This is a randomized controlled trial (RCT), within-subject, crossover, double-blind, placebo-controlled in non-treatment-seeking individuals with Alcohol Use Disorder (AUD) (N=40, 50% female) randomized to IN insulin or placebo. In a bar laboratory setting, randomized participants will receive a single dose of IN insulin (80IU) or an IN matched placebo (0.9% Saline). Participants will undergo a cue-reactivity paradigm followed by an alcohol challenge that includes an alcohol drink designed to raise the breath alcohol content (BrAC) to 0.08g/dL.

Start Date25 Mar 2024

Sponsor / Collaborator

Brown University

NCT06072963 / RecruitingPhase 2IIT

Combination of Intranasal Insulin With Oral Semaglutide to Improve Cognition and Cerebral Blood Flow: a Feasibility Study

The investigators propose a proof of concept RCT (randomized clinical trial), testing the efficacy of intranasal insulin (INI) with semaglutide, a combination therapy with strong biological plausibility to benefit impaired cognition through vascular mechanisms, in older adults with MetS (metabolic syndrome) and MCI (Mild Cognitive Impairment), who are enriched for cerebrovascular disease and at high dementia risk. The study will focus on cognitive and biological outcomes, allowing identification of relevant mechanisms.

Start Date30 Jan 2024

Sponsor / Collaborator

Rutgers State University of New Jersey

[+1]

NCT05866367 / RecruitingPhase 1IIT

Measurement of Insulin Levels in Cerebral Spinal Fluid (CSF) of Healthy Adults After a Single Intranasal Dose

The purpose of this study is to find out whether insulin, a drug approved by the FDA for the treatment of diabetes mellitus, reaches the brain and spinal cord when delivered as a nasal spray (intranasally). Intranasal insulin has been shown to improve memory and mood in patients with mild cognitive impairment and dementia, but more evidence is needed to support the ability to effectively target the brain through intranasal routes.
12 healthy adults will be randomly assigned to receive a single dose of either 40 units ("low dose" group) or 80 units ("high dose" group) of insulin. Participants will undergo image-guided lumbar puncture (spinal tap) performed by a study radiologist. Samples of cerebrospinal fluid (a fluid surrounding the brain and spinal cord) and blood will be collected at 5 timepoints during the lumbar puncture: once prior to the administration of intranasal insulin, and again at 10, 20, 30, and 40 minutes after the dose is given. Samples will be tested to determine the level of insulin detected in the cerebrospinal fluid and blood at each time point. Results of this study will provide essential information about the ability of the SipNose device to effectively deliver insulin to the central nervous system of humans as measured in the cerebrospinal fluid.

Start Date16 Aug 2023

Sponsor / Collaborator-

100 Clinical Results associated with Insulin human (rDNA origin, Novo Nordisk)

100 Translational Medicine associated with Insulin human (rDNA origin, Novo Nordisk)

100 Patents (Medical) associated with Insulin human (rDNA origin, Novo Nordisk)

318

Literatures (Medical) associated with Insulin human (rDNA origin, Novo Nordisk)

27 Jun 2023·Clinical chemistry and laboratory medicine

Simultaneous analysis of antihyperglycemic small molecule drugs and peptide drugs by means of dual liquid chromatography high-resolution mass spectrometry

Article

Author: Vollmer, Aline C ; Weber, Armin A ; Wagmann, Lea ; Meyer, Markus R

Abstract:

Objectives:

The study aimed to evaluate dual liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) for the simultaneous analysis of small and large molecule drugs by development and application of a validated bioanalytical method.

Methods:

The oral antihyperglycemic drugs (OAD) dapagliflozin, empagliflozin, glibenclamide, glimepiride, metformin, pioglitazone, repaglinide, saxagliptin, sitagliptin, and vildagliptin, as well as the antihyperglycemic peptides exenatide, human insulin, insulin aspart, insulin degludec, insulin detemir, insulin glargine, insulin glulisine, insulin lispro, and semaglutide were included in the analytical procedure. Analytes were extracted using a combination of protein precipitation and solid-phase extraction. Two identical reversed-phase columns were used for separation followed by Orbitrap high-resolution mass spectrometry. The whole procedure was validated according to international recommendations.

