In this study the investigators will investigate the acute effects of increasing glucagon exposure on metabolic parameters in healthy participants.
Participants will participate in one study day. After initial baseline blood samples, a three-hour intravenous infusion with glucagon will be initiated. The infusion rate will be increased every 30 minutes.

Start Date01 Apr 2025

Sponsor / Collaborator

University of Copenhagen

NCT06424106

/ RecruitingNot ApplicableIIT

Effect of Glucagon on Fasting Insulin Secretion and Glucose Metabolism in Subjects Without Type 2 Diabetes

Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.

Start Date01 Apr 2025

Sponsor / Collaborator

Mayo Clinic

NCT06877208

/ Not yet recruitingNot Applicable

The Effect of Glucagon on Cerebral Glucose Metabolism in Healthy Humans

This is a pilot study in which the investigators will investigate the effect of exogenous glucagon on cerebral glucose metabolism in healthy humans.
Participants will participate in either part C or part D of the study, and each participant will participate in three study days. During a study day the participant will receive an intravenous infusion of either glucagon, glucose (in an adjustable rate to match to glucose concentrations achieved with the glucagon infusion) or saline. During each study day an 18F-flouro-deoxy-glucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) scan will be performed to quantify cerebral glucose metabolism during the first part (acute effect) of the glucagon/glucose/saline infusion (part C) or the last part (later effect) of the glucagon/glucose/saline infusion (part D).

Start Date01 Mar 2025

Sponsor / Collaborator

University of Copenhagen

100 Clinical Results associated with Glucagon

100 Translational Medicine associated with Glucagon

100 Patents (Medical) associated with Glucagon

8,654

Literatures (Medical) associated with Glucagon

01 May 2025·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

LYPLAL1 enzyme activity is linked to hepatic glucose metabolism

Article

Author: Lefebvre, David ; Chen, Xinhzu ; Bélanger, Étienne ; Filip, Roxana ; Pezacki, John Paul ; Uguccioni, Spencer M

The serine hydrolase LYPLAL1 is a poorly characterised enzyme with emerging roles in hepatic metabolism. A multitude of association studies have shown links between variants of this gene locus and metabolic conditions such as obesity and insulin resistance. However, the enzyme's function is still largely unknown. Recent biochemical studies have revealed that it may play a role in hepatic glucose metabolism and that its activity is allosterically regulated. Herein, we use a selective activity-based probe to delineate LYPLAL1's involvement in hepatic metabolism. We show that the enzyme's activity is modulated during metabolic stress, specifically pointing to a putative role in negatively regulating gluconeogenesis and upregulating glycolysis. We also determine that knock-out of the enzyme does not affect liver lipid profiles and bring forth evidence for insulin-mediated control of LYPLAL1 in HepG2 cells. Furthermore, LYPLAL1 activity appears to be largely post-translationally regulated as gene expression levels remain largely constant under insulin and glucagon treatments. Taken together these data point to an enzymatic role in regulating glucose metabolism that may be part of a feedback mechanism of signal transduction.

01 Apr 2025·DIABETIC MEDICINE

Exploring low‐dose glucagon for exercise‐induced hypoglycaemia in type 1 diabetes: A randomised controlled trial

Article

Author: Ranjan, Ajenthen Gayathri ; Lundemose, Sissel Banner ; Laugesen, Christian ; Nørgaard, Kirsten

Abstract:

Aims:

This study was designed to compare the effectiveness of a single subcutaneous (s.c.) glucagon dose versus the same total dose split into a dose before and after and placebo (PBO) in preventing exercise‐induced hypoglycaemia in adults with type 1 diabetes (T1D).

Methods:

Twenty‐two adults with T1D participated in a randomised, single‐blinded, three‐arm crossover study. Participants underwent a 60‐min bout of moderate‐intensity cycle ergometry (~50% HRmax) in fasted state, followed by 2 h of rest. Plasma glucose (PG) concentrations were monitored at 5‐ and 15‐minute intervals. Participants were randomly assigned to receive two separate injections before (t = 0 min) and just after (t = 60 min) exercise: (i) 150 μg s.c. glucagon (G150) before and PBO after; (ii) 75 μg s.c. glucagon (G75*2) before and after; or (iii) PBO before and after. Insulin pump users reduced their basal insulin rate by 50% during cycling.

