With the surge in use of glucagon-like peptide 1-receptor agonists (GLP-1RAs) for weight management, "Ozempic Face," one of the dermatologic effects describing facial hollowing, sinking cheeks, and skin laxity, has drawn public attention. While substantial media discourse has surrounded certain dermatologic effects, patient-reported data is needed to more accurately characterize them. This study identifies patient-reported changes in skin, hair, and nails associated with weight management treatment with GLP-1RAs, including the frequency of dermatologic effects relative to weight loss. Our study was conducted through an IRB-approved, voluntary, anonymous survey developed via collaboration between obesity medicine physicians and dermatologists. The survey was then distributed to patients of a virtual cardio-kidney-metabolic treatment program. Responses (n = 1226) were sorted by the percent body weight lost and categorized by medication regimen (glucagon-like peptide 1-receptor agonists; GLP-1RA, nonGLP-1RA, or combination therapy). Patients reported dermatologic and overall physical changes. Dermatologic effects were reported more frequently with greater weight loss. Of respondents reporting greater than 20% body weight loss, (n = 325) 233 (72%; 95% CI 67-76) reported skin sagging, (n = 325) 170 (52%; 95% CI 47-58) reported hair loss, (n = 325) 163 (50%; 95% CI 45-55) reported decreased facial volume, and (n = 325) 107 (33%; 95% CI 28-38) reported reduced strength. Of respondents reporting 10-20% weight loss, (n = 395) 172 (44%; 95% CI 39-49) reported skin sagging, (n = 395) 119 (30%; 95% CI 26-35) reported hair loss, (n = 395) 147 (37%; 95% CI 33-42) reported decreased facial volume, and (n = 395) 76 (19%; 95% CI 16-23%) reported reduced strength. In comparison, of respondents reporting less than 10% weight loss, only (n = 380) 57 (15%; 95% CI 12-19) reported skin sagging, (n = 380) 65 (17%; 95% CI 13-21) reported hair loss, (n = 380) 48 (13%; 95% CI 10-16) reported decreased facial volume, and (n = 380) 35 (9%; 95% CI 7-13) reported reduced strength. The frequency of adverse patient-reported outcomes increased significantly with increasing percentage of body weight loss. Cochran-Armitage trend testing identified significant positive trends across the < 10%, 10-20%, and > 20% body weight loss categories for skin sagging (Z = 15.22), hair loss (Z = 9.91), decreased facial volume (Z = 10.70), and reduced strength (Z = 7.85), with P values of < 0.001. Among survey respondents on at least one GLP-1RA medication therapy, improvement was reported in certain preexisting inflammatory and hormonally driven skin conditions, including hidradenitis suppurativa (n = 15), 13 (87%; 95% CI 60-98); acanthosis nigricans (n = 12), 9 (75%; 95% CI 43-93); psoriasis (n = 47), 22 (47%; 95% CI 32-62); acne (n = 41), 17 (41%; 95% CI 27-57); eczema (n = 64), 17 (27%; 95% CI 17-39); hirsutism (n = 14), 4 (29%; 95% CI 10-56); seborrheic dermatitis (n = 16), 4 (25%; 95% CI 8-52); and skin tags (n = 57), 14 (25%; 95% CI 15-37). This large analysis of patient-reported outcomes suggests that greater weight loss, which often occurred with GLP-1RA treatment regimens versus other weight management therapies, was associated with higher reports of negative aesthetic impacts, most notably skin laxity, facial volume loss, and hair shedding, although with improvement in preexisting inflammatory and hormonally driven dermatological conditions. This calls for further studies to determine the potential mechanisms and incidence behind patient-reported outcomes associated with significant weight loss on GLP-1RA medications.
