Liraglutide 6mg/ml solution for injection 3ml pre-filled disposable devices

ObjectiveTwo glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus. This systematic review and network meta-analysis aims to compare the efficacy of these agents against each other.MethodsA comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library was conducted from inception to May 2025. Phase 3 randomized controlled trials (RCTs) in adult patients (≥ 18 years) with at least one arm of tirzepatide, semaglutide, or liraglutide were included. A frequentist random-effects network meta-analysis was performed using R 4.3.3.ResultsOf 1420 articles identified, 15 RCTs with 14,059 patients were included. All agents significantly reduced body weight compared to placebo. The largest reduction occurred with the maximum tolerated dose of tirzepatide, followed by tirzepatide 15 mg and 10 mg, semaglutide 2.4 mg, tirzepatide 5 mg, and liraglutide 3 mg. Tirzepatide and semaglutide were associated with a higher risk of any adverse event compared with placebo, whereas liraglutide was not.ConclusionsTirzepatide, particularly at higher doses, provides the greatest weight reduction in adults without diabetes. Future studies should evaluate discontinuation, weight regain, metabolic outcomes, cost-effectiveness, and patient preferences.

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ObjectiveTo evaluate glucagon-like peptide-1 receptor agonist (GLP-1 RA)-specific associations with hair loss, characterize reported alopecia subtypes and discuss potential underlying mechanisms.MethodsA systematic literature search was conducted across four databases (PubMed, Embase, Scopus, and Web of Science) according to PRISMA guidelines and registered in PROSPERO (CRD420261297384). Studies were included if they were primary articles assessing hair loss related to GLP-1 RA use.ResultsOf 133 studies identified, 24 met inclusion criteria. Among GLP-1 RAs, semaglutide and tirzepatide demonstrated the highest incidence rates of hair loss and more frequent signal detection in pharmacovigilance studies. Although infrequently classified overall, androgenetic alopecia and telogen effluvium were the predominant subtypes of hair loss reported. Tirzepatide, associated with the greatest magnitude of weight loss, was most frequently linked to telogen effluvium. Hair loss associated with semaglutide appeared to be dose-dependent, with doses < 2mg weekly rarely implicated while higher obesity-treatment doses were more commonly associated with hair loss. Females appeared to be disproportionately affected. Rapid weight loss emerged as a potential contributor, particularly for telogen effluvium. In contrast, fewer studies assessed hair loss with liraglutide, dulaglutide, lixisenatide and exenatide, and they typically exhibited lower reported risk when compared to semaglutide and tirzepatide.ConclusionsAccumulating evidence from pharmacovigilance databases and clinical cohorts suggests an increased risk of hair loss with certain GLP-1 RAs, particularly semaglutide and tirzepatide. Further studies are needed to clarify the etiology of drug-induced weight loss, identify vulnerable populations, and establish causality and temporal relationship through large, prospective randomized trials.

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BackgroundObesity plays a pivotal and modifiable role in the development and progression of type 2 diabetes mellitus (T2DM). Clinicians increasingly use lower doses of liraglutide (1.2 mg and 1.8 mg) to achieve clinically meaningful weight loss while maintaining effective glycemic control in people with T2DM and obesity. In this meta-analysis, we compared the efficacy and safety of liraglutide 1.2 mg and 1.8 mg in this population.MethodsWe systematically searched PubMed, the Cochrane Central Register of Controlled Trials, LENS, ClinicalTrials.gov, and the Virtual Health Library (VHL) for randomized controlled trials published in English up to 30 September 2024. We included trials with 24-52 weeks of treatment that evaluated liraglutide at doses of 1.2 mg or 1.8 mg against placebo or glucose-lowering therapies (GLTs). Comparators included insulin, sulfonylureas, dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), other glucagon-like peptide-1 receptor agonists (GLP-1RAs), and oral antidiabetic drugs (OADs). We assessed changes in body weight and HbA1c as efficacy outcomes and evaluated the occurrence of nausea and vomiting as safety outcomes. Two reviewers independently extracted data and assessed study quality using PRISMA guidelines and the Cochrane Risk of Bias 2 tool.ResultsWe included 25 RCTs comprising 10,593 participants. Liraglutide 1.2 mg (8 studies, 3,455 participants) produced a mean weight reduction of -1.24 kg versus GLTs, -0.75 kg versus placebo, and -2.46 kg versus OADs. Liraglutide 1.8 mg (22 studies, 8,259 participants) achieved significantly greater weight loss of -2.30 kg versus GLTs, -1.93 kg versus placebo, and -2.81 kg versus OADs. When compared with oral semaglutide, exenatide, dulaglutide, lixisenatide, and albiglutide, liraglutide showed comparable efficacy. For glycemic control, liraglutide 1.2 mg reduced HbA1c by -0.24% versus OADs, while liraglutide 1.8 mg reduced HbA1c by -0.26% versus GLTs. Liraglutide 1.2 mg showed a numerically lower incidence of nausea and similar rates of vomiting compared with other GLP-1RAs.ConclusionLiraglutide 1.2 mg and 1.8 mg doses improve weight and glycemic outcomes with a favourable safety profile, supporting its role as an effective therapeutic option for comprehensive management of T2DM with comorbid obesity.

