Delving into the Latest Updates on Liraglutide with Synapse

Overview

Basic Info

Drug Type

Recombinant polypeptide

Synonyms

Liraglutide (Genetical Recombination), Liraglutide Recombinant, Saxenda

+ [20]

Target

GLP-1R

Action

agonists

Mechanism

GLP-1R agonists(Glucagon-like peptide 1 receptor agonists)

Therapeutic Areas

Endocrinology and Metabolic DiseaseNervous System DiseasesUrogenital Diseases+ [1]

Active Indication

ObesityOverweightDiabetes Mellitus, Type 2+ [4]

Inactive Indication

Arthritis, PsoriaticBinge-Eating DisorderCardiovascular Diseases+ [23]

Originator Organization

Novo Nordisk A/S

Active Organization

Novo Nordisk A/S

Izmir Ekonomi ÜniversitesiNovo Nordisk, Inc.

+ [4]

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

European Union (30 Jun 2009),

Diabetes Mellitus, Type 2

Regulation-

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Structure/Sequence

Sequence Code 50953

Source: *****

Diabetes-associated cognitive dysfunction (DACD), a serious central nervous system complication of diabetes mellitus, poses a heavy global burden due to its intricate pathogenesis and lack of effective therapies. Mounting evidence identifies programmed cell death (PCD) as a pivotal driver of DACD progression. This review systematically elaborates on the molecular mechanisms of various PCD modalities (including apoptosis, autophagy, pyroptosis, and ferroptosis) in DACD, with a particular focus on the role of ferroptosis as a core pathogenic mechanism. Hyperglycemia disrupts cerebral iron homeostasis, induces mitochondrial dysfunction and oxidative stress, leading to inhibition of glutathione peroxidase 4 (GPX4) activity and accumulation of lipid peroxides. This cascade ultimately triggers ferroptosis in neurons, glial cells, and the blood-brain barrier, resulting in impaired synaptic plasticity and cognitive decline. Furthermore, the review delineates the complex interactive regulatory network between ferroptosis and other PCD forms (e.g., autophagy, pyroptosis), which can converge into the coordinated cell death program of PANoptosis. Intervention strategies targeting ferroptosis, such as iron chelators (deferoxamine), antioxidants (N-acetylcysteine), GPX4 activators, natural products (resveratrol, curcumin), repurposed traditional medicines (liraglutide, metformin), and non-pharmaceutical interventions (exercise, electroacupuncture), have demonstrated significant potential in improving cognitive function in preclinical models. This review aims to provide novel insights into the pathophysiology of DACD and establish a theoretical foundation for developing precise therapeutic strategies centered on targeting ferroptosis.

01 Apr 2026·JOURNAL OF NUTRITIONAL BIOCHEMISTRY

Olive-derived elenolic acid surpasses metformin and rivals liraglutide in managing blood glucose and obesity in a mouse model of type 2 diabetes

Article

Author: Cao, Xinyi ; Rachi, Md Abu T ; Vaughan, Reagan ; Kale, Balaji ; Silte, Abeje ; Zhang, Yan ; Rainville, Jennifer ; Hodes, Georgia E ; Liu, Dongmin ; Xu, Bin ; Wang, Yao ; Alkhalidy, Hana

Obesity and type 2 diabetes (T2D) are among the most common metabolic diseases that are associated with increased risk of noncommunicable diseases globally. Elenolic acid (EA), derived from olives, was shown to possess potent acute effects on obesity and diabetes that were associated with increased gut hormone secretion. Here, we investigate the long-term effects of EA in two mouse models of obesity and diabetes. In diet-induced obese mice, oral administration of EA (50 mg/kg/day) for 7 weeks, normalized fasting blood glucose (from 176.6±4.5 mg/dL to 120.8±4.0 mg/dL), and restored glucose tolerance and insulin sensitivity to levels comparable to lean mice. These improvements were associated with increased circulating peptide YY and gastric inhibitory polypeptide concentrations, downregulation of hypothalamic agouti-related peptide (AgRP), reduced food intake (∼20%), and weight loss. Acutely, EA slowed gastric emptying rate by about 50% and increased glucagon like peptide-1 levels. In db/db mice, EA reduced non-fasting blood glucose from 459.0±51.1 mg/dL to 208.9±10.3 mg/dL, an effect comparable to liraglutide and greater than metformin. EA also lowered fasting blood glucose levels similar to liraglutide and significantly below those observed with metformin. Moreover, EA-treated mice exhibited less weight gain than those receiving either drug. These effects were accompanied by decreased AgRP expression and increased c-fos activation. These results suggest that EA is a novel, multi-target agent with therapeutic potential for treating T2D and obesity.

