Review
This systematic review evaluated the clinical trial evidence base for pharmacological treatments of Hypoactive Sexual Desire Disorder (HSDD) in adult women by systematically searching ClinicalTrials.gov in accordance with PRISMA 2020 guidelines. Nine completed interventional clinical trials met the inclusion criteria, most of which were Phase II or Phase III randomized, double-blind, placebo-controlled studies enrolling primarily premenopausal women with acquired, generalized HSDD. The most extensively studied agents were flibanserin and bremelanotide, both of which target central nervous system pathways involved in sexual desire. Efficacy was most commonly assessed using validated patient-reported outcome tools such as the Female Sexual Function Index desire domain and the Female Sexual Distress Scale. The review found notable heterogeneity across trials in endpoint designation, reporting completeness, and safety data presentation, which limited cross-trial comparisons. Adverse events generally reflected the pharmacological mechanisms of the agents studied. The authors concluded that while progress has been made, significant gaps remain in the pharmacological treatment landscape for HSDD, and called for more standardized trial methodologies and comprehensive outcome reporting to strengthen the overall evidence base. A key limitation is that findings were synthesized descriptively without pooled quantitative (meta-analytic) analysis.
Frontiers in medicine · 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 ↗ Limited · human
This pharmacovigilance study investigated reports of dysesthesia (abnormal skin sensations, particularly burning sensations) associated with GLP-1 receptor agonists, including semaglutide, tirzepatide, exenatide, and others. The researchers conducted a disproportionality analysis using VigiBase — the WHO's global drug safety database — focusing on the High Level Term "Paraesthesia and dysesthesia," supplemented by a qualitative review of case narratives from the French Pharmacovigilance database and a broader literature review. The analysis found that exenatide was significantly associated with hypoesthesia and oral paraesthesia, while semaglutide and tirzepatide were associated with hyperaesthesia; semaglutide was also linked to dysesthesia and burning sensations specifically. The study suggests dysesthesia may be dose-dependent and more frequent with more potent agents used at higher doses. Many reported cases involved drug discontinuation followed by spontaneous resolution, and some rechallenge cases were documented. Key limitations include the inherent biases of spontaneous reporting systems (underreporting, confounding, notoriety bias), the inability to establish causality, and the absence of controlled comparison groups. The authors conclude that pharmacovigilance data reinforces signals already observed in clinical trials of semaglutide, tirzepatide, and retatrutide.
European journal of clinical pharmacology · May 2026DOI ↗ Limited · human
This observational cohort study measured serum levels of two circulating peptides — Nardilysin (NRDc) and MOTS-c — in 150 participants (118 kidney transplant recipients [KTRs] and 32 age-matched controls) to explore their potential roles as cardiometabolic biomarkers in this high-risk population. Using commercial ELISA kits, the researchers found that median serum NRDc and MOTS-c levels were significantly higher in KTRs compared to controls. Penalized logistic regression revealed an inverse association between elevated NRDc levels and prevalent cardiovascular (CV) disease in KTRs, suggesting that higher NRDc may be associated with lower odds of existing CV disease. KTRs were followed for a median of approximately 29 months, during which renal allograft loss and all-cause mortality were analyzed using Fine-Gray competing risk regression. The authors propose that elevated NRDc and MOTS-c in KTRs may reflect altered metabolic and inflammatory pathways unique to this population. Key limitations include the observational design, the relatively small and single-center cohort, the cross-sectional nature of the CV disease association, and the lack of incident CV event data. The authors acknowledge that longitudinal studies are needed to clarify causal relationships.
Kidney & blood pressure research · 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 ↗ Strong · human
This systematic review and meta-analysis pooled data from four randomized controlled trials (n = 5,023 adults with overweight or obesity) to evaluate the efficacy and safety of cagrilintide — a long-acting amylin analogue — and its combination with semaglutide (CagriSema) versus placebo. The primary outcome was percent change in body weight. The authors followed PRISMA 2020 and AMSTAR 2 guidelines and used Cochrane RoB 2 for bias assessment, with random-effects models throughout. Key findings: cagrilintide alone was associated with a mean body weight reduction of approximately 6.1% versus placebo (95% CI: −8.0% to −4.1%), and CagriSema with approximately 6.0% (95% CI: −10.6% to −1.3%). CagriSema also significantly reduced waist circumference and HbA1c; cagrilintide alone showed modest blood pressure improvements without significant glycemic effects. Adverse events were more frequent with active treatment, though discontinuation rates were comparable to placebo. Notable limitations include the small number of pooled trials (n = 4) and potential heterogeneity across study populations and durations. The authors conclude that both therapies show clinically meaningful weight loss and acceptable tolerability, positioning them as emerging options in obesity pharmacotherapy.
