Review
This review examines the evolving medical management of short bowel syndrome intestinal failure (SBS-IF), a condition historically associated with lifelong dependence on home parenteral support (HPS) and, in select cases, intestinal transplantation (iTx). The authors describe how recent pharmacological advances—particularly glucagon-like peptide-2 (GLP-2) analogues and GLP-1 receptor agonists—have been integrated alongside conventional antimotility and antisecretory therapies to promote intestinal adaptation. The review argues that SBS-IF should now be understood as a dynamic and potentially modifiable form of organ failure rather than a static, irreversible condition. According to the authors, GLP-2 analogues represent the first pathophysiology-targeted, pro-adaptive therapies in this disease, while GLP-1 receptor agonists are highlighted as promising adjuncts, especially for patients with high-output phenotypes. The paper contends that multidisciplinary intestinal rehabilitation and gut-directed pharmacotherapy have meaningfully altered the natural history of SBS-IF, reducing HPS dependence and improving patient-centered outcomes. A key implication discussed is that iTx has been repositioned from a default end-stage intervention to a targeted rescue option used after optimized rehabilitation. Limitations include the review format, which synthesizes existing literature without presenting new primary data or meta-analytic pooling.
Current opinion in organ transplantation · Jun 2026DOI ↗ Review
This article provides practical, evidence-informed clinical guidance on incorporating oral semaglutide — the first oral glucagon-like peptide-1 (GLP-1) receptor agonist — into obesity management. The authors draw on data from clinical trials, including the OASIS 4 trial, as well as expert clinical insights. The paper highlights that oral semaglutide has demonstrated weight loss outcomes comparable to subcutaneous GLP-1 therapies, with associated improvements in cardiometabolic risk factors, and has received regulatory approval for obesity management and cardiovascular risk reduction in adults. A central focus is the formulation's strict administration requirements, which are necessary to optimize absorption and bioavailability. The article emphasizes the importance of person-centered consultations between healthcare professionals and patients prior to treatment initiation, covering realistic expectations, adherence strategies, and adverse event management. Key limitations include that this is a guidance/review article rather than a primary clinical trial, meaning its conclusions reflect the authors' synthesis and interpretation of existing evidence rather than new experimental data. It does not establish independent causal efficacy and is subject to potential expert bias.
Postgraduate medicine · Jun 2026DOI ↗ Review
This narrative review examines the potential ocular effects of geroprotective agents — pharmacologic compounds studied for longevity and systemic aging benefits — with a focus on their relevance to age-related eye diseases including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal vein occlusion (RVO), and glaucoma. The authors argue that shared mechanisms of neurodegeneration, microvascular injury, and chronic inflammation underlie both systemic aging and major retinal diseases, making geroprotectors a pharmacologically relevant class for ophthalmic consideration. The review covers a broad range of agents: GLP-1 receptor agonists, metformin, SGLT-2 inhibitors, statins, cannabinoids, calcium channel blockers, spermidine, taurine, NAD+ precursors, rapamycin, and mifepristone. The authors note that GLP-1 receptor agonists have been associated with potential glaucoma risk reduction but also with unconfirmed reports of nonarteritic anterior ischemic optic neuropathy. The review acknowledges that ocular effects of these agents are incompletely characterized, variably reported, and sometimes controversial. Key limitations include reliance on heterogeneous observational and preclinical data, absence of dedicated ophthalmic clinical trials, and potential confounding in real-world studies. The authors aim to support clinical awareness and identify gaps for future investigation.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · Jun 2026DOI ↗ Review
This narrative review proposes a novel conceptual framework for integrating GLP-1 receptor agonists (GLP-1 RAs) into bariatric surgical care, drawing an analogy from oncology's neoadjuvant and adjuvant treatment models. The authors suggest that GLP-1 RAs used before surgery ("neoadjuvant") could reduce perioperative risk—particularly in super-obese patients—by promoting early weight loss and improving dyslipidemia. Used after surgery ("adjuvant"), GLP-1 RAs may address weight regain and sustain metabolic improvements in patients with suboptimal surgical outcomes. The review synthesizes findings from prospective trials, retrospective analyses, and meta-analyses, noting that preoperative GLP-1 RA use appears generally safe but requires monitoring for metabolic adaptation and a potential "ceiling effect" on postoperative results. The authors introduce a proposed "perioperative management ladder" as a structured decision-making tool. Importantly, the framework is described as primarily hypothesis-generating and intended to inform the design of future randomized controlled trials. Key limitations include the review's narrative (non-systematic) methodology, reliance on heterogeneous primary studies, and the absence of original data.
