Review
This review examines the emerging role of GLP-1-based medications (such as GLP-1 receptor agonists) in the prevention and treatment of heart failure (HF), with a particular focus on heart failure with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). The authors summarize and discuss findings from recent clinical studies reporting HF-related outcomes with these agents. The review highlights the strong pathophysiological connections between type 2 diabetes, obesity, and heart failure, positioning GLP-1-based therapies as potentially beneficial across these overlapping conditions. The authors conclude that accumulating evidence supports beneficial effects on HF outcomes—particularly in HFpEF and possibly HFmrEF—while noting that the utility of these medications in heart failure with reduced ejection fraction (HFrEF) remains unclear and requires further investigation. As a narrative review, this paper synthesizes existing literature rather than generating new primary data, and its conclusions are therefore dependent on the quality and scope of the studies it includes. It does not establish causality or provide definitive clinical guidance on specific patient populations.
Medicina (Kaunas, Lithuania) · May 2026DOI ↗ Review
This narrative review evaluates the emerging evidence for glucagon-like peptide-1 receptor agonists (GLP-1RAs) — a drug class established for type 2 diabetes and obesity — as potential treatments for alcohol use disorder (AUD), a condition with currently limited pharmacological options. The authors searched PubMed, Google Scholar, and ClinicalTrials.gov, ultimately including 13 preclinical studies, 14 clinical studies, and 4 published interventional trials, while noting 19 additional trials in progress or completed but unpublished. The review describes convergent signals from both animal models and human studies suggesting that GLP-1RAs may reduce alcohol consumption and improve alcohol-related outcomes. Mechanistic preclinical work is highlighted to contextualize how these agents might modulate reward-related pathways. Clinical evidence includes observational studies drawing on real-world and electronic health record data, as well as a small number of randomized controlled trials. The authors acknowledge that the existing RCT evidence base remains limited and that further trials are needed to firmly establish efficacy. Mechanistic studies are also called for to more fully explain how GLP-1RAs may reduce alcohol intake. Case reports, commentaries, and preprints were excluded. This review does not itself generate new primary data.
Alcohol, clinical & experimental research · May 2026DOI ↗ Review
This paper argues that body image has been largely overlooked in research on glucagon-like peptide-1 receptor agonists (GLP-1s) such as semaglutide and tirzepatide, despite its central relevance to why people seek these treatments and how they psychologically adjust to the bodily changes that follow. Drawing on existing literature across body image, weight loss interventions, weight stigma, and cosmetic procedures, the authors conceptualise body image not simply as an outcome of GLP-1 use, but as a motivator, mediator, and moderator across the entire treatment trajectory. The paper identifies several critical research gaps, including the absence of prospective and longitudinal studies tracking body image before, during, and after GLP-1 use, as well as limited understanding of individual vulnerability factors and heterogeneity in psychological responses. The authors also highlight broader societal concerns, including the potential reinforcement of weight stigma, inequities in access to these medications, and the role of media representation. They call for body image-informed psychological support for people using GLP-1s, as well as professional education and training. As a narrative review, the paper does not present new empirical data and its conclusions are based on inference from adjacent literatures rather than direct evidence.
Body image · Apr 2026DOI ↗ Review
This narrative review compared tirzepatide (a dual GIP/GLP-1 receptor agonist) and semaglutide (a selective GLP-1 receptor agonist) across weight loss, glycemic control, cardiometabolic, and safety outcomes by synthesizing evidence from clinical trials, real-world observational studies, and cardiovascular outcome analyses. The authors found that in completed head-to-head randomized trials, tirzepatide consistently produced greater reductions in body weight and HbA1c compared with semaglutide in people with obesity or type 2 diabetes. Regarding cardiovascular outcomes, the review noted that semaglutide currently holds the most mature evidence for cardiovascular risk reduction, supported by the SUSTAIN-6, PIONEER-6, and SELECT trials. Tirzepatide's SURPASS-CVOT trial demonstrated non-inferiority to dulaglutide for cardiovascular outcomes along with improvements in cardiometabolic risk factors, but direct cardiovascular superiority data versus semaglutide remain limited. Real-world studies on cardiovascular outcomes were characterized as heterogeneous. The authors concluded that treatment selection should be individualized. Key limitations include the narrative (non-systematic) methodology, potential for selection bias in literature inclusion, and the absence of a completed direct head-to-head cardiovascular outcomes trial between the two agents.
