Review
This review examines the relationship between glucagon-like peptide-1 (GLP-1) receptor agonists — a class of drugs used to treat obesity and type 2 diabetes — and cancer risk. The authors note that obesity and type 2 diabetes are established risk factors for several cancers, and that GLP-1 receptor agonists have become transformative treatments for these conditions. The review synthesizes current clinical evidence across multiple cancer types, including thyroid, pancreatic, gastrointestinal, and hormone-dependent malignancies. The authors report that recent meta-analyses generally do not support an increased cancer incidence with GLP-1 receptor agonist use, and suggest a potential risk-lowering effect in some cancer types. Preclinical studies are also discussed, with findings pointing to possible anticancer mechanisms even in non-obese models, including immune-modulating effects that may reflect direct action on immune cells or stem from improved metabolic function. The review highlights ongoing clinical trials and identifies key gaps in translational research, including questions about treatment timing, duration, concurrent anticancer therapies, and the distinction between cancer risk versus progression models. As a narrative review, it does not generate new primary data, and conclusions depend on the quality of the underlying studies reviewed.
The Journal of clinical investigation · Nov 2025DOI ↗ Review
This review paper examines the potential role of nutrient-stimulated hormone-based therapies (NuSHs) — particularly GLP-1 receptor agonists — in the prevention and management of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC). The authors contextualize MASH as the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), which is now the most prevalent chronic liver disease in Western populations. The review synthesizes emerging clinical and preclinical evidence suggesting that NuSHs can resolve MASH without worsening fibrosis, primarily through weight loss and improved insulin sensitivity. However, the authors note that benefits appear less pronounced in cirrhotic patients, implying greater utility in early disease stages. Preclinical models suggest NuSHs may reduce MASH-related HCC incidence and tumor burden through systemic metabolic improvements rather than direct anti-cancer mechanisms. Observational data from bariatric surgery populations further support a preventive role for weight loss. The authors also propose that integrating NuSHs into post-locoregional HCC treatment pathways could delay systemic therapy, improve immunotherapy synergy, and enhance transplant eligibility. Key limitations include the indirect nature of evidence, inconsistent fibrosis regression data, and an absence of trials with oncological primary endpoints.
Journal of clinical and translational hepatology · Oct 2025DOI ↗ Review
This updated narrative review examines the efficacy and safety of anti-obesity medications (AOMs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). The authors synthesize evidence on several pharmacologic classes, with particular focus on incretin-based therapies. GLP-1 receptor agonists, specifically liraglutide and semaglutide, are reported to reduce hepatic steatosis, improve liver enzyme profiles, and attenuate fibrosis progression. Tirzepatide, a dual GLP-1/GIP agonist, is noted to produce superior weight loss compared to GLP-1 monotherapy, though data on hepatic histological outcomes in MASLD/MASH remain limited. Retatrutide, a triple GLP-1/GIP/glucagon agonist, showed the most pronounced metabolic effects overall, but its liver-specific histological impact is described as underexplored. The review also flags safety concerns with other AOMs such as bupropion-naltrexone and phentermine-topiramate, citing potential hepatotoxicity risks. The authors note that advanced MASLD may alter drug pharmacokinetics, complicating treatment decisions. Key limitations include the review's narrative design, heterogeneity of cited primary studies, and a general lack of large-scale, liver-histology-focused trials for newer agents.
World journal of gastroenterology · Oct 2025DOI ↗ Review
This article is a regulatory milestone review summarizing the development history of mazdutide (Xinermei®), a dual glucagon receptor (GcgR) and glucagon-like peptide-1 receptor (GLP-1R) agonist co-developed by Eli Lilly and Innovent Biologics. The review traces the compound's path to its first regulatory approval in China in June 2025 for long-term body weight management in adults with obesity (BMI ≥28 kg/m²) or overweight with comorbidities (BMI ≥24 kg/m²), alongside diet and physical activity. A subsequent Chinese approval for glycemic control in type 2 diabetes followed in September 2025. The article also notes ongoing clinical investigations into metabolic dysfunction-associated fatty liver disease, obstructive sleep apnea, and alcohol use disorder. As a "First Approval" narrative review, it consolidates developmental milestones rather than presenting original trial data. It does not independently report clinical outcomes, efficacy effect sizes, or safety data from primary studies, limiting the ability to assess the strength of underlying evidence directly from this article alone.