Current obesity reports · Jun 2026DOI ↗ Review
This systematic review examined existing evidence on the use of second-generation incretin analogs — specifically semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GLP-1/GIP receptor agonist) — in adults with type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA). Researchers screened 3,053 records from six major databases and ClinicalTrials.gov, ultimately identifying 11 eligible publications. These comprised two systematic reviews, one post hoc subgroup analysis, six narrative or consensus reviews, and two LADA case reports. Three key themes emerged from the synthesis: (1) LADA is frequently misdiagnosed or diagnosis is delayed due to its heterogeneous presentation; (2) both tirzepatide and semaglutide show potential benefits in LADA and in certain T1D subtypes, particularly in individuals retaining residual beta-cell function; and (3) existing clinical management frameworks may guide practice while robust trial data are awaited. The authors concluded that current evidence is promising but moderate in quality, and that well-designed, adequately powered randomized controlled trials in clearly defined LADA and T1D populations are needed to establish long-term efficacy and safety. Notable limitations include the small number of eligible studies, the predominance of review-level and narrative publications, and only two primary patient-level reports.
Journal of the American Association of Nurse Practitioners · Jun 2026DOI ↗ Review
This narrative review examines the continued clinical relevance of dulaglutide, a once-weekly GLP-1 receptor agonist, in the treatment of type 2 diabetes (T2D) amid growing adoption of newer incretin-based therapies such as semaglutide and tirzepatide. The authors synthesize evidence from major cardiovascular outcome trials, including the REWIND trial—which they highlight as the only GLP-1 receptor agonist trial to demonstrate a statistically significant reduction in major adverse cardiovascular events (MACE) in a predominantly primary prevention population over more than five years—and the SURPASS-CVOT, which established tirzepatide's non-inferiority to dulaglutide for cardiovascular outcomes. The review acknowledges that semaglutide and tirzepatide show superior HbA1c reduction and weight loss compared to dulaglutide, but argues that dulaglutide's fixed-dose, no-titration regimen, established cardiovascular safety profile, real-world tolerability, and lower cost support its continued use—particularly in low- and middle-income countries. Limitations include the narrative (non-systematic) review design, which is susceptible to selection bias, and the lack of head-to-head cardiovascular outcome trials directly comparing dulaglutide to semaglutide or tirzepatide.
Diabetology international · Jun 2026DOI ↗ Review
This paper is a commentary/review published in Cell Host & Microbe that discusses the expanding role of the gut microbiome in mediating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists. The authors highlight findings from a study by Bian et al., which investigates how the gut microbiome may be involved in the psychological effects of GLP-1 receptor agonist drugs. The commentary contextualizes these findings within the broader landscape of GLP-1 pharmacology, noting that there is substantial evidence for the wide-ranging health benefits of GLP-1 receptor agonists. The paper underscores the concept of drug-microbe-host interactions, suggesting that the therapeutic and psychological effects of GLP-1 receptor agonists may not be solely attributable to direct drug action but may also involve modulation of the gut microbiome. Limitations include the nature of the article as a secondary commentary rather than primary research, meaning it does not present original experimental data. Its conclusions are largely interpretive, and the strength of any causal claims about the microbiome's role depends on the primary studies it references.
Cell host & microbe · Jun 2026DOI ↗ Review
This commentary examines the Institute for Clinical and Economic Review (ICER) report on GLP-1 receptor agonists (GLP-1 RAs) — specifically semaglutide and tirzepatide — for obesity management, evaluating both their clinical value and the challenges surrounding their financing. The authors note that while these agents demonstrate meaningful weight loss and cardiometabolic benefits and were deemed cost-effective versus lifestyle modification alone by ICER, even modest real-world uptake surpasses ICER's annual budget impact threshold, raising access concerns. The commentary highlights that real-world persistence with these medications is notably lower than in clinical trials, leading to frequent weight regain upon discontinuation and limiting anticipated long-term medical cost offsets. Evidence on medical spending is described as mixed: cost-offset signals appear primarily in patients with both obesity and diabetes using high-potency injectable agents, while obesity-only populations may see spending increases. To address these tensions, the authors recommend pairing drug coverage with lifestyle management programs, avoiding arbitrary treatment duration limits, applying targeted prior authorization, and exploring innovative payment models. Key limitations include the commentary format, reliance on heterogeneous real-world data, and lack of primary data collection.
