Semaglutide

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered safe, effective medications for type 2 diabetes (T2D) and weight loss, used by millions worldwide. While their cardiometabolic benefits are well established, emerging observations suggest a potential association between GLP-1RA use and new-onset nonarteritic anterior ischemic optic neuropathy (NAION).

Abstract

Over the past 2 decades, treatment for type 2 diabetes (T2D) has evolved with the introduction of medications that offer greater simplicity. The Simplicity of Diabetes Treatment Questionnaire (Sim-Q™) was developed to assess the simplicity or complexity of treatment for T2D. This study assessed the psychometric properties of the Sim-Q.

Abstract

Obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), and chronic kidney disease (CKD) are overlapping conditions that drive premature morbidity and mortality worldwide. Care remains siloed and reactive despite shared risk factors and strong evidence for early intervention. To support integrated disease management, the American Heart Association (AHA) recently introduced the concept of cardiovascular-kidney-metabolic (CKM) syndrome, recognizing the bidirectional links between metabolic, kidney, and cardiovascular health. Kuwait faces one of the highest burdens of CKM-related diseases globally. Three-quarters of adults are overweight or have obesity, and 28% have diabetes, both of which are leading causes of mortality and health system strain. Yet multidisciplinary care remains limited, and innovative pharmacotherapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are underused. A panel of Kuwaiti endocrinologists, cardiologists, and nephrologists convened to assess barriers to optimal CKM care and define practical recommendations. Discussions focused on current gaps in screening, care coordination, provider education, and access to therapies. Evidence on GLP-1 RAs was reviewed, considering the demonstrated benefits for weight loss, glycemic control, cardiovascular outcomes, and CKD progression. The expert group agreed that multidisciplinary, risk-stratified, and patient-centered approaches are urgently needed. Recommendations include earlier screening and diagnosis, improved integration across specialties, healthcare provider upskilling, public awareness campaigns, and broader access to GLP-1 RAs. Semaglutide was highlighted as a clinically valuable option owing to its broad efficacy and safety profile. Adopting a CKM care model tailored to Kuwait's specific challenges, with appropriate use of GLP-1 RAs, can reduce disease burden, improve outcomes, and increase healthcare system efficiency. The local implementation of evidence-based, cross-specialty strategies is key to altering the trajectory of CKM syndrome in high-risk populations.

Abstract

Use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer (BC) survivors remain unclear.This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in BC survivors at an academic institution receiving GLP1-RA. We evaluated patients with non-metastatic (ductal carcinoma in situ (DCIS), stage 1-3) BC who received GLP1-RA (2005 - 2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free survival (DFS) and overall survival (OS) between GLP1-RA users versus non-users in the subgroup with invasive disease. We identified 1,022 patients; 79% had DM2. Median weight and body mass index at GLP1-RA initiation were 86.8 kg (47.2-175.0 kg) and 33.5 kg/m2 (18.9-61.8 kg/m2). In semaglutide or tirzepatide users (442, 43.2%), median weight change at 3, 6, and 12 months after GLP1-RA initiation was -1.9% (-13.2%-14.9%), -3.1% (-20.2%-19.0%), and -2.6% (-27.8%-11.5%), respectively. Endocrine therapy and metformin use were associated with weight gain and loss, respectively; invasive disease stage was linked to greater weight loss. GLP1-RA was not associated with DFS, but OS significantly differed between GLP1-RA users (n=810) and non-users (n=1620) (HR 0.37, 95% CI: 0.27-0.53, p<0.0001). In conclusion, in this real-world study in BC survivors, GLP1-RA was associated with modest weight loss and improved all-cause survival. Clinical trials are warranted to study GLP1-RA in this population.

Abstract

The aim of this research is to evaluate the clinical and economic benefits of semaglutide in patients with type 2 diabetes mellitus (T2DM) in real-world setting in tertiary hospital in Saudi Arabia.

Abstract

Semaglutide (SEM) is a glucagon-like peptide-1 (GLP-1) receptor agonist formulated for oral delivery with the absorption enhancer salcaprozate sodium (SNAC). Although oral SEM achieves 0.4-1% bioavailability through gastric epithelial uptake, gastrointestinal (GI) adverse events remain a major cause of therapy discontinuation. This study examined the effects of SEM (0.74 mg/kg/day), SNAC (22 mg/kg/day), and combined SEM-SNAC (1:33 w/w) treatments on microbiota and metabolic function, in healthy Sprague Dawley rats over 21 days. Whilst microbial α-diversity remained stable, SNAC significantly altered β-diversity (PERMANOVA, p < 0.05) and depleted primary fermenters in Muribaculaceae (-62%) and Bacteroidaceae (-77%) compared to the control group. These compositional changes correlated with reduced predicted saccharolytic enzyme abundance and fecal butyrate concentrations (-77% SNAC, -75% SEM-SNAC). Plasma cytokine analysis showed elevated tumor necrosis factor-α (TNF-α, 70%) and suppressed brain-derived neurotrophic factor (BDNF, 85%), consistent with changes in circulating inflammatory and neurotrophic markers from SNAC monotherapy. SNAC-treated animals also exhibited increased liver weight and reduced caecum mass, occurring alongside microbiota compositional changes and altered fermentation-associated markers. Spearman correlations linked Muribaculaceae and Bacteroidaceae loss with decreased saccharolytic enzyme abundance, lower SCFA levels, and increased TNF-α. While these findings are associative and require mechanistic validation, they indicate that chronic SNAC exposure is linked to concurrent microbial, metabolic, and inflammatory marker changes in healthy rats, highlighting the potential need for alternative, microbiota-safe strategies for oral peptide delivery.

Abstract

Physical activity helps maintain a healthy stable body weight. One mechanism underlying this beneficial effect could be the improved coupling between energy intake and expenditure, since hunger and satiety are better regulated in active individuals. Whether this enhancement of appetite control by exercise is reflected in overall adaptations in the gut and gut-brain communication remains poorly defined.

Abstract

To compare the effects of diet restriction and semaglutide treatment on body composition (BC), energy expenditure (EE), and metabolic adaptation (MA) in Göttingen Minipigs as a model for human obesity.

Abstract

Background and objective Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), especially semaglutide, are commonly used to treat obesity and diabetes. They may influence sebaceous gland activity, hidradenitis suppurativa (HS), and acne via metabolic and anti-inflammatory pathways. This study aimed to assess the effects of semaglutide on acne severity, HS activity, and sebaceous gland function, and to evaluate associations with metabolic improvements. Materials and methods This prospective, observational, single-arm study was conducted at the Department of Dermatology, Hayatabad Medical Complex, Peshawar, from January 2023 to December 2024. Adults with acne, HS, or increased sebaceous gland activity who initiated semaglutide therapy between the ages of 18 and 65 years were included. Sebumetry, HS severity using the Hidradenitis Suppurativa Area and Severity Index - Revised (HASI-R), and acne grading using the Investigator's Global Assessment (IGA) were evaluated at baseline and at three, six, 12, 18, and 24 months. Concurrent measurements of metabolic markers, including BMI, HbA1c, fasting glucose, and insulin, were also obtained. Statistical analyses included Pearson and Spearman correlations, multivariate regression to adjust for confounders, and paired t-tests for pre- and post-treatment comparisons. P-values below 0.05 were considered statistically significant. Results Of the 120 enrolled participants, 110 completed the follow-up (91.7%). Over 24 months, acne severity decreased from 1.92 ± 0.78 to 1.21 ± 0.63, HS activity declined from 11.34 ± 4.56 to 7.45 ± 3.21, and sebaceous gland activity was reduced from 186.45 ± 52.34 to 138.56 ± 42.78 µg/cm². Improvements in BMI, HbA1c, fasting glucose, and insulin were significantly associated with dermatologic improvement (p < 0.05). Adverse events were mild and transient and occurred in 17 participants (15.45%). Conclusions Semaglutide therapy was significantly associated with improvement in acne, HS activity, and sebaceous gland function, independently correlated with metabolic enhancements. These findings indicate a potential dermatologic benefit of GLP-1 agonists, supporting the need for further controlled studies.

Abstract

To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and intestinal cancers and to explore the risk factors for these associations.

Abstract

We aimed to analyse trends and demographic and clinical profiles in initial prescriptions of semaglutide ("Ozempic") by general practitioners in New South Wales between 2020 and 2023.

Abstract

To evaluate the impact of semaglutide on body mass index (BMI) and cardiometabolic markers in adolescents with obesity and genetic variants associated with monogenic or syndromic obesity.

Abstract

Metabolic disorders have been recognized as a major contributor to the occurrence and progression of osteoarthritis (OA). Identifying novel therapeutic agents to ameliorate the progression of OA with metabolic disorder is crucial. In this study, we demonstrate that semaglutide (SG), a glucagon-like peptide-1 receptor (GLP-1R) agonist, exhibits strong chondroprotective effects in an OA mouse model with obesity, as evidenced by reduced pathological changes, including cartilage degeneration, osteophyte formation, synovial lesion, and pain sensitivity. A randomized pilot clinical study (ChiCTR2200066291) further supports these findings. By designing a precise diet-controlled setting to rule out the effect of appetite suppression and weight loss induced by SG, we demonstrate a weight loss-independent mechanism. Through regulating the "GLP-1R-AMPK-PFKFB3" axis, the SG reprograms chondrocyte metabolism profile from glycolysis to oxidative phosphorylation under inflammatory conditions, resulting in cartilage restoration.

Abstract

Semaglutide, a glucagon-like peptide-1 receptor agonist, has gained increasing popularity for managing both type 2 diabetes mellitus and obesity. However, as its use increases, new adverse events are emerging. This case report presents a 70-year-old patient who developed pleural and pericardial effusions likely related to semaglutide use.

Abstract

Obesity adversely affects atrial fibrillation (AF) outcomes and is associated with higher recurrence after catheter ablation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) promote weight loss and improve metabolic inflammation, but their role as adjuncts to ablation has not been completely defined. This study investigated the impact of semaglutide on post-ablation rhythm outcomes in obese patients with AF.

Abstract

Glaucoma is a multifactorial disease, where metabolic and mitochondrial dysfunction may play a major role in the progressive loss of retinal ganglion cells that characterize the disease. Currently, treatment strategies consist of IOP-lowering approaches with no available neuroprotective agent. In epidemiological studies and models of glaucoma, GLP-1 receptor agonists (GLP-1RAs) reduce the risk of glaucoma and provide protection against the loss of retinal ganglion cells.

Abstract

Pharmacological therapies are recommended for individuals with obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1), and tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist (GIP/GLP-1), are among the leading pharmacological options for obesity treatment. This network meta-analysis (NMA) aims to evaluate the comparative efficacy of these two agents in reducing body weight and improving glycemic parameters.

Abstract

Peripheral artery disease (PAD) is a prevalent and debilitating complication of diabetes and obesity, yet it remains underrecognized and undertreated. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, have shown cardiovascular benefits, but their impact on peripheral vascular outcomes remains unclear.

Abstract

Peptide-based therapeutics represent a rapidly expanding class of drugs. Endogenous peptides typically exhibit short elimination half-lives due to proteolytic cleavage and renal filtration. However, modifications such as amino acid substitutions and fatty-acid conjugation can significantly prolong their half-lives, enabling, for example, once weekly dosing. This study revisits the systemic pharmacokinetics of peptide drugs using classical pharmacokinetic principles and elucidates the scaling of peptide pharmacokinetics across species.

Abstract

Glucagon-like peptide 1 (GLP-1) agonists continue to gain popularity in treating an increasing number of chronic conditions. As such, it is imperative that providers keep a vigilant eye on patients utilizing these medicines, monitoring for both known and novel side effects. Herein, we present the case of a patient who developed a rash with features characteristic of acute generalized exanthematous pustulosis (AGEP) one month after increasing her dose of semaglutide (Ozempic®). Her eruption occurred outside of the normal timeline for AGEP but had phenotypic and histopathologic findings consistent with this condition, emphasizing the need for providers to maintain a broad differential when assessing cutaneous eruptions. In addition, this case represents the need to do a thorough ingredient analysis when investigating new symptoms, as it was elucidated that her reaction was likely due to the excipient propylene glycol rather than the active ingredient in semaglutide (Ozempic®). The safety of patients using semaglutide requires close correlation of clinical presentation, histopathologic findings, and multidisciplinary collaboration with pharmacists.

Abstract

Since obesity and its associated metabolic dysregulation are recognized risk factors for cognitive decline, this study investigated whether semaglutide, a glucagon-like peptide-1 receptor agonist proven to have cardiometabolic benefits, could provide potential neuroprotective effects on brain structure and function.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP1-RA) have potent glucose-lowering and weight loss benefits, but their effects on bone remain unclear.

Abstract

Semaglutide, a glucagon-like peptide-1 receptor agonist, is increasingly used for the treatment of diabetes and weight loss, including in women of reproductive age. However, its impact on pregnancy outcomes remains largely unknown, with limited data available. The manufacturer advises against using semaglutide within two months prior to planned pregnancy, but some patients may unknowingly use it during early pregnancy.

Abstract

Arteriovenous fistulae (AVF) are necessary for hemodialysis in patients with end-stage kidney disease (ESKD) but are frequently complicated by thrombosis, stenosis, and need for revision. Glucagon-like peptide-1 receptor agonist (GLP-1RA) are increasingly used in type 2 diabetic patients with kidney disease, with recent evidence of both cardiovascular and renoprotective effects, yet their influence on AVF outcomes is unknown. The aim of this study was to investigate the impact of GLP-1RA on AVF outcomes in patients with ESKD.

Abstract

Unimolecular triagonists drive substantial weight loss in patients with obesity by engaging the glucagon-like peptide 1 receptor (GLP-1R) and glucose dependent insulinotropic polypeptide receptor (GIPR) to reduce food intake (FI) and the hepatic glucagon receptor (GcgR) to enhance energy expenditure (EE). However, their development has been challenged by deleterious cardiovascular (CV) effects including increased heart rate (HR), elongated QTc, and arrhythmia mediated by GcgR agonism. GLP-1R mono-agonists on the other hand improve both obesity and CV outcomes with negligible effects on EE. We sought to imbue peptide GLP-1R agonists with an EE enhancing effect by combining them with ectopic GLP-1R expression and agonism in hepatocytes.

Abstract

Type 2 diabetes mellitus (T2DM) significantly impacts the patients' quality of life due to chronic complications and associated comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated benefits in glycemic control. This study evaluates the effect of oral semaglutide on quality of life, metabolic parameters, and treatment adherence of T2DM patients.

Abstract

In late 2025, the White House announced new Most Favored Nation (MFN) pricing agreements for the glucagon-like peptide-1 receptor agonist (GLP-1RA) class, including three semaglutide products, establishing substantially lower prices for Medicare and Medicaid. Shortly after, the Centers for Medicare and Medicaid Services (CMS) released Maximum Fair Prices (MFPs) for selected drugs under IPAY 2027, revealing semaglutide prices that differed from the MFN prices and from earlier assumptions used in prior economic evaluations, including our prior paper. Using previously published forecasting methods, we updated our ten-year (2026-2035) Medicare spending estimates for semaglutide across all FDA-approved indications under both the newly announced MFP and MFN price structures. Incorporating revised 30-day MFPs for Ozempic, Rybelsus, and Wegovy, as well as patient cost-sharing assumptions and future generic entry, we now estimate Medicare savings of $463 million under base-case MFP conditions, with alternative uptake scenarios producing $328-$599 million in savings and up to $1.78 billion with loss-of-exclusivity assumptions. Using the lower MFN price of $245 per month and a $600 annual patient copay, estimated Medicare savings increase substantially to $1.76 billion, ranging from $1.03 to $2.50 billion across uptake scenarios and reaching $2.63 billion with generic entry. These findings highlight the significant fiscal impact of recent price negotiations and underscore uncertainties regarding the durability and future scope of MFN-based drug pricing arrangements.

Abstract

We present the case of a 60-year-old woman with metastatic breast cancer who underwent 18 F-FDG PET/CT for treatment response assessment. Beyond oncologic findings, the scan revealed abnormal gastric retention, gallbladder, colonic, and renal uptake patterns suggestive of Semaglutide-induced gastroparesis, cholecystitis, colitis, and possible acute kidney injury secondary to dehydration. Suspicions were confirmed by clinical evaluation. Symptoms resolved after supportive therapy and withholding of semaglutide. To our knowledge, this is the first report of multi-organ side effects seen on 18 F-FDG PET/CT following a single semaglutide dose administration, emphasizing the need for nuclear medicine physicians to recognize glucagon-like peptide-1 receptor agonist medication-related side effects and their imaging manifestations.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes mellitus and weight management, with growing off-label use in young adults. While GLP-1RAs are generally well tolerated, emerging evidence suggests potential associations with thromboembolic events. We report the case of a 16-year-old male with mild conventional risk factors for thrombosis [overweight body mass index (BMI) and prolonged sedentary behavior] who developed acute left lower extremity deep venous thrombosis (DVT) within two weeks of initiating oral semaglutide (Rybelsus, 7 mg daily) for weight reduction without medical supervision. He presented with progressive leg pain and swelling, and duplex ultrasonography revealed thrombosis of the distal superficial femoral and popliteal veins. An extensive thrombophilia workup, including cardiolipin and β2-glycoprotein antibodies, returned negative. Anticoagulation with low molecular weight heparin followed by apixaban resulted in significant clinical improvement. This case suggests a possible association between oral semaglutide and venous thrombosis in an adolescent, highlighting the need for careful supervision during off-label use. Possible contributing mechanisms include hemoconcentration from gastrointestinal adverse effects, interaction with sedentary behavior, and potential effects of GLP-1RAs on coagulation or endothelial function. Similar cases have been described with injectable semaglutide and other GLP-1RAs, but limb DVT associated with oral semaglutide has not previously been reported. Oral semaglutide may rarely predispose to thrombotic complications. Clinicians should maintain vigilance, especially in adolescents and individuals self-prescribing for weight loss. Further pharmacovigilance and mechanistic studies are warranted to clarify this potential association.

Abstract

Re-cellularization via electroporation therapy (ReCET) is an endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent re-epithelization in the duodenum. ReCET has demonstrated a positive effect on glycaemia. In this study, a single ReCET procedure was combined with a glucagon-like peptide-1 receptor agonist (GLP-1RA) with the goal of eliminating insulin treatment in patients with type 2 diabetes (T2D). At 12 months 86% of patients remained off insulin. Here we report the longer-term efficacy and safety of ReCET combined with GLP-1RA over 24 months.