Results:

The occurrence of hypoglycaemia did not significantly differ between arms (G150: 7, G75*2: 5 and PBO: 6 events, p = 0.078). Mean PG levels throughout the trial were lower in the PBO arm compared to both glucagon arms (G150: 8.6 ± 2.9, G75*2: 8.9 ± 3.4 and PBO: 7.3 ± 2.6 mmol/L, p = 0.015). Time spent with PG in target range (3.9–10.0 mmol/L) was higher in the PBO arm versus both glucagon arms (G150: 63.9 ± 38.9%, G75*2: 60.0 ± 34.1% and PBO: 82.7 ± 29.6%, p = 0.005), driven by less time above range (G150: 32.9 ± 41.3%, G75*2: 35.9 ± 36.4% and PBO: 13.2 ± 30.2%, p = 0.007).

Conclusions:

Low‐dose native glucagon did not offer any advantages in preventing exercise‐induced hypoglycaemia in individuals with T1D, regardless of glucagon dosing variations.

01 Apr 2025·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Molecular characterization of AMP-activated protein kinase (AMPK) α1/α2 from Cyprinus carpio and its roles in glucolipid metabolism and immune response

Article

Author: Yan, Xiao ; Zhao, Mengjuan ; Qin, Chaobin ; Zhi, Shaoyang ; Yang, Liping ; Li, Yijie ; Wang, Junli ; Wang, Yiran ; Nie, Guoxing

AMPKα1 and AMPKα2, key kinases in regulating energy homeostasis, have not been previously cloned or characterized in common carp (Cyprinus carpio). This study identified the open reading frame (ORF) sequences of ampkα1 (1722 bp, encoding 573 amino acids) and ampkα2 (1659 bp, encoding 552 amino acids) through homologous cloning. Sequence alignment and phylogenetic analysis showed a high similarity of both genes with fish homologs. Expression analysis revealed that ampkα1 and ampkα2 are widely expressed across tissues in carp, with ampkα1 highly expressed in the gonads and ampkα2 in the heart. Fasting significantly reduced ampkα1 expression in the heart, adipose tissue, and foregut but increased it in the hindgut and white muscle. Similarly, ampkα2 expression decreased in the hypothalamus and muscle during fasting, with an increase in the midgut. Glucose tolerance tests showed dynamic regulation of ampkα1 and ampkα2, with initial downregulation followed by upregulation in the hepatopancreas, red muscle, and brain. High-glucose and high-fat diets significantly increased ampkα1 and ampkα2 expression in multiple tissues. Insulin and glucagon treatment induced time-dependent changes in both genes in hepatocytes, while Aeromonas hydrophila infection, LPS, and Poly (I:C) stimulation upregulated ampkα1 and ampkα2 in immune-related tissues. Knockdown of ampkα2, but not ampkα1, reduced glut1b mRNA levels, while both knockdowns of ampkα1 and ampkα2 promoted the expression of gsk3β, pygm, acc, fas, srebp, cs, and pro-inflammatory cytokines, suggesting their involvement in metabolic and immune regulation in carp.

