InsufficientPreprint
This bibliometric study compared the 100 most-cited articles on GLP-1 receptor agonists (GLP-1RA) with the 100 most-cited articles on metabolic bariatric surgery (MBS), using the Bibliometrix software to analyze citation patterns, journal distribution, and journal impact factors (IF). The study found that GLP-1RA articles accumulated more total citations (91,660 vs. 72,243) and had a higher median citation count (718 vs. 551) than MBS articles. GLP-1RA research was also more internationally collaborative (57% vs. 26%) and appeared more frequently in journals with IF above 40 (41% vs. 25%). The weighted 5-year mean IF was substantially higher for GLP-1RA journals (35.4 vs. 21.6). The authors argue that these differences may reflect a "prestige-journal effect," whereby GLP-1RA trials' placement in flagship journals such as the NEJM and Lancet inflates citation counts relative to MBS research, which is more dispersed across surgical specialty journals. A key limitation is that this study analyzes publication patterns rather than clinical outcomes, and cannot establish whether citation differences reflect true differences in scientific merit. The authors conclude that journal-impact inequalities should be considered when making citation-based comparisons between therapeutic fields.
Unknown journal · Jun 2026DOI ↗ InsufficientPreprint
This study investigates GHK-Cu — a copper-based amino acid complex — as an interfacial modifier inserted between the perovskite layer and the Spiro-OMeTAD hole-transport layer (HTL) in perovskite solar cells (PSCs). The researchers found that GHK-Cu's molecular flexibility and polarity-responsive coordination chemistry allowed it to expose multiple functional groups (─C=O, ─COOH, and ─NH₂) that interact with undercoordinated ionic defects via coordination bonds and hydrogen bonding. These interactions drove GHK-Cu to self-assemble into a mesoporous architecture at the interface, which then reorganized Spiro-OMeTAD into a hybrid mesoporous@Spiro-OMeTAD HTL. The authors report that this structure creates continuous hole-transport channels, reduces thermomechanical stress, and suppresses ion migration. Devices incorporating this interlayer reportedly achieved a power conversion efficiency (PCE) of 26.72%, with a certified PCE of 26.34%, and retained 95% of initial efficiency after 1,600 hours of maximum power point tracking at 85°C. Limitations include the preprint status of the work, meaning it has not yet undergone formal peer review, and the results reflect a specific device architecture that may not generalize broadly.
Unknown journal · Jun 2026DOI ↗ InsufficientPreprint
This paper presents a theoretical hypothesis arguing that current GLP-1 and dual GIP/GLP-1 receptor agonist therapies (e.g., semaglutide, tirzepatide) produce weight loss plateaus because they only address one side of what the authors term the "mass balance equation" — net mass inflow (NMI) — while net mass outflow (NMO) passively and actively declines over time. The authors propose a "mass balance model" (MBM) as an alternative explanatory framework to the conventional energy balance model, framing the plateau as a predictable physical consequence rather than a vague compensatory metabolic adaptation. Based on this framework, the authors hypothesize that combining an NMI-reducing agent with an NMO-stabilizing or NMO-enhancing agent could produce greater, more durable weight loss and improved body composition. Candidate NMO-targeting agents discussed include SGLT2 inhibitors, activin/myostatin pathway inhibitors, and mitochondrial uncouplers. The paper is entirely theoretical; no original experimental data, clinical trials, or systematic evidence synthesis are presented. Its primary limitation is that the MBM framework and the dual-action hypothesis remain untested in human or animal studies.
Unknown journal · Jun 2026DOI ↗ Insufficient
This News and Perspectives article, published in JMIR, examines the intersection of US policy changes and the growth of digital health platforms as factors influencing the affordability and accessibility of GLP-1 receptor agonist medications for obesity. The piece discusses how emerging access models—combining policy reform with telehealth and online pharmacy platforms—may expand patient access to these treatments, which have historically been cost-prohibitive for many individuals. As a journalistic and opinion-oriented piece rather than an original empirical study, it does not present primary data, clinical trial results, or systematic evidence. It instead contextualizes current trends and speculates on potential implications for the healthcare landscape. Key limitations include the absence of original research data, no patient outcomes measured, and an inherently perspective-driven framing. Readers should note that the article reflects one correspondent's analysis of a rapidly evolving policy and commercial environment, and conclusions about real-world impact on patient outcomes remain untested at this stage.