Results:

Different MS parameters had to be used for the two analyte groups, but dual LC separation allowed elution of all analytes within 12 min using the same column type. The analytical procedure was accurate and precise for most of the compounds except for exenatide, semaglutide, and insulin glargine, which were included qualitatively in the method. Analysis of proof-of-concept samples revealed OAD concentrations mostly within their therapeutic range, insulins could be detected in five cases but at concentrations below the lower limit of quantification except for one case.

Conclusions:

Dual LC in combination with HRMS was shown to be a suitable platform to analyze small and large molecules in parallel and the current method allowed the determination of a total of 19 antihyperglycemic drugs in blood plasma within 12 min.

04 May 2023·Current eye research

Beneficial Effects of Plasma Rich in Growth Factors (PRGF) Versus Autologous Serum and Topical Insulin in Ocular Surface Cells

Article

Author: Muruzábal, Francisco ; Merayo-Lloves, Jesús ; de la Sen-Corcuera, Borja ; Sánchez-Ávila, Ronald M. ; Anitua, Eduardo ; de la Fuente, María

PURPOSE:

In the last few decades, several blood derived products such as platelet-rich plasma (PRP), plasma rich in growth factors (PRGF) and autologous serum (AS) have been used for the treatment of ocular surface disorders. Recently, insulin has been proposed to be used as an alternative for the treatment of ocular surface diseases. The aim of this study was to evaluate the biological potential of PRGF eye drops in comparison with AS and insulin on ocular surface cells.

METHODS:

Blood from three healthy young donors was collected to obtain autologous serum (AS) eye drops and plasma rich in growth factors (PRGF) eye drops. Insulin (Actrapid^®) was diluted at 1 and 0.2 IU/mL. The biological potential of PRGF, AS and insulin was assessed by proliferation in HCE, HK and HConF cells. Wound healing assay was performed in HCE cells after incubation with the different treatments. HConF and HK cells were differentiated to myofibroblast after treatment with 2.5 ng/mL of TGF-β1 and then incubated with all treatments.

RESULTS:

PRGF eye drops induced significantly higher proliferation rate compared to AS or insulin in HConF and HK cells, but not in HCE cells. In addition, the percentage of wound healing area was significantly reduced after PRGF treatment in comparison with AS or insulin treatment. Furthermore, PRGF significantly reduced the number of myodifferentiated cells compared to AS and insulin at both concentrations analyzed.

CONCLUSION:

The results obtained in the present study show that PRGF increases the biological activity of the ocular surface cells and reduces the expression of fibrosis marker compared to insulin or AS.

TRANSLATIONAL RELEVANCE:

The present study suggests that plasma rich in growth factors eye drops are a more effective therapy than insulin and autologous serum eye drops for the treatment of ocular surface diseases.

10 Mar 2023·The Journal of clinical endocrinology and metabolism

Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men

Article

Author: Bass, Joseph ; Smith, Kenneth ; Phillips, Bethan ; Wilkinson, Daniel ; Gates, Amanda ; Williams, John ; Jandova, Tereza ; Idris, Iskandar ; Abdulla, Haitham ; Lewis, Johnathan ; Atherton, Philip ; Limb, Marie

Abstract:

Introduction:

Ageing skeletal muscles become both insulin resistant and atrophic. The hormone glucagon-like peptide 1 (GLP-1) facilitates postprandial glucose uptake as well as augmenting muscle perfusion, independent of insulin action. We thus hypothesized exogenous GLP-1 infusions would enhance muscle perfusion and positively affect glucose metabolism during fed-state clamps in older people.