News (Medical) associated with Glucagon

17 Apr 2025

·www.pharmaceutical-technology.com

Eli Lilly’s shares up as oral GLP-1RA scores in first Phase III trial

Baqsimi was launched as an option to provide rescue treatment for diabetes patients who take insulin. Credit: Diabetesmagazijn.nl on Unsplash. Eli Lilly’s Phase III trial with its oral weight loss pill, orforglipron, has met its primary endpoint, reducing A1C levels by up to 1.6%. In the first of several readouts expected from a Phase III programme, Lilly said its oral glucagon-like peptide-1 receptor agonist (GLP-1RA) demonstrated significant efficacy while maintaining a safety profile consistent with subcutaneously delivered GLP-1RA drugs. Eli Lilly’s stock jumped up by 13.8% at market open today (17 April). The company has a market cap of $659.93bn. This news comes just days after Pfizer culled its second obesity pill due to a liver injury incident in a patient . The manageable safety profile of Lilly’s drug marks an important development in the field of oral GLP-1RAs . Based on this update and other trials from the programme that are due to read out later this year, Lilly expects to submit an approval application for orforglipron as a weight management treatment to global regulatory agencies by the end of this year, with the submission for the treatment of type 2 diabetes (T2D) anticipated in 2026. If it gains market approval, GlobalData predicts sales of orforglipron to reach $11.8bn in 2030. The global GLP-1RA market is experiencing substantial growth and is projected to reach $125bn by 2033. GlobalData is the parent company of Clinical Trials Arena . Efficacy and safety proven in first study In the randomised, placebo-controlled, double-blind ACHIEVE-1 trial (NCT05971940), the efficacy and safety of three doses – 3mg, 12mg and 36mg – of orforglipron were evaluated in adults with T2D and inadequate glycemic control with diet and exercise alone. The drug reduced A1C levels by an average of 1.3% to 1.6% from a baseline of 8.0% after 40 weeks. It also scored in a key secondary endpoint, with more than 65% of participants taking the highest dose of orforglipron achieving an A1C less than or equal to 6.5%, which is below the American Diabetes Association’s (ADA) defined threshold for diabetes. Finally, there was significant weight loss achieved in the study, with patients losing an average of 16lb (7.9%) in the highest dose cohort. This weight loss had not plateaued, indicating potential further weight loss could be possible with further dosing. Meanwhile, the placebo cohort saw an average weight loss of 3.4lb. In addition to the efficacy, Lilly has also touted that orforglipron’s safety profile in ACHIEVE-1 and said it was consistent with the established GLP-1RA class, with the most commonly reported adverse events (AEs) being gastrointestinal-related and generally mild to moderate in severity. No hepatic safety signal was observed. Treatment discontinuation rates due to AEs were 6% in the low-dose group, 4% in the medium-dose cohort and 8% in the high-dose group compared to 1% with placebo. A Bank of America Securities report said that the four main parameters for assessing orforglipron were weight loss, blood sugar control, tolerability and safety, describing the data for all these as “solid”. This data readout was viewed as a closely watched event, and all eyes are now on Novo Nordisk’s oral GLP-1RA drug Rybelsus, which is approved for T2D, but not for weight management. The report said Rybelsus is a peptide with certain limitations, while orforglipron, being a small-molecule drug, could be easy to scale and produce. Eli Lilly’s CEO David Ricks said: “As a convenient once-daily pill, orforglipron may provide a new option and, if approved, could be readily manufactured and launched at scale for use by people around the world. We look forward to additional data readouts later this year.” Lilly states that orforglipron is the first oral small molecule GLP-1RA, taken without food and water restrictions, to successfully complete a Phase III trial. If approved, the company is confident in its ability to launch orforglipron worldwide without supply constraints, something that until recently has plagued the GLP-1RA market . Data is set to be presented at ADA’s 85th Scientific Sessions in June 2025 and published in a peer-reviewed journal. Lilly already a powerhouse in the weight loss space Eli Lilly has already cemented its name in the GLP-1RA space with its subcutaneous therapy, tirzepatide, which is marketed as Mounjaro for T2D and Zepbound for obesity. GlobalData predicts a global sales forecast for tirzepatide of $26.75bn in 2030. Its main competitor in the space currently is Novo Nordisk, which is also a high flier with its GLP-1RA semaglutide, marketed as Ozempic for T2D and Wegovy for weight loss. Other companies are trying to break into the space, including Viking Therapeutics, which is set to initiate trials of VK2735, with the subcutaneous formulation set to enter a Phase III trial in Q2 2025 and the oral version in an ongoing Phase II study (NCT06828055). While Pfizer pulled its oral candidate, danuglipron, from development earlier this week, the company does have another obesity pill – PF-07976016, which is in a Phase IIa trial.

Phase 3Clinical ResultPhase 2Drug Approval

22 Jan 2025

·www.fiercepharma.com

Xeris, stymied by forgetful physicians, partners with ADA to raise awareness of need for glucagon

The roadmap covers problems that Xeris has identified as barriers to growth of Gvoke. Xeris Pharmaceuticals has teamed up with the American Diabetes Association (ADA) to raise awareness of the importance of prescribing glucagon, positioning the partners to address a fundamental barrier to the use of products such as its Gvoke.The FDA approved Gvoke, a ready-to-use glucagon product, for the treatment of severe hypoglycemia in 2019. The format is potentially more convenient than traditional glucagon kits from the likes of Fresenius Kabi and Amphastar, but Xeris has struggled to penetrate the vast opportunity. Xeris said it ended 2024 with a 35% market share, but the vast majority of people at risk of low blood glucose don’t carry an emergency kit.Supported by Xeris, the ADA wants to rectify low rates of glucagon prescriptions. The multi-year pact between the organizations will support development of education materials and training resources for healthcare professionals and people living with diabetes. A push to educate those groups on who is at risk for severe hypoglycemia and should have glucagon is also on the agenda.The roadmap covers problems that Xeris has identified as barriers to the growth of Gvoke. ADA guidelines state that “glucagon should be prescribed for all individuals taking insulin or at high risk for hypoglycemia” and that ready-to-use preparations are preferred. Despite that, uptake of Gvoke and rival ready-to-use kits is low. Speaking at a Piper Sandler event last month, Kevin McCulloch, chief operating officer at Xeris, estimated that 15 million people with diabetes in the U.S. are at “outsized risk of having their blood sugar go too low.” Yet, McCulloch said, only around 1 million people carry a glucagon product—and he claimed to know why.“We find that the No. 1 reason that a prescriber doesn't prescribe Gvoke might surprise you: It’s they don't remember. It isn't any of the other things that you might traditionally associate with barriers to the adoption of pharmaceuticals. It's actually in remembering,” McCulloch said. “Very busy clinicians treating diabetes have a hard time remembering something like this that's brand new.”According to McCulloch, Xeris is the only glucagon company “out there advocating for the new guidelines and promoting in the space.” Amphastar's intranasal glucagon dry powder, Baqsimi, and Novo Nordisk’s dasiglucagon auto-injector, Zegalogue, compete with Gvoke. McCulloch said he had yet to see the rivals make a big contribution to the awareness push as of last month.“We're still really not hearing much from others, and we'd welcome more noise out there to create more awareness,” McCulloch said. “We think this is really just the reason for the delta between who has it and who should have it.”