01 Apr 2026·METABOLISM-CLINICAL AND EXPERIMENTAL

Proteomic effects of short-term liraglutide vs. placebo in a blinded crossover RCT: Implications for efficacy, safety, and comparison with semaglutide

Article

Author: Gutierrez de Piñeres, Valeria ; Mantzoros, Christos S ; Stefanakis, Konstantinos ; Veeragandham, Preethi

BACKGROUND:

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert cardiometabolic benefits beyond weight loss, yet their systemic proteomic mechanisms remain incompletely defined. We profiled short-term liraglutide-induced protein changes and compared them with published semaglutide signatures.

METHODS:

In a randomized, double-blind, placebo-controlled, crossover trial (NCT02944500), 20 adults with obesity received liraglutide 3 mg daily or placebo for 5 weeks, separated by a 3-week washout. Plasma and serum samples underwent SomaScan v4.1 profiling of 6249 proteins. Mixed-effects models tested Time×Treatment interactions with and without weight adjustment. Results were benchmarked against the 30-protein semaglutide STEP 1/2 signature.

RESULTS:

Liraglutide significantly modulated 124 proteins (57 FDR < 0.05); 85 % of effects persisted after weight adjustment, indicating largely weight-independent actions. Upregulated proteins included pancreatic enzymes (PNLIP, CTRB1/2, PRSS2), while endothelial and fibrotic markers (ACE, NOS3, FAP) were downregulated. Myostatin (MSTN) was strongly suppressed (log₂ fold change -0.41; p = 1.7 × 10^-6), with concurrent rises in its inhibitors WFIKKN2 and BMPR1A. Liraglutide shared 70-75 % directional overlap with semaglutide, with 25-30 % unique effects enriched in vascular, neurodevelopmental, and musculoskeletal pathways. A semaglutide-based classifier distinguished liraglutide from placebo (AUC = 0.82; sensitivity 0.89; specificity 0.60). Downregulated proteins were genetically linked to coronary artery disease and type 2 diabetes (FDR < 0.05).

CONCLUSIONS/INTERPRETATION:

Short-term liraglutide reproduces the core GLP-1RA proteomic fingerprint while uniquely suppressing myostatin and vascular remodeling pathways. These rapid, largely weight-independent molecular responses indicate early cardioprotective and myostatin-inhibitor signaling changes that could be relevant for future muscle-preserving strategies, supporting individualized GLP-1RA use beyond weight loss alone.

359

News (Medical) associated with Liraglutide

27 Jan 2026

·nanexa.com

Nanexa Announces Breakthrough Preclinical Data Demonstrating Exceptional Pharmacokinetic Profile for Monthly Semaglutide Formulation