Review
This review examines the expanding cardiovascular applications of glucagon-like peptide-1 (GLP-1) receptor agonists, a class of peptide-based agents originally developed for type 2 diabetes management. The authors synthesize molecular mechanistic data alongside clinical evidence from major cardiovascular outcome trials (CVOTs) to characterize how GLP-1 agonists may reduce risk across conditions including atherosclerosis, heart failure, stroke, and vascular dementia. Proposed mechanisms discussed include anti-inflammatory, anti-atherogenic, endothelial-protective, and direct cardioprotective effects. The review highlights findings from multiple CVOTs reporting reductions in major adverse cardiovascular events (MACEs), myocardial infarction, stroke, and cardiovascular mortality. Notably, the SELECT trial is cited as evidence extending potential benefit to non-diabetic individuals with obesity and established CVD. The review also addresses emerging dual GLP-1/GIP agonists such as tirzepatide and its own CVOT data. The authors acknowledge important limitations, including high drug costs, unresolved long-term safety questions, and real-world implementation barriers. As a narrative review, this paper does not generate primary data and is subject to the inherent risk of selective literature synthesis. It provides a useful conceptual overview but does not independently establish causality or efficacy.
Journal of clinical medicine · Sep 2025DOI ↗ Review
This scoping review examined the potential role of incretin mimetics — specifically GLP-1 receptor agonists (e.g., semaglutide), dual GLP-1/GIP receptor agonists (e.g., tirzepatide), and the investigational triple agonist retatrutide — as treatments for polycystic ovarian syndrome (PCOS). Following PRISMA guidelines and drawing on literature from EBSCO Medline and PubMed, the authors explored how these agents compare to traditional PCOS pharmacotherapy such as metformin and estradiol-progesterone combination pills. The review found that all three classes of incretin mimetics were associated with meaningful improvements in weight loss and insulin sensitivity relative to conventional treatments. Dual- and triple-acting agonists, which additionally target the GIP receptor, appeared to produce greater reductions in weight and improvements in insulin sensitivity than GLP-1-only agents. Some included studies also reported PCOS-specific symptom improvements, such as reductions in dysmenorrhea and changes in ovarian morphology. The authors note that the precise mechanisms by which incretin mimetics may address the hormonal dysregulation of PCOS remain unclear, and they call for further research to optimize the integration of these agents with existing standard-of-care therapies. Key limitations include the scoping review design, heterogeneity of included studies, and limited long-term human trial data.
Review
This review paper examines survodutide, a dual glucagon and glucagon-like peptide-1 (GLP-1) receptor agonist, and its potential role in cardiometabolic disease management. The authors synthesize findings from Phase 2 clinical trials, which reported weight loss of up to 18.7% and HbA1c reductions of up to -1.71%, suggesting survodutide may outperform semaglutide on weight outcomes while achieving comparable glycemic control. The paper also discusses Phase 2 evidence showing improvements in liver fat content and fibrosis markers in patients with metabolic dysfunction-associated steatohepatitis (MASH), alongside proposed mechanisms for cardiovascular benefit, including reductions in visceral and epicardial adiposity, systemic inflammation, and fibrosis-related remodeling. Early signals of renal benefit are noted. Limitations acknowledged include higher rates of gastrointestinal adverse events and modest heart rate increases compared to some comparators, contributing to elevated discontinuation rates. The authors emphasize that definitive evidence from cardiovascular outcomes trials is still lacking, with the ongoing SYNCHRONIZE-CVOT trial expected to address this gap. As a narrative review relying primarily on Phase 2 data, the paper does not establish long-term cardiovascular efficacy or safety.
Cardiology in review · Sep 2025DOI ↗ Review
This review paper examines the challenge of preserving muscle mass during weight loss induced by GLP-1–based pharmacotherapies, including GLP-1 receptor agonists (e.g., semaglutide), dual GLP-1/GIP agonists (e.g., tirzepatide), and triple GLP-1/GIP/glucagon agonists (e.g., retatrutide). The authors note that while these agents can produce clinically meaningful weight loss (5–10% or more of body weight), a portion of that loss comes from lean mass, including skeletal muscle, which may contribute to long-term weight regain and increase the risk of sarcopenia. The paper discusses the biology of myokines—over 600 signaling proteins released during muscle contraction identified in human myocyte research—as potentially important targets for protecting or expanding muscle mass. The authors explore emerging anti-obesity agents and their potential combinations with incretin-based therapies to preferentially reduce fat mass while sparing or building muscle. The paper calls for further research to clarify the functional consequences of lean mass changes during weight loss and maintenance. As a narrative review, it synthesizes existing literature without conducting original trials, and no new clinical data are presented. Generalizability is limited by the review format and the evolving evidence base for newer agents.
