- |||||||||| Symlin (pramlintide) / AstraZeneca, cagrilintide (AM833) / Novo Nordisk
Review, Journal: Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity. (Pubmed Central) - Feb 10, 2024
Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Symlin (pramlintide) / AstraZeneca, Mounjaro (tirzepatide) / Eli Lilly
Review, Journal: Weight-centric treatment of type 2 diabetes mellitus. (Pubmed Central) - Nov 22, 2023
Experts in the fields of endocrinology and obesity recommend utilizing a weight-centric approach when treating T2DM. Considering the high prevalence and debilitating complication of T2DM, it is of utmost importance to shift from a weight gain approach (i.e., insulin, sulfonylureas) into a weight loss/neutral one (i.e., GLP-1 agonists, SGLT-2 inhibitors, metformin).
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment open: FCL: A Fully Automated Insulin and Pramlintide Delivery System for Adults With Type 1 Diabetes (clinicaltrials.gov) - Nov 13, 2023
P2/3, N=30, Recruiting,
Considering the high prevalence and debilitating complication of T2DM, it is of utmost importance to shift from a weight gain approach (i.e., insulin, sulfonylureas) into a weight loss/neutral one (i.e., GLP-1 agonists, SGLT-2 inhibitors, metformin). Not yet recruiting --> Recruiting
- |||||||||| Symlin (pramlintide) / AstraZeneca
Management options for treating obesity in type 1 diabetes patients (HALL B) - Oct 15, 2023 - Abstract #ATTD2024ATTD_108;
It's important to note that there is no other drug other than insulin that is approved for managing patients with T1D. Pramlintide that was approved in the US as adjunctive therapy for people with T1D was hardly used because of serious side effects of hypoglycemia.
- |||||||||| Symlin (pramlintide) / AstraZeneca, Qsymia (topiramate/phentermine) / IEH Biopharma, Alvogen, Xenical (orlistat) / Roche, GSK
Review, Journal: Treating obesity in type 1 diabetes mellitus - review of efficacy and safety. (Pubmed Central) - Oct 11, 2023
Treatments also have varying adverse effect profiles which may impact T1D treatment. In this review, we aim to summarize study outcomes in people with T1D, including risks and benefits, of on- and off-label weight loss treatments.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion date, Trial primary completion date: DTAD: Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease (clinicaltrials.gov) - Aug 1, 2023
P1, N=240, Recruiting,
We believe our results bring us one step closer to finding an optimal effective hypoglycemic regimen that also protects against AMD development in diabetic patients. Trial completion date: Jul 2023 --> Nov 2026 | Trial primary completion date: Jul 2023 --> Dec 2024
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date: Biological Outcomes of Pramlintide in Resectable Cutaneous Squamous Cell Carcinoma: A Pilot Study (clinicaltrials.gov) - Jun 28, 2023
P1, N=0, Withdrawn,
Trial completion date: Jul 2023 --> Nov 2026 | Trial primary completion date: Jul 2023 --> Dec 2024 N=16 --> 0 | Trial completion date: Apr 2024 --> Jun 2023 | Suspended --> Withdrawn | Trial primary completion date: Apr 2024 --> Jun 2023
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Human IAPP is a contributor to painful diabetic peripheral neuropathy. (Pubmed Central) - Apr 18, 2023
Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects...Thus, we provide evidence that hIAPP aggregation is neurotoxic and mediates peripheral neuropathy in mice. The increased abundance of hIAPP aggregates in the skin of T2DM patients supports the notion that hIAPP is a potential contributor to T2DM neuropathy in humans.