Journal of managed care & specialty pharmacy · Jun 2026DOI ↗ Review
This review examines what happens to body weight after patients stop taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer dual/triple co-agonists used for obesity treatment. The authors note that these medications can produce mean weight losses of 10–30%, far exceeding what is typically achievable through lifestyle changes alone. However, the review highlights that real-world data suggest up to 65% of patients discontinue GLP-1 RAs within one year of starting treatment, and randomized controlled trial data indicate that approximately two-thirds of lost weight is regained within a year of stopping the medication. The review explores the physiological, behavioral, and environmental mechanisms that drive this weight regain once pharmacological appetite suppression is removed. The authors conclude that sustaining weight loss after discontinuation will require integrated, patient-centered approaches that combine ongoing lifestyle interventions, behavioral support, and system-level strategies. As a review article, it synthesizes existing evidence but does not generate new primary data, and its conclusions are limited by the quality and scope of the studies it draws upon.
EClinicalMedicine · May 2026DOI ↗ Review
This review synthesizes evidence from randomized controlled trials and high-quality meta-analyses on approved and investigational obesity medications, examining their effects beyond weight loss alone. Medications reviewed include phentermine-topiramate, naltrexone-bupropion, GLP-1 receptor agonists (liraglutide, semaglutide), and newer multiagonist agents (tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). The authors evaluated impacts across a broad range of obesity-related comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnea, polycystic ovary syndrome, osteoarthritis, muscle mass, depression, quality of life, food cravings, binge-eating disorders, substance use disorders, and neurodegenerative diseases. The review concludes that GLP-1-based and multiagonist therapies demonstrate beneficial effects across these conditions. Notably, the authors report that while many benefits appear to be mediated through weight reduction, accumulating evidence suggests weight loss-independent mechanisms, particularly for GLP-1 receptor agonist-based therapies. Key limitations include its reliance on synthesized rather than primary data and variability in evidence quality across the individual conditions reviewed.
The lancet. Diabetes & endocrinology · May 2026DOI ↗ Review
This review article argues that GLP-1 receptor agonists (GLP-1 RAs) — such as semaglutide and tirzepatide — should be understood as catalysts for, rather than replacements of, lifestyle intervention in cardiometabolic care. The authors propose the guiding principle "lifestyle first and lifestyle always, but not lifestyle only," acknowledging that GLP-1 RAs have produced meaningful clinical benefits including substantial weight loss, improved glycemic control, and reduced cardiovascular and renal risk. However, the authors contend that pharmacotherapy alone cannot address the full spectrum of cardiometabolic risk drivers, including sarcopenia, physical deconditioning, poor sleep, psychological stress, and social determinants of health. The article highlights that discontinuation of GLP-1 RAs without structured lifestyle support is commonly associated with weight regain. Key lifestyle pillars emphasized include high-quality nutrition, regular physical activity (including resistance training), restorative sleep, stress management, and social connectedness. The authors advocate for integrated, interprofessional care models combining pharmacologic and lifestyle strategies, supported by systemic and policy-level change. As a narrative review, the paper does not present original data, conduct a systematic literature search, or include a meta-analysis, which limits the directness of its evidentiary contribution.
American journal of lifestyle medicine · May 2026DOI ↗ Review
This clinical review synthesizes current evidence on glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug class increasingly used to manage type 2 diabetes, obesity, and expanding metabolic and cardiorenal conditions. The authors describe the physiological mechanisms underlying GLP-1 RA action, survey established and emerging clinical indications, and outline practical safety considerations relevant to growing use in younger, healthier, and more diverse patient populations. A central focus is the management of adverse effects—particularly gastrointestinal intolerance—for which the authors propose a structured algorithm to guide early symptom management in clinical practice. The review also addresses communication strategies intended to support shared decision-making, reduce weight-related stigma, and align therapy with individual patient goals and values. As a narrative review without original data collection, the paper does not generate new clinical outcome data and is subject to the selection biases inherent to non-systematic literature reviews. Nonetheless, it offers a clinically oriented framework intended to help practitioners translate evolving GLP-1 RA evidence into individualized, patient-centered care. No external funding was reported.
EClinicalMedicine · May 2026DOI ↗ Review
This systematic review examined the clinical outcomes of GLP-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 receptor agonists in children and adolescents (aged 6–19 years) with overweight or obesity, with or without type 2 diabetes. Researchers searched PubMed, Scopus, and ClinicalTrials.gov following PRISMA 2020 guidelines, ultimately analyzing 15 studies (12 interventional, 3 observational) comprising 1,448 participants across six agents: liraglutide, exenatide, semaglutide, dulaglutide, tirzepatide, and lixisenatide. Study durations ranged from 6 to 68 weeks. The review found that BMI reductions varied across agents and study designs, with semaglutide trials reporting reductions of up to –16.1%. A key finding was the substantial heterogeneity in how concomitant lifestyle interventions were reported—ranging from general dietary advice to structured multidisciplinary programs—making it impossible to isolate the independent contributions of pharmacological versus behavioral components. The authors conclude that while GLP-1 RAs appear to be a promising therapeutic option in this population, the evidence base is limited by inconsistent lifestyle co-intervention reporting. They call for standardized reporting frameworks (e.g., TIDieR), validated behavioral measures, and factorial or stratified study designs to disentangle drug and lifestyle effects in future pediatric trials.