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Anti-obesity medications (AOMs), led by the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have produced substantial weight reduction and growing signals of benefit that extend well beyond adiposity. These agents are now discussed in relation to longevity and aesthetic medicine, raising the question of whether their effects reach ageing biology and appearance. This narrative review (PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, and Clinical trial registries; January 2010-June 2026) integrates mechanistic studies, randomised cardiovascular and renal outcome trials, ageing-biomarker analyses, body-composition data, and patient-facing aesthetic phenomena. The evidence indicates that AOMs reduce major cardiovascular events, slow kidney and liver disease progression, and lower all-cause mortality in selected populations; exploratory proteomic and epigenetic analyses further suggest effects partly independent of weight loss, though these do not establish slowed ageing. Newer multi-receptor agents act with greater metabolic specificity: glucagon-containing agents such as survodutide and the triple agonist retatrutide preferentially reduce visceral and hepatic fat (liver-fat reductions of roughly 60-80% in places), a quality of weight loss arguably more relevant to healthspan than its quantity. Concurrently, rapid large-magnitude weight loss drives soft-tissue and appearance changes colloquially termed "Ozempic face" and "Ozempic body", alongside accelerated skin laxity and loss of lean mass, the latter tempered by data showing lean-loss proportions comparable to established agents.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded beyond the treatment of type 2 diabetes mellitus (T2DM) and obesity, with increasing relevance to dermatologic practice as more patients present while receiving these therapies. This medication class now includes oral formulations including oral semaglutide and the first non-peptide oral GLP-1RA, orforglipron as well as next-generation triple agonists such as retatrutide, which demonstrated up to 24.2% body weight reduction in phase 2 trials and a favorable body composition profile, with preferential fat over lean mass loss. Although GLP-1 RAs provide substantial metabolic and weight reduction benefits, their growing use has introduced a broad spectrum of systemic and cutaneous adverse effects that dermatologists must recognize and monitor. This review summarizes the current evidence regarding the safety profile of GLP-1RAs with emphasis on dermatologic implications and interdisciplinary monitoring considerations. Common adverse effects include gastrointestinal (GI) intolerance, nutritional deficiencies, gallbladder disease, pancreatitis, and loss of lean body mass. Other rarer potential side effects include anemia, neuropsychiatric, and sexual health effects. Emerging data also suggest associations with ophthalmologic complications, skeletal fragility in older adults, and alterations in body composition that may influence cosmetic and procedural outcomes. Dermatologic adverse events include alopecia, eczematous and hypersensitivity eruptions, bullous and pustular dermatoses, acneiform eruptions, hyperhidrosis, and significant facial volume loss ("Ozempic face"). Current evidence regarding GLP-1RA use in pregnancy remains limited and evolving, with recommendations generally advising discontinuation prior to conception. Given the increasing overlap between metabolic disease management and dermatologic care, dermatologists should understand contraindications, screening strategies, nutritional monitoring, and counseling considerations associated with GLP-1RA therapy. A multidisciplinary approach involving primary care physicians, endocrinologists, ophthalmologists, dietitians, and dermatologists is essential to optimize patient safety while maintaining the substantial therapeutic benefits of these medications.
The first part of this two-part article discussed the physiology of glucagon-like peptide-1 (GLP-1), described the discovery and development of GLP-1 receptor agonists (RAs), examined the findings of major clinical trials and their substudies showing that GLP-1 RAs reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes and atherosclerotic cardiovascular disease, and finally, reviewed the evidence indicating that semaglutide protects against MACE in patients with obesity and established cardiovascular disease but not type 2 diabetes. This second part reviews recent clinical trials indicating that these drugs reduce symptom burden, increase exercise tolerance, and improve quality of life in patients with heart failure with preserved but not reduced ejection fraction. The article also discusses mechanisms by which GLP-1 RAs produce cardiovascular protection in patients with atherosclerotic cardiovascular disease or heart failure.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, are widely used for Type 2 diabetes mellitus (T2DM), obesity and related metabolic conditions. Evidence on potential neuropsychiatric effects remains inconsistent. This systematic review and meta-analysis evaluated depression risk among patients receiving semaglutide. Following PRISMA 2020 guidelines, major biomedical databases, trial registries, pharmacovigilance databases, conference abstracts and grey literature were searched from inception to January 2026. Eligible studies included randomised controlled trials, observational studies, large database analyses and pharmacovigilance disproportionality studies involving patients receiving semaglutide. Risk of bias was assessed using ROBINS-I and the Newcastle-Ottawa Scale. The pooled risk ratio for depression was 1.25 (95% CI: 0.95-1.65; I2 = 98%). For anxiety and suicidal ideation/attempt, pooled risk ratios were 1.22 (95% CI: 0.93-1.60; I2 = 99%) and 1.20 (95% CI: 0.90-1.62; I2 = 92%), respectively. No statistically significant differences were observed between semaglutide and comparator/placebo groups for outcomes. Pooled estimates did not show a statistically significant increase in depression, anxiety or suicidal ideation/attempt among patients receiving semaglutide compared with comparator groups. However, the certainty of evidence was limited by substantial heterogeneity, risk of bias and reliance on heterogeneous data sources, including spontaneous-reporting studies. These findings are reassuring but should be interpreted as the absence of a detected increased risk in the available evidence, rather than definitive proof of no psychiatric risk.
Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver. It is highly prevalent, particularly among individuals with overweight or obesity, and substantially impairs health-related quality of life. Semaglutide 2.4 mg received accelerated approval from the US Food and Drug Administration in August 2025 for adults with noncirrhotic MASH and fibrosis stages F2-F3 based on results from the ESSENCE trial. This study aimed to estimate the impact of semaglutide on health utility in this population. This exploratory analysis used Week 72 data from ESSENCE Part 1, a phase 3, randomized, double-blind, placebo-controlled trial. Adults with biopsy-confirmed MASH and fibrosis stage F2 or F3 were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo plus standard of care. EuroQol 5-‍Dimension (EQ-5D) utilities were mapped from Short Form-36 (SF-36) scores using the Rowen et al. (2009) algorithm. Change from baseline was analyzed with treatment, baseline diabetes status, fibrosis stages as covariates. A total of 800 participants were included in this analysis (semaglutide 2.4 mg n=534; placebo n=266). Mean age was 56.0 years; 57.1% were female; mean body mass index was 34.6 kg/m2 and 55.9% had type 2 diabetes. Baseline mapped EQ-5D utility was approximately 0.78 in both groups. At Week 72, semaglutide significantly improved mapped EQ-5D utility versus placebo (estimated treatment difference 0.03; 95% confidence interval [CI]: 0.01, 0.06; nominal p=0.0015), with consistent effects across fibrosis stages. In adults with MASH and F2 or F3 fibrosis, once-weekly semaglutide 2.4 mg was associated with statistically significant improvements in mapped EQ-5D health utility versus placebo. These exploratory findings provide utility estimates that may help to inform cost-effectiveness evaluations and health technology assessments. This study provides the first estimation of EuroQol 5-Dimension (EQ-5D) health utility gains associated with once-weekly semaglutide 2.4 mg in people with metabolic dysfunction-associated steatohepatitis (MASH) and F2/F3 fibrosis. The findings are important for payers and clinicians because they demonstrate a statistically significant improvement in mapped EQ-5D health utility with semaglutide 2.4 mg over 72 weeks. These results can directly inform cost-effectiveness models and support healthcare decision-making by quantifying the health-related quality of life benefits of semaglutide using a widely accepted preference-based metric. Given the use of mapped rather than directly measured utilities and the UK-specific tariff, the results should be interpreted with appropriate caution.
Semaglutide has shown significant efficacy in several clinical trials for the treatment of obesity. However, real-world data on early weight loss and metabolic response in obesity without diabetes cohort are still limited, particularly with respect to individual patient factors. This study aims to evaluate the real-world effectiveness of semaglutide on anthropometric and metabolic parameters in an obesity cohort, including weight loss (kg and percent) and the percentage of participants achieving the 5%, 10% and 15% weight loss targets at mean 3-month, 6-month and 12-month follow-up. In addition, an assessment of safety and reasons for discontinuation, and sub-analyses of anthropometric outcomes by prior liraglutide exposure, sex, and BMI categories will be included. In this retrospective study, data were collected from adults with overweight/obesity without diabetes treated with weekly subcutaneous semaglutide for at least 3 months and analyzed at 2-4 (T1), 5-8 (T2), and 9-15 (T3) months of follow-up. Among 248 patients (55.0 years, 34.8 kg/m2, 77.5% female), only 10.4% and 5.7%, respectively, discontinued due to non-severe gastrointestinal adverse events or cost. Significant weight loss (WL), %WL goal attainment, and improvements in adiposity and metabolic outcomes, including hepatic steatosis, fibrosis, and visceral adiposity indices, were observed at all follow-up visits. Early metabolic improvements occurred regardless of %WL≥5 target. Reduced early anthropometric response in switchers (24%) vs. naive subjects with similar one-year outcomes and no significant differences by sex or baseline BMI category were observed. These results confirm semaglutide's effectiveness on cardiometabolic risk in real-world obesity management, with a safety profile and early metabolic effects independent of weight loss. The reduced early response in switchers and at low doses highlights the importance of dose optimization to prevent suboptimal initial outcomes after switching. The lack of differences by sex and BMI category supports further studies stratifying patients by age and metabolic risk rather than BMI alone. Low persistence highlights the need for structured, patient-centered support to improve adherence and a better understanding of the drivers of discontinuation.