Frontiers in medicine · Apr 2026DOI ↗ Review
This systematic review (PRISMA-compliant, PROSPERO-registered) examined the association between GLP-1 receptor agonists (GLP-1 RAs) and hair loss by searching four major databases (PubMed, Embase, Scopus, Web of Science). Of 133 studies identified, 24 met inclusion criteria as primary articles. The review found that semaglutide and tirzepatide showed the highest reported incidence of hair loss and the strongest pharmacovigilance signals among GLP-1 RAs. The predominant subtypes reported were androgenetic alopecia and telogen effluvium, with telogen effluvium most frequently linked to tirzepatide—the agent associated with the greatest magnitude of weight loss. The authors noted that hair loss with semaglutide appeared dose-dependent, and that females were disproportionately affected. Rapid weight loss was identified as a potential contributing mechanism, especially for telogen effluvium. Other agents—liraglutide, dulaglutide, lixisenatide, and exenatide—had fewer studies and generally lower reported risk. Key limitations include the reliance on pharmacovigilance data and heterogeneous study designs, which preclude definitive causal conclusions. The authors call for large, prospective randomized trials to establish causality and temporal relationships.
Science progress · Apr 2026DOI ↗ Review
This review examines the current clinical development pipeline for metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, MASH (metabolic dysfunction-associated steatohepatitis), with a particular focus on cardiovascular comorbidities. The authors highlight the strong bidirectional relationship between MASLD and cardiometabolic risk, arguing that effective treatments should address both hepatic and cardiovascular outcomes simultaneously. The review surveys a broad range of drug candidates and mechanisms, including incretin mimetics (e.g., semaglutide), thyroid hormone receptor-beta agonists (e.g., resmetirom), farnesoid X receptor agonists, PPAR agonists, de novo lipogenesis inhibitors, and fibroblast growth factor analogues. The authors note that the two FDA-approved therapies — resmetirom and semaglutide — have demonstrated reductions in major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality in MASH patients, with semaglutide also showing benefit in heart failure with preserved ejection fraction. However, the review emphasizes that cardiovascular outcome data for most other pipeline agents remain limited or absent. A key limitation is that this is a narrative review and does not involve primary data collection or meta-analytic methods.
Biomedicines · Apr 2026DOI ↗ Review
This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence from 15 studies evaluating GLP-1 receptor agonist and dual incretin-based pharmacotherapies for obesity management, including semaglutide, liraglutide, tirzepatide, dulaglutide, and dual GIP/GLP-1 receptor agonists. Study participants were predominantly female (up to 79.3%), ranging in mean age from 22.4 to 59.8 years, with BMIs between 29.3 and 43.0 kg/m², and frequent comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The review found that weight loss was dose-dependent across agents, with dual GIP/GLP-1 therapy showing the greatest reductions. Cardiometabolic outcomes included reductions in HbA1c, systolic blood pressure, and LDL cholesterol across therapies. Gastrointestinal adverse events — particularly nausea, vomiting, and diarrhea — were commonly reported but generally mild, while serious events such as pancreatitis and gallbladder complications were rare. Treatment discontinuation rates were described as generally low. Limitations include the heterogeneity of included studies, variability in populations, and the review's reliance on previously published trial data rather than original participant-level analysis.
Disease-a-month : DM · Apr 2026DOI ↗ Review
This review paper examines the emerging evidence for glucagon-like peptide-1 receptor agonists (GLP-1RAs) — specifically liraglutide, semaglutide, and tirzepatide — as potential interventions in prediabetes. The authors synthesize findings showing that GLP-1RAs were associated with reduced progression to type 2 diabetes mellitus (T2DM), with normoglycaemia achieved in a notable proportion of subjects (up to 66%, 81%, and 93.3% for liraglutide, semaglutide, and tirzepatide, respectively). However, these glycaemic benefits were only partially maintained after drug discontinuation. The review also highlights modest reductions in HbA1c, fasting glucose, body weight, and fat mass, alongside improvements in insulin sensitivity and β-cell function. Potential cardiovascular benefits — including reduced risk of atherosclerotic cardiovascular disease and heart failure — were noted, particularly with tirzepatide. Experimental data suggested possible benefits for metabolic dysfunction-associated steatotic liver disease (MASLD). The safety profile was described as acceptable, with mild-to-moderate gastrointestinal effects being the most commonly reported adverse events. The authors acknowledge that the current evidence base is limited and call for large, well-designed randomised controlled trials to define the precise role of GLP-1RAs in prediabetes management.