Journal of medical Internet research · Jun 2026DOI ↗ Insufficient
This scoping review, conducted following PRISMA-ScR guidelines, examines whether GLP-1 receptor agonists (GLP-1 RAs) — including semaglutide, liraglutide, tirzepatide, and retatrutide — may interfere with autologous fat grafting outcomes. The authors note that millions of patients using GLP-1 RAs for weight loss now present to aesthetic surgeons with facial volume loss and soft tissue deflation, conditions commonly treated with fat grafting. The review synthesizes preclinical and clinical evidence on how GLP-1 RA medications affect adipocyte biology, adipose-derived stem cell (ASC) function, and tissue revascularization. The authors identify several theoretical interference points: GLP-1-mediated adipocyte "browning" and thermogenic activation (including UCP1 upregulation), enhanced lipolysis via ATGL and HSL pathways, suppression of white adipogenic differentiation in ASCs favoring beige/thermogenic lineages, and altered angiogenic and inflammatory signaling during the revascularization window critical to graft survival. The authors explicitly acknowledge that no clinical or preclinical studies have directly examined fat graft outcomes in patients receiving these therapies. The review's conclusions are framed as hypothesis-generating, and any clinical considerations offered are described as mechanism-based rather than evidence-based. This limits the paper's direct applicability to patient care.
Aesthetic surgery journal · Jun 2026DOI ↗ Insufficient
SYNCHRONIZE-JP is an ongoing 76-week, randomized, double-blind, parallel-group, multicenter Phase 3 clinical trial evaluating survodutide — a novel dual glucagon receptor/GLP-1 receptor agonist — for obesity disease management in Japanese adults. The study enrolled 274 participants aged ≥18 years with obesity and at least one qualifying complication (type 2 diabetes capped at 30%, hypertension, or dyslipidemia). Participants were randomized 1:1:1 to one of two doses of once-weekly survodutide or placebo, alongside a reduced-calorie diet and increased physical activity. At baseline, the mean age was 53.1 years, mean BMI was 33.2 kg/m², 47.8% were female, and 24.1% had type 2 diabetes; the most common comorbidities were dyslipidemia (81.4%) and hypertension (72.6%). The co-primary endpoints are percentage change in body weight and proportion achieving ≥5% body weight reduction from baseline to Week 76. A subset will also be assessed for liver fat content and body composition. This publication reports only the trial rationale, design, and baseline characteristics; no efficacy or safety outcome data are yet available, which is a key limitation.
Diabetes, obesity & metabolism · May 2026DOI ↗ Insufficient
This News and Perspectives article, authored by JMIR Correspondent Anna Zucker, examines the landscape of GLP-1 receptor agonist prescribing through telehealth platforms for obesity management. The piece highlights a structural concern: while digital health platforms have significantly expanded access to GLP-1 medications, they may not consistently provide adequate clinical follow-up and ongoing support after the initial prescription is issued. The article argues that this "clinical support gap" — encompassing monitoring, behavioral counseling, and longitudinal care — could undermine the potential benefits of these medications and may pose risks to patients. As a News and Perspectives piece, the article does not present original empirical data or a clinical trial; rather, it synthesizes observations and commentary to frame an emerging issue in digital health delivery. Its limitations include the absence of primary data, quantitative analysis, or a systematic review methodology. The piece is best interpreted as expert opinion and advocacy for improved care structures within telehealth-based GLP-1 treatment models, rather than as direct clinical evidence.
Journal of medical Internet research · May 2026DOI ↗ Insufficient
This brief report, authored for nurse practitioners (NPs), examines the clinical and regulatory challenges arising from patient-driven "microdosing" of GLP-1 receptor agonists (semaglutide and tirzepatide) in the context of FDA restrictions on compounded versions following resolution of drug shortages. The authors describe how affordability barriers push patients toward subtherapeutic dosing strategies, unregulated "research-grade" peptides purchased online, and unsupervised sources such as medical spas. The paper outlines specific safety concerns associated with these practices, including pen manipulation, medication sharing, compounded vials, and dosing errors, as well as the side effect profiles encountered. It also explores how provider weight bias may inadvertently drive patients toward unregulated alternatives and offers practical stigma-reduction strategies for clinical encounters. The authors discuss the legal risks of compounded "copies" and acknowledge a narrow legitimate role for compounding in patients with documented allergies. As a brief report rather than an empirical study, the paper does not present original data or a systematic review; its conclusions are based on regulatory context, clinical observation, and expert opinion. Its primary value lies in synthesizing emerging practice-relevant issues for NPs navigating a rapidly evolving regulatory environment.