Obesity is highly prevalent among patients with chronic musculoskeletal pain and is associated with low back pain, knee osteoarthritis, reduced mobility, and poorer functional outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists and related therapies have transformed obesity medicine and may become more relevant to pain medicine specialists. This narrative review examines whether GLP-1-based medications should be considered within pain practice, particularly for obesity-associated low back pain and knee osteoarthritis. Chronic pain impacts a substantial portion of adults, while low back pain and osteoarthritis remain leading causes of disability worldwide. Obesity is associated with low back pain and knee osteoarthritis, and weight reduction has been shown to improve pain and function in these conditions. GLP-1-based therapies can produce clinically meaningful weight loss in patients with obesity and chronic pain. Literature also suggests possible anti-inflammatory and chondroprotective effects relevant to pain. GLP-1-based medications should not be viewed as primary analgesics or replacements for standard pain evaluation, rehabilitation, pharmacologic care, or interventional treatment. However, they are reasonable to consider as part of comprehensive pain management in patients with obesity when excess weight plausibly contributes to chronic pain, impaired mobility, or reduced rehabilitation tolerance. Pain physicians familiar and comfortable with obesity pharmacotherapy may consider prescribing within appropriate indications and safety parameters. Alternatively, referral to obesity medicine, endocrinology, primary care, or another experienced clinician is appropriate.
IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity by improving glycemic control, promoting weight loss, and reducing cardiovascular risk. This study aimed to evaluate national trends in GLP-1 RA utilization and expenditure in Croatia between 2010 and 2024.MethodsWe conducted a nationwide, retrospective analysis using the International Medical Statistics and IQVIA pharmaceutical databases. Utilization was measured in defined daily doses per 1000 inhabitants per day, and financial expenditure was expressed in euros. Trends were contextualized within evolving clinical evidence, guideline recommendations, and healthcare reimbursement policies.ResultsTotal noninsulin antidiabetic drug consumption more than doubled between 2010 and 2024, with the use of GLP-1 RAs rising from negligible at the time of market entry to that worth 15.99 defined daily doses per 1000 inhabitants per day in 2024, representing 16.1% of total prescriptions. Expenditure on GLP-1 RAs reached 42.07 million euros in 2024, accounting for 42.7% of total noninsulin antidiabetic spending. Semaglutide emerged as the dominant agent according to both utilization and cost, followed by dulaglutide and liraglutide. Obesity-specific indications were underutilized, largely due to lack of reimbursement.ConclusionsGLP-1 RA prescribing has increased substantially in Croatia over the past decade, reflecting their growing therapeutic importance. However, economic constraints, restrictive reimbursement, and sociocultural barriers continue to limit access, particularly in obesity care. Our findings highlight the need to align reimbursement frameworks and clinical practice with emerging evidence to maximize the cardiometabolic and public health benefits of GLP-1 RAs.
Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly encountered in pain practice, but reported pain improvement may reflect direct antinociception, weight loss, metabolic change, or disease-specific effects. This structured narrative review examined these possibilities and relevant safety issues. Methods: PubMed/MEDLINE, Embase, and Web of Science Core Collection were searched through 15 May 2026. Peer-reviewed human studies, key mechanistic preclinical studies, systematic reviews and meta-analyses, and professional guidance relevant to pain outcomes or procedural safety were considered. Metabolic-only and non-peer-reviewed reports were excluded, and human pain-primary evidence was prioritized. Results: Preclinical data support plausible mechanisms involving spinal microglia, interleukin-10, beta-endorphin, neuroinflammation, and sensory-neuron signaling, but direct analgesic efficacy at systemic clinical doses has not been demonstrated. In STEP 9 (n = 407), mean WOMAC pain scores at 68 weeks changed from baseline by -41.7 points with semaglutide 2.4 mg and -27.5 points with a placebo; body weight changed by -13.7% and -3.2%, respectively. Liraglutide produced additional weight loss without superior knee-pain reduction. Diabetic peripheral neuropathy evidence was mainly structural or neurophysiologic; idiopathic intracranial hypertension and ROSE-010-treated irritable bowel syndrome showed disease-specific signals, whereas fibromyalgia- and opioid-related findings remained observational or hypothesis-generating. Gastrointestinal dysmotility, reduced intake, and lean-mass loss may offset functional benefits. Conclusions: GLP-1RAs are not established analgesics. Current human signals are best interpreted as indirect metabolic-functional or disease-specific effects. Future trials should use validated pain-primary outcomes, control for weight loss, and monitor treatment-related harms.
Metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) are highly prevalent conditions and represent a major public health problem. To conduct an updated systematic review of randomized controlled trials evaluating the impact of semaglutide on hepatic outcomes in patients with MAFLD/MASH. A systematic literature search was performed in accordance with PRISMA guidelines. Randomized, placebo-controlled clinical trials assessing the effect of semaglutide on hepatic outcomes in patients with MAFLD/MASH were included, using histological parameters and/or imaging methods. The analyzed studies suggest a benefit of semaglutide compared with placebo in hepatic outcomes. Regarding the outcome of MASH resolution without worsening of fibrosis, consistent results were observed among studies that included liver biopsy. However, when evaluating fibrosis improvement without worsening of MASH, the results were heterogeneous. Imaging studies demonstrated a consistent benefit of semaglutide on hepatic steatosis. Nevertheless, no significant changes in liver stiffness were demonstrated. Differences in sample size, follow-up duration, and analyzed populations may explain these discrepancies. The use of semaglutide in patients with MAFLD/MASH was associated with improvements in variables related to hepatic steatosis and, to a lesser extent, with changes in fibrosis markers. These findings should be confirmed in larger studies with longer follow-up periods. . La enfermedad hepática grasa asociada a disfunción metabólica (MAFLD) y la esteatohepatitis asociada a disfunción metabólica (MASH) presentan una elevada prevalencia y constituyen un importante problema de salud pública. . Realizar una revisión sistemática actualizada de ensayos clínicos aleatorizados que evaluaron el impacto de la semaglutida en los desenlaces hepáticos en pacientes con MAFLD/MASH. . Se efectuó una búsqueda sistemática en la literatura de acuerdo con las guías PRISMA. Se incluyeron ensayos clínicos aleatorizados, controlados con placebo, que evaluaron el efecto de la semaglutida sobre desenlaces hepáticos en pacientes con MAFLD/MASH, utilizando parámetros histológicos y/o métodos de diagnóstico por imágenes. . Los estudios analizados sugieren un beneficio de la semaglutida frente al placebo en los desenlaces hepáticos. En cuanto al evento resolución de la MASH sin empeoramiento de la fibrosis, observamos concordancia entre los estudios que incluyeron biopsia hepática. Al evaluar la mejoría de la fibrosis sin empeoramiento de la MASH, los resultados no fueron uniformes. Los estudios que evaluaron imágenes mostraron un beneficio consistente de la semaglutida sobre la esteatosis hepática. Sin embargo, los estudios no lograron demostrar cambios significativos en la rigidez hepática. Diferencias en el tamaño muestral, el tiempo de seguimiento y las poblaciones analizadas podrían explicar estas discrepancias. . El uso de semaglutida en pacientes con MAFLD/MASH se asoció con mejoras en variables relacionadas con la esteatosis y, en menor medida, con cambios en marcadores de fibrosis. Estos hallazgos deberán confirmarse en estudios de mayor envergadura y con mayores tiempos de seguimiento.