World journal of diabetes · Sep 2025DOI ↗ Review
This review examines the evolving pharmacological landscape for obesity management, with a focus on gut-brain axis hormones and their therapeutic potential. The authors describe how nutrient-stimulated gastroenteropancreatic hormones — including GLP-1, GIP, glucagon, and amylin — have become central targets in obesity drug development. The review covers both marketed agents and those in ongoing clinical trials. GLP-1 receptor agonists (e.g., weekly injectable or daily oral semaglutide) are reported to achieve roughly 15–17% weight loss with a favorable safety profile. The dual GLP-1/GIP agonist tirzepatide is described as achieving up to approximately 22.5% weight loss at higher doses. Combination therapies under investigation — such as cagrilintide plus semaglutide (Cagrisema), GLP-1/glucagon co-agonists, and the triple agonist retatrutide (GLP-1/GIP/glucagon) — are noted as potentially reaching weight loss comparable to bariatric surgery. The review also discusses cardiometabolic benefits and challenges around long-term treatment adherence for both patients and clinicians. As a narrative review, it synthesizes existing trial data rather than generating new primary evidence, and conclusions depend on the quality of the underlying studies cited.
Medicina clinica · Aug 2025DOI ↗ Review
This editorial provides a narrative overview of the rapidly escalating global obesity crisis and the evolving landscape of pharmacological treatments, with a focus on GLP-1 receptor agonists such as oral semaglutide. Drawing on the World Obesity Atlas 2025, the authors highlight that the number of adults living with obesity is projected to more than double—from 524 million in 2010 to 1.13 billion by 2030. The editorial notes that the global market for weight-loss medications has been revised upward to $150 billion by 2035, reflecting explosive growth in demand. The authors discuss the FDA's acceptance of a new drug application for oral semaglutide, potentially the first oral agent approved for long-term weight management. Key concerns raised include the limited long-term and real-world safety and efficacy data for GLP-1 receptor agonists, challenges with treatment adherence, and the proliferation of unregulated compounded ("copycat") versions of these drugs that lack quality and safety evaluation. As an editorial, this piece synthesizes publicly available data and regulatory updates rather than presenting original research, and it does not conduct systematic literature searches or meta-analyses. Its conclusions are opinion-based and should be interpreted accordingly.
Medical science monitor : international medical journal of experimental and clinical research · Aug 2025DOI ↗ Review
This evidence review examines the evolving landscape of incretin-based pharmacotherapy, focusing on GLP-1 receptor agonists (GLP-1RAs) and newer multi-receptor co-agonists for cardiometabolic disease management. The paper surveys established GLP-1RAs — including liraglutide, dulaglutide, albiglutide, exenatide, and semaglutide — noting their reported benefits on glycated hemoglobin, body weight, lipid profiles, liver fat, and cardiovascular outcomes (reduction in major adverse cardiovascular events, or MACE). It also covers emerging agents: dual GIP/GLP-1 agonist tirzepatide (approved for diabetes and obesity), dual GLP-1/glucagon co-agonists (notable for synergistic weight loss), and triple GLP-1/GIP/glucagon receptor agonists such as retatrutide and efocipegtrutide, described as achieving the highest pharmacotherapy-associated weight loss observed to date. Additional novel classes reviewed include GLP-1/amylin agonists (CagriSema, Amycretin), non-semaglutide oral GLP-1 agents, and peptide YY/GLP-1 dual agonists. As a narrative review, the paper does not present original trial data, and its conclusions are based on synthesized existing literature, which may introduce selection bias. The authors anticipate that metabolic benefits will translate into cardiometabolic outcomes, though direct evidence for many newer agents remains limited.
World journal of cardiology · Aug 2025DOI ↗ Review
This review examines the rationale and emerging clinical evidence for triple receptor agonist therapies targeting GLP-1, GIP, and glucagon receptors as next-generation treatments for obesity and type 2 diabetes (T2D). The authors focus primarily on retatrutide, the most clinically advanced triple agonist, which has completed Phase 2 trials. In people with obesity, retatrutide achieved up to 24.2% mean weight loss over 48 weeks; in people with T2D, it produced 16.9% mean weight loss over 36 weeks, alongside a 2.2% reduction in HbA1c and 82% of participants reaching HbA1c ≤ 6.5%. The review also highlights improvements in blood pressure, lipid profiles, waist circumference, and liver fat (82% reduction in hepatic steatosis). Gastrointestinal side effects were the most commonly reported adverse events, with no major safety signals identified in Phase 2. The authors also briefly discuss other unimolecular triple agonists and combination regimens in development. Key limitations include that this is a narrative review of Phase 2 data; Phase 3 confirmatory trials are still ongoing. Conclusions about long-term efficacy, safety, and cardiovascular/renal outcomes remain premature pending those results.
