Pramlintide

The peptide hormone amylin reduces food intake and body weight, and is an attractive candidate target for novel pharmacotherapies to treat obesity. However, the short half-life of native amylin and amylin analogs like pramlintide limits these compounds' potential utility in promoting sustained negative energy balance. Here, we evaluate the ability of the novel long-acting amylin/calcitonin receptor agonist ZP5461 to reduce feeding and body weight in rats, and also test the role of calcitonin receptors (CTRs) in the dorsal vagal complex (DVC) of the hindbrain in the energy balance effects of chronic ZP5461 administration...

Introduction : Insulin and its analogues have so far been the only approved treatment for type 1 diabetes in Europe, while in the US, the amylin analog pramlintide is approved for adjuvant use with insulin. However, in clinical practice, various drugs against type 2 diabetes have been used off label with insulin for type 1 diabetes. Recently, the EMA approved the SGLT inhibitors dapagliflozin and sotagliflozin as adjuvant treatments to insulin for type 1 diabetes in adults. Areas covered : This article is a survey of adjuvant treatments used against type 1 diabetes, focusing on SGLT inhibitors...

BACKGROUND: Lactose-based induction strategy in E. coli cultivation has several advantages over IPTG as it is cheap, does not impart metabolic stress to cells, and is non-toxic to cells. However, complexity of lactose as an inducer limits its application in fed-batch cultivation. A mixed glycerol-lactose based induction strategy is generally opted during fed-batch cultivation of E. coli. However, slow growth of E. coli in glycerol and lactose results in slower induction of heterologous protein...

AIM: To assess whether a FiASP-and-pramlintide closed-loop system has the potential to replace carbohydrate counting with a simple meal announcement (SMA) strategy (meal priming bolus without carbohydrate counting) without degrading glycaemic control compared with a FiASP closed-loop system. MATERIALS AND METHODS: We conducted a 24-hour feasibility study comparing a FiASP system with full carbohydrate counting (FCC) with a FiASP-and-pramlintide system with SMA. We conducted a subsequent 12-day outpatient pilot study comparing a FiASP-and-placebo system with FCC, a FiASP-and-pramlintide system with SMA, and a FiASP-and-placebo system with SMA...

BACKGROUND: Amylin is a 37-amino-acid peptide hormone co-secreted with insulin, which participates in glucose homeostasis. This hormone is able to aggregate in a β-sheet conformation and deposit in islet amyloids, a hallmark in type II diabetes. Since amylin is a gene-encoded hormone, this peptide has variants caused by point mutations that can impact its functions. METHODS: Here, we analyzed the structural effects caused by S20G and G33R point mutations which, according to the 1000 Genomes Project, have frequency in East Asian and European populations, respectively...

Type 1 diabetes is defined as a state of hyperglycemia due to insulin deficiency caused by autoimmune pancreatic beta-cell destruction. The risk among individuals in the general population has been estimated at 0.5%. A family history of diabetes and a personal history of conditions associated with type 1 diabetes (ie, autoimmune diseases) increase the risk. Currently, the American Diabetes Association (ADA) recommends screening asymptomatic patients for type 1 diabetes autoimmune markers in the context of clinical research trials...

OBJECTIVES: A fully automated insulin-pramlintide-glucagon artificial pancreas that alleviates the burden of carbohydrate counting without degrading glycemic control was iteratively enhanced until convergence through pilot experiments on adults with type 1 diabetes. METHODS: Nine participants (age, 37±13 years; glycated hemoglobin, 7.7±0.7%) completed two 27-hour interventions: a fully automated multihormone artificial pancreas and a comparator insulin-alone artificial pancreas with carbohydrate counting...

OBJECTIVE: Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP). METHODS: Thirty-six migraine without aura patients were enrolled in a randomized, double-blind, 2-way, crossover, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days...

Obesity and associated comorbidities are a major health burden, and novel therapeutics to help treat obesity are urgently needed. There is increasing evidence that targeting the amylin receptors (AMYRs), heterodimers of the calcitonin G protein-coupled receptor (CTR) and receptor activity-modifying proteins, improves weight control and has the potential to act additively with other treatments such as glucagon-like peptide-1 receptor agonists. Recent data indicate that AMYR agonists, which can also independently activate the CTR, may have improved efficacy for treating obesity, even though selective activation of CTRs is not efficacious...

Injections of insulin are the main treatment for diabetes, but in the long run this therapy can induce serious drawbacks. This has inspired new drugs able to decrease insulin requirements. For instance, human amylin (hIAPP) is a small hormone cosecreted by pancreatic β-cells with insulin to which is a synergistic partner. 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)...

