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 ↗ Limited · human
This pharmacovigilance study examined safety signals associated with potentially counterfeit semaglutide products by conducting a descriptive and disproportionality analysis of Individual Case Safety Reports (ICSRs) submitted to the European pharmacovigilance database EudraVigilance between January 2018 and December 2025. Researchers identified 234 ICSRs linked to suspected counterfeit semaglutide, of which 73.5% involved female patients and 35.5% involved adults. Notably, 89.3% of reported suspected adverse drug reactions (ADRs) were classified as serious. The most commonly reported suspected ADRs were vomiting, nausea, and hypoglycemia. Disproportionality analysis revealed a statistically higher reporting frequency for hypoglycemia, product use in an unapproved indication, malaise, and drug ineffectiveness compared with reports involving non-counterfeit semaglutide. The authors suggest these signals may reflect contamination, incorrect active ingredients, or subtherapeutic dosing in counterfeit products. Limitations include the inherent biases of spontaneous pharmacovigilance reporting (underreporting, lack of denominator data, and inability to confirm causality), reliance on database classifications of "counterfeit," and the descriptive nature of the analysis. The study concludes that pharmacovigilance databases can play a useful role in detecting safety concerns related to counterfeit medicines, and calls for further research.
Frontiers in pharmacology · Apr 2026DOI ↗ Moderate · human
This study aimed to indirectly compare the efficacy and safety of injectable tirzepatide (a dual GIP/GLP-1 receptor agonist) with oral semaglutide (a GLP-1 receptor agonist) for weight management in adults with overweight or obesity but without type 2 diabetes. Because no head-to-head trial exists, researchers used multilevel network meta-regression (ML-NMR) to adjust for baseline differences in sex, ethnicity, and outcome measures between two pivotal trials: SURMOUNT-1 (tirzepatide, 72 weeks) and OASIS 1 (oral semaglutide, 68 weeks). After adjustment, the analysis found that tirzepatide at two of the three doses studied was associated with statistically significantly greater reductions in body weight and waist circumference compared with oral semaglutide. Tirzepatide was also associated with higher odds of achieving clinically meaningful weight-loss thresholds (≥5%, ≥10%, ≥15%, and ≥20% body weight reduction). Cardiometabolic outcomes and safety profiles were reported as improved or broadly comparable for tirzepatide versus oral semaglutide. Key limitations include the indirect nature of the comparison, differences in trial duration and populations, and the inability to fully control for all confounders across separate trials. The findings should be interpreted cautiously pending direct head-to-head evidence.
Diabetes, obesity & metabolism · 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 ↗ Review
This paper argues that body image has been largely overlooked in research on glucagon-like peptide-1 receptor agonists (GLP-1s) such as semaglutide and tirzepatide, despite its central relevance to why people seek these treatments and how they psychologically adjust to the bodily changes that follow. Drawing on existing literature across body image, weight loss interventions, weight stigma, and cosmetic procedures, the authors conceptualise body image not simply as an outcome of GLP-1 use, but as a motivator, mediator, and moderator across the entire treatment trajectory. The paper identifies several critical research gaps, including the absence of prospective and longitudinal studies tracking body image before, during, and after GLP-1 use, as well as limited understanding of individual vulnerability factors and heterogeneity in psychological responses. The authors also highlight broader societal concerns, including the potential reinforcement of weight stigma, inequities in access to these medications, and the role of media representation. They call for body image-informed psychological support for people using GLP-1s, as well as professional education and training. As a narrative review, the paper does not present new empirical data and its conclusions are based on inference from adjacent literatures rather than direct evidence.