27 January, 2026 - Regulatory Download attachment Nanexa’s atomic layer deposition (ALD) platform PharmaShell® demonstrably improves the pharmacokinetic profile of semaglutide injections. Significantly smoother plasma concentration curve could mitigate many common side effects of GLP-1 drugs. Less frequent dosing and improved adherence are key selling points for the next generation of GLP-1s, and reinforce Nanexa’s ability to secure new commercial partnerships. Nanexa AB today announces exceptional preclinical results for its long-acting semaglutide formulation developed using the company’s proprietary PharmaShell® drug delivery platform. PharmaShell encases active pharmaceutical ingredients at the atomic level in a highly protective, extremely thin film coating (approximately 30 nm thick) of slow-dissolving non-toxic inorganic oxides. Recent preclinical studies demonstrate an extraordinary pharmacokinetic (PK) profile, indicating a very low ratio between the maximum and minimum plasma concentration over the dosing interval following once-monthly subcutaneous administration. The plasma concentration is significantly more stable than that typically achieved with weekly administration of the marketed product Wegovy® (semaglutide). Breakthrough PK Profile with Potential to Reduce Gastrointestinal Side Effects A key hallmark of the new formulation is its low initial peak – a feature considered critical in reducing gastrointestinal (GI) adverse events commonly associated with GLP-1 therapies. By avoiding the sharp plasma concentration spikes often linked to nausea and other GI symptoms, Nanexa’s formulation may offer a more tolerable initiation and maintenance profile for patients. The preclinical results show clear dose-linearity, and significantly improved bioavailability compared with Nanexa’s earlier liraglutide formulations. Improved tolerability is strongly linked to improved adherence, which is a key issue associated with GLP-1 therapies. Strategic Shift: From Liraglutide to Semaglutide With these highly encouraging preclinical findings, Nanexa is shifting its development focus from liraglutide to semaglutide, reflecting the substantial therapeutic and commercial opportunity for long-acting GLP-1 treatments. The advancement of this semaglutide program builds directly on the clinical Phase 1 data from Nanexa’s liraglutide program, presented in 2025, which provided key insights into PharmaShell® performance in humans. Those findings enabled refined modelling, improved formulation strategies, and faster advancement for Nanexa toward clinical readiness for semaglutide. “These latest results represent a major milestone for Nanexa,” said David Westberg, CEO of Nanexa. “Demonstrating such a long release profile and low ratio between the maximum and minimum plasma concentration for monthly administration is exceptional and highlights how powerful the PharmaShell® technology can be for complex molecules like semaglutide. We are excited about this data which will strengthen our position to secure commercial partnerships.” For additional information, please contact: David Westberg – CEO, Nanexa AB (publ) Phone: +46 70 942 83 03 Email: david.westberg@nanexa.se www.nanexa.com Richard Hayhurst – Co-founder, 59 North Communications Phone: +447711 821527 Email: richard.hayhurst@59north.bio The company’s Certified Adviser is Tapper Partners AB. About Nanexa AB (publ) Nanexa is bringing the control, precision and versatility of Atomic Layer Deposition (ALD) technology to drug formulation. The company’s proprietary PharmaShell® platform is a unique drug delivery system that enables a high drug load, thus low injection volume, creating a new generation of ‘super generic’ formulations that will provide greater convenience and reduce costs in the treatment of conditions such as metabolic diseases like type 2 diabetes and obesity, hematology/oncology, cardiovascular disorders, psychiatry, and many others. Nanexa develops its own products and also has collaboration agreements with several pharma companies, including the latest license and option agreement with Moderna. Nanexa’s share is listed on Nasdaq First North Growth Market in Stockholm (NANEXA). Attachments Nanexa Announces Breakthrough Preclinical Data Demonstrating Exceptional Pharmacokinetic Profile for Monthly Semaglutide Formulation

Phase 1License out/inClinical Result

16 Jan 2026

·endpoints.news

European regulators recommended 38 novel drugs in 2025, 15 fewer than the FDA

The European Medicines Agency recommended 104 medicines for approval in 2025, the second-highest number in the past 15 years, according to a report the agency published Thursday. Of the positive recommendations last year, 38 were for new active substances — novel molecules, as opposed to reformulations or generics, for instance — according to the report. That figure markedly lags the 53 new treatments greenlit by the FDA in 2025. The total number was second only to the 114 drugs recommended in 2024. “If you look back over the past 15 years, you will see the number waxes and wanes, but there was a big dip during Covid-19,” EMA chief medical officer Steffen Thirstrup said in a press briefing on Thursday. “Some of what we saw [in 2024] was…a wave of things that had been postponed and protracted during Covid-19, and 104 is still a very high number of approvals from a European perspective.” Several new products were approved in the US last year but are still awaiting European authorization. These include Milestone Pharmaceuticals’ Cardamyst, approved in the US in December for an arrhythmia disorder called paroxysmal supraventricular tachycardia. Milestone has submitted an application in the EU for the drug under the name Tachymist, but a decision is not expected until the first quarter of 2027, showing just how long the delay between the two regulators can be. At least one product was approved in Europe but not in the US, however. The European agency recommended Novo Nordisk’s fixed-dose combination of insulin icodec and semaglutide for type 2 diabetes in September, and it was approved in Europe as Kyinsu in November. US approval of Kyinsu is not imminent. The FDA rejected insulin icodec due to manufacturing concerns in 2024. Novo has since resubmitted insulin icodec in the US, but will have to wait for that decision before filing the fixed-dose combination. As a combination of approved drugs, Kyinsu would not count as a novel medicine, however. Endocrinology was the most popular therapeutic area for medicine approvals in Europe last year. The EMA recommended 29 products for endocrine disorders, including three new treatments. These were Bayer’s Lynkuet for menopause symptoms, Sanofi’s Teizeild for type 1 diabetes and Amgen’s Tepezza for thyroid eye disease. Looking to the year ahead, the EMA said it expects continued innovation in weight management and diabetes. The agency has received the first application for a generic version of Novo Nordisk’s older GLP-1 agonist product liraglutide for both indications. Meanwhile, its safety committee is also looking into possible interactions between the drug class and contraceptive pills.