Nutrients · May 2026DOI ↗ Review
This review examines the evolution of GLP-1–based pharmacotherapies for obesity, tracing the discovery of glucagon-like peptide-1 (GLP-1) and assessing the clinical efficacy of GLP-1 receptor agonists (GLP-1RAs), with particular focus on semaglutide. The authors explore proposed central mechanisms by which GLP-1RAs may reduce appetite and body weight. A substantial portion of the review addresses the "paradox" surrounding glucose-dependent insulinotropic polypeptide receptor (GIPR) targeting: both dual GLP-1R/GIPR agonism (as seen with tirzepatide) and GLP-1R agonism combined with GIPR antagonism (as seen with maridebart cafraglutide) appear to yield favorable metabolic outcomes. The authors note a lack of evidence that GIPR agonism or antagonism alone produces meaningful anorectic effects in humans, raising mechanistic questions about how GIPR modulation enhances GLP-1RA efficacy. The review concludes by exploring additional explanations for why dual-targeting compounds appear to outperform semaglutide monotherapy. As a narrative review, this paper synthesizes existing literature rather than generating new primary data, and its conclusions are dependent on the quality and scope of the studies reviewed.
Annual review of nutrition · May 2026DOI ↗ Review
This structured narrative review synthesized contemporary evidence (January 2020–August 2025) on injectable peptides used in orthopaedics and sports medicine, drawing from PubMed/MEDLINE, Embase, and Web of Science. The authors identified five functional peptide classes: GLP-1 receptor agonists (e.g., semaglutide), collagen-derived injectables, regenerative peptides (e.g., BPC-157, thymosin derivatives), growth hormone secretagogues (e.g., CJC-1295, ipamorelin, tesamorelin), and related compounds. The review found that GLP-1 receptor agonists were the only class supported by reproducible randomized evidence for musculoskeletal benefit—specifically symptomatic improvement in knee osteoarthritis—attributing this primarily to weight loss and putative anti-inflammatory effects rather than proven structural cartilage modification. Collagen-derived preparations showed only preliminary signals from small, single-center prospective studies. All remaining classes were deemed investigational, carrying unresolved safety profiles, significant product quality concerns, and widespread antidoping restrictions. Risk of bias was appraised for included human trials. The authors concluded that clinical use of injectable peptides should be restricted to approved agents for established indications or rigorously designed research protocols, and that clinicians should counsel athletes about uncertain efficacy, safety risks, and antidoping consequences. The study was assigned Level V evidence and a predominantly Grade C strength of recommendation.
JBJS reviews · May 2026DOI ↗ Review
This narrative review examines the relationship between diabetes mellitus (DM) and stroke, and evaluates the cerebrovascular potential of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP receptor agonists (e.g., tirzepatide). The authors summarize evidence from large cardiovascular outcome trials (CVOTs), noting that agents such as semaglutide and liraglutide were associated with reductions in non-fatal stroke incidence, fewer hospitalizations, and improved neurological outcomes in patients with prior stroke or high cardiovascular risk. The review highlights that stroke reduction may represent a class effect of GLP-1 RAs, though differences between individual agents exist, attributed to variations in pharmacokinetics, receptor affinity, and study populations. Evidence in the acute stroke setting is described as preliminary, coming largely from early-phase or ongoing trials. The authors also discuss emerging agents—orforglipron, retatrutide, Maridebart cafraglutide, and CagriSema—as potential future options. Limitations acknowledged include the narrative (non-systematic) design, reliance on trial-level rather than individual patient data, and the absence of large-scale, long-term randomized trials specifically targeting post-stroke populations. The authors conclude that GLP-1-based therapies should currently be considered tools for long-term vascular risk reduction rather than established acute stroke treatments.