Journal of the American Association of Nurse Practitioners · May 2026DOI ↗ Insufficient
This review examines the available information on dulaglutide, a GLP-1 receptor agonist used for type 2 diabetes management, in the context of breastfeeding safety. The authors note a complete absence of clinical data on dulaglutide use during lactation. They reason that, due to dulaglutide's large molecular weight of approximately 59,669 daltons as a protein molecule, transfer into breast milk is theorized to be minimal. Furthermore, even if trace amounts were present in milk, oral absorption by a nursing infant is considered unlikely because the compound would probably be degraded by proteolytic enzymes in the infant's gastrointestinal tract. Despite this theoretical reassurance, the authors conclude that caution is warranted when considering dulaglutide use during breastfeeding, with heightened concern for newborns and preterm infants, whose gastrointestinal systems may be less capable of fully degrading such compounds. The primary limitation of this review is the total lack of empirical human lactation data, meaning all conclusions are based on pharmacokinetic reasoning and extrapolation rather than direct measurement or clinical observation.
Unknown journal · May 2026Source ↗ Insufficient
This review article addresses the safety profile of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, specifically in the context of breastfeeding. The authors note that no empirical data are currently available on liraglutide use during lactation. The discussion is grounded in pharmacokinetic reasoning: liraglutide is a large peptide molecule with a molecular weight of 3,751 daltons, which suggests that transfer into breast milk would likely be minimal. Furthermore, even if trace amounts were present in milk, oral absorption by the nursing infant is considered unlikely, as the peptide would probably be degraded by proteolytic enzymes in the infant's gastrointestinal tract. Despite this theoretically low risk, the authors recommend caution when using liraglutide during breastfeeding, with particular attention to newborns and preterm infants, who may have less developed gastrointestinal and metabolic systems. The article acknowledges the absence of clinical or experimental data as a key limitation, meaning conclusions are based on indirect, mechanistic reasoning rather than direct observation or controlled study.
Unknown journal · May 2026Source ↗ Insufficient
TRANSCEND-CKD (NCT05936151) is a double-blind, placebo-controlled Phase 2b mechanistic trial evaluating retatrutide — a triple agonist of the GIP, GLP-1, and glucagon receptors — in adults with overweight or obesity and chronic kidney disease (CKD). The publication describes the trial's rationale, design, and baseline characteristics of the 146 randomized participants (out of 367 screened). Participants had a mean age of 65.1 years, mean BMI of 35.7 kg/m², and mean measured GFR of 49.3 mL/min/1.73 m² (eGFR range 25–75). Roughly 38% had type 2 diabetes. Participants were randomized 1:1 to once-weekly retatrutide (maximum tolerated dose up to 12 mg) or matched placebo. The primary endpoint is change in measured GFR via iohexol clearance at 24 weeks; secondary endpoints include MRI-assessed kidney hemodynamics, volumes, and perirenal/renal sinus fat. The study is explicitly designed as a mechanistic precursor to the larger cardio-kidney outcomes trial TRIUMPH-Outcomes. Because this paper reports only design and baseline data — with no efficacy or safety outcomes yet — no conclusions about retatrutide's effects on kidney function can be drawn from it.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · May 2026DOI ↗ Insufficient
This analytical chemistry study examined compounded tirzepatide products combined with vitamin B12 analogs that are widely marketed in the United States as alternatives to FDA-approved tirzepatide. Researchers collected samples from multiple U.S. market sources and subjected them to various analytical methods to assess peptide-related impurity profiles and potency. The key finding was the identification of a previously unknown chemical impurity generated by a reaction between tirzepatide and certain B12 analogs. This impurity was described as widespread across the tested samples and present at substantial levels. The authors note that compounded tirzepatide-B12 combinations are mass-marketed without undergoing formal evaluation of potency or impurity profiles, unlike FDA-approved products. The study does not characterize the clinical effects of the identified impurity, which remains unknown. Limitations include the absence of clinical outcome data, lack of information on the specific analytical thresholds used, and no assessment of patient exposure or harm. The authors conclude that the findings highlight quality-control risks associated with compounded therapies marketed outside the drug-approval regulatory framework and reinforce the rationale for pre-market testing and FDA oversight.