Methods:

Eight men (71 ± 1 years) were studied in a randomized crossover trial. Basal blood samples were taken before postprandial (fed-state) insulin and glucose clamps, accompanied by amino acid infusions, for 3 hours. Reflecting this, following insertions of peripheral and femoral vessels cannulae and baseline measurements, peripheral IV infusions of octreotide, insulin (Actrapid), 20% glucose, and mixed amino acids; Vamin 14-EF with or without a femoral arterial GLP-1 infusion were started. GLP-1, insulin, and C-peptide were measured by ELISA. Muscle microvascular blood flow was assessed via contrast enhanced ultrasound. Whole-body glucose handling was assayed by assessing glucose infusion rate parameters.

Results:

Skeletal muscle microvascular blood flow significantly increased in response to GLP-1 vs feeding alone (5.0 ± 2.1 vs 1.9 ± 0.7 fold-change from basal, respectively; P = 0.008), while also increasing whole-body glucose uptake (area under the curve 16.9 ± 1.7 vs 11.4 ± 1.8 mg/kg−1/180 minutes−1, P = 0.02 ± GLP, respectively).

Conclusions:

The beneficial effects of GLP-1 on whole-body glycemic control are evident with insulin clamped at fed-state levels. GLP-1 further enhances the effects of insulin on whole-body glucose uptake in older men, underlining its role as a therapeutic target. The effects of GLP-1 in enhancing microvascular flow likely also affects other glucose-regulatory organs, reflected by greater whole-body glucose uptake.

News (Medical) associated with Insulin human (rDNA origin, Novo Nordisk)