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Background: Psoriasis is a chronic inflammatory disease frequently associated with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for T2DM and obesity, have demonstrated anti-inflammatory and immunomodulatory properties that may be relevant in psoriasis. However, individual GLP-1RAs differ substantially in their pharmacological characteristics and clinical effects. Our objective was to systematically review the available evidence on the effects of individual GLP-1RAs in patients with psoriasis. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and Scopus were searched up to April 2026 for studies evaluating GLP-1RAs in psoriasis. Case reports, case series, observational studies, and randomized controlled trials were included. Preclinical, clinical and safety outcomes were extracted and narratively synthesized. Results: Twenty-six studies met the inclusion criteria. Most involved patients with concomitant obesity and/or T2DM. Overall, semaglutide, liraglutide, exenatide, and tirzepatide were associated with improvements in psoriasis severity, often accompanied by reductions in body weight, glycated haemoglobin, inflammatory markers, and cardiometabolic risk factors. Semaglutide and liraglutide showed the most consistent evidence of benefit. Experimental and clinical data also suggested direct immunomodulatory effects on pathways involved in psoriasis pathogenesis. However, paradoxical psoriasiform eruptions and psoriasis exacerbations were reported with some agents. The evidence base was limited by the predominance of case reports and small observational studies, substantial heterogeneity, and the limited availability of randomized controlled trials. Conclusions: Current evidence suggests that GLP-1RAs may improve both psoriatic disease activity and cardiometabolic outcomes, particularly in patients with obesity or T2DM. Nevertheless, potential differences among individual agents warrant further investigation in larger controlled studies.

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Non-alcoholic fatty liver disease (NAFLD), now increasingly termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing cause of chronic liver disease with limited treatment options. Glucagon-like peptide-1 (GLP-1) receptor agonists, approved for type 2 diabetes and obesity, possess metabolic effects that may render them suitable for treating NAFLD and metabolic dysfunction-associated steatohepatitis (MASH). To evaluate the therapeutic effects of GLP-1 receptor agonists in adults with NAFLD, non-alcoholic steatohepatitis (NASH), MASLD, or MASH. PubMed, Scopus, Embase, and the Cochrane Library were systematically searched using keywords related to NAFLD and GLP-1 receptor agonists. Given heterogeneity in populations, designs, and outcomes, findings were synthesized narratively. The review is registered with PROSPERO (CRD420261337353). Twelve studies met the inclusion criteria. The most consistent outcome was a reduction in hepatic fat, seen with semaglutide, liraglutide, dulaglutide, and beinaglutide. Improvements in liver enzymes, particularly alanine aminotransferase, were less consistent and best regarded as supportive rather than definitive evidence of histological improvement. Histological benefits were strongest for steatohepatitis resolution in non-cirrhotic MASH. Fibrosis findings were mixed, with the greatest benefit in F2-F3 MASH and limited improvement in established cirrhosis. GLP-1 receptor agonists were generally well tolerated, with gastrointestinal symptoms the most common adverse effects. GLP-1 receptor agonists show promising liver-related benefits in NAFLD and MASH, particularly in obesity, type 2 diabetes, or earlier-stage disease. Their effects on advanced fibrosis and long-term outcomes remain uncertain, warranting larger, longer-term studies.