- |||||||||| Symlin (pramlintide) / AstraZeneca
A Pilot Study Evaluating an Insulin and Pramlintide Fully Closed-Loop Delivery System (Room 29; [Board No. 60]) - Apr 10, 2023 - Abstract #ADA2023ADA_120;
The mean total insulin used throughout the interventions was 38.2 (23.5) units on the control arm, 31.8 (18.4) and 32.5 (17.5) on the faster aspart 1:8 and 1:10 respectively, and 36.6 (26.9) and 32.2 (23.5) on the insulin aspart 1:8 and 1:10 arms respectively. This pilot study suggests that our fully automated dual-hormone delivery system has the potential to alleviate carbohydrate counting without degrading time in the target range; and it will be investigated in a larger subsequent study.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment closed, Trial completion date, Trial primary completion date: FCL: A Fully-closed Loop, Pramlintide and Insulin, Artificial Pancreas Clinical Trial for Adults With Type 1 Diabetes (clinicaltrials.gov) - Mar 14, 2023
P=N/A, N=10, Active, not recruiting,
Trial completion date: Nov 2022 --> Apr 2024 | Trial primary completion date: Nov 2022 --> Apr 2024 Recruiting --> Active, not recruiting | Trial completion date: Aug 2022 --> May 2023 | Trial primary completion date: Aug 2022 --> May 2023
- |||||||||| Symlin (pramlintide) / AstraZeneca
A NEW PHARMACOKINETICS ANDPHARMACODYNAMICS MODEL OF SUBCUTANEOUSPRAMLINTIDE INFUSION () - Feb 23, 2023 - Abstract #ATTD2023ATTD_623;
These data suggest an uncoupling of functional and pathology-related events and highlighting a more complex receptor system and pharmacological relationship that must be carefully studied to clarify the role of amylin in CNS function and AD. The results of this work will help developsimulators for evaluating insulin-pramlintide artificial pancreassystems.
- |||||||||| Symlin (pramlintide) / AstraZeneca, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Journal: Recent developments in adjunct therapies for type 1 diabetes. (Pubmed Central) - Jan 20, 2023
As evidence emerges for cardiorenal protection by SGLT2i and GLP1RAs in T2D, it has become increasingly important to know whether people with T1D can also benefit. Here we review recent trials of adjunct agents in T1D and discuss the efficacy and safety of these agents (alone and in combination) in an era in which continuous glucose monitoring is becoming standard of care.
- |||||||||| Symlin (pramlintide) / AstraZeneca, davalintide (AC2307) / BMS
Journal: Islet amyloid polypeptide does not suppress pancreatic cancer. (Pubmed Central) - Jan 10, 2023
In contrast to previous reports, we find that IAPP does not function as a tumour suppressor. This suggests that loss of IAPP signalling likely does not increase the risk of pancreatic cancer in individuals with diabetes.
- |||||||||| 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) - Dec 16, 2022
P=N/A, N=10, Active, not recruiting,
This suggests that loss of IAPP signalling likely does not increase the risk of pancreatic cancer in individuals with diabetes. Trial completion date: Jul 2022 --> Jul 2024 | Trial primary completion date: Jul 2022 --> Jul 2024
- |||||||||| Symlin (pramlintide) / AstraZeneca
Closed-loop with adjunct therapies (Hall A3) - Dec 16, 2022 - Abstract #ATTD2023ATTD_62;
Glucose control could beimproved and carbohydrate counting burden could be reducedwith the addition of adjunct therapies such as pramlintide,SGLT2i, and GLP-1...Adjunct use of SGLT2i with closed-looptherapy improves glucose control during the day and night butincreases ketone concentration and ketosis compared to pla-cebo. Data on the adjunct use of GLP-1 with closed-looptherapy is lacking.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Zn(II) binding to pramlintide results in a structural kink, fibril formation and antifungal activity. (Pubmed Central) - Nov 30, 2022
We provide insight into the bioinorganic chemistry of amylin analogues, showing that the coordination of zinc(II) enhances the antifungal properties of pramlintide, a non-fibrillating therapeutic analogue of amylin. Zinc binds to the N-terminal amino group and His18 imidazole, inducing a kink in the peptide structure, which, in turn, triggers a fibrillization process of the complex, resulting in an amyloid structure most likely responsible for the disruption of the fungal cell.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Alpha-cells and therapy of diabetes: Inhibition, antagonism or death? (Pubmed Central) - Oct 12, 2022