Expert opinion on drug safety · Apr 2026DOI ↗ InsufficientPreprint
This study analyzed a large, publicly available independent testing dataset of 6,441 samples spanning fourteen peptide compounds sold through largely unregulated gray market channels directly to consumers. Compounds examined included BPC-157, semaglutide, tirzepatide, PT-141, TB-500, thymosin beta-4, and others marketed for purposes such as injury recovery, muscle growth, fat loss, and athletic performance. Researchers applied two quality acceptance frameworks — one approximating standards for 503A compounded medications and a stricter model reflecting FDA-approved drug production standards — to assess purity, measured abundance, and endotoxin burden. The study found that between 41.6% and 71.1% of samples failed to meet basic quality criteria depending on the framework applied, and measurable endotoxin contamination was detected in 15% of samples. Gray market peptides were consistently cheaper than FDA-approved alternatives, though cost differentials varied widely (e.g., 72.8% higher for tirzepatide vs. 3,850% higher for PT-141 when comparing FDA-approved options). The authors concluded that consumer-directed third-party testing improves transparency but captures only a fraction of the full safety profile relevant to patients self-administering injectable compounds. Key limitations include reliance on a secondary dataset not collected under controlled research conditions and the inability to assess many other safety dimensions beyond purity and endotoxin levels.
Unknown journal · Apr 2026DOI ↗ InsufficientPreprint
This narrative review examines the pharmacogenomics of GLP-1 receptor agonists — principally semaglutide (Ozempic®/Wegovy®) and the dual GIP/GLP-1 agonist tirzepatide (Mounjaro®/Zepbound®) — with a focus on explaining the wide inter-individual variability in efficacy and tolerability observed in clinical practice. The authors synthesise evidence around key genetic loci, including GLP1R, GIPR, ARRB1, TCF7L2, and MC4R, and highlight a purported April 2026 genome-wide association study (GWAS) conducted by 23andMe (n=27,885) as the largest pharmacogenomic study of GLP-1 therapies to date. The review also surveys the competitive landscape among Novo Nordisk, Eli Lilly, 23andMe Research Institute, and PGxAI, and dedicates substantial attention to South Asian and Indian populations, arguing that their large diabetes burden and undercharacterised pharmacogenomic profiles represent a critical gap. The authors conclude that GLP-1 pharmacogenomics has advanced from exploratory science toward actionable clinical discovery. Limitations include the narrative (non-systematic) design, reliance on a preprint-stage GWAS of uncertain peer-review status, and the absence of prospective clinical validation data for genotype-guided prescribing.
Unknown journal · Apr 2026DOI ↗ Insufficient
This paper describes a pre-registered protocol for a systematic review and network meta-analysis (NMA) examining the comparative efficacy and safety of GLP-1 receptor agonists (GLP-1 RAs) and novel co-agonists (e.g., dual/triple agonists) for weight loss in adults with overweight or obesity who do not have diabetes. The authors plan to search PubMed, Ovid, and Cochrane CENTRAL for randomized controlled trials (RCTs) comparing these agents against placebo or each other. Trials involving participants with diabetes, specific comorbidities, or prior bariatric surgery will be excluded. The primary outcome is relative change in body weight from baseline at approximately 6 months and 1–1.5 years. Secondary outcomes include absolute weight change, total adverse events, gastrointestinal adverse events, serious adverse events, and death. Frequentist random-effects pairwise and network meta-analyses will be conducted, with treatment rankings generated via the surface under the cumulative ranking curve (SUCRA). Risk of bias will be assessed using the Cochrane RoB 2 tool and the RoB-NMA tool. Importantly, this is a protocol paper only — no data have been collected or analyzed yet — so no results or conclusions about the efficacy or safety of any specific agent are available at this stage.
Systematic reviews · Mar 2026DOI ↗ Insufficient
This study investigated compounded semaglutide and tirzepatide products being sold by compounding pharmacies following the resolution of the innovator drug shortage. Researchers conducted a Google-based search of compounding pharmacy websites between February and March 2025, identifying 33 unique compounded GLP-1 products. Two-thirds contained semaglutide and one-third contained tirzepatide. Nearly half of the products combined the active GLP-1 ingredient with additional agents such as cyanocobalamin, glycine, niacinamide, docusate, or ondansetron. Single-ingredient products were predominantly offered in sublingual (82%) or oral disintegrating tablet (ODT) (18%) formulations. The study found that the vast majority of products lacked transparency around beyond-use dating and storage conditions. The authors concluded there was little scientific justification for adding nutrients or docusate sodium to these formulations; while ondansetron co-formulation had a theoretical rationale, evidence for subcutaneous delivery was absent. Sublingual and ODT formats also lacked comparative evidence against FDA-approved oral tablets. A key limitation is that this was an observational web survey, not a clinical study, so no safety or efficacy data on patients were collected or analyzed.
