Effects of exogenous Glucagon-Like Peptide-1 (GLP-1) administration on gastric emptying during hyperglycaemic clamp experiments in healthy volunteers.

Start Date06 Sep 2013

Sponsor / Collaborator-

NCT01218633

/ CompletedPhase 1IIT

A Dose-response Study of the Effects of Exendin-9,39 on Glucose Metabolism, Glucagon and Insulin Secretion and on Insulin Action.

Multiple studies have examined the effect of endogenous GLP-1 secretions by using a competitive antagonist of GLP-1 - Exendin-9,39 - infused at rates of 300pmol/kg/min. However, the presence of an effect does not necessarily imply that this effect is due to the blockade of the endogenous GLP-1 actions at the receptor. It is possible that the supraphysiologic concentrations of Exendin may have effects of its own. To examine the effect of Exendin on glucose metabolism the investigators propose a dose-response study to determine whether the compound has effects in a dose-dependent fashion.

Start Date01 May 2011

Sponsor / Collaborator

Mayo Clinic

NCT01607450

/ CompletedPhase 2/3IIT

Modulation of Human Myocardial Metabolism by GLP-1 Dose Response

The objective of this proposal is to provide quantitative dose-response data for effects of GLP-1 on myocardial glucose uptake in healthy control subjects and obese type 2 diabetic subjects, in support of the design of later studies evaluating therapeutic applications of GLP-1 to heart disease.
Aim 1: To measure the effects of GLP-1 infusion on myocardial fuel selection in lean healthy humans under fasting (fatty acid-dominant) conditions. Four groups of 10 lean healthy subjects will be studied during infusions of 0 (saline control), 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 (one study per subject). Cardiac metabolism will be measured using PET, using a dual-tracer approach which allows measurement of myocardial glucose uptake (the primary endpoint) along with total oxidation rate and myocardial perfusion (secondary endpoints). In concert with measures of circulating metabolites and regulatory hormones, the investigators will produce the most comprehensive assessment of actions of GLP-1 on myocardial metabolism in humans to date. Effects of each dose will be compared to the saline control, plus the investigators will combine all data and use nonlinear curve-fitting to derive sensitivity (ED50) and maximal responses for GLP-1 effects on myocardial glucose uptake.
Aim 2: To measure the effects of GLP-1 infusion on myocardial fuel selection in obese type 2 diabetic humans under fasting (fatty acid-dominant) conditions Four groups of 10 obese type 2 diabetic subjects will be studied during infusions of 0, 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 as under Aim 1. Analyses will be parallel to those described under Aim 1. Results from Aims 1 and 2 will be combined to allow direct comparison of the dose-response between nondiabetic control and type 2 diabetic subjects.
No literature has been published to inform dose selection in the design of clinical trials of GLP-1 for modulation of heart fuel selection. With our expertise and experience in PET measurement of heart metabolism in diabetes, the investigators are uniquely positioned to fill this gap in knowledge. These studies are a necessary preamble to further evaluation of the potential for GLP-1 based treatments in heart disease.

Start Date01 May 2010

Sponsor / Collaborator

Indiana University

[+1]

100 Clinical Results associated with Glucagon-like peptide-1 ( MannKind Corporation)

100 Translational Medicine associated with Glucagon-like peptide-1 ( MannKind Corporation)

100 Patents (Medical) associated with Glucagon-like peptide-1 ( MannKind Corporation)

382

Literatures (Medical) associated with Glucagon-like peptide-1 ( MannKind Corporation)

31 Dec 2025·Journal of Pharmaceutical Policy and Practice

Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado

Article

Author: Saseen, Joseph J. ; Dardouri, Mouna ; Nair, Kavita V. ; Moore, Gina D. ; DiStefano, Michael J.

Background:

High prices and other access barriers have contributed to the rise of a market for compounded glucagon-like peptide-1 receptor agonists for weight loss in the United States. This market has not been systematically studied. We conducted a pilot study to assess the prevalence, characteristics, and advertising content of direct-to-consumer providers of compounded glucagon-like peptide-1 products for weight loss in Colorado.

