Could Glucagon-Like Peptide-1 (GLP-1) receptor antagonists be used to treat obstructive sleep apnoea in children and adolescents with obesity?

The aim of this systematic review was to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on medical complications, implant failure rates, and health-care-related costs in patients undergoing hip or knee arthroplasty. A comprehensive search of electronic databases, including PubMed, Embase, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trials Registry Platform (ICTRP), and the UK Clinical Trials Gateway, was conducted and was limited to studies from database inception to March 31, 2025. Inclusion criteria comprised randomized controlled trials or cohort studies involving adults (≥18 years old) undergoing total joint arthroplasty (TJA) while receiving a GLP-1 RA treatment of any dosage or duration. The risk of bias was assessed using the Cochrane risk-of-bias tool and ROBINS-I (Risk Of Bias In Non-Randomized Studies - of Interventions) assessment. Due to substantial heterogeneity in the study designs, a qualitative synthesis approach was employed. Eight retrospective studies met the inclusion criteria, encompassing 22,611 GLP-1 RA users and 77,810 controls. The mean patient age ranged from 56 to 64 years. Hospital readmission rates showed the most consistently favorable results among GLP-1 RA users, with 3 studies reporting significant reductions of 29% to 47% during the 90-day postoperative period. Five studies demonstrated that GLP-1 RA use was associated with significant reductions, ranging from 30% to 44%, in periprosthetic joint infection (PJI) rates, whereas 3 studies found no significant differences. Hospital resource utilization favored GLP-1 RA therapy, with several studies demonstrating shorter hospital stays and lower 90-day costs. Medical complications yielded variable results: some studies reported increased vascular and pulmonary events among GLP-1 RA users, whereas others observed reduced sepsis and hypoglycemic events in those patients. GLP-1 RA therapy was associated with reduced hospital readmissions and decreased hospital costs within 90 days postoperatively, although its benefits for PJI prevention showed mixed results, with some studies demonstrating significant reductions in PJI while others showed no difference. No consistent clinical advantages were observed at the 2-year follow-up. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone involved in glucose regulation. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in the treatment of type 2 diabetes mellitus and obesity, as well as in cardiovascular risk reduction. Recent evidence suggests that GLP-1 receptors are expressed in cutaneous tissues; however, their role in skin homeostasis and aging remains insufficiently clarified. This review summarizes recent experimental and clinical studies examining the effects of GLP-1 receptor agonists on skin homeostasis, wound healing, regeneration, and aging processes. Experimental data indicate that GLP-1 RAs may promote wound healing through modulation of inflammatory pathways, enhancement of keratinocyte migration, improved microvascular perfusion, and support of fibroblast function. Antioxidant and cytoprotective mechanisms have also been described. Conversely, rapid weight loss associated with GLP-1 RA therapy has been linked to structural facial changes, including reduction in dermal white adipose tissue and decreased collagen synthesis, which may clinically resemble accelerated skin aging. Mechanistic findings suggest heterogeneous and pathway-dependent effects. Overall, the impact of GLP-1 receptor agonists on skin biology appears multifaceted, and further well-designed clinical studies are required to determine their precise dermatological implications.

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) improve glycaemia and reduce body weight, yet their organ-level actions on skeletal muscle remain incompletely defined. Framing skeletal muscle as an integrated unit of vasculature and muscle cells, we synthesize evidence with emphasis on glucose and protein metabolism. GLP-1 and GLP-1 RAs recruit microvasculature in muscle, expanding capillary surface area and increasing delivery of insulin, glucose, and amino acids. Microvascular recruitment increases interstitial insulin availability and potentiates insulin-stimulated glucose uptake and glycogen synthesis, whereas direct effects of GLP-1 on muscle cells remain under investigation. For protein metabolism, microvascular recruitment can enhance muscle protein synthesis when plasma amino acid availability is elevated, whereas effects under basal (fasted) conditions remain unclear. Elucidating the uncertainty regarding GLP-1 receptor localization in human muscle cells will clarify whether direct signaling occurs within muscle cells, thereby improving our understanding of the relative contribution of direct versus perfusion-mediated actions of GLP-1 RAs. Clinically, GLP-1 RAs reduce lean body mass, likely reflecting energy-deficit-mediated effects, but studies directly assessing muscle mass are still limited. Overall, current evidence indicates that GLP-1 RAs exert beneficial effects on muscle vasculature and muscle glucose metabolism. However, their influence on muscle protein turnover remains unclear-primarily due to observed reductions in muscle mass-despite preclinical data suggesting potential favorable effects on muscle protein metabolism that remain to be confirmed in humans.

Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has surged among non-diabetic individuals in response to the obesity epidemic. Their influence on musculoskeletal healing and orthopedic surgical outcomes remains poorly characterized. The purpose of this study is to evaluate postoperative outcomes following primary rotator cuff repair (RCR) in non-diabetic patients treated with GLP-1 RA. A retrospective cohort study was conducted using the TriNetX database to identify non-diabetic patients who underwent RCR. Patients prescribed GLP-1 RA were propensity score-matched 1:1 with non-users based on demographics and comorbidities. Surgical and medical outcomes were compared using risk ratios (RRs) with 95% confidence intervals. GLP-1 RA use was associated with significantly lower rates of re-tear (RR = 0.699, p < 0.001) and occupational therapy utilization (RR = 0.686, p < 0.011). There were no significant differences in readmission rates, emergency department utilization, or mortality between groups. However, GLP-1 RA users had higher rates of cardiovascular complications (RR = 1.426, p = 0.038). GLP-1 RA use was associated with reduced rates of re-tear and occupational therapy utilization. No differences were observed in readmission rates, emergency department utilization, or mortality. These findings suggest a potential benefit of GLP-1 RA in musculoskeletal healing, though further investigation is needed to understand the mechanisms involved.

Childhood obesity is a growing public health concern associated with long-term metabolic and cardiovascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown efficacy in reducing weight, and improving glycemic and metabolic parameters in adults. This systematic review and meta-analysis evaluated the efficacy and safety of GLP-1 RAs in children and adolescents with obesity. A systematic search of Embase, Cochrane Library, MEDLINE, and Web of Science were conducted to identify randomized controlled trials (RCTs) assessing GLP-1 RAs in pediatric obesity. Methodological quality was evaluated using the revised Cochrane risk of bias tool (RoB 2), and certainty of evidence was assessed using the GRADE approach. Data were pooled using a random-effects model and reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CIs). Five RCTs involving 600 participants were included. Compared with placebo, GLP-1 RAs significantly reduced body mass index (BMI) (MD -2.33), body weight (MD -6.69), waist circumference (MD -4.53), hemoglobin A1c (MD -0.14), and systolic blood pressure (MD -2.25). Heterogeneity was high for most anthropometric outcomes but absent for systolic blood pressure. Overall safety was comparable between groups; however, gastrointestinal adverse events, particularly nausea and vomiting, were more frequent with GLP-1 RAs. GLP-1 RAs improve anthropometric and selected cardiometabolic outcomes in pediatric obesity with an overall favorable safety profile. Larger, high-quality trials are needed to confirm these findings.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for weight loss and may therefore have a role in preoperative optimisation for arthroplasty candidates. However, their effect on arthroplasty outcomes remains unclear. This systematic review aims to evaluate existing evidence on preoperative GLP-1 RA use and postoperative outcomes following joint arthroplasty, and to identify priorities for future research and perioperative optimisation. A systematic literature search of PubMed, Embase, ClinicalTrials.gov and the Cochrane Library was conducted for articles published from inception to 29th July 2025, using terms related to GLP-1 RAs and arthroplasty, in accordance with the PRISMA 2020 guidelines. Studies were included if they assessed postoperative outcomes in adult patients undergoing arthroplasty with documented preoperative GLP-1 RA use. Data were extracted on study design, participant characteristics, GLP-1 RA use, arthroplasty procedure, outcome measures, duration of follow-up, and key results. Fifteen retrospective studies met the inclusion criteria, comprising a total of 39,355 patients undergoing hip, knee or shoulder arthroplasty. Nine studies reported more favourable postoperative outcomes among GLP-1 RA users, three showed mixed results, two predominantly reported worse outcomes, and one found no significant difference. The most frequently reported favourable associations were lower periprosthetic joint infection and hospital readmission rates following hip and knee arthroplasty, particularly among individuals with diabetes or morbid obesity, although results were not uniform across studies. In contrast, evidence relating to shoulder arthroplasty outcomes was limited and showed greater variability. Preoperative GLP-1 RAuse has been associated with lower rates of periprosthetic joint infection and readmission in several retrospective database studies, particularly in diabetic and morbidly obese arthroplasty populations; however, the overall certainty of evidence is low due to non-randomised designs, heterogeneity and risk of bias. These findings should be considered hypothesis-generating, and well-designed prospective studies and randomised controlled trials are required to establish the role of GLP-1 RAs in preoperative optimisation.