The Annals of pharmacotherapy · Feb 2026DOI ↗ Insufficient
This systematic review surveyed ClinicalTrials.gov (from inception through July 2025) to map the landscape of registered clinical trials investigating glucagon-like peptide-1 receptor agonists (GLP-1RAs) as potential treatments for substance use disorders (SUDs). Of 192 records identified, 33 trials met inclusion criteria. The most commonly studied SUD was alcohol use disorder (15 trials), followed by nicotine/tobacco (9), cocaine (4), opioid (4), and methamphetamine (1); no trials targeting cannabis use disorder were identified. Agents under investigation included semaglutide, exenatide, tirzepatide, liraglutide, dulaglutide, and pemvidutide. The review found that trial designs and outcome measures were highly heterogeneous, often blending self-reported measures (e.g., Timeline Follow-Back, craving scales) with objective indices (e.g., urine toxicology). The authors note that most registered trials rely on older-generation GLP-1RAs and that significant gaps exist for methamphetamine and cannabis use disorders. As a registry-based systematic review, it does not report clinical efficacy data from completed trials. The authors conclude that next-generation GLP-1RAs and trials using FDA-recommended endpoints are needed to establish efficacy and safety across the full spectrum of SUDs.
Addictive behaviors reports · Jan 2026DOI ↗ Insufficient
This exploratory simulation study compared the quality of responses generated by a large language model (GPT-4o) versus standard internet searches (Google) when answering 17 common patient-style questions about GLP-1 receptor agonist (GLP-1RA) therapy for obesity. Questions were selected based on Google Trends data and covered indications, expected treatment course, side effects, and specific risks. Two independent evaluators scored responses using a 5-point Likert scale across six domains: safety, guideline consensus, objectivity, reproducibility, relevance, and explainability. The study found that LLM responses scored significantly higher than internet search results in objectivity and reproducibility, while no significant differences were observed in the remaining four domains. Interrater agreement was high (Gwet AC ≈ 0.879). Qualitatively, LLM responses were noted to lack coverage of emerging clinical issues due to static training data, whereas internet results were more current but often commercially biased and inconsistent. The authors conclude that LLMs may offer a more reliable and objective source of health information for patients, though human oversight and real-time data integration remain important limitations to address. The study is limited by its small, simulated question set and lack of real patient interaction data.
JMIR formative research · Nov 2025DOI ↗ Insufficient
The DREAMS-3 trial is a randomized, open-label Phase 3 study designed to compare the efficacy and safety of mazdutide (a glucagon receptor/GLP-1 receptor co-agonist) versus semaglutide (a GLP-1 receptor agonist) in Chinese adults with type 2 diabetes (T2D) and obesity. This publication reports the trial's rationale, design, and baseline characteristics rather than outcome results, as the study is ongoing with an expected completion date in early 2026. A total of 349 participants (mean age 42.4 years; 44.7% male) were randomized 1:1 to either treatment arm for a 32-week active-controlled period followed by a 24-week extension. At baseline, participants had a mean HbA1c of 8.0%, body weight of 90.5 kg, and BMI of 33.0 kg/m². The mean T2D duration was 1.8 years, and approximately 39.5% were on metformin. The primary endpoint is the proportion of participants achieving HbA1c targets. Notably, comorbidities such as metabolic-associated fatty liver disease and gout/hyperuricemia showed strong associations with BMI. As a design and baseline data paper, no efficacy or safety outcomes are yet available, limiting current evidence value.
Contemporary clinical trials · Nov 2025DOI ↗ Insufficient
SYNCHRONIZE™-2 is an ongoing double-blind, randomized, placebo-controlled Phase 3 trial evaluating survodutide — an investigational dual glucagon receptor/GLP-1 receptor agonist — for weight reduction in adults with obesity and type 2 diabetes (T2D). This paper reports only the baseline characteristics of the 752 enrolled participants across 133 sites in 19 countries; efficacy and safety results are not yet available. Participants were randomized 1:1:1 to one of two doses of weekly subcutaneous survodutide or placebo, alongside diet and physical activity guidance. At baseline, the cohort had a mean age of 55.7 years, mean BMI of 36.5 kg/m², mean body weight of 104.1 kg, and mean HbA1c of 7.4%; roughly half were female. Common comorbidities included hypertension (69%), dyslipidaemia (68%), and obstructive sleep apnoea (17%). The geographic distribution included participants from Europe, North America, and East Asia, suggesting reasonable diversity. Primary endpoints are percentage change in body weight and achievement of ≥5% weight loss at Week 76. A key limitation of this publication is that it presents only baseline data — no outcomes are yet reported — so no conclusions about efficacy or safety of survodutide can be drawn from this paper alone.
Diabetes, obesity & metabolism · Nov 2025DOI ↗