Body image · Apr 2026DOI ↗ Review
This narrative review compared tirzepatide (a dual GIP/GLP-1 receptor agonist) and semaglutide (a selective GLP-1 receptor agonist) across weight loss, glycemic control, cardiometabolic, and safety outcomes by synthesizing evidence from clinical trials, real-world observational studies, and cardiovascular outcome analyses. The authors found that in completed head-to-head randomized trials, tirzepatide consistently produced greater reductions in body weight and HbA1c compared with semaglutide in people with obesity or type 2 diabetes. Regarding cardiovascular outcomes, the review noted that semaglutide currently holds the most mature evidence for cardiovascular risk reduction, supported by the SUSTAIN-6, PIONEER-6, and SELECT trials. Tirzepatide's SURPASS-CVOT trial demonstrated non-inferiority to dulaglutide for cardiovascular outcomes along with improvements in cardiometabolic risk factors, but direct cardiovascular superiority data versus semaglutide remain limited. Real-world studies on cardiovascular outcomes were characterized as heterogeneous. The authors concluded that treatment selection should be individualized. Key limitations include the narrative (non-systematic) methodology, potential for selection bias in literature inclusion, and the absence of a completed direct head-to-head cardiovascular outcomes trial between the two agents.
Frontiers in medicine · Apr 2026DOI ↗ Limited · human
This large-scale observational study used a federated biomedical data platform to analyze 135,349 individuals treated with GLP-1 receptor agonists (GLP-1RAs) — specifically semaglutide (Wegovy) and tirzepatide (Zepbound) formulations — to characterize differences between "super responders" (>15% weight loss), "moderate responders" (5–15% weight loss), and a "minimal weight-loss" group. The study found substantial heterogeneity in weight-loss outcomes across patients receiving the same therapies. Notably, super responders to Zepbound showed reduced risk of developing certain comorbidities, including conditions at relative risks as favorable as 0.5 for osteoarthritis (P = .001), while Wegovy super responders showed an association with psoriasis (RR = 2.5, P = .03). The authors conclude that differences in weight trajectories likely reflect a combination of biological, behavioral, and social factors. Key limitations include the observational, retrospective design (which cannot establish causation), the reliance on federated real-world data (subject to coding variability), and lack of randomization. The authors call for prospective studies to develop more individualized weight-loss strategies.
Biology methods & protocols · Apr 2026DOI ↗ Limited · human
This real-world observational study examined weight trajectories in 4,182 patients during the 6 months following their last documented semaglutide or tirzepatide prescription, drawn from a federated health network. The study found that approximately two-thirds of the full cohort showed stable weight or continued weight loss after their final prescription. In a representative subset of 300 patients whose clinical notes were analyzed using a large language model (LLM), treatment discontinuation was confirmed in 119 patients (40%), and of those, 72% did not demonstrate weight regain. The study also noted that exercise counseling was documented more frequently among patients who maintained weight loss compared to those who experienced weight regain (26.2% vs. 14.7%; P = .04). Key limitations include the observational and retrospective design, reliance on documented prescriptions rather than confirmed medication use, potential incompleteness of clinical records, use of an LLM for data curation introducing possible inaccuracies, and the inability to establish causation. The authors acknowledge that further studies are needed to understand the mechanisms behind these real-world patterns of weight maintenance after GLP-1 receptor agonist discontinuation.
Biology methods & protocols · Apr 2026DOI ↗ Review
This systematic review (PRISMA-compliant, PROSPERO-registered) examined the association between GLP-1 receptor agonists (GLP-1 RAs) and hair loss by searching four major databases (PubMed, Embase, Scopus, Web of Science). Of 133 studies identified, 24 met inclusion criteria as primary articles. The review found that semaglutide and tirzepatide showed the highest reported incidence of hair loss and the strongest pharmacovigilance signals among GLP-1 RAs. The predominant subtypes reported were androgenetic alopecia and telogen effluvium, with telogen effluvium most frequently linked to tirzepatide—the agent associated with the greatest magnitude of weight loss. The authors noted that hair loss with semaglutide appeared dose-dependent, and that females were disproportionately affected. Rapid weight loss was identified as a potential contributing mechanism, especially for telogen effluvium. Other agents—liraglutide, dulaglutide, lixisenatide, and exenatide—had fewer studies and generally lower reported risk. Key limitations include the reliance on pharmacovigilance data and heterogeneous study designs, which preclude definitive causal conclusions. The authors call for large, prospective randomized trials to establish causality and temporal relationships.