Diabetes therapy : research, treatment and education of diabetes and related disorders · Apr 2026DOI ↗ Review
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly marketed in sports medicine contexts, spanning both FDA-approved compounds (e.g., tesamorelin/Egrifta) and unapproved "gray market" substances (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, and others). The authors note that while many unapproved peptides show promising tissue repair and metabolic effects in animal models, rigorous human safety and efficacy data are largely absent. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses the potential for serious patient harm. Notably, the authors address the placebo effect as a possible mediator of perceived peptide efficacy and examine how social media may amplify this effect. A clinician-oriented framework is proposed to guide evidence-based patient discussions about peptide use for musculoskeletal healing and athletic performance, including consideration of alternative treatments. Key limitations include the narrative (non-systematic) review methodology and the inherently limited and heterogeneous evidence base for most compounds discussed, particularly in human populations.
Sports medicine (Auckland, N.Z.) · Apr 2026DOI ↗ Review
This narrative review examines the skeletal consequences of modern obesity treatments, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs) and bariatric/metabolic surgery. The authors challenge the historical assumption that obesity is bone-protective due to mechanical loading, citing emerging evidence of qualitative bone deterioration and site-specific fracture risks in individuals with obesity. The review synthesizes findings showing that intentional weight loss via caloric restriction or bariatric surgery consistently accelerates bone turnover and reduces bone mineral density (BMD), with surgical approaches carrying the most pronounced skeletal impact. Regarding GLP-1RAs, the authors report that available data suggest modest BMD declines largely proportional to the degree of weight loss, potentially driven by mechanical unloading. Interestingly, the review also notes that preclinical studies suggest GLP-1 signaling may have direct osteoanabolic and anti-resorptive properties, though these effects remain to be confirmed in humans. The authors recommend integrating resistance exercise, adequate calcium, vitamin D, and protein intake, and skeletal monitoring for high-risk patients into obesity care. Limitations include reliance on heterogeneous primary literature and the absence of long-term fracture outcome data for newer pharmacological agents.
Endocrinology and metabolism (Seoul, Korea) · Apr 2026DOI ↗ Review
This comprehensive review examines the genetic underpinnings of obesity and the evolving landscape of pharmacological treatment informed by genetic insights. The authors distinguish between rare monogenic obesity — driven by mutations in single genes such as LEP, POMC, and MC4R within the leptin-melanocortin neuroendocrine signaling pathway — and common polygenic obesity, which results from the cumulative small effects of hundreds of genetic variants, including loci identified through genome-wide association studies (GWAS) such as FTO and SEC16B. The review also discusses how gene-environment interactions contribute to the heterogeneity of obesity phenotypes. On the pharmacotherapy side, the authors highlight recent advances including GLP-1 receptor agonists and dual/triple incretin agonists, noting their reported efficacy across diverse genetic backgrounds. The potential clinical utility of polygenic risk scores for early risk identification and prevention is explored. Limitations of this paper include its nature as a narrative review — it synthesizes existing literature rather than generating new empirical data — and it does not perform a systematic or meta-analytic evaluation. The authors acknowledge ongoing challenges in integrating genomic data into clinical practice and call for further research into genetic screening protocols and gene-environment interactions to advance precision medicine in obesity management.
Acta biochimica Polonica · Apr 2026DOI ↗ Review
This narrative review examines the expanding therapeutic landscape of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) beyond their established roles in glycemic control and the metabolic-cardiovascular-renal axis. The authors searched PubMed, Scopus, and Google Scholar for publications from 2014 to 2026, with over 80% of included studies published between 2020 and 2026. The review synthesizes findings across a broad range of conditions, reporting associations between GLP-1 RA use and potential benefits in substance use disorders, mental health disorders, neurodegenerative diseases, liver disease (including reduced hepatic steatosis and lower risk of hepatocellular carcinoma), genitourinary disorders, polycystic ovary syndrome (PCOS), male fertility and libido, prostate cancer, osteoarthritis, and sleep apnea. The authors note that GLP-1 RAs currently represent the most effective pharmacological agents for obesity treatment. Key limitations include the narrative (non-systematic) review design, which is susceptible to selection bias, and the authors' own acknowledgment that much of the supporting evidence is preliminary, requiring further large-scale, well-designed clinical trials to establish efficacy and safety across these emerging indications.