30 Apr 2024

·www.biospace.com

Biotts Becomes First Company to Successfully Deliver Insulin Through Skin

Marks the first-time insulin has ever been administered in a form other than injection Testing shows insulin administered in transdermal form can persist much longer in the blood than insulin administered by subcutaneous injection Patients with Type 1 diabetes could replace up to 20 insulin injections over a period of five days Work completed within framework of Proof-of-Concept project carried out jointly with Warsaw-based Bioton S.A. Wroclaw, Poland--(News - April 30, 2024) - Wrocław, Poland-based Biotts, a biopharmaceutical company and global pioneer in Transdermal Drug Delivery (through the skin in the form of patches without injections), has become the world's first company to successfully complete transdermal delivery of insulin. The Proof-of-Concept project, carried out jointly with Warsaw, Poland-based Bioton, has just concluded, with an active form of insulin successfully transferred using Biotts' patented transdermal technology. The project objectives have been met with results so promising that both companies are prepared to proceed to the next phase. "This is a major breakthrough. In addition to proving that insulin can successfully be delivered through the skin, this study also demonstrated that insulin administered in this way can persist in the body significantly longer compared with injected insulin," says Dr. Paweł Biernat, CTO and co-founder of Biotts. "Animal testing showed that when insulin was transferred through the skin it remained at a constant level in the body for at least five days, comparing very favorably with injected insulin, which remains active for less than one day. It is also worth noting that the insulin administered in transdermal form, had a much more stable concentration pro that delivered by injection, which is a prime benefit of transdermal drug delivery." Dr. Biernat cautions that while these results are very impressive, the company is still in the early stages of its research. "This is another innovative project for Bioton in an effort to help patients with diabetes. Using existing and new molecules with this new drug delivery mechanism will make our products more widely available, as well as reduce the burden for people with diabetes. We are proud to be on this journey with another Polish biotech company. Biotts and we remain committed to improving patient care," says Bioton CEO Jeremy Launders. He adds that drug delivery devices have a pivotal role in ensuring effective treatments and enhancing the quality of life of patients. Positive results from the Proof-of-Concept study have proven the effectiveness of Biotts' patented transdermal carrier system MTC-YTM once again. Biotts has demonstrated that large molecules, much larger than the 500 Da (human insulin is a 5808 Da - monomer - molecule) reported in earlier studies, can be efficiently transported through the skin. Insulin in the form of a transdermal patch can realistically improve patient care and convenience while significantly reducing medical waste. "An important takeaway from the study is that we showed bioavailability of transdermal insulin of 55%. This means that patients with type 1 diabetes will be able to replace up to 20 insulin injections over a period of five days with a single patch that only needs to be worn for a few hours. Thus, patients will receive better and more comfortable treatment, without an increase in the cost of therapy, and without generating excess medical waste. This confirms that this state-of-the-art product can be a viable alternative for patients who are seeking non-invasive alternatives to diabetes treatment. The number of these patients is increasing every year. This is especially meaningful considering the impact this can have on children with T1D, particularly in the developing world. Our goal is to provide patients with effective treatment in the most convenient way possible, and the Proof-of-Concept results demonstrate that we are getting closer than ever to fulfilling that promise," says Jan Henk Hendriks, CEO of Biotts. Biotts is the first company to successfully complete transdermal delivery of insulin. "Patients will receive better and more comfortable treatment, without an increase in the cost of therapy, and without generating excess medical waste," says Jan Henk Hendriks, CEO of Biotts. To view an enhanced version of this graphic, please visit: "This is a major breakthrough. In addition to proving that insulin can successfully be delivered through the skin, this study also demonstrated that insulin administered in this way can persist in the body significantly longer compared with injected insulin." - Dr. Pawel Bierant, Chief Technical Officer and Co-Founder of Biotts. To view an enhanced version of this graphic, please visit: The company is currently taking next steps to bring transdermal insulin to market and make it available to patients around the world as quickly as possible, conceivably as soon as 2027. For more information, visit: . About Biotts Headquartered in Wrocław, Poland, Biotts is driven by its mission to enhance the quality of life for patients through the relentless pursuit of technological innovation. Comprised of a dedicated team of scientists and pharmacists boasting decades of collective experience, Biotts specializes in the development of proprietary drug products and transdermal systems. The company is committed to crafting impactful solutions that empower patients and revolutionize healthcare outcomes. With a passion for pioneering advancements, Biotts is at the forefront of shaping a brighter, healthier future for individuals worldwide. About Bioton S.A. European Biotech Company producing human insulin: API and finished forms in cartridges and vials. For more than 20 years, we have been providing people with diabetes with efficacious and safe medicines. Bioton S.A. is an unquestionable leader on the Polish market, and in the world's top eight commercial manufacturers of recombinant human insulin. Bioton S.A. continuously invests in the development of Polish biotechnology. We were the first company in Poland, which in cooperation with a Polish scientific institute, managed to commercialize the results of the Biotech Transfer. We apply the most current therapeutic and technological solutions to alleviate diabetes treatment for patients. We strive to build comprehensive solutions for the prevention and treatment of diabetes. Bioton S.A. offers CMO/CDMO and QC services. Our activities are based on QbD in line with cGMP standards. Bioton S.A. supplies also a range of innovative gastroenterological FSMP (Foods for Special Medical Purposes). Media contact Resource Advantage Dan Green dgreen@resourceadvantage.com To view the source version of this press release, please visit

09 Nov 2023

·www.fiercepharma.com

It's the end of the line for Bayer's PI3K Aliqopa and Novo's insulin Levemir after 2 market pulls

