Evaluation of PET/MR Enterography for Differentiation of Fibrotic and Inflammatory Strictures in Patients With Crohn's Disease Using a Collagen-binding Radiotracer.

In this study twenty-five (25) subjects with Crohn's disease scheduled for possible surgical intervention will be recruited for this study and a PET/MR scan using the collagen-binding radiotracer will be performed. The study aims to establish the performance figures of PET/MR using [68Ga]CBP8-PET for preoperative detection and differentiation of strictures with a fibrotic component in patients with Crohn's disease by using surgical and histologic findings (when available) as the standard for comparison. Furthermore, the investigators will determine the performance figures with which strictures are identified and characterized by PET/MR using [68Ga]CBP8-PET compared to each modality in isolation (PET alone or MR alone). Blood and tissue markers for fibrostenosis will be explored (either predictive or as biomarkers for fibrotic burden), using histologic and molecular testing by using surgical and histologic findings (when available) as the standard for comparison. Lastly the investigators want to determine the performance figures with which strictures are identified and characterized by PET/MR using [68Ga]CBP8-PET compared to each modality in isolation (PET alone or MR alone).

Start Date19 Dec 2023

Sponsor / Collaborator

Takeda Development Center Americas, Inc.

NCT05960565 / RecruitingPhase 2IIT

Glucagon Enhanced Insulin Absorption in Diabetes Mellitus Type 1

The investigators will study the effect of microdoses of glucagon at the site of subcutaneous insulin injection. The investigators have unpublished data from anesthetized pigs indicating a major enhancement of insulin absorption.

Start Date20 Jun 2023

Sponsor / Collaborator

St. Olavs Hospital hf

NCT05500586 / RecruitingPhase 1/2IIT

The Effects of Glucagon on Hepatic Metabolism

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

Start Date20 Oct 2022

Sponsor / Collaborator

Mayo Clinic

100 Clinical Results associated with Glucagon

100 Translational Medicine associated with Glucagon

100 Patents (Medical) associated with Glucagon

8,144

Literatures (Medical) associated with Glucagon

01 Dec 2024·Clinical endocrinology

Paediatric perspectives in the diagnosis of polyuria‐polydipsia syndrome

Review

Author: Huynh, Tony ; Signal, Dana ; Christ‐Crain, Mirjam

Abstract:

The elucidation of the underlying cause of polyuria‐polydipsia syndrome (PPS) is a challenging—especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated‐copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population—incorporating the differences in physiological regulation of water homeostasis, and safety requirements—before there is widespread adoption into clinical practice.

01 Dec 2024·CELLULAR AND MOLECULAR NEUROBIOLOGY

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon

Review

Author: Alrouji, Mohammed ; Papadakis, Marios ; Assiri, Abdullah A ; Hadi, Najah R ; Al-Kuraishy, Hayder M ; Batiha, Gaber El-Saber ; Al-Gareeb, Ali I ; Welson, Nermeen N ; Ali, Naif H ; Alexiou, Athanasios

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aβ) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.

01 Nov 2024·Molecular Metabolism

Dietary protein defends lean mass and maintains the metabolic benefits of glucagon receptor agonism in mice

Article

Author: Tan, Tricia M.M. ; Bloom, Stephen R ; Ramos-Pittol, Jose M ; Curtis, Anna ; Murphy, Kevin G ; Lopes, Tatiana ; Hope, David C.D. ; Sardini, Alessandro ; Minnion, James S ; Shrewsbury, Jed V ; Shrewsbury, Jed ; Hope, David Cd ; Carling, David ; Minnion, James S. ; Tan, Tricia Mm ; Bewick, Gavin A ; Davies, Iona ; Dormann, Dirk ; Bewick, Gavin ; Zhou, Zijing ; Bloom, Stephen R. ; Owen, Bryn M ; Owen, Bryn M. ; Ramos-Pittol, Jose M. ; Murphy, Keving G.