Drug Approval

14 Jan 2026

·www.pharmaceutical-technology.com

Drugmakers welcome FDA’s GLP-1RA suicide warning removal request

Zepbound, Wegovy, and Saxenda’s labels will now be updated after the FDA’s request. Ciara Kimsey via Shutterstock.com. The US Food and Drug Administration (FDA) has requested that pharma companies marketing glucagon-like peptide-1 receptor agonists (GLP-1RAs) no longer include warnings about a potential risk of suicide thoughts, after the agency completed a review. The FDA said it is asking drug application holders to remove information regarding the risk of suicidal ideation and behaviour (SI/B) from the labelling of weight loss branded GLP-1RAs, which currently list SI/B as a warning. Eli Lilly’s Zepbound (tirzepatide) and Novo Nordisk’s Wegovy (semaglutide) are affected by the change. Novo’s older GLP-1RA, Saxenda (liraglutide), will also have its label updated. In July 2023, after receiving post-marketing reports of SI/B in patients taking GLP-1RA medications, the FDA initiated an investigation into whether there is an established link between the drugs and the psychiatric adverse events. The FDA has since completed a meta-analysis of 91 clinical trials across GLP-1RA drug development that included 60,338 patients treated with the weight loss drugs. The agency also conducted a retrospective cohort study using administrative healthcare claims data. In its conclusion after a two-year review, the FDA stated that there was no relationship between the use of GLP-1 RAs and the occurrence of SI/B. An Eli Lilly spokesperson told Pharmaceutical Technology : “We appreciate the FDA’s careful consideration of this important safety issue. Patient safety is Lilly’s top priority, and we will continue to work with the FDA on next steps to ensure that appropriate safety information is available to prescribers. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence A Novo Nordisk spokesperson told Pharmaceutical Technology: “We are happy to see the FDA’s recommendation to remove the warning regarding the risk of suicidal ideation and behaviour from GLP-1RA labels that currently include such language…We prioritise patient safety and will continue to collaborate closely with the FDA and other regulatory authorities to monitor the safety of all our GLP-1RA medicines.” The outcome of the FDA investigation follows a similar decision by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) in September 2024. After its own evaluation, the MHRA found no links between the medication and suicidal, self-injurious thoughts or actions. Global sales for Lilly’s Zepbound surged 185% in Q3 2025 to bring in $3.59bn, while sales for Wegovy also increased in Q3 to DKr20.35bn ($3.2bn). The label update comes at a time of change in the obesity market. Dominated by subcutaneous administration over recent years, Novo won FDA approval for the first oral GLP-1RA indicated for weight loss in December 2025. Speaking at J.P. Morgan Healthcare Conference, held in San Francisco from 12 to 15 January, new CEO of Novo Nordisk, Maziar Mike Doustdar, placed importance on the pill for reaching more patients in the weight loss arena.

Drug Approval

100 Deals associated with Liraglutide

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Liraglutide	A10BJ02	DB06655

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Obesity	United States	Novo Nordisk, Inc.	23 Dec 2014
Overweight	United States	Novo Nordisk, Inc.	23 Dec 2014
Diabetes Mellitus, Type 2	European Union	Novo Nordisk A/S	30 Jun 2009
Diabetes Mellitus, Type 2	Iceland	Novo Nordisk A/S	30 Jun 2009
Diabetes Mellitus, Type 2	Liechtenstein	Novo Nordisk A/S	30 Jun 2009
Diabetes Mellitus, Type 2	Norway	Novo Nordisk A/S	30 Jun 2009