Drug Approval

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

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	Canada	Eli Lilly Canada, Inc.	25 Sep 2019
Hypoglycemia	United States	Eli Lilly & Co.	14 Nov 1960

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 1	Phase 3	Canada	Eli Lilly & Co.	01 Sep 2013
Diabetes Mellitus, Type 2	Phase 3	Canada	Eli Lilly & Co.	01 Sep 2013
Common Cold	Phase 1	Canada	Eli Lilly & Co.	01 Mar 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ODP313 (ENDO2022)	Not Applicable	Diabetes Insipidus copeptin	-	Glucagon (Healthy Participants)	weesandmcd(uzsibhlzaf) = dztrewlknf orpaxwhhny (vvtdkconxg, 2.38 - 28.03)	Positive	01 Nov 2022
				Glucagon (Patients with Central Diabetes Insipidus)	weesandmcd(uzsibhlzaf) = icbhozolmb orpaxwhhny (vvtdkconxg, 0.21 - 1.65)
Baqsimi (ESPE2022)	Not Applicable	HbA1c	68	Baqsimi® 3 mg	kobkzpwkwq(ogfpvhgpfz) = 21% qwtvtldfkm (cmlopwscwx ) View more	Positive	15 Sep 2022
ADA2022	Not Applicable	-	-	Intraislet Glucagon (GCGRKOβ-cells-/-)	tfbtwpsfca(yqiezxqowc) = cpldcukmsj edpqaanojq (uvswqhojjg )	-	01 Jun 2022
				Intraislet Glucagon (Littermate controls)	tfbtwpsfca(yqiezxqowc) = dyczejaxlh edpqaanojq (uvswqhojjg )
ADA2022	Not Applicable	Diabetes Mellitus	-	Nasal Glucagon	hsbuaoaqjt(sbzesoeblr) = cfjqrrbfsp mvbwzesrzi (qqrvutwkbe )	-	01 Jun 2022
EASD2021	Not Applicable	Hypoglycemia type 2 diabetes	-	Nasal Glucagon (NG)	qevihafkub(ibvkfygmgq) = hogfywmfrz jxveliqash (imhquntrfa ) View more	Positive	30 Sep 2021
				Liquid Stable Glucagon Rescue Pen (GRP)	qevihafkub(ibvkfygmgq) = ahcslzzdvt jxveliqash (imhquntrfa ) View more
ADA2021	Not Applicable	Hypoglycemia	-	Nasal Glucagon	mksipqqnia(dafovixyqm) = ftxojpqgtv uesvzwiuhd (lyxigbqwbm )	-	01 Jun 2021
				Liquid Stable Glucagon Rescue Pen	mksipqqnia(dafovixyqm) = tbrigiwnon uesvzwiuhd (lyxigbqwbm )
ADA2021	Not Applicable	Hypoglycemia	-	Nasal Glucagon	rgcptmipqi(cycvspsisw) = cvrwxeyxpz iugsusinrl (rjlrgfizto ) View more	-	01 Jun 2021
				Reconstituted Injectable Glucagon	rgcptmipqi(cycvspsisw) = bzkhvzsrdv iugsusinrl (rjlrgfizto ) View more
NCT03421379 \| NCT03339453 (EASD2020)	Not Applicable	Hypoglycemia	-	Nasal glucagon	pyzyuygrjc(dlnnvwoiis) = lutwakyalx gvwbshqxby (jfntqjhbhr ) View more	Positive	24 Sep 2020
				Injectable glucagon	pyzyuygrjc(dlnnvwoiis) = szbbnfrhhw gvwbshqxby (jfntqjhbhr ) View more
EASD2020	Not Applicable	-	-	Glucagon infusion	qqnkxdwufj(ffsfbvibpc) = nefbxvcbaq cwrypyorib (fnmnxoqaga ) View more	-	22 Sep 2020
				Control (no glucagon)	qqnkxdwufj(ffsfbvibpc) = cugprjqurv cwrypyorib (fnmnxoqaga ) View more

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