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Doxorubicin (DOX)-induced cardiotoxicity remains a major limitation of cancer therapy. Incretin-based therapies are established cardiometabolic agents with pleiotropic cardiovascular effects; however, their potential role in mitigating DOX-related cardiac injury has not been systematically synthesized. We conducted a PRISMA 2020-compliant systematic review to evaluate the effects of incretin-based therapies on DOX-induced cardiotoxicity, with a focus on functional, structural, biomarker, and mechanistic outcomes. PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched through 20 October 2025. Eligible studies included in vivo rodent models of DOX cardiotoxicity and any clinical studies directly evaluating incretin-based therapy during DOX exposure; in vitro studies, non-DOX models, combination-treatment studies, studies not focused on cardiotoxicity, gene therapy-based interventions, and reviews/editorials were excluded. Risk of bias and certainty of evidence were assessed using the SYRCLE tool and GRADE adapted for preclinical research. Thirteen rodent studies were included, and no eligible human study was identified. Investigated agents included liraglutide (n = 4), exenatide/exendin-4 (n = 4), semaglutide (n = 2), and tirzepatide (n = 3). In chronic cumulative-dose DOX models, incretin-based therapies were generally associated with preservation of left ventricular systolic function, with between-study improvements of approximately 7-20 percentage points in left ventricular ejection fraction, along with reductions in injury biomarkers. These effects were accompanied by attenuation of oxidative stress, inflammation, apoptosis, and, in some studies, ferroptosis. In contrast, findings were less consistent in acute single-dose models. Co-treatment during DOX exposure showed the most reproducible protective signal, whereas isolated pretreatment with liraglutide or tirzepatide and post-treatment with exenatide did not show a clear additional benefit. The evidence base is limited by exclusive reliance on small heterogeneous animal studies, predominantly male models, variable dosing/timing protocols, and low-to-very-low certainty of evidence. Overall, incretin-based therapies show biologically plausible cardioprotective effects in preclinical DOX cardiotoxicity, but these findings should be regarded as hypothesis-generating until confirmed in carefully designed clinical studies.

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Adolescent obesity is an escalating global health concern associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and long-term metabolic complications. Although lifestyle interventions remain first-line therapy, their limited long-term effectiveness has led to increasing interest in pharmacological approaches. This narrative review evaluates the mechanisms, clinical efficacy, and safety of glucagon-like peptie-1 (GLP-1) receptor agonists, as well as emerging dual and triple incretin-based therapies, in the management of adolescent obesity. A literature search was conducted using PubMed and Scopus, focusing on clinical trials, systematic reviews, and real-world studies published between 2010 and 2024. Evidence from pediatric and adolescent populations was prioritized, while adult data were included where adolescent-specific evidence remains unavailable and are interpreted cautiously. Among single-agent therapies, GLP-1 receptor agonists have demonstrated clinically meaningful weight reduction and metabolic benefits in adolescents. In the STEP TEENS trial, once-weekly semaglutide resulted in approximately 16% mean body weight reduction over 68 weeks, while liraglutide produced more modest reductions. Dual agonists such as tirzepatide and emerging triple agonists, including retatrutide, have shown superior weight-loss efficacy in adult populations; however, pediatric data for these agents remain limited or unavailable. Across all incretin-based therapies, gastrointestinal adverse effects are the most commonly reported side effects. In conclusion, GLP-1 receptor agonists represent an effective pharmacological option for adolescents with obesity, while dual and triple incretin agonists offer promising future therapeutic potential. Nevertheless, the clinical application of multi-receptor agonists in adolescents requires caution, as long-term safety, developmental outcomes, and real-world adherence data in pediatric populations are still lacking. Further well-designed pediatric trials are essential before broader adoption can be recommended.

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BackgroundThe incidence of Alzheimer's disease (AD) is increasing globally but there are limited effective therapies available. Recently, evidence has demonstrated a role of GLP-1 receptor (GLP-1R) agonists, commonly used in the treatment of type 2 diabetes, may have therapeutic potential in AD. GLP-1R agonists have exhibited their neuroprotective role by targeting tau hyperphosphorylation and the accumulation of beta-amyloid (Aβ) plaques. This systematic review aims to evaluate the effectiveness of liraglutide, semaglutide, exenatide and dulaglutide on AD pathology with a focus on the key biomarkers: hyperphosphorylated tau and Aβ.MethodsA systematic literature search was conducted using PubMed, Embase and Cochrane Library. Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology. Randomised and non-randomised studies were included. Exclusion criteria involved studies evaluating GLP-1R agonists other than those specified.ResultsThis review examined thirty preclinical studies investigating the effects of four GLP-1 receptor agonists on Alzheimer's disease pathology, particularly Aβ plaque accumulation and tau hyperphosphorylation. Most studies focused on liraglutide, which consistently reduced both Aβ and tau pathology in animal and cell models. Dulaglutide, although studied less frequently, consistently reduced tau phosphorylation and Aβ accumulation in mouse models while also improving cognitive outcomes. Semaglutide also showed largely positive effects with four studies reporting reduced Aβ or tau pathology, though one study reported no benefit. Two clinical studies were also reviewed. A phase II trial of Exenatide showed reduced plasma Aβ42 in extracellular vesicles but not cognitive benefit. A smaller liraglutide trial demonstrated no reduction in Aβ burden or cognitive change though it preserved brain glucose metabolism. An EXSCEL trial showed significant changes in systemic inflammatory markers. While pre-clinical data has been encouraging, clinical evidence remains limited.ConclusionsThere is consistent preclinical evidence that GLP-1R agonists are effective in reducing Aβ levels and hyperphosphorylated tau. While the neuroprotective effect in preclinical studies is clear, clinical findings have so far failed to demonstrate an arresting effect on cognitive.RegistrationPROSPERO CRD420251029748.