OBJECTIVE:

Glucagon has long been proposed as a component of multi-agonist obesity therapeutics due to its ability to induce energy expenditure and cause weight loss. However, chronic glucagon-receptor agonism has been associated with a reduction in circulating amino acids and loss of lean mass. Importantly, it is currently not known whether the metabolic benefits of glucagon can be maintained under contexts that allow the defence of lean mass.

METHODS:

We investigate the metabolic effects of the long-acting glucagon receptor agonist, G108, when administered to obese mice at low-doses, and with dietary protein supplementation.

RESULTS:

Dietary protein supplementation can only fully defend lean mass at a low dose of G108 that is sub-anorectic and does not reduce fat mass. However, in this context, G108 is still highly effective at improving glucose tolerance and reducing liver fat in obese mice. Mechanistically, liver RNA-Seq analysis reveals that dietary protein supplementation defends anabolic processes in low-dose G108-treated mice, and its effects on treatment-relevant glucose and lipid pathways are preserved.

CONCLUSION:

Glucagon-mediated energy expenditure and weight loss may be mechanistically coupled to hypoaminocidemia and lean mass loss. However, our data suggest that glucagon can treat MAFLD at doses which allow full defence of lean mass given sufficient dietary protein intake. Therefore, proportionate glucagon therapy may be safe and effective in targeting hepatocytes and improving in glycaemia and liver fat.

News (Medical) associated with Glucagon

05 Nov 2024

·endpts.com

Zealand’s ‘aspirational’ mission for its amylin drug to be first-line in obesity

SAN ANTONIO — Zealand Pharma, hoping to create the next “foundational” therapy for obesity, detailed more Phase 1 data on its amylin analog that was the backbone of a $1 billion raise this summer. Researchers said Zealand’s drug, dubbed petrelintide, led to up to 8.6% mean weight loss in an early-phase trial. Also, all gastrointestinal disorders observed in the study were mild, save for a moderate case of nausea and a moderate incidence of vomiting. The data were presented Tuesday at the annual ObesityWeek conference in Texas. Zealand initially toplined the data in June and quickly raised $1 billion for the “ crown jewel .” Analysts have predicted petrelintide could reach peak sales of $10 billion. At week 16 in the Phase 1, patients on 2.4 mg petrelintide lost a mean 4.8% body weight. The middle-dose group, 4.8 mg, lost the most at 8.6%, and the 9 mg group saw 8.3% reductions, the researchers said. The drop was 1.7% for the placebo cohort. Petrelintide could potentially have GLP-1-like weight loss of 15% to 20% in larger studies, Zealand chief medical officer David Kendall told Endpoints News on the sidelines of the conference. It also believes amylin agonists could help preserve lean muscle mass, an issue that has come up with the GLP-1 class. The company will dose the first patient in a Phase 2 trial in the coming days or weeks, Kendall said. The study will “elucidate” the differences between the 4.8 mg and 9 mg doses, he said. Zealand is positioning the drug as a potential standalone replacement for GLP-1s or as the first medicine that patients go to for obesity, but the company isn’t excluding the opportunity to combine with GLP-1s or other mechanisms, Kendall said. Novo Nordisk and Eli Lilly have dominated the field so far, but their GLP-1-based medicines carry GI tolerability baggage, among other challenges. Rather than suppress appetite and give patients a “food aversion” signal like the GLP-1s, amylin emphasizes the satiety signal, Kendall said. In his career, he’s worked in both the amylin field at Amylin Pharmaceuticals and on GLP-1s and other mechanisms at Lilly. “If you’ve had a meal here in Texas, you know what satiety feels like. That sense of, I’ve had enough, maybe a little bit too much,” Kendall said. “It actually enhances that signal so you don’t have that same food aversion, the lack of interest. So people tend to eat.” Petrelintide has a 240-hour half-life, or about 10 days, Kendall said. Novo, Lilly, AstraZeneca and multiple other drugmakers are also working on amylin. The field awaits a key Phase 3 readout this quarter from Novo’s CagriSema, a combination of the amylin asset cagrilintide and its blockbuster semaglutide. Novo’s amylin drug “will always be tied to semaglutide,” Kendall said. “We see petrelintide as the next potentially foundational class of therapies going forward. I know it seems maybe aspirational to say over and above what is a pretty successful GLP-1-based therapeutic class.” Structure Therapeutics, which plans to start testing its amylin candidate in humans next year, is looking up to Zealand’s progress. “Zealand is probably the pioneer in terms of pushing the monotherapy as part of their strategy,” Structure CEO Raymond Stevens said in an interview on the sidelines of the conference. “Some of the hypothesis is: amylin has the potential for better tolerability by itself, amylin alone, versus GLP-1.” As Zealand works on the Phase 2, it is looking for a large pharma to help carry petrelintide into Phase 3 and make it a standalone drug. With a fresh $1 billion, though, Zealand is “not backs-against-the-wall,” Kendall said. “The most important thing is not just to find someone with lots of people and deep pockets, but someone who believes in the positioning we’ve talked about.” Zealand already has a partner for its lead obesity drug, the Boehringer Ingelheim-allied survodutide, a glucagon/GLP-1 receptor dual agonist.