Science progress · 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 ↗ Review
This review examines the current clinical development pipeline for metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, MASH (metabolic dysfunction-associated steatohepatitis), with a particular focus on cardiovascular comorbidities. The authors highlight the strong bidirectional relationship between MASLD and cardiometabolic risk, arguing that effective treatments should address both hepatic and cardiovascular outcomes simultaneously. The review surveys a broad range of drug candidates and mechanisms, including incretin mimetics (e.g., semaglutide), thyroid hormone receptor-beta agonists (e.g., resmetirom), farnesoid X receptor agonists, PPAR agonists, de novo lipogenesis inhibitors, and fibroblast growth factor analogues. The authors note that the two FDA-approved therapies — resmetirom and semaglutide — have demonstrated reductions in major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality in MASH patients, with semaglutide also showing benefit in heart failure with preserved ejection fraction. However, the review emphasizes that cardiovascular outcome data for most other pipeline agents remain limited or absent. A key limitation is that this is a narrative review and does not involve primary data collection or meta-analytic methods.
Biomedicines · Apr 2026DOI ↗ Review
This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence from 15 studies evaluating GLP-1 receptor agonist and dual incretin-based pharmacotherapies for obesity management, including semaglutide, liraglutide, tirzepatide, dulaglutide, and dual GIP/GLP-1 receptor agonists. Study participants were predominantly female (up to 79.3%), ranging in mean age from 22.4 to 59.8 years, with BMIs between 29.3 and 43.0 kg/m², and frequent comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The review found that weight loss was dose-dependent across agents, with dual GIP/GLP-1 therapy showing the greatest reductions. Cardiometabolic outcomes included reductions in HbA1c, systolic blood pressure, and LDL cholesterol across therapies. Gastrointestinal adverse events — particularly nausea, vomiting, and diarrhea — were commonly reported but generally mild, while serious events such as pancreatitis and gallbladder complications were rare. Treatment discontinuation rates were described as generally low. Limitations include the heterogeneity of included studies, variability in populations, and the review's reliance on previously published trial data rather than original participant-level analysis.
Disease-a-month : DM · Apr 2026DOI ↗ Review
This review paper examines the emerging evidence for glucagon-like peptide-1 receptor agonists (GLP-1RAs) — specifically liraglutide, semaglutide, and tirzepatide — as potential interventions in prediabetes. The authors synthesize findings showing that GLP-1RAs were associated with reduced progression to type 2 diabetes mellitus (T2DM), with normoglycaemia achieved in a notable proportion of subjects (up to 66%, 81%, and 93.3% for liraglutide, semaglutide, and tirzepatide, respectively). However, these glycaemic benefits were only partially maintained after drug discontinuation. The review also highlights modest reductions in HbA1c, fasting glucose, body weight, and fat mass, alongside improvements in insulin sensitivity and β-cell function. Potential cardiovascular benefits — including reduced risk of atherosclerotic cardiovascular disease and heart failure — were noted, particularly with tirzepatide. Experimental data suggested possible benefits for metabolic dysfunction-associated steatotic liver disease (MASLD). The safety profile was described as acceptable, with mild-to-moderate gastrointestinal effects being the most commonly reported adverse events. The authors acknowledge that the current evidence base is limited and call for large, well-designed randomised controlled trials to define the precise role of GLP-1RAs in prediabetes management.