OBJECTIVE: Pramlintide has been shown to improve postprandial Blood Glucose (ppBG) as an adjunct to insulin. So far, pramlintide and insulin have to be injected separately as a co-formulation was not available. ADO09 is a stable co-formulation of pramlintide and an insulin analog formulated at acidic pH. This double-blind, double-dummy, randomised, cross-over meal test trial compared the safety, pharmacokinetics and pharmacodynamics of ADO09 with insulin lispro (lispro) and separate subcutaneous injections of human insulin and pramlintide (Ins&Pram) in 24 subjects with T1D...

PURPOSE OF REVIEW: Insulin is the mainstay of treatment in people living with type 1 diabetes mellitus due to an immune-mediated loss of beta cells. Yet despite advances in insulin therapy and other technological advances, glycemic control remains difficult to achieve. Therefore, we aim to highlight risks and benefits of adjunctive therapies that may improve type 1 diabetes care. RECENT FINDINGS: We identified studies assessing clinical outcomes of adjunctive therapies that are both Food and Drug Administration (FDA)-approved and off-label in type 1 diabetes...

Background and purpose: Irregularities of angiogenesis may participate in the pathogenesis of diabetes complications. Pramlintide is an amylin analogue administered for the treatment of type 1 and type 2 diabetes. The present investigation aimed at surveying the effect of pramlintide on angiogenesis-related markers in human umbilical vein endothelial cells (HUVECs). Experimental approach: The proliferation of cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) method...

AIM: To assess the efficacy and safety of glucose-lowering drugs used as an adjunct to insulin therapy in adults with type 1 diabetes. METHODS: We searched Medline, Embase and the Cochrane Central Register of Controlled Trials up to 24 January 2020 for randomized controlled trials. Our primary outcome was change in HbA1c. We additionally assessed eight efficacy and six safety secondary endpoints. We performed random effects frequentist network meta-analysis to estimate mean differences (MDs) and odds ratios (ORs), alongside 95% confidence intervals (CIs)...

A large proportion of persons with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) do not reach the glycosylated haemoglobin (HbA1c) target of < 7% (53 mmol/mol) with an increasing proportion of them being overweight or obese. In both T1DM and T2DM, there is accelerated gastric emptying and postprandial hyperglucagonemia. Furthermore, insulin therapy itself is associated with risk of hypoglycemia and weight-gain both of which are barriers to achieving good control. Medications which can achieve significant HbA1c and weight reduction associated with an ability to delay gastric emptying and suppress the glucagon secretion with minimal/no hypoglycemia are of particular interest as an adjuvant to insulin...

Amylin is a pancreatic hormone cosecreted along with insulin and involved in pancreatic amyloidosis and β-cell apoptosis in diabetic cats and humans. Amylin is usually elevated in early stages of type 2 diabetes but recently was found to be increased in acute and chronic pancreatitis in humans. Currently, there are little data about feline amylin propensity to fibrillate and no information on circulating levels of this hormone during feline pancreatitis. 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...

PURPOSE OF REVIEW: Obesity is increasing in prevalence among patients with type 1 diabetes (T1D) and is associated with insulin resistance and increased cardiovascular risk. The management of obesity in this population is complicated by defects in pancreatic islet hormone secretion and the effects of exogenous insulin treatment. Here, we review the effects of antiobesity medications and adjunct-to-insulin medications on body weight in T1D. RECENT FINDINGS: There is a profound evidence gap around the use of drugs for the treatment of obesity in T1D since systematic studies have not been performed in this population...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In spite of developments with novel insulin preparations, novel modes of insulin delivery with insulin infusion pumps, and the facility of continuous glucose monitoring, only 20% of patients with type 1 diabetes are under adequate control. The need for innovation is clear, and, therefore, the use of adjunct therapies with other pharmacological agents currently in use for type 2 diabetes, has been tried. Currently, pramlintide is the only agent licensed for use in this condition in addition to insulin. 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...

Objective: To report a massive increase in subcutaneous insulin requirements following spinal cord injury in a type 1 diabetic and how it was managed over a 22-month period with pramlintide. Methods: A case report and brief literature review is presented. Results: The patient is a 43-year-old male who was diagnosed with type 1 diabetes mellitus at age 18. He remained relatively well-controlled without end-organ complications until age 37, when he developed a spinal epidural abscess following a methicillin-resistant Staphylococcus aureus cellulitis of the foot...