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 ↗ Limited · human
This review evaluated the potential role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing lipedema, a chronic disorder marked by disproportionate subcutaneous fat accumulation, pain, inflammation, and fibrosis, for which liposuction remains the primary treatment. Authors searched PubMed through March 2026 using terms related to lipedema, GLP-1 RAs, tirzepatide, inflammation, and insulin resistance. Of 13 publications identified, only two specifically examined GLP-1 RAs in lipedema, and just one provided direct patient-level evidence: a small uncontrolled case series of 5 patients treated with exenatide that reported improvements in pain and limb volume. Additional translational evidence suggested GLP-1 RAs, particularly tirzepatide, may influence inflammatory and fibrotic pathways relevant to lipedema. The authors concluded that GLP-1 RAs have not been proven to directly affect lipedema progression, but may offer adjunctive benefit through weight reduction and metabolic improvement. Key limitations include the very small evidence base, absence of controlled trials in lipedema populations, and reliance on indirect evidence from obesity and fibroinflammatory research. The review highlights a significant gap in rigorous clinical data for this patient population.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] · May 2026DOI ↗ Moderate · human
This systematic review and meta-analysis investigated whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is associated with hair loss. Researchers searched four electronic databases through August 2025, identifying nine interventional studies (seven RCTs and two prospective non-randomized trials) involving 4,114 GLP-1 RA users. Using a random-effects model, the pooled analysis found that GLP-1 RA users had a significantly higher risk of hair loss compared to placebo users (risk ratio: 3.252; 95% CI: 1.437–7.358). This association remained significant in a subgroup analysis restricted to RCTs enrolling patients with overweight or obesity (RR: 3.587; 95% CI: 2.100–6.124). A single-arm analysis estimated the overall event rate of hair loss at approximately 3.9%. Limitations of this study include the relatively small number of included studies (n=9), potential variability in how hair loss was defined and reported across trials, and the inability to fully disentangle hair loss attributable to the drug itself versus rapid weight loss—a known independent trigger of telogen effluvium. The authors conclude that GLP-1 RA use is significantly associated with an increased risk of hair loss.
Diabetes research and clinical practice · May 2026DOI ↗ Limited · human
This case series describes four critically ill patients with type 2 diabetes mellitus who developed metformin-associated lactic acidosis (MALA) in the context of co-prescription of high-dose metformin with either a GLP-1 receptor agonist or a dual GIP/GLP-1 receptor agonist. In each case, MALA appeared to be precipitated by the introduction or dose escalation of the incretin-based therapy, or by an acute gastrointestinal illness occurring while the patient was on a maintenance GLP-1 receptor agonist dose. All four patients required acute renal replacement therapy. The authors propose that the shared gastrointestinal side-effect profile of these drug classes—including nausea, vomiting, decreased appetite, and abdominal pain—may contribute to dehydration and impaired renal metformin clearance, thereby elevating the risk of MALA. The study is limited by its small sample size (n=4), lack of a comparison group, and the inherent reporting biases of a case series design. The authors conclude that clinicians should exercise caution when co-prescribing these medication classes, with attention to kidney function monitoring and patient education on sick-day management rules.
Clinical nephrology. Case studies · 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 ↗ Limited · human
This retrospective observational study analyzed GLP-1 receptor agonist (GLP-1 RA) prescription records from the LUX MED private healthcare network in Poland between 2018 and 2025. Among 42,423 patients with more than one prescription, the study characterized how frequently patients switched between GLP-1 RA agents and identified factors associated with switching. The primary analysis used a discrete-time hazard model at the prescription-transition level, with subcutaneous semaglutide as the reference comparator. The study found that nearly 30% of patients switched agents at least once, and over 14% switched two or more times. After adjusting for switching opportunity and calendar time, liraglutide was associated with substantially lower odds of switching compared to subcutaneous semaglutide, while oral semaglutide and dulaglutide did not differ significantly. Temporal analyses revealed episodic peaks in switching and accelerating uptake of tirzepatide following its market entry. Key limitations include the retrospective, observational design; the lack of data on reasons for switching (e.g., tolerability, cost, availability); restriction to a single private-sector network; and the inability to establish causality. The authors characterize findings as hypothesis-generating.
Acta diabetologica · 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 ↗ 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 ↗ Limited · humanPreprint
This observational cohort analysis describes weight-loss outcomes and adverse event rates in 503 overweight adults who completed six months of the "Trimsulin Weight Loss Program," a nutraceutical regimen combining two proprietary products (a powdered drink mix and a capsule) with a structured diet and exercise protocol. The authors compare their results descriptively — without inferential statistics — to published real-world data for the prescription GLP-1 receptor agonist semaglutide and the dual GIP/GLP-1 agonist tirzepatide. The study reports that Trimsulin participants experienced mean weight reductions of 7.3% at 3 months and 14.1% at 6 months, numerically exceeding the comparator figures drawn from a separate published cohort. Adverse events were self-reported by 4.8% of Trimsulin participants versus much higher rates cited for the pharmacological comparators. Key limitations are substantial: there is no randomization, no placebo or active control arm, no blinding, no direct head-to-head comparison, reliance on self-reported adverse events, a highly selected completer-only analysis (503 of 1,000+ enrollees), differing baseline BMI profiles across cohorts, and the absence of any inferential statistical testing. The program's dietary and behavioral components cannot be disentangled from any supplement effect. The authors acknowledge the need for randomized controlled trials. The paper is identified as a preprint.