Diabetes therapy : research, treatment and education of diabetes and related disorders · Apr 2026DOI ↗ Strong · human
This network meta-analysis pooled data from 11 randomized controlled trials (n = 83,215) to compare the cardiovascular (CV) efficacy and safety of GLP-1 receptor agonists (GLP-1RAs) in adults with type 2 diabetes and established cardiovascular disease or high CV risk. Trials were identified through a systematic search of five major databases up to December 2025. Using a frequentist random-effects framework, the authors found that several GLP-1RAs — including subcutaneous semaglutide, efpeglenatide, albiglutide, tirzepatide, oral semaglutide, liraglutide, and dulaglutide — significantly reduced three-point major adverse cardiovascular events (MACE) compared with placebo, with no detected heterogeneity or inconsistency. Subcutaneous semaglutide, efpeglenatide, and albiglutide ranked highest by P-score. No agent significantly reduced all-cause or CV mortality versus placebo. Tirzepatide and dulaglutide were associated with reduced stroke risk. Tolerability signals showed higher rates of discontinuation due to gastrointestinal adverse events with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650. The authors concluded that MACE reduction is the most consistent efficacy signal across GLP-1RAs in this population. Limitations include the indirect nature of network comparisons and differing trial designs and populations across included studies.
Canadian journal of diabetes · Apr 2026DOI ↗ Moderate · human
This large genome-wide association study (GWAS) investigated whether genetic variants explain why people respond differently to GLP-1 receptor agonists (GLP-1 RAs) such as semaglutide and tirzepatide. Researchers analyzed self-reported weight loss and side effects in 27,885 individuals on GLP-1 RA therapy. The study identified a missense variant in the GLP1R gene significantly associated with greater weight loss efficacy, with carriers of the effect allele losing an additional estimated 0.76 kg per copy. Separate genetic associations were found linking variants in both GLP1R and GIPR to nausea or vomiting during GLP-1 RA treatment; notably, the GIPR association appeared specific to tirzepatide users, consistent with tirzepatide's dual GLP-1/GIP receptor mechanism. The authors built a broader predictive model incorporating these findings, suggesting the potential to stratify patients by expected efficacy and side effect risk—a step toward precision medicine for obesity. Key limitations include reliance on self-reported outcomes, which may introduce recall and reporting bias, and the observational nature of the design, which limits causal inference beyond the genetic associations themselves.
Animal only
This animal study compared the anti-atherosclerotic effects of tirzepatide (a dual GIP/GLP-1 receptor agonist) and semaglutide (a selective GLP-1 receptor agonist) in ApoE knockout mice. Mice were treated with streptozotocin to induce diabetes and divided into early diabetes, late diabetes, and non-diabetic groups, each receiving either agent or saline for 12 weeks. The study found that in the early diabetes group, both tirzepatide and semaglutide significantly reduced aortic plaque formation compared to controls, with modest improvements in blood glucose and lipid levels. No significant vascular effects were observed in the late diabetes or non-diabetic groups in terms of plaque reduction. Tirzepatide more broadly reduced inflammatory markers—including Mcp-1, Il-6, I-cam, and Cd68—compared to semaglutide. Anti-inflammatory effects were also detected in non-diabetic mice, suggesting possible vascular protective mechanisms independent of metabolic control. The authors conclude that dual incretin receptor agonism may offer cardiovascular benefits, though the specific contribution of GIP signaling requires further investigation. Key limitations include the use of an animal model, which may not translate directly to human cardiovascular disease.
Scientific reports · Apr 2026DOI ↗ Strong · human
This systematic review and network meta-analysis compared the weight-loss efficacy and safety of three FDA-approved agents—tirzepatide (a dual GIP/GLP-1 agonist), semaglutide, and liraglutide—in non-diabetic adults with obesity. Researchers searched four major databases through May 2025 and identified 15 Phase 3 RCTs encompassing 14,059 patients. Using a frequentist random-effects network meta-analysis, the authors found that all three agents produced statistically significant body weight reductions compared to placebo. Ranking by magnitude of effect, the highest tolerated dose of tirzepatide demonstrated the greatest weight reduction, followed by lower tirzepatide doses, then semaglutide, and finally liraglutide. On the safety side, tirzepatide and semaglutide were each associated with a higher risk of any adverse event compared to placebo, while liraglutide was not. The authors note that the analysis was limited to Phase 3 RCTs and did not assess long-term outcomes such as weight regain after discontinuation, metabolic endpoints, cost-effectiveness, or patient preferences, which they identify as priorities for future research.