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cerebrovascular Disorders	Phase 3	Germany	Novo Nordisk A/S	01 Nov 2020
Chronic heart failure	Phase 3	Germany	Novo Nordisk A/S	01 Nov 2020
Coronary Disease	Phase 3	Germany	Novo Nordisk A/S	01 Nov 2020
Peripheral Vascular Diseases	Phase 3	Germany	Novo Nordisk A/S	01 Nov 2020
Polycystic Ovary Syndrome	Phase 3	United States	Novo Nordisk A/S	26 Sep 2018
Binge-Eating Disorder	Phase 3	United States	Novo Nordisk A/S	29 Sep 2017
Prader-Willi Syndrome	Phase 3	United States	Novo Nordisk A/S	09 Nov 2015
Prader-Willi Syndrome	Phase 3	Australia	Novo Nordisk A/S	09 Nov 2015
Prader-Willi Syndrome	Phase 3	Canada	Novo Nordisk A/S	09 Nov 2015
Prader-Willi Syndrome	Phase 3	France	Novo Nordisk A/S	09 Nov 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03948347 (LAMP, Pubmed \| JAMA Intern Med) Manual	Phase 3	Diabetes Mellitus, Type 2 \| Ischemic Attack, Transient \| Acute Ischemic Stroke	636	Liraglutide	uexuaqotpi(wxrrqqazly) = fhlswrtflf qmnpcisdaw (wgnekutaiq ) View more	Positive	03 Nov 2025
				Control	uexuaqotpi(wxrrqqazly) = bdnsavxlnf qmnpcisdaw (wgnekutaiq ) View more
NCT03260881 (CTgov)	Phase 4	Diabetes Mellitus, Type 2 \| Coronary Artery Disease	38	liraglutide (Study Group)	ncrkhgyhnk(wosistrddj) = lovzbytzjn hjjpizxgkh (oyxvvrgxnk, 0.60) View more	-	08 Jul 2025
				placebo (Control Group)	ncrkhgyhnk(wosistrddj) = axfyreomwg hjjpizxgkh (oyxvvrgxnk, 2.3) View more
NCT02516657 (CTgov)	Phase 3	Diabetes Mellitus, Type 1	5	Liraglutide	hmpyeffyxi(mdkxnsqxls) = hhbzsiegdm eyumxfejib (mlpykmayij, 35) View more	-	20 Apr 2025
NCT04881110 (STARDUST, CTgov)	Phase 4	Diabetes Mellitus, Type 2 \| Peripheral Arterial Disease	60	Liraglutide (Liraglutide Group)	lsmeifmrzj(zbzojcyukm) = njurqkzoqm ltywnbnucu (prulfvkrvg, 5.9) View more	-	03 Mar 2025
				Control (Control Group)	lsmeifmrzj(zbzojcyukm) = ywflaprbzx ltywnbnucu (prulfvkrvg, 4.8) View more
ASCO_GU2025	Phase 3	Prostatic Cancer	-	GLP-1 receptor agonists (GLP-1RAs)	zfgikqhjaa(rmpjzxygwm) = zyyjlrwlao mhvvogiunc (vossgxtzpb )	Negative	13 Feb 2025
				Placebo/non-GLP-1 RA regimens	zfgikqhjaa(rmpjzxygwm) = gycaazyvah mhvvogiunc (vossgxtzpb )
Pubmed Manual	Not Applicable	Overweight \| Obesity	15,491	Tirzepatide 15 mg once weekly	cdbtpchyqw(bfeyrghfsk) = wduwitakmr wpcgwqzpka (jtlowsqdau )	Positive	07 Jan 2025
				Semaglutide 2.4 mg once weekly	cdbtpchyqw(bfeyrghfsk) = wvzutiaszx wpcgwqzpka (jtlowsqdau )
NCT02098395 \| NCT01836523 (ADJUNCT ONE and ADJUNCT TWO, Pubmed \| J Diabetes Sci Technol)	Phase 3	Diabetes Mellitus, Type 1 C-peptide	-	Liraglutide 1.8 mg	cohudshimu(onrtjpishw) = uicgwlcqku szqlcktscs (dvdhpcliod ) View more	-	24 Dec 2024
				Liraglutide 1.2 mg	cohudshimu(onrtjpishw) = xeckkjbwzd szqlcktscs (dvdhpcliod ) View more
NCT06439056 (NEWS)	Phase 1	Diabetes Mellitus, Type 2	3	利拉鲁肽-NEX-22A	snxaesocqb(jfotoyhplh) = Clinical results have reached the endpoint hunfthubhl (qvzhcqxvci ) View more	Positive	22 Nov 2024
NCT04883346 (LBODP002, CTgov)	Phase 2	Obesity	34	Liraglutide	plrermmjkg = tlvldykxmr vghkgflinw (bvntwsjcdx, euqaxqduzq - ytdzclrsmw) View more	-	20 Nov 2024
NCT01794143 (Pubmed \| PLoS One)	Phase 3	Diabetes Mellitus, Type 2	-	Glargine	ytetfnzpno(kcazlpyfya) = afdohhdtjx pjjfqdtlpm (nxcrggfepj ) View more	Positive	15 Nov 2024
				Glimepiride	ytetfnzpno(kcazlpyfya) = jgoancwwxx pjjfqdtlpm (nxcrggfepj ) View more

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