Phase 1Clinical ResultPhase 3Phase 2

11 Oct 2024

·www.globenewswire.com

Zealand Pharma provides U.S. regulatory update on dasiglucagon in congenital hyperinsulinism

Zealand Pharma provides U.S. regulatory update on dasiglucagon in congenital hyperinsulinism U.S. Food and Drug Administration (FDA) issues Complete Response Letter (CRL) for dasiglucagon in CHI for up to three weeks of dosing due to the timing of a third-party manufacturing facility reinspection The reinspection of the facility was completed in August/September 2024 for which a new inspection classification is pending Zealand remains committed to working with the FDA and the third-party manufacturer to bring dasiglucagon to patients in the U.S. as soon as possible October 9, 2024 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for Part 1 of the New Drug Application (NDA) for dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with congenital hyperinsulinism (CHI) for up to 3 weeks of dosing. The CRL is related to the timing of a reinspection at a third-party contract manufacturing facility that was completed in August/September 2024. The third-party manufacturer has not yet received its inspection classification following the reinspection. A prior inspection of the facility had identified deficiencies that did not involve dasiglucagon. These prior deficiencies had been resolved as of this reinspection. The CRL did not state any concerns about the clinical data package or safety of dasiglucagon. “We at Zealand Pharma are acutely aware of the significant unmet medical need for newborns and children with congenital hyperinsulinism who have either no or very limited treatment options today,” said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. “We are committed to working with the FDA and our third-party manufacturing partner to bring dasiglucagon to patients living with this devastating disease in the months ahead.” The regulatory review of dasiglucagon is being conducted in two parts under the same NDA. Part 1 relates to dosing of up to 3 weeks and Part 2 relates to the use beyond 3 weeks. Supporting the use of dasiglucagon in CHI beyond 3 weeks, the FDA requested additional analyses from existing continuous glucose monitoring (CGM) datasets from the Phase 3 clinical program. Zealand expects to submit these data by the end of 2024. Congenital hyperinsulinism (CHI) is a severe, ultra-rare genetic disease, primarily affecting infants and children, in which the pancreatic beta cells dysfunction and secrete too much insulin, leading to frequent, recurrent, and often severe episodes of hypoglycemia. Persistent episodes of hypoglycemia can result in seizure, brain damage and death.1,2 It is estimated that CHI develops in one out of 50,000 (or more) children, corresponding to 180-300 newborns being diagnosed with the disease in the US and Europe every year.3,4 CHI has a significant impact on patient quality of life. Complex care requirements, including continuous intravenous infusion of glucose, can result in lengthy and frequent hospitalizations and make daily social activities difficult for both patients and their families. The only currently approved medical treatment for hyperinsulinism is diazoxide, which can be associated with increased risk of fluid retention, pulmonary hypertension, and congestive heart failure.5 Glucagon and the somatostatin analog octreotide may be used but are not approved therapies. It is estimated that more than 50% of CHI patients do not respond adequately to the medical treatment options currently available, so there remains a significant unmet medical need for more and better treatment options.6 Dasiglucagon is a glucagon receptor agonist that works by causing the liver to release stored sugar to the blood and is being evaluated for the prevention and treatment of hypoglycemia in infants and children with congenital hyperinsulinism. Dasiglucagon is designed to be administered by continuous subcutaneous infusion using a wearable pump system. Zealand Pharma has a collaborative development and supply agreement with DEKA Research & Development Corporation and affiliates for the wearable subcutaneous infusion pump system. Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products. Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand’s business and activities, please visit www.zealandpharma.com. References 1) Thornton PS et al. (2015) Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children, J Pediatr. 2015;167(2):238-45. 2) Banerjee I et al. (2022) Correction to: Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families, Orphanet J Rare Dis. 2022;17:61. 3) Arnoux JB et al. (2011) Congenital hyperinsulinism: current trends in diagnosis and therapy, Orphanet J Rare Dis. 2011; 6:63. 4) Yau et al. (2020) Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389, Plos One. 2020;15(2). 5) PROGLYCEM® (diazoxide) oral suspension package insert (07/18/2024) https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/017453s024lbl.pdf (accessed October 7, 2024) 6) Yorifuji et al. (2017) Clinical practice guidelines for congenital hyperinsulinism, Clin Pediatr Endocrinol. 2017;26(3):127-152. The content above comes from the network. if any infringement, please contact us to modify.