Current cardiovascular risk reports · Jul 2025DOI ↗ Review
This review article, published as part of a special issue on GLP-1 receptor agonists, examines the emerging class of glucagon receptor (GCGR)-based multi-agonist drugs as pharmacological treatments for obesity. The authors discuss several investigational agents — mazdutide, pemvidutide, survodutide, and retatrutide — all of which are in advanced stages of clinical development. According to the review, early-phase trial data for these agents suggest they can produce significant weight loss, potentially exceeding that seen with currently available therapies. The article also highlights their potential to address obesity-related comorbidities such as type 2 diabetes and cardiovascular disease, and notes that some agents are being evaluated in cardiovascular outcomes trials. The authors position GCGR-based multi-agonists as potentially important additions to future obesity treatment guidelines, particularly for patients who have not responded adequately to existing medications or lifestyle interventions. Key limitations and considerations noted include cost, access, and the need for long-term safety data as these drugs progress toward regulatory approval. As a narrative review, this article synthesizes existing trial data but does not generate new primary evidence.
Drugs in context · Jul 2025DOI ↗ Review
This narrative review examines how rapidly advancing obesity pharmacotherapies — particularly GLP-1 receptor agonists, dual and triple incretin agonists, and amylin-based combination therapies — are challenging the longstanding criteria used to determine eligibility for bariatric surgery. The authors note that current surgical guidelines were established when effective medical alternatives were limited, and argue that newer agents achieving 15–25% body weight reduction now approach outcomes historically associated only with surgery. The review compares surgical and pharmacologic interventions across dimensions of efficacy, safety, metabolic benefit, and cost-effectiveness, and considers whether a stepwise, pharmacotherapy-first approach may be appropriate — particularly for individuals with a BMI of 30–40 kg/m². The authors also discuss potential roles for pharmacotherapy in perioperative care and long-term obesity management, and call for personalized treatment strategies. As a narrative review, the paper does not conduct a systematic search or meta-analysis, which limits its ability to make definitive comparative claims. It reflects the authors' interpretive synthesis of existing literature rather than new primary data, and is subject to selection bias inherent to the narrative format.
Medicina (Kaunas, Lithuania) · Jul 2025DOI ↗ Review
This review paper provides a comprehensive overview of the current and emerging pharmacological landscape for metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD). The authors describe MASH as a growing global health burden, closely tied to obesity and type 2 diabetes, and carrying significant risks of cirrhosis, hepatocellular carcinoma, and liver failure. The review synthesizes evidence from advanced-stage clinical trials evaluating several therapeutic classes, including incretin-based therapies (GLP-1 receptor agonists, dual, and triple agonists such as semaglutide, tirzepatide, and survodutide), metabolic modulators (PPAR agonists like lanifibranor, FGF21 analogues like pegozafermin, and thyroid hormone receptor-beta agonists like resmetirom), and novel agents such as fatty acid synthase inhibitors. The authors note that regulatory endpoints currently rely on histological assessment, while noninvasive biomarkers and personalized approaches are gaining traction. Genetic factors, such as PNPLA3 polymorphisms, and artificial intelligence are highlighted as emerging tools for patient stratification and trial design. Key limitations acknowledged include unresolved questions about treatment duration, response heterogeneity, long-term adherence, and the evolving definition of therapeutic success.
The Journal of clinical investigation · Jul 2025DOI ↗ Review
This review paper examines whether two major antihyperglycemic drug classes — sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) — may have a therapeutic role in gout management, particularly in patients who also have type 2 diabetes mellitus (T2DM). The authors describe gout as the most common form of inflammatory arthritis, driven by hyperuricemia that leads to monosodium urate crystal deposition in joints and tissues. The review summarizes evidence from multiple clinical studies suggesting that SGLT2 inhibitors lower serum urate (SU) levels, likely by promoting urinary uric acid excretion, which could benefit gout patients with comorbid T2DM. The paper also notes that SGLT2 inhibitors have demonstrated reductions in cardiovascular and renal events. By contrast, the effect of GLP-1 RAs on SU levels and urinary uric acid excretion in humans is described as unclear. The authors review mechanisms of action, structure-activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects for both drug classes. Key limitations include the review design, reliance on studies conducted primarily in T2DM populations, and the absence of dedicated gout-specific clinical trials for either drug class.