Pharmaceutics · May 2026DOI ↗ Review
This review examines the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) — including exenatide, semaglutide, dulaglutide, and the dual GLP-1R/GIP-R agonist tirzepatide — as pharmacological treatments for alcohol use disorder (AUD). The authors synthesized data from preclinical rodent and non-human primate studies, registered clinical trials, observational/pharmacoepidemiologic studies, and social media reports. In animal models, multiple GLP-1RAs were found to reduce alcohol consumption, alcohol-seeking behavior, alcohol-induced locomotor stimulation, reward memory, and relapse drinking, while also appearing to blunt alcohol's activation of the mesolimbic dopamine system. In the limited available human data, clinical trials of exenatide, semaglutide, and dulaglutide reported reductions in alcohol consumption, and pharmacoepidemiologic studies observed decreased rates of alcohol-related events among AUD patients prescribed GLP-1RAs or tirzepatide. The authors conclude that the GLP-1 system appears to be involved in AUD-related processes and that GLP-1RAs represent a promising but still tentative treatment avenue. Key limitations include the small number of human trials, heterogeneous study designs, and reliance on observational data for most clinical findings.
International journal of molecular sciences · May 2026DOI ↗ Review
This narrative review examines the potential role of incretin-based therapies in treating metabolic dysfunction-associated steatotic liver disease (MASLD), a condition strongly linked to metabolic syndrome and a leading cause of chronic liver disease. The authors highlight that no approved pharmacological treatments currently exist for MASLD and that progression to advanced fibrosis poses a significant clinical challenge. The review synthesizes evidence on GLP-1 receptor agonists, which the authors report have shown efficacy in reducing hepatic steatosis, inflammation, and fibrosis-related biomarkers, largely attributed to weight loss and improved insulin sensitivity. Dual agonists such as tirzepatide (GLP-1/GIP) are described as demonstrating superior hepatic and metabolic outcomes. Emerging agents including cotadutide (GLP-1/glucagon dual agonist) and retatrutide (GLP-1/GIP/glucagon triagonist) are presented as a novel frontier, with early clinical data suggesting potent hepatoprotective effects and favorable metabolic remodeling. The authors acknowledge that evidence on fibrosis progression remains limited. As a narrative review without systematic search methodology or meta-analysis, this paper is susceptible to selection bias and does not establish causality. It provides a useful synthesis of the current landscape but should be interpreted with appropriate caution.
Medicina (Kaunas, Lithuania) · May 2026DOI ↗ Review
This narrative review synthesizes current evidence on glucagon-like peptide-1 (GLP-1)-based therapies—primarily semaglutide and tirzepatide—for the management of obesity-related heart failure with preserved ejection fraction (HFpEF). Drawing on PubMed and Scopus literature published between January 2020 and March 2026, the authors incorporated randomized trials, pooled analyses, mechanistic studies, and observational data. The review describes how obesity-related HFpEF arises from a complex interplay of excess lipids, chronic inflammation, and metabolic dysregulation, which also interact with GLP-1 pathways. According to the authors, GLP-1-based therapies demonstrated meaningful improvements in symptoms, exercise capacity, and quality of life in this population, with benefits attributed to weight reduction, decreased systemic inflammation, and improved congestion indices. Tirzepatide was additionally associated with reductions in heart failure-related complications. Proposed mechanisms include coordinated effects on metabolism, inflammation, hemodynamics, and cardiac remodeling. The authors note that evidence for improvements in morbidity appears stronger than evidence for reductions in mortality. Key limitations include the narrative (non-systematic) review methodology, potential selection bias in study inclusion, and the absence of long-term mortality data. The authors conclude that further research is needed to clarify long-term outcomes, refine patient selection, and guide clinical integration.
Journal of clinical medicine · May 2026DOI ↗ Review
This registry-based cross-sectional qualitative analysis examined the landscape of completed clinical trials investigating GLP-1 receptor agonists (GLP-1 RAs) for obesity, using data retrieved from ClinicalTrials.gov in October 2025. The authors identified 227 completed interventional studies and analyzed their design characteristics, research themes, and outcome domains. Liraglutide was the most studied agent (n = 86), followed by semaglutide and tirzepatide (n = 18 each) and exenatide (n = 15). Phase 3 and 4 trials predominated, though most studies enrolled fewer than 200 participants, suggesting relatively modest individual sample sizes. The authors reported a notable surge in completed trials after 2018, coinciding with the emergence of newer GLP-1 analogues. Primary outcomes were predominantly weight-related, but the synthesis identified a growing research focus on hepatic, cardiometabolic, and inflammatory endpoints. The study's key limitation is its registry-based, qualitative design — it does not synthesize individual-level patient outcome data or conduct meta-analysis, and therefore cannot draw conclusions about comparative efficacy or safety. Rather, it maps the structural and thematic evolution of the GLP-1 obesity research field. The authors conclude that the field is maturing beyond glycaemic and weight outcomes toward broader organ-specific endpoints.
Diabetes, metabolic syndrome and obesity : targets and therapy · May 2026DOI ↗