Metabolic dysfunction-associated steatohepatitis (MASH), formerly nonalcoholic steatohepatitis (NASH), is a progressive liver disease and a leading cause of cirrhosis and liver-related mortality worldwide, affecting approximately 3%-5% of the global adult population and up to 30%-40% of individuals with type 2 diabetes mellitus (T2DM) or those attending dedicated diabetes and endocrine centers. For decades, treatment was limited to lifestyle interventions. The years 2024 and 2025 marked a paradigm shift with the first-ever FDA approvals of pharmacologic agents for MASH. This comprehensive narrative review synthesizes the evidence for newly approved and emerging pharmacotherapies for MASH, addressing the mechanisms of action, pivotal clinical trial data, efficacy, safety profiles, and place in therapy for resmetirom and semaglutide. It also discusses key agents including pioglitazone, saroglitazar, and vitamin E, and evaluates the non-invasive testing (NIT) toolkit-including FIB-4, VCTE, shear wave elastography, MRE, and ELF-in the context of a structured, risk-stratified clinical algorithm. Resmetirom (Rezdiffra), a THR-β agonist, achieved MASH resolution in 26%-30% versus 10% placebo and fibrosis improvement in 24%-26% versus 14% placebo at 52 weeks in the MAESTRO-NASH trial. Semaglutide 2.4 mg (Wegovy) demonstrated a 28.7% delta over placebo in MASH resolution in the ESSENCE trial. Pioglitazone has additional evidence for reducing the FIB-4 index in real-world studies. Saroglitazar, a PPAR-α/γ dual agonist approved in India, has shown significant reductions in ALT, liver fat, and metabolic parameters in Phase 2 studies and is advancing to Phase 2b. Shear wave elastography is a clinically important alternative to VCTE for fibrosis staging, particularly in patients with obesity, and offers value in resolving discordant FIB-4/VCTE results. The approval of resmetirom and semaglutide marks a new era in MASH management. A risk-stratified algorithmic approach using NITs guides patient selection, with liver biopsy reserved for specific clinical scenarios. The therapeutic landscape is rapidly evolving, with saroglitazar and combination approaches representing key frontiers.
Given the unprecedented rise in glucagon-like peptide-1 receptor analogue (GLP-1RA) therapy over the past decade, we aimed to investigate potential unintended laryngeal manifestations. A retrospective cohort study was conducted using the TriNetX United States Collaborative Network. Adults with obesity on GLP-1RA medications (n = 617,296) from January 1, 2016 to December 3, 2025, were compared with controls (n = 3,503,102), excluding patients with head and neck neoplasms, head and neck radiation therapy, autoimmune diseases, airway disorders or acute respiratory conditions via ICD-10 and CPT codes. Laryngeal symptoms within 1, 3, and 6 months of initiation of GLP-1RA were assessed in propensity score-matched cohorts by age, sex, race, and ethnicity. Outcomes were reported as risk differences (RD) and odds ratios (OR) with 95% confidence intervals (CI). GLP-1RA therapy increased the 6-month risk of any laryngeal manifestations (OR 1.19, 95% CI 1.16-1.21; p < 0.0001). Higher odds were observed for cough (OR 1.46, p < 0.0001), foreign body sensation (OR 1.1.41, p < 0.001), and voice and resonance disorders (OR 1.19, p = 0.002). Across agents, exenatide, liraglutide, semaglutide, dulaglutide, and lixisenatide showed significant elevated 6-month risk of laryngeal manifestations (OR 1.16-1.91-1.48; p < 0.05), while albiglutide and tirzepatide did not. GLP-1RA/GIP use in adults is linked to higher rates of laryngeal symptoms, most notably cough and voice and resonance disorders. While absolute risk differences were small, the large number of affected individuals underscores the potential clinical and public health relevance of these findings, in the context of the rapidly growing prevalence of GLP-1RA/GIP use.
