Review
This narrative review, aimed at obstetricians and gynecologists, synthesizes current evidence on GLP-1 receptor agonists (e.g., semaglutide) and dual GLP-1/GIP agonists (e.g., tirzepatide) as they relate to women's health. The authors highlight that phase 3 trials have reported 15–21% body weight reduction with these agents, with tirzepatide showing greater efficacy than semaglutide. In women with polycystic ovary syndrome (PCOS), the authors cite meta-analyses finding improvements in insulin resistance, androgen levels, and ovulation rates. Regarding contraception, the review notes that tirzepatide's gastric-emptying delay has prompted manufacturer guidance about backup contraception around initiation and dose escalation. On pregnancy safety, the authors describe emerging human cohort data suggesting no significantly increased risk of major congenital malformations from inadvertent early pregnancy exposure, while noting that animal teratogenicity data still warrant caution. Perioperative guidance has shifted toward individualized risk-stratified approaches rather than blanket discontinuation. The authors call for formal pregnancy registries to address persistent knowledge gaps. As a review, this paper does not generate new primary data, and its conclusions are limited by the underlying evidence base, which in several areas remains preliminary or indirect.
Current opinion in obstetrics & gynecology · May 2026DOI ↗ Review
This narrative review examines whether tirzepatide — a dual GIP/GLP-1 receptor agonist — may act as a disease-modifying therapy in obesity-related obstructive sleep apnea (OSA), beyond its well-established effects on weight reduction. The authors searched PubMed, Scopus, and Web of Science through January 2026, synthesizing evidence from randomized controlled trials, meta-analyses, and mechanistic studies on incretin-based therapies in obesity and OSA. The review reports that tirzepatide is associated with meaningful reductions in apnea-hypopnea index (AHI) alongside significant weight loss. Notably, the authors propose that OSA improvements may not be fully explained by weight loss alone, highlighting potential weight-independent mechanisms such as modulation of systemic inflammation, improvements in insulin sensitivity, changes in adipokine profiles, and effects on autonomic regulation and ventilatory chemosensitivity. The authors acknowledge that current evidence is insufficient to definitively separate weight-dependent from weight-independent effects, and they call for dedicated mechanistic and long-term clinical studies. A key limitation is the review's narrative — rather than systematic — design, which introduces selection bias. The paper frames tirzepatide as a potential shift from purely device-based OSA management toward integrated, pathophysiology-driven treatment strategies, but stops short of confirming disease-modifying status.
Life (Basel, Switzerland) · May 2026DOI ↗ Review
This narrative review evaluates whether incretin-based therapies — specifically GLP-1 receptor agonists (e.g., semaglutide) and dual GLP-1/GIP receptor agonists (e.g., tirzepatide) — warrant consideration as first-line antihypertensive agents. The authors synthesize findings from recent large-scale trials demonstrating that these agents are associated with significant reductions in body weight, blood pressure, and adverse cardiovascular outcomes. Mediation analyses cited in the review suggest that weight loss accounts for a substantial portion of the observed blood pressure reductions; however, the authors also highlight putative direct mechanisms, including improvements in vascular function, renal sodium handling, and neurohumoral pathway modulation. The review notes that beneficial effects on blood pressure appear consistent across diverse patient populations, including those without established hypertension. A key limitation acknowledged by the authors is the absence of randomized controlled trials specifically designed with blood pressure as a primary endpoint. Based on the available evidence, the authors conclude that incretin-based therapies may have an emerging role in hypertension management guidelines, particularly for selected high-risk populations. As a review article, conclusions are dependent on the quality and interpretation of the underlying primary studies cited.