Methods:

We conducted a cross-sectional study of websites advertising compounded glucagon-like peptide-1 products for weight loss in Colorado. Websites were identified using Google searches focused on census-defined statistical areas. Searches were conducted between March 21 and April 12, 2024. Data collected from websites included physical addresses, business type, highest reported staff credential, advertised glucagon-like peptide-1 products, whether businesses referred to Food and Drug Administration approval when describing products, and whether businesses referred to products as 'generic'.

Results:

We identified 93 business websites advertising compounded glucagon-like peptide-1 products for weight loss corresponding to 188 physical locations throughout Colorado. Most businesses were self-categorized as medical/health spas (33/93) or weight loss services (26/93). Advertised products included semaglutide (92/93), tirzepatide (40/93), liraglutide (2/93), and retatrutide (1/93). Advertised combination products included B vitamins (8/93), levocarnitine (1/93), mannitol (1/93), BPC-157 (1/93), and glycine (1/93). Seven websites advertised oral formulations. Additionally, 41/93 websites referred to Food and Drug Administration approval in their descriptions of compounded products and 5/93 referred to products as 'generic'.

Conclusion:

This study identified several instances of unapproved glucagon-like peptide-1 products being compounded and advertised in Colorado. Additionally, 1 product was advertised as compounded with BPC-157, a substance determined by the Food and Drug Administration to be unsafe for compounding. This study also identified numerous examples of misleading claims regarding the regulatory status of compounded glucagon-like peptide-1 products. Regulatory action is needed to ensure the benefits of compounded GLP-1 products outweigh the risks.

09 May 2025·ENDOCRINE REVIEWS

Antiobesity Pharmacotherapy for Patients With Genetic Obesity Due to Defects in the Leptin-Melanocortin Pathway

Review

Author: van den Akker, Erica L T ; van Rossum, Elisabeth F C ; Welling, Mila S

Abstract:

Lifestyle interventions are the cornerstone of obesity treatment. However, insufficient long-term effects are observed in patients with genetic obesity disorders, as their hyperphagia remains untreated. Hence, patients with genetic obesity often require additional pharmacotherapy to effectively manage and treat their hyperphagia and obesity. Recent advancements in antiobesity pharmacotherapy have expanded the range of available antiobesity medications (AOM). This includes the targeted AOM setmelanotide, approved for specific genetic obesity disorders, as well as nontargeted AOMs such as naltrexone-bupropion and glucagon-like peptide-1 analogues. Targeted AOMs have demonstrated significant weight loss, reduced obesity-related comorbidities, and improved hyperphagia and quality of life in patients with specific genetic obesity disorders. Small observational studies have shown that similar benefits from nontargeted AOMs or off-label pharmacotherapies can be achieved in patients with specific genetic obesity disorders, compared to common multifactorial obesity. In the future, novel and innovative pharmacotherapeutical options, including combination therapies and possibly gene therapy, will emerge, offering promising effects on body weight, hyperphagia, and, most importantly, quality of life for patients with a variety of genetic obesity disorders.

01 Apr 2025·DIABETOLOGIA

Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial

Article

Author: Chen, Liming ; Benamar, Malik ; Yabe, Daisuke ; Fu, Ariel ; Zueger, Thomas ; Réa, Rosângela ; Riveline, Jean-Pierre ; Jódar, Esteban ; Nishida, Tomoyuki ; Lingvay, Ildiko

Abstract:

Aims/hypothesis:

COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications.

Methods:

This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions. Adults with type 2 diabetes (HbA1c 53.0–85.8 mmol/mol [7.0–10.0%]) receiving GLP-1 RA therapy with or without additional oral glucose-lowering medications were randomly assigned 1:1 to once-weekly IcoSema or once-weekly semaglutide 1.0 mg. The primary endpoint was change in HbA1c from baseline to week 52; superiority of IcoSema to semaglutide 1.0 mg was assessed. Secondary endpoints included change in fasting plasma glucose and body weight (baseline to week 52), and combined clinically significant (level 2; <3.0 mmol/l) or severe (level 3; associated with severe cognitive impairment requiring external assistance for recovery) hypoglycaemia (baseline to week 57).