NDADrug Approval

09 Oct 2024

·www.biospace.com

Zealand Hit With CRL for Ultrarare Genetic Disease Treatment

iStock, Odairson Antonello The rejection is related to the timing of the FDA’s reinspection of Zealand’s third-party manufacturer, which previously had deficiencies. The FDA on Tuesday denied approval for Zealand Pharma’s dasiglucagon, which the Danish biotech was proposing for the treatment of congenital hyperinsulinism. According to the company’s announcement, the rejection is due to the timing of the FDA’s reinspection of a third-party contract manufacturer. In an initial visit, the FDA flagged “deficiencies” in the outside manufacturer that had been resolved by the time of its second inspection. However, Zealand’s service provider has yet to receive its inspection classification after the regulator’s second visit in August/September 2024. The FDA did not identify concerns regarding dasiglucagon’s clinical data package, nor did it find safety issues with the drug candidate. CMO David Kendall said in a statement that Zealand will continue working with its contract manufacturer and the FDA to “bring dasiglucagon to patients living with this devastating disease in the months ahead.” Congenital hyperinsulinism (CHI) is an ultrarare genetic disease that affects one out of 50,000 children. In the U.S. and Europe, around 180 to 300 newborns are diagnosed with CHI every year. CHI develops when beta cells in the pancreas are dysfunctional and secrete too much insulin. Patients suffer from frequent and severe hypoglycemic episodes, which in turn can lead to seizures, brain damage and even death. Currently, the only FDA-approved therapy for hyperinsulinism is the potassium channel activator diazoxide, which carries risks of fluid retention, congestive heart failure and pulmonary hypertension. Other patients are given glucagon or ocreotide, but these are not approved for CHI. Patients with CHI “have either no or very limited treatment options today,” Kendall said. Zealand’s answer to CHI is dasiglucagon, a glucagon receptor agonist that works by triggering the secretion of stored sugars from the liver. This mechanism of action allows dasiglucagon to counteract the excess insulin typical in CHI patients. In May 2022, Zealand posted Phase III CHI data for dasiglucagon, touting a 55% reduction in the need for intravenous glucose versus placebo. Dasiglucagon is approved for the treatment of severe hypoglycemia in diabetes patients, for which it is marketed under the brand name Zegalogue. The FDA is reviewing Zealand’s CHI application for dasiglucagon in two parts . The first, which was handed the rejection on Tuesday, covers dosing for up to three weeks. The second part is for dasiglucagon dosing beyond three weeks, for which Zealand expects to analyses by the end of 2024.