2024 won't see either Bayer's Aliqopa or Novo Nordisk's Levemir on the U.S. market. While Novo Nordisk struggles with manufacturing concerns and patient coverage on its long-acting insulin Levemir, Bayer missed a primary endpoint in a confirmatory trial for its PI3K inhibitor Aliqopa. Now, both companies are opting to pull their products from the market. First up is Novo, which made the call on Levemir after “careful consideration,” citing global manufacturing issues, decreasing patient coverage and the availability of other options for patients to chose from, it said in a discontinuation notice. The drug, which was originally approved all the way back in 2005, will likely face supply disruption of its pre-filled FlexPen in mid-January 2024 before discontinuation April 1. Meanwhile, Levemir vials will wrap up by the end of next year. Earlier this year, Novo opted to slash Levemir’s price point by 65%, a move which was to go in effect come Jan. 1. The company also sliced the cost of its NovoLog insulin by 75% and matched Levemir’s 65% for its Novolin. Meanwhile, Bayer’s Aliqopa was required to show proof of benefit through a confirmatory trial after securing FDA accelerated approval in 2017 for relapsed follicular lymphoma in patients who have received at least two prior systemic therapies. While full data from the phase 3 CHRONOS-4 study in relapsed indolent non-Hodgkin lymphoma have yet to be revealed, a Bayer spokesperson confirmed in an emailed statement to Fierce Pharma that the trial missed its primary endpoint. After offering the FDA a voluntary withdrawal, the company is now exploring access options for patients currently receiving the therapy with no suitable alternative treatments, the spokesperson added, noting that the withdrawal will not have a “relevant financial impact” on Bayer. Aliqopa’s original approval was based on a single-arm phase 2 study. Last year, the FDA flagged PI3K nods based on single-arm studies after six randomized trials suggested that four marketed drugs in the class might shorten blood cancer patients’ life expectancy due to their toxicity. The agency determined that future approvals should instead require randomized clinical trials with active comparators, which an advisory committee later backed. Bayer’s drug won’t be the first PI3K to flee the market after the FDA spotlight. Gilead Sciences and Incyte have pulled their drugs or scrapped filing plans, while the agency snatched back its approval for TG Therapeutics’ Ukoniq. Bayer also in 2021 withdrew its application for Aliqopa in non-Hodgkin lymphoma.

Phase 3Drug ApprovalAccelerated ApprovalPhase 2Clinical Result

09 Nov 2023

·www.biospace.com

Novo to Discontinue Long-Acting Insulin Injection Levemir by the End of 2024

Pictured: Novo Nordisk building in California/iStock, hapabapa Novo Nordisk will discontinue its long-acting insulin treatment Levemir in the U.S. by the end of next year, the company announced Wednesday. The decision was driven by “global manufacturing constraints, formulary losses impacting patient access, and the availability of alternative options,” Novo said in a posting on its website. “We will continue to provide Levemir FlexPen and Levemir vials to wholesalers while supplies last, up to the discontinuation dates, but supply disruptions should be expected.” FlexPen supplies will see disruptions starting in mid-January 2024, leading up to the product’s complete discontinuation by April 1, 2024. Levemir vials will continue to be available beyond that until the full brand is discontinued on Dec. 31, 2024. Levemir’s discontinuation comes amid strong pressure from U.S. lawmakers to lower insulin prices. In March 2023, Sen. Bernie Sanders (I-VT), chairman of the Committee on Health, Education, Labor and Pensions, wrote to Novo and Sanofi urging them to follow Eli Lilly’s example and lower the costs of their insulin products. Novo agreed a few days later, announcing that it would cut the list prices for several of its insulin products by up to 75%. In its announcement at the time, the company specifically named Levemir, which would take a 65% price cut. Novo also committed to lowering the prices of Novolin and NovoLog, as well as its unbranded biologics to match the reduced costs of the branded reference products. These new prices are set to take effect on Jan. 1, 2024. Novo is also facing additional pricing pressure from the Inflation Reduction Act’s Drug Price Negotiation Program. In August 2023, the Centers for Medicare and Medicaid Services announced the first 10 drugs that will be impacted by the negotiations. The CMS list includes Novo’s insulin products Fiasp and NovoLog, alongside other highly prescribed medicines such as Lilly’s Jardiance (empagliflozin) and Amgen’s Enbrel (etancercept). Novo has reluctantly agreed to participate in the drug price negotiations. Nevertheless, even as Novo faces price reductions on its insulin products, the company is still enjoying strong sales growth, driven mainly by its weight-loss franchise. In its third-quarter financial report, Novo reported that Wegovy (semaglutide) earned almost $3.1 billion in revenue during the first nine months of 2023. This represents approximately 490% sales growth compared to the prior year period. Demand for Wegovy is expected to grow even stronger, particularly as Novo appears to be eyeing an expansion into renal and cardiovascular spaces. Last month, the company ended the Phase III FLOW trial ahead of schedule due to strong signals of efficacy in kidney outcomes. In August 2023, Novo reported that Wegovy also cleared the Phase III STEP trial in patients with heart failure with preserved ejection fraction. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3Financial Statement