Journal of diabetes and metabolic disorders · May 2026DOI ↗ In vitro
This study describes the computational design and preliminary laboratory characterization of SR18, a rationally engineered 18-amino acid peptide candidate intended to act as a GLP-1 receptor (GLP-1R) agonist for potential use in Type 2 diabetes (T2DM). The researchers used in silico methods—including molecular docking and 1-microsecond molecular dynamics (MD) simulations—to design SR18 to be resistant to DPP-4 cleavage and to retain key amino acids that interact with GLP-1R, similar to endogenous GLP-1 and approved drugs like Semaglutide and Liraglutide. In laboratory experiments, circular dichroism confirmed that synthesized SR18 adopts a stable α-helical conformation across various solvent conditions. Dynamic light scattering, cytotoxicity, and hemolytic assays suggested acceptable basic pharmaceutical and safety properties for a lead peptide candidate. Computational analyses indicated that SR18 may bind GLP-1R with comparable or favorable affinity relative to GLP-1 and Semaglutide. Limitations include the absence of any cell-based receptor activation assays, animal studies, or human data; the evidence remains entirely in silico and in vitro. No conclusions about clinical efficacy can be drawn at this stage.
Frontiers in pharmacology · May 2026DOI ↗ Limited · human
This single-arm pragmatic trial examined psychosocial outcomes in 180 adults with obesity (mean age 44.1 years; 91% female; 81% white; mean weight 102.6 kg) enrolled in a telemedicine program (WeightWatchers Clinic) who received semaglutide or tirzepatide alongside an adjunctive virtual behavioral intervention tailored for patients on long-acting incretin therapy. Psychosocial measures—including depression (PHQ-8), perceived stress (Perceived Stress Scale), well-being (WHO-5), weight bias internalization (WBIS-2F), and weight-related quality of life (IWQOL-Lite)—were collected at baseline, 12 weeks, and 24 weeks. Wilcoxon signed-rank tests with False Discovery Rate correction were used; an intent-to-treat analysis using last observation carried forward (LOCF) was also performed. The study found statistically significant improvements from baseline to 24 weeks across all five psychosocial outcomes. Key limitations include the absence of a control group, a predominantly white and female sample limiting generalizability, and the inability to separate medication effects from behavioral intervention effects. The findings suggest an association between the combined telehealth and behavioral approach and improved psychosocial outcomes, but causality cannot be established.
Obesity science & practice · May 2026DOI ↗ Review
This narrative review critically examines BPC-157 (body protection compound 157), a synthetic pentadecapeptide derived from a gastric protein fragment, through a biopharmaceutical and drug development lens rather than a purely pharmacodynamic one. The authors searched multiple major databases and patent/regulatory sources through April 2026, synthesizing evidence on physicochemical properties, pharmacokinetics, formulation challenges, and translational barriers. Key findings include: BPC-157 demonstrates unusual gastric stability and reported preclinical activity across multiple organ systems via oral, parenteral, and topical routes; a formal two-species preclinical ADME study confirmed a sub-30-minute plasma half-life, linear dose-proportional kinetics, and intramuscular bioavailability of 14–51%; a preliminary two-subject human pilot reportedly corroborated the short half-life; and a striking disconnect exists between this rapid clearance and prolonged biological effects lasting hours to days. Critically, the review identifies that no pharmaceutical-grade formulation has been developed or validated, BPC-157 lacks BCS classification data and formal excipient compatibility studies, and available human clinical data span fewer than 30 subjects across three uncontrolled pilot studies with no standardized pharmaceutical preparations. No Phase II trial has been completed. The authors conclude that the primary barrier to clinical translation is the absence of foundational pharmaceutical science, not biological activity.
Pharmaceutics · 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 paper introduces and quantifies the concept of "mercy sex" — defined as sexual activity engaged in by women diagnosed with hypoactive sexual desire disorder (HSDD) despite a documented absence of sexual desire or receptivity. The authors reviewed baseline data on sexually satisfying events (SSEs) drawn from a convenience sample of published, peer-reviewed, prospective, randomized, placebo-controlled clinical trials evaluating HSDD pharmacotherapies (including testosterone, flibanserin, and bremelanotide) conducted over nearly a decade. Baseline SSE data were analyzed across variables including time, age, reproductive status, and geographic region. The study found that women enrolled in these trials reported engaging in sexual activity approximately 2.5 times per month at baseline, despite meeting criteria for HSDD. The authors propose biopsychosocial explanations for this behavior and argue that mercy sex may confound HSDD trial outcomes by inflating baseline SSE rates, potentially skewing assessments of therapeutic efficacy, influencing sample size calculations, and complicating the definition of a clinically meaningful treatment response when SSEs serve as a primary endpoint. Limitations include reliance on secondary analysis of existing trial data and the use of a convenience sample. The paper does not conduct a new primary trial but offers a methodological and conceptual critique of HSDD clinical research design.
