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 examines the current and emerging therapeutic landscape for celiac disease (CeD), an autoimmune enteropathy triggered by dietary gluten. The authors note that while a strict gluten-free diet (GFD) remains the only established treatment, its burdensome nature and incomplete efficacy in some patients have driven significant research into alternatives. The review systematically covers multiple therapeutic categories: gluten-degrading enzymes (e.g., AN-PEP, Latiglutenase, Zamaglutenase), gluten-sequestering agents (e.g., AGY-010, BL-7010), intestinal permeability modulators (e.g., Larazotide acetate, IMU-856), immune-modulating agents (e.g., ZED1227, AMG 714, EQ102), immune tolerization strategies (e.g., TAK-101, KAN-101, Nexvax2), probiotics, nutraceuticals, and food modification technologies. The authors conclude that despite encouraging preclinical and early clinical results across these approaches, no therapy has yet been conclusively proven as an effective GFD alternative. Key limitations of the review include its narrative rather than systematic design, potential selection bias in literature cited, and the absence of head-to-head comparisons between strategies. The authors emphasize the urgent need for further research to validate efficacy, optimize dosing, and establish safety in broader patient populations.
Nutrients · 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 paper systematically compares four major oncology and gynecology clinical practice guidelines — ASCO (2018), ESO-ESMO (2022), NCCN (2024), and SOGC (2024) — regarding the management of sexual health concerns in female cancer survivors. The authors grouped recommendations across five domains of sexual dysfunction: vaginal dryness, low sex drive, pain, orgasmic dysfunction, and psychological concerns. All four guidelines consistently recommend non-hormonal therapies (lubricants and moisturizers) as first-line treatment for vaginal dryness, with low-dose local estrogen as a second-line option. All guidelines endorse multidisciplinary care including psychosocial counseling, relationship counseling, specialist referral, and cognitive behavioral therapy. Three guidelines (ASCO, NCCN, SOGC) support vaginal dilators and pelvic floor physical therapy for pain. ASCO uniquely recommends any form of stimulation to improve sexual response, while NCCN and SOGC endorse sexual aids for arousal. Pharmacological agents for low libido — including androgens, bupropion, flibanserin, bremelanotide, and buspirone — are mentioned in all guidelines except ESO-ESMO, though the authors note the underlying evidence base is limited. A key limitation is that this is a narrative comparison of guidelines rather than a primary study. The authors conclude that while consensus exists in several areas, further research on pharmacological and counseling interventions is needed.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 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 ↗ Review
This scoping review systematically examined clinical research on anti-obesity medications (AOMs) conducted in Arab countries, drawing on five databases and covering publications up to October 2024. Researchers identified 59 eligible clinical studies published between 2014 and 2024, the large majority of which (89.8%) were observational in design. Most research originated from Saudi Arabia (40.7%) and the United Arab Emirates (20.3%). Glucagon-like peptide-1 (GLP-1) receptor agonists were the most studied drug class, appearing in 72.9% of studies, with liraglutide being the single most investigated agent (54.2%). The primary efficacy outcomes reported across studies were changes in total body weight, body mass index, and proportion of weight loss. Gastrointestinal side effects were noted in 32.2% of patients across studies. Risk of bias was assessed using the Newcastle-Ottawa scale and a modified randomized controlled trial tool. The authors highlight a notable gap: newer agents such as semaglutide and tirzepatide are underrepresented in the literature. Key limitations include the predominance of observational designs, geographic concentration, and limited data on diverse Arab subpopulations, which collectively constrain causal inference and generalizability.
Saudi medical journal · May 2025DOI ↗ Review
This narrative review examines emerging therapeutic strategies for four major pediatric gastroenterological conditions: celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH). For CeD, the authors discuss gluten-degrading enzymes (latiglutenase, Kuma030), the zonulin inhibitor larazotide acetate, transglutaminase 2 inhibitors (ZED-1227), and monoclonal antibodies such as AMG 714, noting inconsistent clinical outcomes and limited pediatric data. For EoE, biologics including dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), mepolizumab, reslizumab, benralizumab (IL-5/IL-5R inhibitors), and the TSLP inhibitor tezepelumab are reviewed with varying reported efficacy. IBD coverage includes biologics (vedolizumab, ustekinumab, risankizumab) and small molecules (tofacitinib, etrasimod, upadacitinib), alongside personalized approaches integrating therapeutic drug monitoring. Emerging AIH therapies for refractory or steroid-dependent cases are also explored. The authors highlight proteomics and precision medicine as growing tools to individualize care. A key limitation is the narrative design, which is subject to selection bias, and the scarcity of pediatric-specific trial data across all discussed treatments.
Healthcare (Basel, Switzerland) · Apr 2025DOI ↗ Review
This review paper synthesizes approximately 25 years of research on Epitalon (also called Epithalon or Epithalone), a synthetic tetrapeptide (Ala-Glu-Asp-Gly, or AEDG) derived from the amino acid composition of Epithalamin, a bovine pineal gland extract. The authors compile findings from in vitro, in vivo, and in silico studies examining Epitalon's biological and pharmacodynamic properties. According to the review, the compound has been associated with geroprotective and neuroendocrine effects, attributed in part to antioxidant, neuroprotective, and antimutagenic mechanisms. Specific findings cited include a reported direct influence on melatonin synthesis, alterations in interleukin-2 mRNA levels, modulation of murine thymocyte mitogenic activity, and enhancement of enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and telomerase. The authors acknowledge that whether these represent the complete mechanisms of action remains uncertain. Notably, the review also highlights that physicochemical and structural investigations of the peptide remain limited relative to the volume of biological research. Key limitations include the predominance of preclinical data and the absence of robust human clinical trial evidence, leaving the translation of these findings to human health outcomes unclear.
International journal of molecular sciences · Mar 2025DOI ↗