Journal of clinical medicine · Apr 2026DOI ↗ ReviewPreprint
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly encountered in sports medicine and athletic performance contexts, including both approved agents (e.g., tesamorelin/Egrifta, sermorelin) and unapproved "gray market" compounds (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, SS-31, and thymosin beta-4). The authors note that while many unapproved peptides show promising tissue repair and metabolic outcomes in animal models, rigorous human safety and efficacy data remain scarce. The review highlights the emergence of a direct-to-consumer gray market operating outside regulatory oversight and the potential for serious patient harm. It further discusses the placebo effect as a potential mediator of perceived peptide efficacy, and how social media may amplify this effect. The authors provide a clinical framework to guide patient-provider discussions and promote evidence-based practice for musculoskeletal healing. Key limitations include the narrative (non-systematic) review design, reliance on preclinical literature for most unapproved compounds, and the absence of head-to-head human trials for the majority of agents discussed.
Unknown journal · Apr 2026DOI ↗ Review
This comprehensive narrative review examines nine therapeutic peptides with proposed applications in healthy aging and age-related conditions: tirzepatide (metabolic dysfunction), epitalon (telomere biology), GHK-Cu (dermal regeneration), BPC-157 and TB-500 (tissue repair), Semax (neuroprotection), CJC-1295 and ipamorelin (growth hormone modulation), and bremelanotide (sexual function). The authors searched PubMed, Scopus, and regulatory databases through January 2026, selecting 20 primary sources based on relevance and methodological quality. The review found that FDA-approved agents such as tirzepatide and bremelanotide have robust safety and efficacy data from large-scale trials, while investigational peptides such as epitalon, BPC-157, and TB-500 show promising signals primarily from preclinical and limited clinical studies. The authors highlight significant knowledge gaps, including the absence of long-term safety data for non-approved peptides, undefined optimal dosing regimens, unknown combination therapy effects, and lack of validated biomarkers for monitoring efficacy. The authors conclude that while therapeutic peptides offer mechanistically diverse approaches to aging hallmarks, investigational agents require rigorous clinical trial validation before clinical adoption. As a narrative review, findings are subject to selection bias and do not represent a quantitative synthesis of evidence.
Frontiers in aging · Apr 2026DOI ↗ Review
This review examines the acute contractile effects of glucagon-like peptide-1 receptor (GLP-1R) agonists on the human heart, with a focus on isolated atrial and ventricular cardiac preparations from both failing and non-failing hearts. The paper discusses how GLP-1R stimulation in cell cultures, neonatal cardiomyocytes, and adult atrial cardiomyocytes elevates adenylyl cyclase activity and increases cAMP levels, a key intracellular signaling pathway. The authors explore the expanding landscape of receptor agonists — including single GLP-1R agonists as well as dual and triple agonists targeting the glucagon receptor (GCGR) and/or the GIP receptor (GIPR) — in the context of treating type 2 diabetes, obesity, liver disease, and cardiovascular conditions. GLP-1R expression across different cardiac regions of the human heart is also reviewed. The paper critically evaluates existing experimental and clinical data, notes that several newer agents remain in early clinical development phases, and identifies gaps requiring further research. A key limitation is that the review synthesizes heterogeneous experimental and early-phase clinical data rather than presenting original controlled trial findings, limiting the strength of conclusions about cardiac efficacy or safety in humans.
Pharmaceutics · Apr 2026DOI ↗ Review
This review paper examines the role of amylin — a pancreatic hormone — in regulating food intake, body weight, and reward processing through its actions in the brain. The authors outline how early research focused on hindbrain regions as the primary sites where amylin suppresses feeding, but highlight more recent evidence pointing to mesolimbic brain structures (associated with reward and motivation) as additional key targets. The review discusses findings suggesting that amylin signaling in these reward-related areas influences not only consumption of palatable foods but also responses to drugs of abuse, raising important considerations for the development of amylin-based obesity therapies. The paper is contextualized within the broader landscape of obesity treatment, acknowledging the success of GLP-1 receptor agonists while arguing that amylin represents a complementary pharmacological avenue. As a narrative review, the paper synthesizes existing literature rather than presenting new experimental data, meaning its conclusions are only as strong as the individual studies it draws upon. It does not provide direct clinical trial evidence, and the breadth of findings discussed spans animal models and limited human data, which constrains the translational certainty of its conclusions.