Phase 3Drug ApprovalClinical ResultOligonucleotide

100 Deals associated with Glucagon

External Link

KEGG	Wiki	ATC	Drug Bank
-	Glucagon	H04AA01	DB00040

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus	CA	Eli Lilly Canada, Inc.	25 Sep 2019
Hypoglycemia	US	Eli Lilly & Co.	14 Nov 1960

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 1	Phase 3	US	Eli Lilly & Co.	01 Nov 2013
Diabetes Mellitus, Type 2	Phase 1	CA	Eli Lilly & Co.	01 Jun 2014
Common Cold	Phase 1	CA	Eli Lilly & Co.	01 Mar 2013

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Baqsimi (ESPE2022)	Not Applicable	HbA1c	68	Baqsimi® 3 mg	iodmqyqjgh(jimwqjcfht) = 21% ehpnjlgwtb (ydaqajzzmi ) View more	Positive	15 Sep 2022
ADA2022	Not Applicable	-	-	Intraislet Glucagon (GCGRKOβ-cells-/-)	dsqkkskdxl(ynucoxlzyw) = vdkxrsohtv jmxagcafac (keqsqrtabj )	-	01 Jun 2022
				Intraislet Glucagon (Littermate controls)	dsqkkskdxl(ynucoxlzyw) = uqxmmnjnsq jmxagcafac (keqsqrtabj )
ADA2022	Not Applicable	Diabetes Mellitus	-	Nasal Glucagon	qcertkkshe(vidcjmlozm) = swvuvrjkoa mcmhqodwse (xwjosvzwkg )	-	01 Jun 2022
EASD2021	Not Applicable	Hypoglycemia type 2 diabetes	-	Nasal Glucagon (NG)	flhntlcchn(trqhwdqxyc) = qjjvpxdwam wauvlssykh (fnewyvpvfp ) View more	Positive	30 Sep 2021
				Liquid Stable Glucagon Rescue Pen (GRP)	flhntlcchn(trqhwdqxyc) = nahcejvumo wauvlssykh (fnewyvpvfp ) View more
ADA2021	Not Applicable	Hypoglycemia	-	Nasal Glucagon	xryberndiu(wzdxftlrhs) = jcjfqwejjn ozoagkfcxw (thwtvjeruy )	-	01 Jun 2021
				Liquid Stable Glucagon Rescue Pen	xryberndiu(wzdxftlrhs) = dzbnxdewzn ozoagkfcxw (thwtvjeruy )
ADA2021	Not Applicable	Hypoglycemia	-	Nasal Glucagon	htrgfgyfbs(otjywfaasd) = onauqowziv osexhehwpf (mnkcimcmql ) View more	-	01 Jun 2021
				Reconstituted Injectable Glucagon	htrgfgyfbs(otjywfaasd) = xurcmkfqnl osexhehwpf (mnkcimcmql ) View more
NCT03421379 \| NCT03339453 (EASD2020)	Not Applicable	Hypoglycemia	-	Nasal glucagon	vekskjezio(gmuvedibct) = odlbokfnbf lgtpablaqk (unpojmtmwm ) View more	Positive	24 Sep 2020
				Injectable glucagon	vekskjezio(gmuvedibct) = dytkliycdz lgtpablaqk (unpojmtmwm ) View more
EASD2020	Not Applicable	-	-	Glucagon infusion	redqtobcoy(grvupmpthe) = leglgbqwcj knzmcrfewo (ufvhsagclr ) View more	-	22 Sep 2020
				Control (no glucagon)	redqtobcoy(grvupmpthe) = uuctneksvq knzmcrfewo (ufvhsagclr ) View more
NCT03421379 (Pubmed \| Diabetes Obes Metab) Manual	Phase 3	Diabetes Mellitus	75	Glucagon Nasal Powder	eyzxywjzjm(dxdhohipdg) = xsqqdeyehf ocypcgcqkh (yitoxqeywk )	Non-inferior	01 Jul 2020
				Glucagon Hydrochloride Solution	eyzxywjzjm(dxdhohipdg) = cxcyomqwwt ocypcgcqkh (yitoxqeywk )

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