Journal of sex & marital therapy · May 2026DOI ↗ ReviewPreprint
This scoping review systematically mapped the published and registered evidence on Thymosin Beta-4 (TB4) and the related synthetic peptide TB-500 in tissue healing, regeneration, and musculoskeletal repair. Searching PubMed, Europe PMC, and ClinicalTrials.gov through March 2026, the authors identified 1,772 records and included 80 studies after screening. Key findings include: (1) the evidence base is heavily skewed toward in vitro and animal (preclinical) designs rather than human trials; (2) most research has examined TB4, while direct evidence on TB-500 was limited to a single included study; (3) the most studied tissue categories were wound/skin/soft tissue, vascular/endothelial, and ocular/corneal, with the strongest human evidence concentrated in ocular and wound-healing contexts; and (4) musculoskeletal-specific tissues—such as tendon, ligament, muscle, cartilage, and intervertebral disc—were comparatively underrepresented. The authors concluded that while the literature supports interest in several repair-related biological pathways, it remains unevenly distributed and largely preclinical, and does not yet provide a robust human evidence base for musculoskeletal applications. Scoping reviews do not perform meta-analyses or quality appraisal of individual studies, which limits causal conclusions.
Unknown journal · May 2026DOI ↗ Limited · human
This retrospective pharmacovigilance study analyzed the FDA Adverse Event Reporting System (FAERS) from Q1 2004 through Q2 2025 to identify risk factors for drug-related impaired gastric emptying (IGE), a recognized contributor to perioperative pulmonary aspiration risk. Researchers identified 731 drugs associated with IGE reports. Among the most frequently reported were antidiabetic agents, particularly five GLP-1 receptor agonists (GLP-1RAs): semaglutide, dulaglutide, tirzepatide, exenatide, and liraglutide. The study employed disproportionality analysis, logistic regression, LASSO regression, and time-to-onset analysis to characterize these associations. Multi-factor analysis identified female sex and younger age as patient-level risk factors for drug-related IGE. Key limitations include the inherent biases of spontaneous adverse event reporting (underreporting, confounding by indication, lack of denominator data), the inability to establish causality, and incomplete clinical information in FAERS records. The authors suggest findings may help clinicians identify patients at elevated risk for drug-related IGE and inform perioperative fasting and anesthetic planning, particularly given the growing clinical use of GLP-1RAs.
Frontiers in pharmacology · 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 retrospective cohort study used the TriNetX Research Network — a large federated database — to examine whether GLP-1 receptor agonists (GLPs: semaglutide, tirzepatide, liraglutide, dulaglutide, exenatide, albiglutide, and lixisenatide) were associated with reduced postoperative inflammatory complications (IC) in patients undergoing dermatologic surgery. The study population included patients who underwent Mohs Micrographic Surgery or wide local excisions for melanoma or nonmelanoma skin cancer. Outcomes tracked over one month included wound disruption, hematoma, post-procedure infection, skin and subcutaneous tissue infection, and other procedural complications. After adjusting for demographics and proinflammatory comorbidities using hazard ratios and 95% confidence intervals, the study found that GLP use was associated with a statistically significant reduction in all measured IC categories compared with non-GLP users. Semaglutide and tirzepatide showed the largest individual reductions. Limitations include the retrospective, observational design — which cannot establish causation — along with potential residual confounding, database coding inaccuracies, and inability to control for medication adherence or surgical technique variability.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] · 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 scoping review examined the relationship between glucagon-like peptide-1 receptor agonists (GLP-1RAs) — a class of medications used for type 2 diabetes and weight management — and hair loss (alopecia). Researchers searched PubMed for relevant articles published through April 2026. The review found conflicting evidence overall: some data suggested an association between GLP-1RA use (particularly semaglutide and tirzepatide) and telogen effluvium (a stress-related, diffuse hair shedding) as well as androgenic alopecia, with risk potentially tied to longer treatment duration, greater magnitude of weight loss, and higher doses. Proposed biological mechanisms included weight loss-induced physiological stress, changes in dermal white adipose tissue, and hormonal shifts, though the authors note their relative contributions remain poorly understood. Conversely, a smaller subset of literature indicated possible improvement in inflammatory forms of alopecia, especially in patients with underlying metabolic dysfunction. Key limitations include the scoping design's reliance on heterogeneous existing literature, absence of original clinical trial data, and the difficulty of disentangling drug effects from weight-loss effects. The authors conclude that dermatology practitioners should be aware of this association and consider patient counseling and monitoring.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] · 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 ↗