Comprehensive Physiology · Apr 2026DOI ↗ Review
This review article provides a comprehensive overview of glucagon-like peptide-1 (GLP-1) receptor agonists, a class of incretin-based therapies used in the management of type 2 diabetes mellitus and obesity. The authors describe the multiple mechanisms of action of these agents, including glucose-mediated insulin stimulation, slowing of gastric emptying, glucagon inhibition, favorable shifts in the intestinal microbiome, and direct hypothalamic effects that promote satiety and weight loss. The review highlights findings from large-scale randomized controlled trials demonstrating that GLP-1 receptor agonists can reduce cardiovascular risk and slow progression to renal failure in high-risk individuals and those with type 2 diabetes. It also covers dual GLP-1 and glucose-dependent insulinotropic peptide (GIP) agonists. The authors note that adverse effects are predominantly gastrointestinal and raise concerns about potential loss of muscle and bone mass. Unresolved questions include long-term treatment adherence, weight regain following discontinuation, and the clinical significance of muscle and bone changes. Emerging research is exploring additional therapeutic applications. As a narrative review, it does not present original data, which limits its direct evidentiary weight.
The New England journal of medicine · Apr 2026DOI ↗ Review
This review examines the cardioprotective potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with autoimmune rheumatic diseases (ARDs), a population at elevated risk of premature cardiovascular death. The authors synthesize evidence from landmark randomized controlled trials in diabetes and obesity—where GLP-1RAs demonstrated cardiovascular, kidney, and metabolic benefits—alongside observational studies in ARD populations (including rheumatoid arthritis and systemic lupus erythematosus) that reported reductions in cardiovascular event risk comparable to those seen in broader populations. The review outlines proposed direct and indirect cardioprotective mechanisms: GLP-1RAs address type 2 diabetes and obesity as cardiovascular risk factors, reduce lipid levels by mitigating post-prandial hyperlipidemia, lower blood pressure via carotid body-mediated sympathetic suppression, and exhibit anti-atherogenic and anti-inflammatory properties observed in murine models. Anti-inflammatory effects are attributed to direct activation of GLP-1 receptors on gut intraepithelial lymphocytes and indirect modulation of myeloid cell inflammation through central neuronal GLP-1 receptor activation. The authors acknowledge remaining knowledge gaps and note that much mechanistic evidence derives from animal studies. Overall, they conclude existing evidence is supportive but not definitive for GLP-1RA cardioprotection in ARDs.
Rheumatology (Oxford, England) · Apr 2026DOI ↗ Review
This narrative review synthesizes evidence on how GLP-1-based therapies (liraglutide, semaglutide, tirzepatide, dulaglutide, exenatide) interact with the gut microbiome and influence metabolic dysfunction-associated steatotic liver disease (MASLD/MASH) in the context of type 2 diabetes mellitus (T2DM). The authors searched PubMed, Scopus, and ClinicalTrials.gov (2015–2026), ultimately including 33 studies (18 preclinical, 15 clinical) out of 363 identified. Preclinical findings suggest liraglutide normalized the Firmicutes/Bacteroidetes ratio and increased beneficial bacteria, while tirzepatide reduced hepatic steatosis and increased Akkermansia abundance in diabetic mice, and semaglutide improved gut barrier integrity in murine models. Clinically, tirzepatide achieved MASH resolution in 44–62% of patients in the phase 2 SYNERGY-NASH trial, and the FDA approved semaglutide for MASH with fibrosis in August 2025 based on the Phase 3 ESSENCE trial. A longitudinal study found baseline microbiome composition predicted glycemic response to semaglutide. Key limitations include the narrative (non-systematic) design, heavy reliance on preclinical data, and heterogeneous study populations. The authors conclude that personalized MASLD management informed by microbiome profiling warrants further dedicated clinical investigation.
Biomedicines · Apr 2026DOI ↗ Review
This narrative review synthesizes evidence from randomized controlled trials, meta-analyses, and observational studies through 2026 to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin-based therapies on a range of ocular outcomes. The authors report that recent meta-analyses indicate an overall neutral long-term risk profile for diabetic retinopathy and macular edema with these agents. They describe a transient early worsening of diabetic retinopathy observed primarily in patients with advanced baseline disease undergoing rapid HbA1c reduction, framing this as a "metabolic transition phenomenon" rather than direct retinal toxicity—an interpretation supported by data from the SELECT trial, in which no increased ocular risk was found in a non-diabetic population. The review also notes observational signals suggesting possible protective associations with glaucoma and age-related macular degeneration, a potential safety concern regarding nonarteritic anterior ischemic optic neuropathy at low absolute incidence, and emerging evidence of benefit in ocular surface homeostasis and uveitis. Limitations include reliance on observational data for several signals and the inherent constraints of a narrative review design. The authors conclude that risk-stratified ophthalmic monitoring, aligned with a cited 2025 expert consensus, is preferable to routine treatment avoidance in high-risk diabetic patients.
Journal of obesity & metabolic syndrome · Apr 2026DOI ↗