Real-world glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies face substantial attrition rates in commercial digital weight loss services (DWLSs). Conversational artificial intelligence (AI) has been proposed to enhance patient support at production scale, but robust evidence of its effectiveness in improving medication retention is scarce. To evaluate the effect of integrating an asynchronous AI patient support agent (Junebot) into a commercial DWLS on 6-month medication adherence and to assess the independent relationship of digital engagement on retention. This retrospective analysis evaluated 16 556 adults prescribed semaglutide within an Australian DWLS between May 2024 and October 2025. The primary endpoint was 6-month medication adherence (≥ 6 orders fulfilled within 183 days). Analytical protocols featured a multivariate binary logistic regression on the full intention-to-treat cohort and three distinct 1:1 propensity score matching (PSM) sensitivity analyses to isolate era-based and tier-specific engagement effects. Six-month adherence was higher post-Junebot than in the pre-Junebot control (53.2% vs. 47.3%; p < 0.001). However, the full cohort model (R2 = 0.2236) revealed that the post-Junebot operational era was independently associated with an increase in the odds of attrition (OR: 1.178; 95% CI [1.052-1.318]; p = 0.004), a trend corroborated by the era-matched PSM model (OR of attrition: 1.309; p = 0.038). Non-automation factors dominated retention trajectories: high-intensity tracking during month 1 (> 25 tracks) dramatically predicted attrition (OR: 15.753; p < 0.001), alongside program pauses (OR: 2.508; p < 0.001) and higher program cost (OR: 2.458; p < 0.001). Within-cohort analysis demonstrated a profound, linear curve for active interaction; structured digital engagement spanning 50%-74.99% of weeks significantly optimised adherence odds across both medication-only (OR: 32.016) and medication plus health coaching cohorts (OR: 13.311). Integrating an AI digital assistant did not independently improve medication adherence; programmatic costs, program pauses and initial tracking anxiety were stronger predictors of long-term retention. After matching post-Junebot cohorts, moderate, active digital engagement appeared to correlate with 6-month retention. Digital providers should prioritise proactive behavioural risk screening and financial accessibility over baseline AI integration.
Oral GLP-1 receptor agonists (GLP-1 RAs) offer a non-injectable option for weight management in adults with overweight/obesity without diabetes. This network meta-analysis (NMA) evaluated their effects on body weight. A frequentist random-effects NMA of RCTs comparing oral GLP-1 RAs with placebo in adults without diabetes was conducted by searching databases through 30 April 2026. The primary outcome was percent change in body weight, with secondary outcomes including other weight measures and weight thresholds. Analyses used R (netmeta), and certainty was assessed with CINeMA. Nine RCTs (N = 5766; 20-72 weeks) evaluating oral semaglutide, orforglipron, danuglipron, and lotiglipron were included. All agents except low-dose (LoD) lotiglipron outperformed placebo in percent body weight reduction; high-dose (HiD) semaglutide (MD -11.6%) and orforglipron (MD -11.8%) showed the greatest effects. Orforglipron HiD produced the greatest absolute weight loss (MD -12.2 kg), whereas semaglutide HiD reduced BMI (MD -4.7 kg/m2) and waist circumference (MD -10.0 cm) the most. Danuglipron HiD, semaglutide HiD, and semaglutide LoD ranked highest for ≥ 5%, ≥ 10%, and ≥ 15% weight loss, respectively. Evidence certainty was low to moderate. HiD oral semaglutide and orforglipron demonstrated the most consistent and substantial weight reductions though low-to-moderate certainty and lack of head-to-head comparisons constrain comparative inference.
Semaglutide 2·4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2·4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66·5%) of 242 participants were randomly assigned to semaglutide 2·4 mg and 81 (33·5%) to placebo; 121 (50·0%) participants were female, and 47 (19·4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12·1% [SE 0·6] vs -2·2% [0·8]; estimated treatment difference -9·9 percentage points [95% CI -11·8 to -8·0]; p<0·0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80·5% vs 24·4%; odds ratio [OR] 14·8 [95% CI 7·4 to 29·6]; p<0·0001). Adverse events were reported in 141 (87·6%) of 161 participants in the semaglutide 2·4 mg group and 61 (75·3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. Semaglutide 2·4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. Novo Nordisk A/S. For the Mandarin translation of the abstract see Supplementary Materials section.
Diabetic nephropathy (DN) is a clinical condition characterized by progressive decline in kidney function, with persistent albuminuria. DN pathophysiology involves chronic hyperglycaemia, oxidative stress, glomerulosclerosis, interstitial fibrosis and apoptosis. Semaglutide (S) and acarbose (A), antidiabetic drugs with different mechanisms, were explored in this study in a combination regimen to treat experimentally-streptozotocin (STZ)-induced DN in a rat model. Fifty-six male rats were divided into 7-groups. Except for the non-diabetic negative control rats (group-I), all other groups had DN induced by an I·P injection of STZ. In group-II & III, STZ-diabetic rats did not receive any medication. Diabetic rats in group-IV (DN/S) and group-V (DN/A), administered semaglutide (30 nmol/kg/week/S.C), and acarbose (50 mg/kg/day/orally), respectively, for 4-weeks. Group-VI [DN/S/A(HD)], administrated both drugs. In group-VII [DN/S/A(LD)], diabetic rats administrated semaglutide (20 nmol/kg/week/S·C) and acarbose (30 mg/kg/day/orally) for 4-weeks. Serum glucose, creatinine/KIM-1 levels and albuminuria were measured. Renal; Nrf-2/HO-1 immunoreactivities, NF-κB/TNF-α/IL-10 levels, TGF-β1/Smad 2/3, and cl-caspase-3/Bax/Bcl-2 expressions were assessed. Compared to solo treatment of either drug, semaglutide/acarbose combination (in high and low doses) regenerated the histopathological features and restored kidney functions through stimulation of Nrf-2/HO-1, attenuation of inflammatory signals via modulation of NF-κB/TNF-α/IL-10 levels. Fibrosis and apoptosis were mitigated by suppression of the TGF-β1/Smad and overall reduction in Bax/Bcl-2 ratio, respectively. The combination of semaglutide/acarbose is more effective than the solo treatment with either drug, even upon using lower doses in the combination, suggesting a synergistic effect. The study unveiled a potential therapeutic regimen for DN, that was not evaluated before.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and related incretin therapies have moved rapidly from second-line diabetes agents to widely prescribed cardiometabolic medications, and dermatologists increasingly encounter patients who are already taking them. Obesity is common among dermatology patients and is particularly prevalent in psoriasis and hidradenitis suppurativa, yet most eligible patients are not receiving GLP-1 RA therapy, and nearly all prescriptions originate outside dermatology. This positions dermatologists at the intersection of two distinct clinical questions: how to manage the cutaneous consequences of therapy in patients already receiving these agents, and when to raise the possibility of treatment in patients who may benefit. This narrative review examines patient selection, including the metabolic and inflammatory phenotypes most likely to see dermatologic benefit, and the practical demands of therapy that influence whether treatment succeeds. It reviews the dermatology-relevant adverse effects that patients most often notice, including facial volume loss, hair shedding, and gastrointestinal intolerance, along with a monitoring approach suited to the dermatology visit. Throughout, it argues that shared decision-making offers a useful framework for an area where the evidence is still evolving and where treatment can reshape how patients look and feel.
Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly recognized as a disorder of inter-organelle communication, in which the lipid droplet (LD)-mitochondria interface serves as a central metabolic hub. Under physiological conditions, this interface couples LD lipolysis to mitochondrial β-oxidation, ensuring that fatty-acid release matches energy demand. In MASH, chronic nutrient excess disrupts this coupling, driving the accumulation of lipotoxic metabolites, activating innate immune pathways, and perpetuating hepatocellular injury and inflammation. Among the proteins proposed to operate at this LD-mitochondria interface, hydroxysteroid 17β-dehydrogenase 13 (HSD17B13) has emerged as a particularly compelling candidate. A loss-of-function human genetic variant is associated with reduced risk of chronic liver disease, motivating therapeutic development; however, whether HSD17B13 directly governs physical organelle apposition or merely influences lipid flux remains unresolved, highlighting a key gap between human genetic evidence and experimental models. This review synthesizes current understanding of the molecular organization of the LD-mitochondria axis, critically examines the proposed scaffolding and enzymatic functions of HSD17B13, and discusses the therapeutic potential of restoring organelle communication as a unified strategy in MASH. We conclude that targeting inter-organelle interfaces, rather than isolated metabolic reactions, offers a genetically supported and mechanistically rational path forward.