100 Deals associated with Insulin human (rDNA origin, Novo Nordisk)

External Link

KEGG	Wiki	ATC	Drug Bank
D03230	-	A10AF01 A10AD01 A10AC01	DB00030

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Diabetes Mellitus	US	Novo Nordisk, Inc.	25 Jun 1991
Diabetes Mellitus, Type 1	US	Novo Nordisk, Inc.	25 Jun 1991
Diabetes Mellitus, Type 2	US	Novo Nordisk, Inc.	25 Jun 1991
Hyperglycemia	US	Novo Nordisk, Inc.	25 Jun 1991

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Obesity	Phase 3	ES	Novo Nordisk A/S	01 Apr 2005

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04115384 (CTgov)	Phase 2	Frontotemporal Dementia	3	Novolin-R insulin	fukrbiwujy(kldpgkvqnc) = tlgldlsgtu egodotabwn (cmpbjfeqxx, phvodzeuck - gxuohcoyfe) View more	-	06 Jul 2023
NCT03511521 (CTgov)	Phase 4	Insulin Resistance \| Steroid-induced hyperglycemia	3	Glargine+Humulin N+Novolin N+insulin aspart (NPH Insulin)	gtqdilerbf(muirmpchgs) = ejwfcsrcmz fhblqvpvnj (iminvwztvl, wwgdwhvzvy - ukqhkvibhp) View more	-	11 Sep 2020
				Glargine+insulin aspart (Basal/Bolus Insulin)	gtqdilerbf(muirmpchgs) = xujnarbuaa fhblqvpvnj (iminvwztvl, qiawnsohsu - rgtrzlxska) View more
NCT02138006 (CTgov)	Not Applicable	Diabetes Mellitus, Type 1 \| Stroke \| Renal Insufficiency ... View more	102	Monotard (Intensive Insulin Treatment)	wdwvjgqzkx(pvvsofzwfv) = fbyuauucyw afxaqneirw (xddclelxwu, pdxuzxfowt - kuozaawiys) View more	-	21 Dec 2015
				Standard insulin treatment (Standard Insulin Treatment)	wdwvjgqzkx(pvvsofzwfv) = ufandesncm afxaqneirw (xddclelxwu, cbamqkabng - hgncggvxom) View more
NCT00346996 (PS 037, EASD2013)	Phase 4	-	72	Insulin detemir / insulin aspart	azoftswsas(xqbqrpofrw) = algajolncp oysdjedmvm (nddvevncvd )	Positive	24 Sep 2013
				Human NPH insulin / human regular insulin	azoftswsas(xqbqrpofrw) = myhjbstcko oysdjedmvm (nddvevncvd )
NCT00807092 (CTgov)	Phase 4	Diabetes Mellitus, Type 2	145	Metformin+biphasic insulin aspart 30 (BIAsp 30)	xakpfrvusz(zefyzxysqh) = mzqnopqxvd mjtqxoriyo (hkpetjcpwr, ekslvxband - offtolhclb) View more	-	11 Apr 2011
				biphasic human insulin 30+Metformin (BHI 30)	xakpfrvusz(zefyzxysqh) = yhbdemgkec mjtqxoriyo (hkpetjcpwr, nfvpbzhqvd - rohgfcvkkb) View more

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

Regulation

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

view full example data

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. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Insulin human (rDNA origin, Novo Nordisk)

Overview

Basic Info

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation