Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed metabolic care but are increasingly associated with rapid, region-specific facial volume loss, commonly referred to as "Ozempic face." Current literature remains descriptive and largely focused on late-stage correction. To propose a conceptual, anatomy-driven framework for early identification and prevention of GLP-1 RAs-associated facial aging. This manuscript presents a hypothesis-generating model developed through integration of facial aging biomechanics, emerging literature on GLP-1 RAs-associated changes, and clinical pattern recognition. We introduce a risk-stratification model based on anatomical phenotype and a four-phase conceptual prevention algorithm aligned with weight-loss kinetics. The framework incorporates early intervention strategies, clinical "off-ramps," and patient-specific modifiers to guide anticipatory management. This conceptual model proposes a shift from reactive correction to preventive, anatomy-based management of GLP-1 RAs-associated facial changes. Future studies are needed to validate and refine this framework. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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To assess the efficacy and safety of weekly injectable semaglutide in obese type 2 diabetes mellitus patients. The retrospective, cross-sectional study was conducted at the Endocrinology Department, Shifa International Hospital, Islamabad, Pakistan, and comprised data from January 1, 2021, to January 31, 2023, of adult type 2 diabetes mellitus patients of either gender who had been prescribed weekly injectable semaglutide. Efficacy assessment was based on measuring the changes in glycated haemoglobin, bodyweight and body mass index at 3, 6, 9 and 12 months. The incidence of adverse events was also noted. Data was analysed using SPSS 26. Of the 102 patients, 57(56%) were females and 45(44%) were males. Overall mean age was 50±11.17 years, and the mean diabetes duration was 8.13±6.67 years. Mean values for glycated haemoglobin, bodyweight and body mass index were significantly different at 3, 6, 9 and 12 months post-intervention compared to baseline. Nausea was reported by 26(25.5%) patients. The most common reason for stopping semaglutide was no further benefits in 37(47%). Injectable semaglutide was found to be quite effective in managing type 2 diabetes mellitus. The treatment was well tolerated, establishing semaglutide as a valuable addition to diabetes care in Pakistan.
Co-occurring opioid and alcohol use disorders (OUD + AUD) are associated with morbidity, yet medications for these disorders remain underused. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RA), prescribed for metabolic disease, may influence substance-related outcomes. This study aims to estimate associations between GIP/GLP-1 RA prescriptions, first-line AUD and OUD medications and several adverse healthcare outcomes among those with co-occurring OUD + AUD. We conducted a retrospective cohort study using de-identified electronic health records from Oracle Health Real-World Data (149 U.S. health systems; 2014-2024). Among 107,217 patients aged ≥12 years with dual OUD + AUD diagnoses, time-varying exposures included medications for OUD (MOUD), medications for AUD (MAUD), and GIP/GLP-1 RA prescriptions. Outcomes over 2 years included overdoses and intoxications, SUD-related hospitalizations, detoxification, positive drug screens, mental health events, incident liver conditions, and liver biomarkers. Marginal structural survival models with stabilized inverse probability of treatment weighting estimated adjusted hazard ratios (aHRs) overall and stratified by MOUD/MAUD status, type 2 diabetes (T2DM), and obesity. GIP/GLP-1 RA prescriptions are associated with lower risk of all-drug overdose among patients not receiving MOUD/MAUD (aHR 0.61; 95% CI 0.32-0.98). In stratified analyses, lower overdose risk is observed among patients with T2DM receiving MAUD only (aHR 0.15; 95% CI 0.01-0.41) and among those receiving both MOUD and MAUD (T2DM: aHR 0.46; 95% CI 0.24-0.87; obesity: aHR 0.19; 95% CI 0.04-0.97). Protective associations for SUD-related hospitalization are observed across most strata. In this large EHR cohort, GIP/GLP-1 RA prescriptions are linked to reduced overdose and hospitalization risk among patients with co-occurring OUD + AUD. Findings are exploratory and limited by small subgroup sizes; prospective studies are needed to confirm benefit and evaluate safety. Individuals with opioid and alcohol use disorders rarely receive the medications they need to treat their substance use symptoms. Recent research shows diabetic/obesity medications such as Ozempic and Wegovy may impact substance use outcomes. Among patients with co-occurring opioid and alcohol use disorders, this project used past medical records to calculate the associations between Ozempic and other similar medications and drug overdose, hospitalization, and other related outcomes. We found that patients prescribed diabetic/obesity medications displayed reduced overdose and hospitalization risk. If future research can confirm and extend our findings, certain diabetes/obesity medications may be considered as alternative treatment options for individuals with problematic substance use.
In adults with optic disc drusen and type-2-diabetes or obesity, glucagon-like peptide-1 receptor agonists exposure was not associated with increased nonarteritic anterior ischemic optic neuropathy hazard, though moderate risk increases could not be excluded statistically.
The American College of Physicians (ACP) developed this clinical guideline for internal medicine physicians and other clinicians caring in outpatient settings for adults with overweight or obesity. This guideline is based on systematic reviews of pharmacologic treatments in adults with overweight or obesity and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. ACP suggests initiating one of the following pharmacologic treatments with lifestyle modifications for weight management in nonpregnant adults with obesity (body mass index ≥30 kg/m2) in outpatient settings (conditional recommendation): First-line treatments are semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line treatment is phentermine-topiramate (low-certainty evidence); third-line treatment is liraglutide (low-certainty evidence); fourth-line treatment is naltrexone-bupropion (low-certainty evidence). When initiating a recommended medication for weight management or switching to another recommended medication because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (for example, the requirement for monthly pregnancy tests with use of phentermine-topiramate, the contraindication to phentermine-topiramate in those with cardiovascular disease, and suicidal ideation with naltrexone-bupropion). ACP suggests initiating one of the following pharmacologic treatments with lifestyle modifications for weight management in nonpregnant adults with overweight (body mass index ≥27 to 30 kg/m2) and type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease (conditional recommendation): First-line treatments are semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line treatment is liraglutide (low-certainty evidence). When initiating a recommended medication for weight management or switching to another recommended medication because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (for example, use in pregnancy).
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular (CV) benefits, but their effects across the heart failure (HF) spectrum remain uncertain. We synthesized randomized evidence comparing GLP-1 RAs with placebo in adults with HF across ejection fraction phenotypes by searching PubMed, Cochrane CENTRAL, and ClinicalTrials.gov through February 2026. The primary outcome was the composite of CV death and first HF hospitalization, and random-effects meta-analysis used restricted maximum likelihood (REML) estimation with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment. We included 14 studies (six dedicated HF trials and eight cardiovascular outcomes trials (CVOT) HF subgroup analyses) encompassing 18,184 patients. The primary composite outcome was not statistically significant (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.01; P=0.067; I²=47%). GLP-1 RAs reduced all-cause mortality (ACM; HR 0.86, 95% CI 0.79-0.95; P=0.008; low certainty according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE)) and major adverse CV events (MACE; HR 0.80, 95% CI 0.69-0.93), and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) by 7.4 points and 6-minute walk distance (6MWD) by 17.6 m. However, the mortality benefit was driven by CVOT subgroups, whereas dedicated HF trials showed directional harm. GLP-1 RAs did not significantly reduce the primary composite outcome but improved quality of life and functional capacity in heart failure with preserved ejection fraction (HFpEF) and obesity. The pooled mortality reduction should be interpreted cautiously, given the divergence between indirect and direct evidence.
To evaluate 24-week weight changes with lower-dose semaglutide in routine care among Chinese adults with obesity and to examine whether diabetes and ectopic fat in the liver and pancreas are associated with heterogeneity in weight-loss response. Adults with obesity were enrolled from the HARMONY study, a real-world observational cohort in China. Participants received once-weekly subcutaneous semaglutide, titrated to a maintenance dose (0.5 or 1.0 mg) based on clinical response and tolerability, alongside lifestyle counselling and periodic metabolic monitoring. The primary endpoint was the percentage change in body weight from baseline at weeks 12 and 24. Subgroup analyses were conducted according to baseline type 2 diabetes status and ectopic fat status in the liver and pancreas. Overall, 143 participants were included at week 12 and 113 at week 24. Mean percent weight change was -7.3% at week 12 and -9.9% at week 24, corresponding to mean absolute weight losses of 6.7 and 9.1 kg, respectively. By week 24, 76.1% of participants achieved 5% weight loss or more. At week 24, participants with type 2 diabetes experienced lower weight change than those without diabetes (-7.4% vs. -12.4%, p < 0.001). Weight loss also differed by baseline intrapancreatic fat deposition (IPFD) status, with attenuated weight change among patients with baseline IPFD (-9.0% with IPFD vs. -11.6% without IPFD, p = 0.043). In routine clinical care, lower doses of semaglutide were associated with clinically meaningful 24-week weight loss in Chinese adults with obesity.
Epigenetic aging clocks estimate age from DNA methylation patterns and have become central tools in longevity research. More recently, next-generation clocks have been developed to better compensate for the known divergence between chronological age and epigenetic age in ways that relate to lifestyle, health, and age-related disease. Although epigenetic clocks represent investigational biomarkers, these newer models are more strongly associated with all-cause mortality risk than first-generation clocks. As such, interventions that modify them are of interest. To test this, we performed a series of systematic searches and identified 41 human studies reporting the effects of interventions on at least one next-generation epigenetic clock. Our data suggest that a diverse range of pharmaceutical, lifestyle, supplementation, non-pharmaceutical clinical, and psychosocial interventions can decrease epigenetic age, including exercise, a plant-rich diet, the GLP-1 receptor agonist semaglutide, caloric restriction, ketamine, omega-3 fatty acids, a multivitamin-multimineral supplement, umbilical cord plasma, and the cholesterol-lowering drug pitavastatin. Nicotinamide riboside, rapamycin, senolytics, and several other interventions showed no detectable effect, whereas plasmapheresis and other therapeutics accelerated epigenetic aging. We also summarize reported effect sizes and compare next-generation clocks with respect to their frequency of use and responsiveness to intervention.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for obesity management; however, adverse events (AEs) remain a clinical concern. This study presents a computational pharmacovigilance framework integrating real-world safety data with graph-based modeling to characterize AE patterns associated with GLP-1 RA therapy and to explore herb-AE associations in an exploratory manner. We conducted a cross-sectional analysis of AE reports from the food and drug administration adverse event reporting system (2015-2025). Clinical characteristics included outcomes, reporting frequency, demographics, time-to-onset, and subgroup distributions. Signal detection employed disproportionality metrics and Bayesian approaches. Herb-compound-target-AE networks were constructed using HERB 2.0 and the Comparative Toxicogenomics Database, incorporating drug-likeness and pharmacokinetic filtering. Graph convolutional networks were applied to model herb-AE associations, followed by literature-based contextual evaluation. Among 142,705 GLP-1 RA AE reports, 4,090 involved obesity indications. Gastrointestinal events predominated, with 76% of reports involving female patients and onset clustering within 0-30 days. Semaglutide demonstrated a distinct onset distribution, including a higher proportion of late-onset cases (≥ 360 days). Strong signals were detected for biliary, pancreatic, renal, and coagulation events, with semaglutide-associated pairs showing reporting odds ratios > 10, whereas tirzepatide exhibited negative log-transformed reporting odds ratios for several gastrointestinal events. Network analysis and graph convolutional network modeling prioritized established medicinal herbs including Liquorice Root, Mulberry Leaf, Dahurian Angelica Root, Danshen Root, and Ginkgo Leaf as top candidates following degree debiasing and exclusion of non-herbal database entries. The graph convolutional network achieved area under the receiver operating characteristic curve/area under the precision-recall curve values of 0.798/0.841 (validation) and 0.666/0.719 (test), indicating moderate predictive performance within a sparse pharmacovigilance context. These findings describe real-world AE reporting patterns associated with GLP-1 receptor agonists and present a hypothesis-generating computational framework for prioritizing herb-AE signal associations. The results are exploratory and should be interpreted in light of the inherent limitations of spontaneous reporting systems and computational modeling frameworks, and require independent experimental and clinical validation prior to any clinical application.
While glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide are effective in treating obesity, up to 45% of the resulting weight loss can be attributed to skeletal muscle loss. Given the critical role of skeletal muscle in health and mobility, this may have long-term adverse consequences. Herein we investigated whether oral ketone ester supplementation could prevent semaglutide-induced muscle loss and explored the underlying molecular mechanisms. Obese, glucose-intolerant mice received vehicle, semaglutide, or semaglutide plus a β-hydroxybutyrate-generating ketone ester for three weeks. Body composition, muscle strength, and endurance were assessed longitudinally. Semaglutide monotherapy reduced lean mass, impaired muscle strength, and suppressed mitochondrial gene expression while elevating atrophy-related genes in skeletal muscle samples. Co-administration with ketone ester preserved skeletal muscle mass and function without compromising fat loss. Mechanistically, ketone ester co-treatment prevented semaglutide-induced changes in mitochondrial and atrophy-related gene expression, suggesting mitochondrial defects and impaired ketone metabolism contribute to GLP-1RA-induced muscle loss. Together, these findings demonstrate that ketone ester supplementation can maintain muscle mass and performance during semaglutide-driven weight loss. These preclinical findings support ketone therapy as a promising strategy to counteract the sarcopenia-promoting effects of GLP-1RAs and warrant clinical evaluation to assess its translational potential.
This study aimed to assess the quality and reliability of health information in the 100 most-viewed YouTube videos related to semaglutide for weight loss, as of December 2024. The study also explored the relationship between engagement metrics and content quality, with attention to the prevalence of misinformation. A cross-sectional evaluation was conducted in December 2024. The top 100 English-language YouTube videos retrieved using the search term "semaglutide weight loss" were analyzed. Each video was assessed using 2 validated tools: the Global Quality Score and the Modified DISCERN (quality assessment tool for consumer health information) instrument. Viewer engagement data - including likes, comments, and views - were recorded. Statistical analyses included descriptive statistics and multiple linear regression to examine relationships between engagement metrics and content quality. Videos from academic and healthcare-affiliated sources generally scored higher in quality assessments, while those produced by individual users tended to lack source citations and balanced information. Although certain engagement metrics, such as the number of likes and comments, showed modest associations with higher Global Quality Scores, view count did not consistently predict quality. A notable portion of user-generated videos lacked discussion of semaglutide's risks and contraindications. The study highlights the variability in quality among semaglutide-related videos on YouTube. Engagement does not necessarily reflect the reliability of content, underscoring the importance of guiding viewers toward credible health sources. Enhancing digital health literacy and promoting greater visibility of evidence-based content may help improve the quality of health information encountered on widely used digital platforms.
Alcohol use disorder (AUD) is a specific psychological state induced by repeated heavy drinking, and withdrawal symptoms such as anxiety are closely related to relapse after withdrawal. While neuronal damage caused by alcohol is considered a significant precipitating factor for withdrawal-induced anxiety, the underlying molecular mechanisms remain unclear. In this study, we established a mouse model of alcohol withdrawal through 3 months of chronic ethanol exposure (CEE) followed by withdrawal. Mice were treated with semaglutide (0.03 mg/kg) via intraperitoneal injection and subjected to behavioral, biochemical, and morphological analyses. Our results demonstrate that the glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide alleviates anxiety-like behaviors in CEE withdrawal mice and reverses the downregulation of GLP-1R and its downstream effector CREB in the mitochondria of prefrontal cortex (PFC) neurons. Enhancing the GLP-1R/CREB pathway regulates mitochondrial quality control, including fission, fusion, and mitophagy, to maintain mitochondrial function and ameliorate synaptic impairment. These findings suggest that activation of GLP-1R ameliorates alcohol withdrawal-induced anxiety-like behaviors by regulating neuronal mitochondrial function, providing a potential therapeutic target for AUD.
A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide. This review provides a broad perspective on the drug and the various formulation strategies that can be developed to increase semaglutide's oral bioavailability, encompassing work on enteric coating, gut-targeted delivery, etc. Databases searched include Scopus, google scholar, PubMed, clinicaltrials.gov etc. This review also discussed and summarized all patents and clinical trials related to semaglutide formulations. Although various formulation approaches have been explored to improve semaglutide's oral bioavailability, this review proposes novel and promising strategies for gut-targeted delivery and enteric coating. These methods aim to prevent semaglutide from acidic degradation or neutralization in the stomach and from enzymatic degradation, thereby enhancing its intestinal uptake.
The widespread adoption of GLP-1 receptor agonists such as semaglutide for weight loss has led to an increasing number of non-diabetic patients seeking body contouring procedures after pharmacologic weight reduction. However, concerns have emerged regarding postoperative complications potentially linked to GLP-1 therapy, particularly when continued up to the time of surgery. This retrospective cohort study aimed to evaluate the impact of preoperative semaglutide discontinuation timing on short-term postoperative outcomes in aesthetic lipoabdominoplasty. Eighty patients who underwent primary lipoabdominoplasty were divided into four groups: continued semaglutide until surgery (Group A), 2-week discontinuation (Group B), 4-week discontinuation (Group C), and semaglutide-naïve controls (Group D). All patients were matched for age, BMI, and surgical technique. Postoperative complications within 30 days were assessed. Group A exhibited the highest complication rate (45%), including wound dehiscence, infection, and seroma formation. Group B showed moderate improvement (30% complication rate), while Group C demonstrated a significant reduction in adverse outcomes (10%), comparable to the control group (10%). Gastrointestinal intolerance and prolonged drain duration were also more frequent in patients with ongoing semaglutide use. No reoperations or readmissions occurred. Continuation of semaglutide until surgery significantly increases postoperative complication risk in lipoabdominoplasty. A 4-week preoperative discontinuation period effectively normalizes outcomes, supporting its use as a safety measure in aesthetic surgery candidates. These findings emphasize the need for standardized perioperative management protocols for patients on GLP-1 therapy and underscore the importance of interdisciplinary coordination and nutritional assessment. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Semaglutide 2.4 mg causes substantial weight loss, but its average effect on patient-reported physical function requires interpretation against clinically meaningful thresholds and routine clinical expectations. This systematic review and meta-analysis aimed to evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on patient-reported physical functioning and weight-related quality-of-life outcomes in adults with overweight or obesity. In this prospectively registered systematic review and meta-analysis, MEDLINE via PubMed, Embase via Elsevier Embase.com, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov were searched for randomised placebo-controlled trials of once-weekly subcutaneous semaglutide 2.4 mg in adults with overweight or obesity reporting SF-36v2 or IWQOL-Lite-CT outcomes. Four STEP trials, including 4182 participants, contributed SF-36v2 Physical Functioning data. Semaglutide improved SF-36v2 Physical Functioning compared with placebo, with a mean difference of 1.71 points and a 95% confidence interval of 1.07 to 2.35; heterogeneity was moderate, with I2 = 52.8%. However, this estimate was below the 3.7-point meaningful within-patient change threshold. Two trials, including 2768 participants, reported IWQOL-Lite-CT outcomes. Effects were larger in participants without type 2 diabetes and smaller in participants with type 2 diabetes, and both remained below published thresholds. The available randomised evidence comes from the semaglutide development programme. Semaglutide statistically improves patient-reported outcomes, but average functional gains are modest and should be communicated cautiously.
The SUSTAIN-7 trial demonstrated greater HbA1c and bodyweight reductions with once-weekly semaglutide versus dulaglutide in type 2 diabetes, but strict eligibility criteria limit external validity. We evaluated the comparative real-world effectiveness and safety of these agents in UK primary care. Using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, a Cegedim Database, we included adults with type 2 diabetes initiating semaglutide or dulaglutide between 01-Jan-2019 and 01-Dec-2022, followed through 30-Jun-2023. Co-primary outcomes were 1-year changes in HbA1c and bodyweight, estimated using a new-user, active-comparator cohort design with marginal structural models and inverse probability of treatment weighting. Treatment heterogeneity was assessed in the primary per-protocol analysis by SUSTAIN-7 trial-eligibility. Safety events were assessed while-on-treatment. Among 6616 new users, 4636 (70.1%) remained on-treatment and 1980 (29.9%) discontinued early. Semaglutide new users (n = 1901) achieved greater 1-year reductions than dulaglutide new users (n = 2735) in HbA1c (estimated treatment difference [ETD] -0.22 percentage points [95% CI -0.30, -0.15]) and bodyweight (ETD -1.92 kg [95% CI -2.91, -0.93]). While semaglutide's benefits were preserved across the 87.7% (n = 4064) not meeting SUSTAIN-7 trial-eligibility (HbA1c: ETD -0.23 percentage points [95% CI -0.31, -0.15]; bodyweight: ETD -2.01 kg [95% CI -3.07, -0.95]), reductions in HbA1c and bodyweight were greater among trial-eligible individuals (12.3%; n = 572) for both agents (trial-eligible [semaglutide/dulaglutide] versus non-eligible [semaglutide/dulaglutide] individuals, HbA1c: -1.10/-1.02 versus -0.83/-0.60 percentage points; bodyweight: -5.72/-4.18 versus -5.50/-3.49 kg). Early discontinuers showed attenuated treatment effects and higher gastrointestinal event rates than those remaining on-treatment (23.5-26.1 versus 10.6-13.8 per 100 person-years). New users of semaglutide achieved greater reductions in HbA1c and bodyweight than new users of dulaglutide with comparable safety, with benefits preserved across SUSTAIN-7 trial-eligible and non-eligible individuals, supporting preferential use of semaglutide in UK clinical practice. Swiss National Science Foundation.
There is little real-world evidence on semaglutide effectiveness in the United Arab Emirates (UAE), despite the high local burden of type 2 diabetes (T2DM) and obesity. The aim of this study was to evaluate real-world cardiometabolic outcomes and predictors of response following initiation of semaglutide in a tertiary endocrine clinic. This was a retrospective, observational cohort study of adults with T2DM initiating once-weekly subcutaneous semaglutide (June 2022 to January 2025). Primary outcomes were changes in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure (SBP) at 6 and 12 months. Responder and composite endpoints were assessed at 12 months. Predictors of glycemic (HbA1c reduction ≥ 1%) and composite response (HbA1c reduction ≥ 1% and ≥ 5% weight loss) were analyzed by multivariable logistic regression. In total, 278 patients were included. Adjusted HbA1c decreased by -0.89% (95% confidence interval (CI) -1.07 to -0.70) at 6 months and -0.71% (95% CI -0.91 to -0.50) at 12 months (both p < 0.001). Weight decreased by -3.09 kg (-4.19 to -2.00) and -4.77 kg (-6.00 to -3.53) at 6 and 12 months, respectively (p < 0.001). SBP decreased by -3.56 mmHg (-6.17 to -0.96; p = 0.007) at 6 months. Overall, 39% achieved an HbA1c reduction ≥ 1%, 43% achieved ≥ 5% weight loss, and 23% achieved the composite endpoint at 12 months. Higher baseline HbA1c predicted HbA1c response (odds ratio [OR] 1.85; 95% CI 1.26 to 2.88). Semaglutide improved glycemia and weight and resulted in modest reductions in SBP in real-world practice. These findings support semaglutide as an effective component of cardiometabolic risk reduction strategies in adults with T2DM in the region, especially in those with at-risk glycemic profiles.
Oral semaglutide is the only oral glucagon-like peptide-1 receptor agonist approved for type 2 diabetes (T2D) management. Although its efficacy and safety are established from randomized controlled trials (RCTs), real-world evidence (RWE) may differ. No comprehensive systematic review and meta-analysis (SRM) has holistically analysed the RWE on oral semaglutide. This SRM analysed the RWE outcomes of oral semaglutide. Electronic databases were searched for real-world studies reporting outcomes in adults with T2D receiving oral semaglutide. Primary outcomes were changes in glycated haemoglobin (HbA1c) at 6 and 12 months. Secondary outcomes included changes in body mass index, blood pressure, lipids and adverse events (AEs). Subgroup analyses compared outcomes between Asian and non-Asian cohorts. A total of 59 studies (24,859 individuals) were analysed. The pooled mean HbA1c reduction was -1.11% (95% confidence interval: -1.37 to -0.86; I²=98.8%) at 6 months and -1.19% at 12 months, with 54.7% achieving HbA1c <7%. Weight reduction averaged -4.38 kg at 6 months and -5.96 kg at 12 months. Significant improvements were observed in cardiometabolic parameters. The pooled prevalence of total AEs, gastrointestinal AEs, nausea, diarrhoea and hypoglycaemia was 28.9%, 20.5%, 12.5%, 5.9% and 2.2%, respectively. Discontinuation and dose reduction due to AEs occurred in 8.7% and 4.2% of patients, respectively. Efficacy and safety outcomes were consistent across regions (p for subgroup >0.05). Oral semaglutide demonstrates robust real-world efficacy and safety in T2D and obesity management, similar to RCTs, consistent across Asian and non-Asian populations.