Pharmaceutics · Jun 2025DOI ↗ Review
This review examines metabolic dysfunction-associated steatotic liver disease (MASLD) as it specifically affects people with HIV (PWH). The authors highlight that MASLD is highly prevalent in this population and follows a more aggressive clinical course than in HIV-negative individuals. The review discusses how HIV-specific factors — including altered body composition, chronic immune activation, enhanced gut permeability, and antiretroviral therapy (ART) side effects — compound the common pathogenic mechanisms of MASLD, accelerating disease progression. The authors note the recent adoption of updated MASLD nomenclature and the first FDA-approved MASLD therapy, emphasizing that these advances have not yet been adequately studied in PWH. They identify a critical evidence gap in evaluating emerging MASLD therapies specifically within this population. Among interventions studied in PWH, the review highlights early promise from glucagon-like peptide-1 (GLP-1) receptor agonists and the growth hormone-releasing hormone analog tesamorelin. The authors conclude that MASLD is a meaningful driver of both liver-related and cardiovascular morbidity in PWH, and that the distinct pathophysiology of MASLD-HIV necessitates tailored diagnostic and management strategies. Limitations include the review format and the scarcity of dedicated clinical trial data in PWH.
Current opinion in HIV and AIDS · May 2025DOI ↗ Review
This review examines amylin, a neuroendocrine hormone co-secreted with insulin, exploring its physiological mechanisms and therapeutic potential in diabetes and obesity. The authors describe how amylin suppresses glucagon secretion, delays gastric emptying, increases energy expenditure, and promotes satiety — making it a candidate for addressing multi-hormonal dysregulation in both type 1 and type 2 diabetes. The paper notes that amylin is deficient in people with diabetes and that pramlintide, currently the only approved amylin analog, has shown efficacy in improving postprandial and overall glycemic control without increasing hypoglycemia risk or promoting weight gain in people with advanced β-cell dysfunction. The authors also discuss barriers to broader clinical translation, including complex receptor biology, amyloidogenic properties, and pharmacokinetic challenges. Emerging strategies covered include PEGylation, carbohydrate conjugation, oral formulations, and combination therapies — notably CagriSema, a co-formulation of a GLP-1 receptor agonist and an amylin agonist showing early promise in weight management and glucose regulation. As a narrative review, this paper synthesizes existing literature rather than generating new primary data, which limits its ability to establish causation or provide definitive efficacy conclusions.
Diabetes therapy : research, treatment and education of diabetes and related disorders · May 2025DOI ↗ Review
This review article examines the management of type 2 diabetes and obesity, with a particular focus on CagriSema, an investigational combination drug pairing cagrilintide (an amylin analog) with semaglutide (a GLP-1 receptor agonist). The authors begin by contextualizing the scale of diabetes in the United States—affecting over 37 million people—and highlight the interplay between obesity and type 2 diabetes, noting that genetic and physiological barriers often make weight loss difficult without pharmacological support. The article reviews the pathophysiology of diabetes, current clinical guidelines, and the risks associated with intensive glycemic control, particularly hypoglycemic events such as cardiac arrhythmias, confusion, coma, and death. It then surveys the existing evidence for approved weight loss and antidiabetic medications before summarizing recent clinical trial data on CagriSema, which is being investigated as a potentially superior agent for reducing both HbA1c and body weight. The authors argue that CagriSema may offer a favorable safety and efficacy profile, though they acknowledge the drug remains under investigation. Key limitations include the review format itself—primary trial data are summarized rather than independently analyzed—and the absence of long-term safety data for CagriSema in the published literature reviewed.
Cardiology in review · May 2025DOI ↗ Review
This narrative review examines the current landscape and future directions of Type 2 Diabetes Mellitus (T2DM) treatment. The authors begin by describing conventional therapies — including metformin, sulfonylureas, and insulin — noting their limitations such as adverse effects, declining efficacy over time, and suboptimal glycemic control in many patients. The review then surveys a range of emerging therapeutic strategies. Dual incretin receptor agonists (e.g., tirzepatide), which co-activate GLP-1 and GIP receptors, are highlighted for their effects on insulin secretion, glucagon suppression, and weight loss. Dual SGLT1/2 inhibitors (e.g., sotagliflozin) are discussed for their dual gut-and-kidney glucose-lowering mechanism. Additional experimental approaches covered include glucagon receptor antagonists, GPR119 agonists, FGF21 analogs, AMPK activators, and CRISPR-Cas9 gene editing technologies. The authors acknowledge that while these novel therapies demonstrate promise in early-stage research, long-term safety and efficacy data in humans remain limited. As a narrative review, this paper does not present original clinical data, does not include a systematic search protocol or meta-analytic methodology, and is subject to selection bias in the literature discussed.
Biochemistry and biophysics reports · May 2025DOI ↗