Results:

Overall, 683 participants were randomised using a Randomisation and Trial Supply Management system to IcoSema (n=342) or semaglutide 1.0 mg (n=341). Mean ± SD baseline characteristics were as follows: HbA1c 64.0±8.2 mmol/mol (8.0±0.7%); diabetes duration 12.6±6.9 years; and BMI 31.1±4.7 kg/m2. From baseline to week 52, mean change in HbA1c was −14.7 mmol/mol (−1.35%-points) in the IcoSema group and −9.88 mmol/mol (−0.90%-points) in the semaglutide group; the estimated treatment difference (ETD) was –4.85 (95% CI −6.13, −3.57) mmol/mol (−0.44 [95% CI −0.56, −0.33]%-points), confirming superiority of IcoSema to semaglutide (p<0.0001). The estimated mean change in fasting plasma glucose from baseline to week 52 was statistically significantly reduced with IcoSema vs semaglutide (−2.48 mmol/l vs −1.41 mmol/l, respectively; ETD −1.07 [95% CI −1.37, −0.76] mmol; p<0.0001). Mean change in body weight from baseline to week 52 was statistically significantly different between groups: +0.84 kg for IcoSema vs −3.70 kg for semaglutide (ETD 4.54 kg [95% CI 3.84, 5.23]; p<0.0001). There was no statistically significant difference in the rate of combined clinically significant or severe hypoglycaemia between IcoSema and semaglutide (0.042 vs 0.036 episodes per person-year of exposure; estimated rate ratio 1.20 [95% CI 0.53, 2.69]; p=0.66). The proportion of participants experiencing gastrointestinal adverse events was similar between treatment groups (IcoSema 31.4%; semaglutide 34.4%).

Conclusions/interpretation:

In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema in comparison with once-weekly semaglutide 1.0 mg demonstrated superiority in HbA1c reduction, similar rates of clinically significant or severe hypoglycaemia, and similar frequency of gastrointestinal adverse events. However, weight change from baseline to week 52 was statistically significantly in favour of semaglutide 1.0 mg.

Trial registration:

ClinicalTrials.gov NCT05259033

Funding:

This trial was funded by Novo Nordisk

Graphical Abstract:

News (Medical) associated with Glucagon-like peptide-1 ( MannKind Corporation)

31 Mar 2025

·www.drugs.com

More Type 1 Diabetics Are Obese, Taking GLP-1 Drugs

MONDAY, March 31, 2025 -- Use of cutting-edge weight-loss drugs like Ozempic and Zepbound has increased dramatically among people with type 1 diabetes , raising safety concerns among experts, a new study says. Both adults and children with type 1 diabetes are taking the drugs more often to manage obesity, researchers reported in the journal Diabetes, Obesity and Metabolism . The problem is that these Glucagon-like peptide-1 (GLP-1) drugs were initially approved to treat type 2 diabetes, and later received approval as weight-loss medications, researchers said. Their use in type 1 diabetes is not approved by the U.S. Food and Drug Administration and raises potential safety concerns, researchers explained. There's also concern that using the GLP-1 drugs will put people with type 1 diabetes at greater risk for severe bouts of hypoglycemia. “These findings highlight the urgent need for better data — including clinical trials — on the effectiveness and safety of GLP-1 receptor agonists in people with type 1 diabetes, to inform clear guidelines on their use in these patients,” senior researcher Dr. Jung-Im Shin , an associate professor at Johns Hopkins Bloomberg School of Public Health, said in a news release. People with type 1 diabetes are born without the ability to make enough insulin for their bodies, while those with type 2 diabetes develop insulin resistance over time. Historically, people with type 1 diabetes have tended to be thin, because their insulin deficiency led to the breakdown of their fat and muscle for energy, causing weight loss, researchers said in background notes. But insulin treatment for type 1 diabetes combined with today’s society have caused obesity rates to increase in those patients – and along with that, the use of GLP-1 drugs. GLP-1 drugs mimic the GLP-1 hormone, which helps control insulin and blood sugar levels, decreases appetite and slows digestion of food. For the new study, researchers tracked more than 217,000 patients with type 1 diabetes from more than 30 health systems across the U.S. between October 2008 and September 2023. During that period, obesity among 2- to 19-year-olds with type 1 diabetes rose from 18% to 26%, and from 30% to 38% among adults 20 and older. Prescriptions for GLP-1 drugs rose even faster, climbing from 4% to 33% among severely obese adults with type 1 diabetes and 3% to 21% among severely obese children, results show. “In the most recent periods, there were big increases in the use of semaglutide (Ozempic) and tirzepatide (Zepbound) — the most potent versions of these drugs for weight loss — which again underscores the need for clinical trial data on these patients,” said Yunwen Xu , a postdoctoral researcher in the Bloomberg School’s Department of Epidemiology. Researchers are following up with a more targeted study looking into the risk of severe hypoglycemia among people with type 1 diabetes using GLP-1 drugs. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Clinical ResultDrug Approval