With the rapid global uptake of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), scalable behavioral adjuncts are urgently needed to support lifestyle change alongside pharmacotherapy. Microsteps, small behavior change prompts, could be one route to introduce lifestyle change. To evaluate whether digitally delivered microsteps, augmented with short video boosters, increases behavioral expectation to adopt lifestyle behaviors among adults using GLP-1 RAs. This 3-arm online randomized clinical trial was conducted between June 19 and July 1, 2025, with baseline data collection, immediate postexposure, and a 2-week follow-up. Participants were English-speaking adults using GLP-1 RAs in the US, the UK, and other countries and were recruited online through Prolific Academic. Data were collected via the Stanford Medicine Qualtrics platform. Participants received a single exposure to either written microsteps plus a short (approximately 2-minute) storytelling video (arm A) or written microsteps plus a short didactic video (arm B) compared with a do-nothing control condition (arm C). Behavioral nudges focused on small dietary improvements, physical activity, stress management strategies, and sleep hygiene. The primary outcome was behavioral expectation to adopt health nudges, immediately after exposure and 2 weeks later. The effect on the main outcome of the microsteps intervention vs the control condition was compared; the effect of the intervention with a storytelling vs didactic video was also compared. Secondary outcomes were postexposure hope and happiness, as well as changes (over 2 weeks) in 3 key self-reported diet and exercise behaviors. Data from 5054 adults using GLP-1 RAs (mean [SD] age, 38.8 [12.6] years; 3361 females [66.5%]) were analyzed. Of these, 3437 (68%) lived in the US and the UK and 1617 (32%) lived in other countries. Immediately after exposure to the interventions, compared with control, standardized effects in SD units across the 8 microsteps expectation outcomes ranged from 0.30 (95% CI, 0.25-0.35) to 0.72 (95% CI, 0.68-0.77) in arm A and from 0.26 (95% CI, 0.21-0.32) to 0.77 (95% CI, 0.72-0.81) in arm B, with smaller effects 2 weeks later. The storytelling video was more effective across 7 of the 8 microsteps (breathe when stressed: arm A, 0.57 [95% CI, 0.52-0.62] vs arm B, 0.50 [95% CI, 0.44-0.55] and go outside for 5 minutes: arm A, 0.53 [95% CI, 0.49-0.58] vs arm B, 0.48 [95% CI, 0.43-0.52]). Immediate increases in hope (arm A, 0.31 [95% CI, 0.27-0.34]; arm B, 0.25 [95% CI, 0.22-0.28]) and happiness (arm A, 0.26 [95% CI, 0.23-0.30]; arm B, 0.22 [95% CI, 0.19-0.25]) were observed but dissipated by 2 weeks. At follow-up, the storytelling video group also reported reduced sugar-sweetened beverage consumption compared with the control group (-0.10 [95% CI, -0.16 to -0.03]). In this randomized clinical trial, a low-cost digital intervention increased expectation to adopt health behaviors among adults using GLP-1 RAs, with effects persisting for 2 weeks. These findings suggest a potential role for the written microsteps intervention plus short video boosters as adjuncts to pharmacotherapy. Longer trials are warranted to determine whether the behavioral expectations stimulated by such interventions may lead to sustained behavior change. ClinicalTrials.gov Identifier: NCT06967337.

Glucagon-like peptide1 receptor agonists (GLP-1 RAs) are widely used for weight management and type2 diabetes, but reports of reduced skin laxity and volume have raised aesthetic concerns. This study evaluates the first integrated skincare protocol designed for GLP-1 RA users. This 12-week, double-blind, randomized, split-face/split-neck study included 25 GLP-1 RA users (mean age 53.36years) with mild-to-moderate skin aging, including male and female participants with Fitzpatrick skin types II to VI. All participants applied a topical regimen featuring Proxylane and wild fruit flavonoids (Flavo-Proxylane) to one side of the face/neck and a placebo to the other. After 4weeks of topical monotherapy, participants received a single focused ultrasound treatment, followed by an additional 8weeks of topical therapy. Outcomes included blinded image evaluation, 13 clinical grading parameters (via modified Griffiths scale), Global Aesthetic Improvement Scale scores, tolerability, and patient-reported satisfaction. All participants completed the study and lost an average of 3.7lb. After 4weeks of Flavo-Proxylane monotherapy, significant improvements were observed for facial skin laxity (- 16%; P < 0.001) and marionette lines (- 5%; P < 0.05), while no significant changes were observed with placebo. By week12, the combined regimen achieved amplified improvements versus baseline, week4, and placebo (all P < 0.001), with total reductions of 44% in skin laxity and 34% in marionette lines. Significant improvements were observed across all 13 clinical parameters. Overall improvement rating favored Flavo-Proxylane, with 94% reporting moderate-to-significant improvement versus 30% for placebo. Flavo-Proxylane treatment was well tolerated, with 84% reporting improved skin appearance and only three mild, self-resolving adverse events. This study demonstrates that an integrated regimen with Flavo-Proxylane products and ultrasound may improve aesthetic outcomes in a diverse range of participants undergoing GLP-1 RA treatment.

Globally, conditions like type 2 diabetes mellitus (T2DM) are on the rise. This situation is brought on by an increase in insulin volume and a decrease in insulin manifestation. Currently available medications are designed to either improve insulin activity or promote insulin resilience. The prevalence of type 2 diabetes mellitus in the US exceeds 26 million individuals. Long-term glycaemic control in T2D patients is still difficult to achieve despite the abundance of available therapeutic choices. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide a therapeutic option that enhances glycaemic regulation and facilitates weight loss, while presenting a little risk of hypoglycemia. A novel approach to enhancing glycaemic control and addressing the complex ecology of type 2 diabetes is to reduce dependence on glucagon and glucagon-like peptide 1 (GLP- 1). Therapeutic interventions focused on glucagon-like peptide 1 (GLP-1) offer a promising initial approach to managing type 2 diabetes mellitus (T2DM), as they effectively reduce body fat percentage and have a significant impact on cardiovascular health. The scientists involved have discovered that individuals with type 2 diabetes have inadequate responses to supraphysiological infusions of glucose-dependent insulinotropic polypeptide (GIP), resulting in its initial dismissal as an inefficient hypoglycaemic agent. The simultaneous administration of GLP-1 and GIP, as opposed to their separate administration, resulted in an altered insulin and glucagon static response, as demonstrated in a more recent study. This article provides a concise overview of the latest findings on dual glucagon and GLP-1 agonists, including a description of their mechanisms of action, clinical outcomes, advantages and disadvantages, and challenges to their development.

A 58-year-old man scheduled for an elective upper endoscopy followed standard preprocedural fasting guidelines and withheld one weekly dose of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA). Despite these measures, substantial residual gastric contents led to procedure cancelation. Notably, the same patient previously underwent a combined upper endoscopy and colonoscopy after withholding an identical semaglutide weekly dose, with no residual gastric contents were observed. This case suggests that adherence to standard preprocedural recommendations alone may not reliably prevent residual gastric contents in patients receiving GLP-1 RAs, and that a 24-hour liquid diet may be necessary.

Glutamatergic neurons represent 40% of neurons in the human central nervous system. Glutamate accounts for approximately 90% of all excitatory neurotransmitters. Previous research reports the presence of glucagon-like peptide-1 (GLP-1) receptors on neurons that produce glutamate. Herein, we aim to evaluate whether GLP-1 receptor agonists' (GLP-1 RAs) modulate glutamatergic signaling and whether GLP-1 RAs' anti-obesity effects are mediated through the glutamatergic system. We conducted a systematic review of extant literature published on PubMed, Ovid and Scopus databases from inception to March, 2025. Identified studies were screened independently by two reviewers (S.W. and G.H.L.) using the Covidence platform. We sought to include in vitro, in vivo, and human clinical studies. A total of 31 studies were identified as meeting eligibility for an inclusion in this review. No human studies were identified. Across the included preclinical and pharmacologic studies, GLP-1 RAs were associated with increased glutamate release, NMDA/AMPA receptor activation and increased release of neurotrophic factors associated with neurogenesis, neurodifferentiation, and synaptic plasticity. In addition, GLP-1 RA-induced suppression of food intake was reported to be dependent on AMPA, but not NMDA, receptor signaling. The effect of GLP-1 RAs on feeding behavior is mediated via central glutamatergic signaling. A comprehensive mechanistic framework mediating GLP-1 RA activity implicates crosstalk between GLP-1 and ionotropic glutamate receptors. The aforementioned trends instantiate a need to evaluate the therapeutic efficacy of GLP-1 RAs for disparate neuropsychiatric disorders. Conducting target engagement studies of GLP-1 RAs with the glutamatergic system in humans is a future research vista.

Background and objectiveGlucagon-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 methodsThis 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.ResultsOf 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%).ConclusionsSemaglutide 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.

In particular, type 2 diabetes mellitus (T2DM) is a fast growing global health concern associated with high rates of morbidity, mortality, and financial burden. Despite the availability of various pharmacological treatments, the long-term management of type 2 diabetes remains challenging due to weight gain, hypoglycemia, increasing β-cell dysfunction, and the limited cardiovascular benefits of standard therapy. The introduction of incretin-based drugs, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is a significant advancement in the treatment of diabetes. GLP-1, an endogenous incretin hormone secreted by intestinal L-cells, inhibits the release of glucagon, postpones stomach emptying, promotes satiety, and increases glucose-dependent insulin production. Native GLP-1 is rapidly broken down by dipeptidyl peptidase-4 (DPP-4), whereas synthetic GLP-1 RAs are made to resist this breakdown and preserve glycemic control. A. GLP-1 RAs effectively demonstrate a low risk of hypoglycemia, promote significant weight loss, and reduce glycated hemoglobin (HbA1c) by 0.8–1.5%, according to clinical research. Several important cardiovascular outcome trials, such as LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide), have shown reductions in major adverse cardiovascular events and renal protection in addition to lowering blood sugar, establishing GLP-1 RAs as disease-modifying medications. Recent developments that have improved patient acceptance and adherence include oral semaglutide and once-weekly formulations. While tirzepatide and other next-generation dual and triple incretin agonists show promise for improved metabolic outcomes, future research focuses on expanding its use beyond diabetes to include obesity, non-alcoholic steatohepatitis, and neurodegenerative diseases. Long-term safety, stomach intolerance, and high cost are still problems and accessibility in resource-constrained settings. Lastly, GLP-1 receptor agonists represent a paradigm shift in the management of type 2 diabetes by providing numerous benefits that go well beyond glucose control. The therapeutic value of multi-agonist therapy is expected to rise over the next 10 years due to greater research in precision medicine and novel delivery technologies.

Obesity and diabetes are two faces of the same coin, as both disorders are characterized by insulin action defects. The two gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide-1 (GLP-1), play a crucial role in glycemic control. Semaglutide is a GLP-1 receptor agonist, while Tirzepatide acts as a dual agonist for the GLP-1 and GIP receptors. Despite its effectiveness in weight loss, various side effects were reported. This review seeks to explore post-marketing concerns regarding the long-term safety and tolerability of these drugs. Both drugs showed gastrointestinal issues, including nausea, vomiting, pancreatitis, and diarrhea. Moreover, bone remodeling, kidney and thyroid disorders were detected. Tirzepatide was preferred over the commonly used single GLP-1 RAs as it has less reported side effects and enhanced benefits in promoting bone formation and its protective renal effects, especially on decreasing albuminuria and eGFR slopes.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) and obesity. Their expanding clinical use, particularly that of the single-agonist semaglutide (Ozempic/Wegovy) and the dual GLP-1/GIP agonist tirzepatide (Mounjaro/Zepbound), has led to increased exposure in the reproductive-age population, raising critical questions about their impact on human fertility. Objective: To summarize the mechanistic and clinical evidence regarding the effects of semaglutide and tirzepatide on human fertility in both sexes, focusing on the interplay between metabolic improvement and direct reproductive signaling. Methods: This narrative review synthesizes studies published between 2015 and 2025 in PubMed, Scopus, and Embase, focusing on the reproductive and endocrine effects of semaglutide and tirzepatide in men and women. Results: GLP-1 RAs show potential beneficial effects on fertility, primarily via indirect mechanisms, including significant weight reduction, improved insulin sensitivity, and subsequent hormonal normalization. Direct effects are suggested by GLP-1 receptor expression in the gonadal tissues. However, while clinical evidence points to improved ovulation rates in women with obesity/PCOS and better sperm parameters in men with obesity-related hypogonadism, reproductive safety data, particularly long-term safety and pregnancy outcomes, are limited. Conclusion: Evidence suggests possible fertility improvement in cases of metabolic-related infertility. However, the lack of robust human data, coupled with preclinical findings of teratogenicity, necessitates a cautious approach. Long-term safety and pregnancy outcomes require urgent further research, and clinicians must counsel patients on preconception discontinuation.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefit in patients with type 2 diabetes and, more recently, in obese adults without diabetes. However, real-world uptake of these agents during their early introduction remains unclear. The objective of this study was to describe the prevalence of GLP-1 RA use and provide baseline, pre-uptake, population-level estimates of major adverse cardiovascular events (MACE, including myocardial infarction, stroke, and cardiovascular death) and mortality among obese adults without diabetes, in the United States (US), using pooled National Health and Nutrition Examination Survey (NHANES) 2011-2018 data.Methods: We analyzed adults aged ≥20 years with measured obesity (BMI ≥30 kg/m²) who did not meet criteria for diabetes in NHANES 2011-2018 (unweighted n = 6,065, representing a weighted US population of ≈69 million). Medication use was ascertained from the prescription drug questionnaire (medications taken in the prior 30 days). Baseline demographics, anthropometrics, and cardiometabolic risk factors are reported as survey-weighted estimates. Mortality (all-cause and cardiovascular) was ascertained via linkage to the 2019 National Death Index.Results: Among 6,065 obese, non-diabetic adults, none reported GLP-1 RA use in the 30 days preceding survey participation. The mean age was 45.9 years, and the mean body mass index was 35.7 kg/m². The cohort included 37,127,528 (53.6%) female and 44,259,809 (63.9%) non-Hispanic White participants. Hypertension was reported by 25,745,249 (37.2%), and 29,749,000 (42.9%) had smoked ≥100 cigarettes. Over follow-up, 2,661,169 (3.8%) of participants died from any cause, and 786,635 (1.1%) from cardiovascular causes. Because no GLP-1 RA users were identified, comparative (adjusted odds) analyses were not possible.Conclusion: In NHANES 2011-2018, GLP-1 RA use among obese US adults without diabetes was absent, reflecting minimal community uptake in this period. These survey-weighted estimates provide baseline, pre-uptake cardiovascular and mortality benchmarks and emphasize the need for analyses using more recent data to evaluate real-world GLP-1 adoption and outcomes.

Repurposing glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of depression: A systematic review of preclinical, observational and clinical investigations.

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively manage type 2 diabetes mellitus (T2DM) but may impair gastrointestinal motility, increasing the risk of small intestinal bacterial overgrowth (SIBO). Diagnostic evaluation of SIBO commonly involves breath testing and clinical assessment. This study aimed to assess the association between GLP-1 RAs or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are associated with incident SIBO. Methods: We conducted a retrospective cohort study using the TriNetX global database, identifying adult T2DM patients initiating GLP-1 RA or dual GLP-1/GIP RA therapy versus other second-line T2DM agents (OSLT2DM) from 1 January 2006 to 2 December 2024. Patients with major abdominal surgery, connective tissue disorders, gastroparesis, or other high-risk conditions for SIBO were excluded. 1:1 Propensity score matching was applied. Short-term (<1 year) and long-term (up to 5 years) risks were evaluated with Kaplan–Meier curves and univariable Cox models. Results: After matching, 216,173 patients per cohort were analyzed. Short-term analysis demonstrated a higher incidence of diagnostically confirmed SIBO in patients treated with GLP-1 RA/GIP (0.177 per 1000 patient-years) compared to OSLT2DM (0.083 per 1000 patient-years; HR 2.14, 95% CI 1.13–4.07; p = 0.0491). Long-term analysis indicated a non-significant trend toward increased risk in the GLP-1 RA/GIP group (HR 2.02, 95% CI 0.98–4.12), though Kaplan–Meier analysis revealed a sustained divergence (p = 0.017). Conclusions: GLP-1 RA and dual GLP-1/GIP RA therapy are associated with increased short-term SIBO risk. Symptom-driven SIBO breath-test evaluation may be warranted in patients initiating these agents.

Objectives:Glucagon-like-peptide-1 (GLP-1) agonists, also known as GLP-1 receptor agonists (GLP-1 RAs), incretin mimetics, or GLP-1 analogs are a class of medications that have surged in popularity since their approval. Originally developed and indicated for the treatment of type 2 diabetes mellitus, GLP-1 RAs have now also been approved for the treatment of obesity, with more uses currently under investigation. Thus, GLP-1 RA use is only expected to increase. Despite this, little research has been done to assess the possible adverse effects of GLP-1 RA use, especially on surgical complications. In this study, we queried the TriNetX database to investigate the effects of GLP-1 RA therapy on the incidence of several 90-day surgical complications in total shoulder arthroplasty (TSA) patients.Methods:The TriNetX research network was queried to identify all patients undergoing primary anatomic TSA between May 2005 and July 2024 across 66 healthcare organizations. Patients were then sorted into two different cohorts based on preoperative GLP-1 use. Propensity score matching was performed to account for prior differences in demographics, lab values, and comorbidities. Data analysis and risk calculations for the selected 90-day complications were performed using TriNetX’s built-in analysis platform.Results:A total of 59,180 patients underwent TSA, with 1,489 of them using GLP-1 RAs pre-operatively. After propensity score matching, there were 1390 patients in the GLP-1 and no GLP-1 cohorts undergoing TSA. Subsequently, we found no statistically significant differences in the risk of various 90-day complications after TSA between those who used GLP-1 RAs and those who did not. These included readmission, ED utilization, revision surgery, superficial surgical site infection, infection of prosthesis, deep vein thrombosis, pulmonary embolism, acute renal failure, aspiration, and mortality.Conclusions:GLP-1 RA use preoperatively was not associated with any statistically significant change in the risk of complications within 90 days of undergoing TSA. Patients taking GLP-1 RAs experienced similar risks of all examined complications as those who were not prescribed GLP-1 RAs. Thus, our results indicate that GLP-1 RAs are likely safe for patient use prior to TSA and do not increase the risk of 90-day complications described in this study.