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Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder characterized by recurrent upper airway collapse, intermittent hypoxemia, and increased cardiovascular risk. Obesity is the principal modifiable risk factor, and weight loss has been shown to improve OSA severity. Recently, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist tirzepatide have emerged as promising pharmacotherapies for obesity-related OSA. We conducted a systematic review in accordance with PRISMA 2020 guidelines to evaluate the impact of GLP-1 RAs (semaglutide, liraglutide) and tirzepatide on apnea-hypopnea index (AHI). Databases including PubMed, Google Scholar, and SciSpace were searched up to May 2026. Eligible studies involved adults with OSA receiving GLP-1–based therapies with quantitative AHI outcomes. A total of 40 studies were included. Tirzepatide demonstrated greater reductions in AHI (−25.3 to −29.3 events/h; 50.7%–58.7%) compared with liraglutide (−12.2 events/h; ~25%). Meta-analyses showed an overall AHI reduction of −16.57 events/h. These effects were largely mediated by weight loss, with additional evidence suggesting weight-independent mechanisms.GLP-1–based therapies, particularly tirzepatide, represent effective treatment options for obesity-related OSA, especially in patients with poor adherence to continuous positive airway pressure therapy.

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Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder, and while metformin is widely used in its management, its efficacy remains variable. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as potential alternatives due to their metabolic benefits. In this systematic review, we have evaluated the effectiveness of GLP-1 RAs on body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), and total testosterone (TT) in women with PCOS. Randomised controlled trials (RCTs) comparing the effect of GLP-1 RAs with metformin, standard, or placebo on BMI, HOMA-IR, and TT in women with PCOS were selected following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in various databases, including PubMed, Scopus, Embase, MEDLINE, Web of Science, Cochrane, and CINAHL through May 20, 2025. Eighteen RCTs comparing GLP-1 RAs with placebo, metformin, or standard therapy were included. Quality assessment was done using Cochrane's 'Risk of Bias tool (RoB2)'. Review Manager (RevMan) version 5.4.1 (The Cochrane Collaboration, London, United Kingdom) was used to perform random-effects meta-analysis. Continuous outcomes were pooled as mean differences (MD) when measured on the same scale and as standardised mean differences (SMD) when the scales differed, each with a 95% confidence interval (CI). Inter-study heterogeneity among the trials was assessed using the chi-squared test for heterogeneity, with I² to quantify the level of heterogeneity. The certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. GLP-1 RAs significantly reduced BMI compared with control interventions (MD: -1.09 kg/m²; 95% CI: -1.80 to -0.38; p = 0.003), with liraglutide showing superiority over both metformin and placebo in subgroup analyses. Insulin resistance improved significantly (SMD: -0.38; 95% CI: -0.61 to -0.16; p = 0.001), particularly with exenatide. However, no significant overall effect on TT levels was observed (SMD: -0.10; 95% CI: -0.38 to 0.18; p = 0.49). Risk of bias was generally low, with minor concerns in select domains. Funnel plots suggested minimal publication bias. The certainty of evidence was moderate for BMI and HOMA-IR and very low for TT. GLP-1 receptor agonists are effective in improving metabolic outcomes in PCOS, particularly in reducing BMI and insulin resistance. However, their effect on androgen levels remains inconclusive. These agents may represent a promising therapeutic option, especially in overweight or obese women with PCOS, though further large-scale studies are needed to confirm long-term benefits.

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