28 Mar 2025

·www.pharmaceutical-technology.com

Weill Cancer Hub East launches to transform treatment

A portfolio of trials will be provided by the hub, inclusive of those assessing the GLP-1 agonist effects on cancer subjects’ immune responses and results. Credit: PeopleImages.com – Yuri A/Shutterstock. The Weill Cancer Hub East, a collaborative initiative formed by Weill Cornell Medicine, Princeton University, The Rockefeller University and the Ludwig Institute for Cancer Research, has been established to explore the interplay between nutrition, metabolism and immunotherapy in cancer treatment. The initiative was launched with a $50m gift from the Weill Family Foundation. The Weill Cancer Hub East brings together experts from the four institutions to improve immunotherapy, a therapeutic strategy that uses a patient’s immune cells for treatment. It aims to drive cross-field partnerships, combining cancer biology, immunology, trials, metabolism and nutrition experts. With philanthropy from each partner institution, total funding will exceed $125m. Up to 2034, the hub will explore the connection between solid tumours and their environment. It also aims to understand how diet and beneficial microbes that help metabolise food can influence cancer treatment effectiveness. The initiative will investigate how emerging therapeutics such as glucagon-like peptide-1 (GLP-1) agonists are used in diabetes and anti-obesity treatments, which may affect cancer progression and treatment. The Weill Cancer Hub East will leverage metabolomics, computational analysis, immunology and AI to study how metabolism impacts the immune system’s cancer-controlling ability. It will provide seed funding for collaborative projects focusing on reprogramming the tumour microenvironment and augmenting cell function through patients’ metabolisms and microbiomes. The hub will provide a portfolio of trials, including assessment of the GLP-1 agonist effects on cancer subjects’ immune responses and results. The outcomes may also apply to metabolic, autoimmune and cardiovascular conditions. The Ludwig Institute for Cancer Research, a cancer research sponsor, is funding studies in cancer metabolism and immunotherapy, providing additional support to the hub’s efforts. A scientific steering committee, with leaders from each academic institution, will oversee the hub’s activities. The scientific strategy of the hub will be directed by a leadership committee, including representatives from partner institutions and the Weill Family Foundation. The adaptable structure of the hub will allow it to respond to upcoming directions in cancer research. The hub is the second collaborative entity established by the Weill family and the Weill Family Foundation through their philanthropy. Weill Family Foundation founder and Weill Cornell Medicine Board of Fellows chair emeritus Sandy Weill stated: “The Weill Cancer Hub East will offer doctors and scientists a tremendous opportunity to revolutionise the treatment of cancer, a disease that complicates so many lives.”