Obesity (Silver Spring, Md.) · Apr 2026DOI ↗ Moderate · human
This systematic review and meta-analysis pooled data from three head-to-head randomized or controlled trials comparing tirzepatide (a dual GIP/GLP-1 receptor agonist) with semaglutide (a selective GLP-1 receptor agonist) in adults with obesity and/or type 2 diabetes. Studies were identified through searches of PubMed, Embase, and ScienceDirect up to February 2026. Using a random-effects model, the authors found that tirzepatide was associated with significantly greater weight reduction compared to semaglutide (pooled mean difference: −5.19 kg) and a higher likelihood of achieving ≥10% weight loss (pooled risk ratio: 1.50). No statistically significant differences were observed in overall adverse events or gastrointestinal events between the two agents; however, serious adverse events were reported more frequently with tirzepatide (risk ratio: 1.83). Key limitations include a very small number of included studies (n=3), substantial statistical heterogeneity in weight-related outcomes (I² >86%), and insufficient follow-up duration to draw conclusions about long-term cardiovascular safety. The authors note that further studies with longer follow-up are needed to confirm the cardiometabolic safety profile of tirzepatide relative to semaglutide.
Nepal journal of epidemiology · Apr 2026DOI ↗ In vitro
This in vitro study examined the effects of three incretin-based therapies — semaglutide (GLP-1 receptor agonist), tirzepatide (dual GLP-1/GIP agonist), and cagrilintide (amylin analogue) — on mitochondrial function in C2C12 skeletal muscle myotubes under both normal and lipotoxic conditions. Lipotoxicity was induced using palmitic acid (PA), which significantly reduced basal oxygen consumption rate and ATP production in treated cells. The study used Seahorse XFp metabolic flux analysis, mitochondrial DNA copy number quantification (qPCR), and oxidative phosphorylation complex protein expression (western blotting), with key findings replicated in primary human skeletal muscle cells. The researchers found that semaglutide and cagrilintide transiently reduced basal respiration in healthy myotubes, while tirzepatide demonstrated more sustained improvements in mitochondrial respiration under both healthy and lipotoxic conditions. The study's primary limitations include its reliance on cell culture models, meaning findings may not directly translate to whole-organism physiology, and the use of a single lipotoxic stimulus. The partial replication in human primary cells adds some translational relevance, but in vivo validation remains absent.
Journal of cachexia, sarcopenia and muscle · Apr 2026DOI ↗ Limited · human
This cross-sectional study conducted in Saudi Arabia (January–June 2025) investigated the frequency, characteristics, and predictors of hair loss among 254 adults using GLP-1 receptor agonists (GLP-1RAs) — specifically semaglutide (Ozempic), tirzepatide (Mounjaro), liraglutide (Saxenda), or liraglutide (Victoza) — primarily for weight loss. Data were collected via structured questionnaires covering demographics, clinical characteristics, and hair loss details such as timing, severity, and progression. The majority of participants were female (71.3%), with a mean age of approximately 33 years. The study found that overall hair loss prevalence did not differ significantly across GLP-1RA types (p = 0.116); however, severe hair loss was reported significantly more often among Mounjaro (43.4%) and Saxenda (42.9%) users. Female sex and Mounjaro use were identified as notable predictors of hair loss. The authors noted that the hair loss observed was generally non-scarring and potentially reversible, but associated with psychological distress and possible impacts on treatment adherence. Key limitations include the cross-sectional design (precluding causal inference), reliance on self-reported data, the single-country sample limiting generalizability, and the absence of a control group not using GLP-1RAs.
Journal of cosmetic dermatology · Apr 2026DOI ↗