Unknown journal · May 2026DOI ↗ Limited · human
This case series describes two patients with severe obesity who developed moderate-to-severe cutaneous allodynia — a condition where normally non-painful stimuli such as touch or mild temperature change cause pain — while being treated with the dual GLP-1/GIP receptor agonist tirzepatide for weight management. In both cases, the onset of allodynia was temporally linked to dose escalation, occurring at higher doses, and resolved upon discontinuation of the drug. The allodynia varied between static and dynamic types across the two patients. The authors reviewed the tirzepatide U.S. prescribing information and found no prior documentation of skin pain or allodynia as an adverse event, though a prior FDA Adverse Event Reporting System (FAERS) pharmacovigilance analysis had identified rare allodynia signals across six GLP-1RAs. The authors assert this is the first case series specifically reporting allodynia with tirzepatide. Key limitations include the very small sample size (n=2), absence of a control group, and the inherent inability to establish causality from case reports alone. The temporal association and resolution upon drug withdrawal do, however, provide a suggestive signal warranting further investigation.
The American journal of case reports · 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 ↗ Limited · humanPreprint
This large-scale observational study used an EHR-linked body-composition "digital phenotyping" pipeline — incorporating large language model (LLM)-based data extraction — to compare lean body mass (LBM) changes in routine clinical care among adults initiating GLP-1 receptor agonists (GLP-1RAs). Of 670,422 first-episode GLP-1RA users (456,742 on semaglutide; 213,680 on tirzepatide), 7,965 had paired pre- and post-initiation body-composition measurements analyzable over 12 months. The study found that tirzepatide was associated with greater relative LBM loss than semaglutide at each time point assessed (3, 6, 9, and 12 months), with excess LBM losses ranging from approximately 1.1% to 2.0%. The authors also identified two GLP-1 "metabotypes": a "Depletive" metabotype (>20% total body weight loss with >5% LBM loss), which was more frequent with tirzepatide (10.3%) than semaglutide (6.7%), and a "Prime" metabotype (>10% total body weight loss with preserved LBM). Key limitations include the observational, real-world design; reliance on LLM-extracted EHR data; potential unmeasured confounding; and the relatively small subset with paired body-composition data relative to the overall cohort.
Unknown journal · May 2026DOI ↗ Limited · human
This case report describes two adults living with well-controlled HIV-1 who presented with excess visceral abdominal fat (EVAF) under distinct clinical phenotypes. The first patient had a non-obese visceral adiposity phenotype (BMI 27 kg/m²) with increased waist circumference; treatment with tesamorelin, a growth hormone-releasing hormone analog, was associated with reductions in waist circumference, improved lipid levels, and enhanced functional well-being. The second patient had obesity (higher BMI) and received a GLP-1 receptor agonist; intermittent medication access led to fluctuating weight and persistent abdominal fat, after which the addition of tesamorelin was reported to provide more targeted visceral fat reduction. The authors argue that EVAF in people living with HIV can occur across BMI categories and may not be adequately captured by weight-based assessments alone. They conclude that individualized management informed by fat distribution patterns—rather than BMI or weight—is warranted. Key limitations include the single case-report design (n=2), absence of a control condition, lack of imaging-based visceral fat quantification reporting, and inability to draw generalizable conclusions about comparative efficacy.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 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 ↗ Limited · human
This pharmacovigilance study used the U.S. FDA Adverse Event Reporting System (FAERS) database (Q2 2022–Q2 2025) to examine whether specific GLP-1 receptor agonists (GLP-1 RAs) — exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide — differ in their association with alopecia and reproductive or endocrine-related adverse events. Researchers identified 1,276 alopecia-related and 759 reproductive/endocrine-related cases, then applied disproportionality analyses using crude and adjusted reporting odds ratios (cROR/aROR) from logistic regression, controlling for potential confounders. Sensitivity analyses with positive and negative control drugs were used to validate signal robustness. The study found that semaglutide was significantly associated with disproportionate reporting of alopecia (aROR 1.23) and several hormonal conditions, including polycystic ovary syndrome (aROR 6.59) and menstrual abnormalities. By contrast, dulaglutide and tirzepatide showed negative or non-significant associations for several reproductive outcomes. Important limitations include the inherent biases of spontaneous reporting systems (e.g., underreporting, notoriety bias, inability to establish causation), lack of denominator data, and absence of clinical detail. The authors conclude that agent-specific differences in endocrine and dermatologic safety profiles may warrant personalised prescribing decisions and ongoing surveillance.
Diabetes/metabolism research and reviews · May 2026DOI ↗