Current hypertension reports · May 2026DOI ↗ Review
The 11th Cardiovascular Outcome Trial (CVOT) Summit (November 2025) was a virtual multidisciplinary conference convening experts in endocrinology, diabetology, cardiology, nephrology, hepatology, and general practice to review recent outcome trials and emerging therapies along the cardiovascular-kidney-metabolic (CKM) disease continuum. The report summarizes key 2025 developments, including the first head-to-head CVOT (SURPASS-CVOT), the CONFIDENCE trial examining combination therapy with finerenone (a non-steroidal mineralocorticoid receptor antagonist) and empagliflozin (an SGLT2 inhibitor), the ATTAIN-1 trial of the oral GLP-1 receptor agonist orforglipron, and the BaxHTN trial of the aldosterone synthase inhibitor baxdrostat. The report also covers updated clinical guidelines, policy developments, advances in continuous glucose and ketone monitoring technology, and emerging pharmacological strategies for metabolic liver disease and type 1 diabetes. As a conference summary report rather than a primary trial, this document does not present original trial data and primarily synthesizes and contextualizes findings from multiple studies. Key limitations include the narrative, consensus-driven format and the absence of new primary data.
Cardiovascular diabetology · May 2026DOI ↗ Review
This paper is a commentary/review examining the rapidly evolving landscape of weight-loss pharmacotherapy, focusing on the progression from standard GLP-1 receptor agonists to dual and triple agonists capable of achieving 30–40% body weight reduction — outcomes previously only attainable through bariatric surgery. The authors argue that the pharmaceutical industry's competitive focus on maximizing weight-loss percentages is creating a disconnect between the metric of total body mass reduction and the broader goal of metabolic health. A central concern raised is that aggressive pursuit of high weight-loss targets may come at the cost of metabolic integrity and lean muscle mass preservation. The paper also touches on how escalating clinical benchmarks are influencing investor expectations and market dynamics. Notable limitations include the absence of primary data; the piece offers no original clinical trial results, relies on narrative argument rather than systematic evidence synthesis, and does not present a structured methodology for evaluating the compounds discussed. It does not provide specific dosing guidance but situates the debate within a broader physiological and economic context.
Molecules and cells · May 2026DOI ↗ Review
This review examines the perioperative safety implications of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug class increasingly used for type 2 diabetes and obesity management. The authors focus on the mechanism by which GLP-1 RAs delay gastric emptying and how this pharmacological effect may elevate the risk of pulmonary aspiration during general anesthesia—specifically at induction and emergence—even when patients have followed standard preoperative fasting protocols. The review distinguishes between short-acting GLP-1 RAs, which reportedly cause more pronounced gastric emptying delays, and long-acting agents, whose residual effects may vary by dose and duration of treatment. The authors also survey updated guidance issued by international anesthesia societies in response to these concerns. Key limitations acknowledged include the overall scarcity and inconsistency of available clinical evidence. The review concludes by advocating for individualized, interdisciplinary perioperative management involving collaboration between endocrinologists and anesthesiologists. As a narrative review, it does not generate new primary data, and the conclusions are constrained by the quality of the underlying literature.
The Korean journal of internal medicine · May 2026DOI ↗ Review
This state-of-the-art review synthesizes available evidence on how glucagon-like peptide-1 receptor agonists (GLP-1 RAs) — drugs used for type 2 diabetes and weight management — affect blood pressure (BP). The authors examined data across populations including people with diabetes, obesity, and high cardiovascular risk. The review reports that GLP-1 RAs are associated with modest systolic BP reductions, typically in the range of 2–5 mm Hg, which the authors attribute primarily to weight loss, with potential additional contributions from weight-independent mechanisms such as natriuresis (increased urinary sodium excretion), improved endothelial function, and reduced vascular inflammation. The review notes that while these reductions are smaller than those achieved with traditional antihypertensive medications, they may translate to meaningful cardiovascular risk reduction at a population level and may offer additive benefit alongside conventional therapies. The authors also highlight that small increases in heart rate and possible interactions with volume-regulating medications may require clinical monitoring. Limitations acknowledged include the indirect and heterogeneous nature of the synthesized evidence. The review concludes by calling for further research as newer GLP-based therapies emerge to better inform integrated cardiometabolic care strategies.
American journal of hypertension · May 2026DOI ↗ 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 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 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 ↗ 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 ↗