However, further clinical use of synthalin A was curtailed due its adverse effects and the increased availability of insulin. Overall, these observations with therapeutics that directly target alpha-cells, or GCGR signaling, highlight a largely untapped potential for diabetes therapy that merits further detailed consideration.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Amylin Pharmacology in Alzheimer's Disease Pathogenesis and Treatment. (Pubmed Central) - Sep 20, 2022
The traditional "gain of toxic function" properties assigned to amyloid proteins are, however, contrasted by several reports highlighting neuroprotective effects of amylin and a recombinant analog, pramlintide, in the context of these two diseases...However, the nature of amylin receptor signaling is highly complex and not well studied in the context of CNS function. Therefore, to begin to address this pharmacological paradox in amylin research, the goal of this review is to summarize the current research on amylin signaling and CNS functions and critically address paradoxical nature of this hormone's signaling in the context of AD pathogenesis.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion, Trial completion date, Surgery, Bariatric surgery: Pramlintide (Symlin) for the Treatment of Hypoglycemia Following Gastric Bypass Surgery (clinicaltrials.gov) - May 26, 2022
P4, N=22, Completed,
These data suggest that in osteosarcoma cells with altered p53, p63, and p73 and a high glycolytic function, Pramlintide therapy can modulate metabolic programming and inhibit tumor growth. Active, not recruiting --> Completed | Trial completion date: Oct 2021 --> Feb 2022
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion date, Trial suspension, Trial primary completion date: Biological Outcomes of Pramlintide in Resectable Cutaneous Squamous Cell Carcinoma: A Pilot Study (clinicaltrials.gov) - May 13, 2022
P1, N=16, Suspended,
These data are consistent with durable amylinomimetic responses and provide the basis for further development of such long-acting amylinomimetic conjugates for the potential treatment of obesity and associated pathologies. Trial completion date: Apr 2023 --> Apr 2024 | Recruiting --> Suspended | Trial primary completion date: Apr 2022 --> Apr 2023
- |||||||||| ZP 8396 / Zealand Pharma
Antidiabetic Potential of Novel, Long-Acting Amylin Analogue ZP8396 in ZDF Rats (356 (Level 3); Board No. 213) - May 11, 2022 - Abstract #ADA2022ADA_2464;
Clinical efficacy has been demonstrated with short-acting amylin analogue pramlintide...Also, ZP8396 significantly reduced plasma glucagon levels, reaching a 55% difference in ZP8396-treated diabetic rats vs. vehicle group at 24 h post-dose (p <0.05).In conclusion, in diabetic rat ZP8396 improved glycaemic status, supporting that long-acting amylin analogues may provide future valuable therapeutic options to manage diabetes. Further preclinical characterization of the antidiabetes effects of long-term treatment with ZP8396 is ongoing.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Review, Journal: Mediators of Amylin Action in Metabolic Control. (Pubmed Central) - Apr 24, 2022
At least in conjunction with insulin, amylin analogs are also considered important treatment options in diabetic patients, so that new drugs may soon be added to the only currently approved compound pramlintide (Symlin). This review provides a brief summary of the physiology of amylin's mode of actions and its role in the control of the metabolism, in particular energy intake and glucose metabolism.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Pramlintide for Post-Bariatric Hypoglycemia. (Pubmed Central) - Apr 22, 2022
This review provides a brief summary of the physiology of amylin's mode of actions and its role in the control of the metabolism, in particular energy intake and glucose metabolism. In PBH, pramlintide does not modulate glycaemic or insulin responses, satiety, or dumping scores during an MMTT and does not impact glycaemic excursions or decrease low SG levels in the outpatient setting.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial termination: Glucagon Counterregulation in Type 1 Diabetes (clinicaltrials.gov) - Mar 28, 2022
P=N/A, N=13, Terminated,
Findings of the current investigation displayed that pramlintide may act as a protective against oxidative conditions in endothelial cells through modulation of oxidative markers and transcription factor NF-κB. Suspended --> Terminated; Clinical staffing issues and COVID-19 pandemic
- |||||||||| 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.
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