEGF release from HUVECs. Findings of this research revealed the effect of pramlintide on angiogenesis- related markers via enhancing migration and tubulogenesis in vitro, suggesting a worthwhile proposition for further clinical researches on improving vascular complications and healing of diabetic wounds.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Pharmacological therapies to address obesity in type 1 diabetes. (Pubmed Central) - Dec 2, 2020
Currently, antiobesity medications are used off-label for the treatment of patients with T1D. Additional studies are needed to understand the role of these medications in the management of obesity in patients with T1D.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts. (Pubmed Central) - Nov 12, 2020
Increased brain Aβ burden by amylin and pramlintide was associated with synaptic loss, apoptosis, and microglia activation. In conclusion, our findings showed amylin or pramlintide increase Aβ levels and related pathology in TgSwDI mice brains, and suggest that increased amylin levels or the therapeutic use of pramlintide could increase the risk of AD.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Effects of Amylin Against Amyloid-β-Induced Tauopathy and Synapse Loss in Primary Neurons. (Pubmed Central) - Oct 11, 2020
To test the hypothesis, we conducted both in vitro and in vivo experiments with different doses of amylin and with its analog, pramlintide...It demonstrates that amylin has a dose-dependent U-shape effect against AD pathogenesis. Within a physiological range, amylin is a neuroprotective hormone against AD in neurons; but when both Aβ and amylin concentrations are elevated, imbalance of Aβ and amylin may contribute to brain AD pathogenesis.
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