ImmunotherapyClinical Study

11 Mar 2024

·www.prnewswire.com

AANA Publishes Considerations for Anesthesia Care of the Patient on a GLP-1 Receptor Agonist

ROSEMONT, Ill., March 11, 2024 /PRNewswire/ -- (AANA) - Glucagon-like peptide-1 (GLP-1) agonists such as Ozempic® or Wegovy® (semaglutide), Saxenda® (liraglutide), or Zepbound™ (tirzepatide), have become increasingly popular in promoting weight loss. To support the safety of patients and the knowledge of anesthesia professionals, such as Certified Registered Nurse Anesthetists (CRNAs), also known as nurse anesthesiologists or nurse anesthetists, the American Association of Nurse Anesthesiology (AANA) has published "Anesthesia Care of the Patient on a GLP-1 Receptor Agonist." These evidence-based perioperative considerations can be used to develop facility policies and procedures that align with the best available evidence on treating patients taking GLP-1 agonists. GLP-1 agonists, designed initially to manage type 2 diabetes, bind and activate receptors located throughout the body, eliciting a biological response similar to naturally occurring GLP-1, a gut-derived hormone usually released after eating fats and carbohydrates. Patients feel full sooner and tend to eat less. In addition to appetite suppression, these medications also slow gastric emptying. Clinical guidelines call for a patient to fast prior to anesthesia because food remaining in a patient's stomach can cause serious complications such as vomiting and food aspiration. "These medications have exploded in popularity, and CRNAs need to be prepared to see more patients actively take them," says Micah Walden, DNP, CRNA, a member of the AANA Practice Committee. "This means additional preparation for patients, anesthesia providers, and the surgical team to help minimize risks of complications during a procedure." Because of these risks, providers may need to do additional screenings such as a point-of-care ultrasound of a patient's stomach contents before surgery. If the ultrasound indicates that gastric contents are present or imaging is inconclusive, the surgical team may consider delaying an elective procedure or proceeding as "full stomach" to mitigate the risks of regurgitation and aspiration while intubated for anesthesia care. The length of time various GLP-1 medications continue to impact a patient were considered in developing these recommendations. Example recommendations include: If daily dose: Consider holding day of surgery/procedure. If weekly dose: Consider holding one week before surgery/procedure. "Open communication between patients and the surgical team is important with regard to recommendations for withholding GLP-1 agonist medications prior to surgery," says Walden. "As providers, we take that information into account to perform an individualized, case-by-case assessment and create a care plan that will keep the patient safe and comfortable before, during, and after the procedure." CRNAs are highly educated, trained, and qualified anesthesia experts. They provide 50 million anesthetics per year in the United States, working in every setting in which anesthesia is delivered. CRNAs are the primary providers of anesthesia care in rural settings, enabling facilities in these medically underserved areas to offer obstetrical, surgical, pain management, and trauma stabilization services. SOURCE American Association of Nurse Anesthesiology

100 Deals associated with Glucagon-like peptide-1 ( MannKind Corporation)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 1	Netherlands	MannKind Corp.	01 Apr 2007
Diabetes Mellitus	Preclinical	United States	MannKind Corp.	28 Sep 2009

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SKIP (ENDO2022)	Not Applicable	Smoking	255	Dulaglutide 1.5 mg	meuttgqdhh(vemasdflhc) = puxiifchbu rlxyqaosej (kblxsqpblu, 3.3)	Negative	01 Nov 2022
				Placebo	meuttgqdhh(vemasdflhc) = dzdcumhgwc rlxyqaosej (kblxsqpblu, 2.4)
SUN-LB044 (ENDO2019)	Not Applicable	-	18	GLP-1 infusion	bumustkigr(hmzlhdtaab) = sahizgydqg zvxcgnjoow (lakvenymni ) View more	-	30 Apr 2019
				Vehicle infusion	bumustkigr(hmzlhdtaab) = poqncackph zvxcgnjoow (lakvenymni ) View more
EASD2015	Not Applicable	-	-	glucagon-like peptide-1 (Glucolipotoxic stress)	ohsmcszgyv(xgbuzfcwdu) = 2.5-fold ± 0.1 n=3, p<0.01 ndbolpjfgu (uvvdyiugvw ) View more	Positive	17 Sep 2015

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Glucagon-like peptide-1 ( MannKind Corporation)

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation