Case-Based Review of Breast Imaging Changes Associated With GLP-1 Agonists

Background Glucagon-Like Peptide-1 (GLP-1) agonists are widely prescribed for managing type 2 diabetes and have recently gained attention for their potential in promoting weight loss in obese patients. The off-label use of certain GLP-1 agonists for weight loss has been steadily increasing, raising concerns about their safety in non-diabetic patients. Although the gastrointestinal (GI) side effects of GLP-1 agonists are well-documented in diabetic populations, their impact on overweight or obese individuals has not been systematically analyzed. Aims To systematically review and analyze the incidence, severity, and types of GI adverse events (AEs) associated with the use of GLP-1 agonists in overweight or obese patients (BMI: >25 kg/m2) Methods We conducted a systematic search across five databases, including PubMed, Ovid MEDLINE, Embase, Web of Science, and Scopus. Studies were restricted to randomized controlled trials (RCTs) involving GLP-1 agonists whose primary indication was obesity and whose primary outcome was weight loss. Studies that did not report adverse events were excluded. Adverse events were extracted using their preferred terms from the Medical Dictionary for Regulatory Activities (MedDRA). A meta-analysis was performed to pool the relative risk (RR) of GI AEs using the random effects model. A meta-regression was also performed. Results A total of 42 studies (n = 23318 patients) met the inclusion criteria. GLP-1 agonists showed an increased risk of nausea (RR 2.77; 95% CI 2.50–3.10; p < 0.001), diarrhea (RR 2.01; 95% CI 1.78–2.01; p < 0.001), and constipation (RR 2.13; 95% CI 1.90–2.38; p = 0.05) when compared to placebo. The incidence of nausea was higher in those with lower average BMI (coefficient: 3.88; p = 0.005). Additionally, we found no difference between GLP-1 agonists and placebo in the risk of cholelithiasis, cholecystitis, and biliary dyskinesia (RR 1.62; 95% CI 1.22–2.17; p = 0.99). Conclusions Our study found that obese patients are at an increased risk of experiencing nausea, diarrhea and constipation when using GLP-1 agonists compared to placebo. Gallbladder disorders showed no difference in risk. For obese patients, lower average BMI may increase the likelihood of experiencing nausea. FIgure 1. Forest plot indicating relative risk for nausea in obese patients treated with GLP-1 agonists. Error bars represent 95% confidence intervals. Funding Agencies None

The off-label use of glucagon-like peptide 1 (GLP-1) agonists for cosmetic weight loss has captured the interest of the public. However, there is a paucity of published data on their utilization, implications, and management, particularly in the plastic surgery community. This study aims to explore the current practice patterns of aesthetic plastic surgeons regarding the off-label implementation of GLP-1 agonists. A 35-question survey was sent to the 2600 members of The Aesthetic Society in July 2023. The survey collected physician demographics, practice settings, patient population demographics, and the use and management of GLP-1 agonists in their practice. No identifying variables were collected; all responses were anonymous. A total of 368 respondents were included. A quarter of respondents (25.3%) prescribed or utilized GLP-1 agonists in their practice. Nearly a third (29.9%) reported personal use of the medication, of which 71 (70.3%) indicated it was for cosmetic weight loss. Many aspects of the current treatment, counseling, and follow-up practices were similar among prescribing plastic surgeons. However, there were discrepancies in screening, nutrition counseling, and perioperative management. The majority believed that GLP-1 agonists were effective for weight loss (68.9%), profitable for business (57.8%), and would recommend its implementation to other plastic surgeons (68.5%). As leaders in the aesthetic field, it behooves plastic surgeons to take charge of shaping public opinion surrounding the growing off-label use of GLP-1 agonists for cosmetic weight loss. Plastic surgeons' leadership is imperative in establishing safe and ethical guidelines and protocols for proper screening, management, and patient care.

Cardiovascular outcomes in CLL patients receiving GLP-1 agonists and BTK inhibitors: A global propensity-matched study

10607 Background: Elevated body mass index (BMI) and post-diagnosis weight gain increase the risk of breast cancer recurrence and all-cause mortality. Chemotherapy and endocrine therapy can worsen metabolic dysfunction and are associated with weight gain. GLP-1 agonists mimic the action of endogenous GLP-1 and stimulate insulin secretion, delay gastric emptying, and promote satiety. In addition to diabetes treatment, several of these agents induce substantial (8-15%) weight loss and are indicated for obesity weight management. The efficacy of GLP-1 agonists during or after breast cancer treatment is unclear. Methods: Patients with breast cancer and prescribed a GLP-1 agonist from 2015-2023 with follow-up weight data (pre- and on/post-GLP-1 agonist) were included in this retrospective cohort study. A linear mixed effects model with a random intercept for baseline patient weight was used to assess mean weight change at each available follow-up timepoint. Relative weight change from baseline to approximately 12 months after GLP-1 agonist initiation was also computed and a multivariable linear regression was used to assess the association of baseline covariates with relative weight change. Results: 75 patients were included; median age was 52 (range 27-74), 4 (5%) had carcinoma in situ, 64 (85%) had stage I – III, and 4 (5%) had stage IV breast cancer. 62 (83%) had hormone receptor-positive tumors; 14 (19%) had HER2-positive and 8 (11%) had triple negative tumors. 40 (53%) received an aromatase inhibitor concurrently with GLP-1 agonist whereas 3 (4%) received tamoxifen concurrently. Chemotherapy was administered to 56 (75%), and 44 (59%) received radiation. 59 (79%) had a diagnosis of diabetes. Median time from breast cancer diagnosis to GLP-1 agonist prescription was 4.3 years (range -4.4 to 29.5). Median weight at breast cancer diagnosis was 85 kg (range 52-163), median BMI was 32 kg/m2 (range 20-53). Median weight upon GLP-1 agonist initiation was 90 kg (range 58-151) and median BMI was 34 kg/m2 (range 23-50). Median duration of GLP-1 agonist use was 20 months (range 6-111). At 12 months after GLP-1 agonist initiation, mean relative weight change was -5% (SD 6%). Mean weight change from GLP-1 agonist initiation was -2.8 kg (95% CI -0.9 to -4.7) at 6 months, -4.2 kg (95% CI -2.1 to -6.2) at 12 months, and -6.2 kg (95% CI -3.7 to -8.7) post-GLP-1 agonist treatment. Baseline BMI, concurrent anti-estrogen therapy, duration of GLP-1 agonist therapy, and comorbid diabetes were not associated with relative weight change in multivariate models. Conclusions: The use of GLP-1 agonists in this cohort of patients treated for breast cancer was efficacious and associated with modest (5%) weight loss. Based on this observed activity, prospective trials are warranted.

Background: Improved outcomes related to the use of glucagon-like peptide 1 (GLP-1) agonists in patients with cardiovascular disease (CVD) have been well documented. Small studies have shown benefits of GLP-1 agonists in reducing substance use in patients with substance use disorders (SUDs). In patients with CVD, co-occurring SUDs are known to worsen outcomes. The use of GLP-1 agonists to improve outcomes related to both CVD and SUD could improve healthcare disparities in this marginalized population. Hypothesis: The use of GLP-1 agonists in patients with CVD and SUD could improve outcomes related to both disease processes. Aim: Our aim is to describe clinical outcomes in patients with CVD and SUD who were prescribed GLP-1 agonists. Methods: This is a single-center retrospective cohort study of patients with CVD and SUD on a GLP-1 agonist. As previous studies have shown that change in body mass index (BMI) correlates with adherence to GLP-1 agonists, we stratified subjects by change in BMI over a two-year study period. Using SPSS, we analyzed number of hospital visits and conducted frequency analyses by type of CVD, type of SUD, and change in BMI during our study period. Results: The study population consists of 81 patients on GLP-1 agonists who have SUD and CVD. BMI decreased in 55 patients (67.9%), increased in 24 patients (29.6%), and remained the same in 2 patients (2.5%). Correlation analysis was conducted between change in BMI and the number of hospital visits related to SUD and CVD, indicating positive correlation between change in BMI and reduction in hospital visits related to both SUD (r=0.136, p= 0.230) and CVD (r=0.142, p= 0.208). Subgroup analyses were also performed by specific SUD type; patients with cocaine, cannabinoid, or alcohol use disorders had decreased hospital visits related to CVD (p<0.05) while those with opioid or polysubstance use disorders did not (Table 1). Conclusion: GLP-1 agonists, previously established to reduce adverse CVD outcomes, may be especially beneficial in patients with both CVD and SUD. More research is needed to determine how to optimize the benefit from treatment with GLP-1 agonists in this vulnerable patient population.

Objective: The aim of this narrative review of the literature is to address the potential difficulties faced by patients using glucagon-like peptide-1 (GLP-1) agonists during procedures under general and dental anesthesia, with an emphasis on the clinical and pharmacological implications of these medications in the anesthetic context. Methodology: For data collection, searches were performed in electronic databases, including PubMed, PROSPERO, SciELO, The Cochrane Library and ScienceDirect, in addition to using Google Scholar as a complementary tool. The search terms used involved combinations of "GLP-1 agonists", "general anesthesia", "dental anesthesia", "perioperative management", and "complications". Results: The studies analyzed indicate that the use of GLP-1 agonists, such as liraglutide, semaglutide and dulaglutide, may be associated with gastrointestinal adverse effects, such as nausea, vomiting and gastroparesis. These effects can directly interfere with preoperative fasting and gastric emptying, increasing the risk of pulmonary aspiration during general anesthesia. Furthermore, during dental procedures, there are reports of hypoglycemia in poorly monitored diabetic patients, especially when there is prolonged fasting associated with the use of insulin or other antidiabetics. The literature also highlights the need for adjustment or temporary suspension of medication before elective surgical procedures, since there are still no standardized protocols, and individualized evaluation is recommended. In the dental context, glycemic control and coordination between the medical and dental teams are essential to minimize intraoperative and postoperative risks. Conclusion: The use of GLP-1 agonists represents an important advance in the glycemic control of patients with type 2 diabetes, but their continued use has relevant implications for anesthetic management, both general and dental. The presence of gastroparesis, increased risks of aspiration, and metabolic alterations reinforce the need for rigorous and multidisciplinary preoperative evaluation.

7559 Background: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition with limited interventions to reduce progression to multiple myeloma (MM). Glucagon-like peptide-1 (GLP-1) agonists, widely used for glycemic control and weight loss in type 2 diabetes mellitus (T2DM), have demonstrated cardiovascular, renal, and anti-cancer benefits, including reduced risks of obesity-associated cancers. This study assesses the association between GLP-1 agonists and MGUS progression in T2DM patients. Methods: We queried TriNetX – a Research Network - of 141 healthcare organizations from 30 countries between 2011 and 2024.MGUS patients with T2DM were divided into two cohorts: those on GLP-1 agonists and those not on GLP-1. Two sub-analyses were conducted: one in MGUS T2DM patients with a normal body mass index (BMI), and another in patients with BMI ≥25. Patients aged 18–80 years with monoclonal protein <3 g/dL, and GLP-1 use or other diabetic medications ≥2 years prior to MGUS diagnosis were included. Patients with prior diagnosis of MM, progression to MM within 1 year, kappa/lambda light chain >100 mg/dL, osteolytic lesions, creatinine >2 mg/dL, hemoglobin <10 g/dL, calcium >10.2 mg/dL, or prior treatment with bortezomib, lenalidomide, or daratumumab, were excluded. A 1:1 propensity score matching was performed to match the covariates (age, sex, race [white or African American], M protein, kappa/lambda ratio, and BMI). MM rates were compared at 2, 3, 5, 7, and 10 years. Results: The study included 5,901 MGUS patients with T2DM in the main analysis (22.45% on GLP-1 [n=1,325]; 77.55% not on GLP-1 [n=4,576]). The sub-analysis involved 818 normal-BMI patients (22.37% on GLP-1 [n=183]; 77.63% not on GLP-1 [n=635]). Matched cohorts (main analysis: n=1,319 each, sub-analysis n=181each) revealed significantly lower MM rates in GLP-1 users at 2- (1.21% vs 2.50, p=0.014), 3- (1.36% vs 2.50%, p=0.33), 5- (1.36% vs 2.57%, p=0.025), 7- (1.36% vs 2.57%, p=0.025) and 10-years ( 1.51% vs 2.65%, p=0.041). Similar findings were observed in the sub-analysis among patients with MGUS and T2DM with BMI ≥ 25 at 2- (1.08% vs 3.05%, p=0.001), 3- (1.18% vs 3.15%, p=0.002), 5- (1.08% vs 3.05%, p=0.001), 7- (1.18% vs 2.85%, p= 0.07, and 10-years (1.37% vs 3.05%, p=0.01). However, in the sub-analysis, normal-BMI GLP-1 users showed no difference in MM rates compared to non-users at 10-years (5.52% vs 5.52%, p=1.00). Conclusions: The use of GLP-1 agonists was significantly associated with reduced rates of MM among patients with T2DM and MGUS over a 10-year period, particularly in those with a body mass index ≥ 25. The lack of significant effects in normal-BMI patients suggests weight loss or related metabolic changes may mediate these protective effects. These results underscore GLP-1 agonists as a promising therapeutic strategy for managing MGUS in T2DM patients, especially those with elevated BMI.

Body mass index (BMI) > 50kg/m2 is associated with relatively increased morbidity and mortality with bariatric surgery (BS). There is reluctance to consider these patients operative candidates without preoperative weight loss. Glucagon-like peptide-1 (GLP-1) agonists have demonstrated effective weight loss in the post-BS setting. This study aims to determine the safety and efficacy of GLP-1 agonists in the pre-habilitation of patients with BMI > 50kg/m2. This is a retrospective review of bariatric surgery patients with BMI > 50kg/m2 from a single bariatric center. Patients were compared by preoperative GLP-1 therapy status. All patients received medical, surgical, psychiatric, and nutritional evaluation and counseling. Preoperative BMI, change in weight from program intake until surgery, time to surgery, and perioperative complications were evaluated. 31 patients were included in the analysis. 18 (58%) received a GLP-1 agonist preoperatively. GLP-1 agonist use was associated with a 5.5 ± 3.2-point reduction in BMI compared to 2.9 ± 2.4 amongst controls (p = 0.026). There was no difference in the mean length of time in the bariatric program prior to surgery between groups (p = 0.332). There were no reported complications related to GLP-1 use in the preoperative setting and no difference in perioperative complications between groups (p = 0.245). GLP-1 agonist use in patients with a BMI > 50kg/m2 results in significantly more weight loss prior to bariatric surgery, without increased time to surgery or complication rate. Further study is required to evaluate the long-term impact of preoperative GLP-1 agonist use prior to bariatric surgery. This therapy may improve perioperative and long-term outcomes in the very high-risk BMI population.

Background: Reported cases of acute pancreatitis have been associated with the use of GLP-1 agonists for treatment of diabetes mellitus. Hypertriglyceridemia is a well-established but underestimated cause of acute and recurrent pancreatitis. At the present time, there is insufficient data to know if there is a casual relationship. Clinical Case: A 46 y.o. male with past medical history of coronary artery disease, hyperlipidemia, type 2 diabetes mellitus, hypertension, and morbid obesity, was admitted to the hospital with severe abdominal pain radiating to the back associated with non-bilious vomiting, for 1 day. Patient endorsed that 4 years ago he was diagnosed with hypertriglyceridemia. Physical exam findings were notable for a distended abdomen with mild epigastric tenderness, heart rate at 120 bpm, and a body mass index of 37 kg/m2. Active medications include: atorvastatin 40 mg PO daily, fenofibrate 45 mg PO daily, metformin 1,000 mg PO twice a day, glipizide 5 mg PO daily, levemir 60 units SQ twice a day, and most recently he had been started on dulaglutide 0.75 mg SQ weekly. Initial tests were consistent with acute pancreatitis and diabetic ketoacidosis: lipase 944 U/L (n 8.0 - 78 U/L), anion gap 18 mEq/L (n 5 - 13 mEq/L), creatinine 1.6 mg/dL (n 0.72 - 1.25 mg/dL), glucose 479 (n 60–100 mg/dL), β-Hydroxybutyrate 5.3 mmol/L (n <0.3mmol/L), urine glucose >1,000 mg/dL (n Negative mg/dL), urine ketones 20 mg/dL (n Negative), Triglycerides (TG) 5,374 mg/dL (n <150 mg/dL) and Hgb A1C 11.9% (n <5.7%). CT abdomen and pelvis without contrast revealed moderate acute pancreatitis. Patient was admitted to the intensive care unit and was started on intravenous insulin, atorvastatin 80 mg PO daily and fenofibrate 145 mg PO daily. Despite optimization of lipid-lowering agents, TG remained above 2,000 mg/dL. Decision was made to start patient on plasmapheresis until TG was <500 mg/dL. Patient’s TG improved to 370 mg/dL after second treatment. Patient’s dulaglutide was discontinued and patient was advised to avoid GLP-1 agonist use, indefinitely. One-month post discharge patient’s TG level was 370 mg/dL. Conclusion: Pancreatitis should be considered in patients on GLP-1 agonists, that present with persistent severe abdominal pain (with or without nausea), and its use should be discontinued in such patients. Use of GLP-1 agonists should be avoided in subjects with severe hypertriglyceridemia. Further research should be made in order to determine if GLP-1 agonists should be contraindicated in patients with severe hypertriglyceridemia, as both increase risk for pancreatitis.

Background: Glucagon-like peptide-1 (GLP-1) agonists have been shown to improve outcomes across various cardiovascular diseases. However, data regarding the effects of GLP-1 agonists in obstructive hypertrophic cardiomyopathy (HCM) is limited. Objective: This study aimed to evaluate the 5-year outcomes of GLP-1 agonists in patients with HCM. Methods: Using TriNetX Analytics Network, we identified patients aged ≥18 years with a diagnosis of obstructive hypertrophic cardiomyopathy between 1/1/2014 and 1/1/2019. Patients were divided into two groups: those treated with GLP-1 agonists for ≥ 1 year and those who were not. Propensity score matching (PSM) was performed using demographics, cardiac medications, and comorbidities. The study outcomes were 5-year all-cause mortality and cardiac adverse events. Results: A total of 52,978 patients with HCM were identified, including 2,654 (5.0%) patients treated with GLP-1 agonists. After PSM, 2,588 patients in each group were analyzed. Patients on GLP-1 agonists were associated with lower odds of all-cause mortality (5.0% vs. 15.6%, p&lt;0.01), all-cause hospitalization (46.3% vs. 67.8%, p&lt;0.01), acute decompensated heart failure ((9.4% vs. 21.4%, p&lt;0.01), cardiac arrest (3.6% vs. 5.4%, p&lt;0.01), cerebrovascular accidents (9.5% vs. 14.1%, p&lt;0.01), and cardiogenic shock (1.4% vs. 3.6%, p&lt;0.01). Additionally, reduced rates of new ICD implantation (3.5% vs. 7.9%, p&lt;0.01) and septal reduction therapy (1.7% vs. 3.5%, p&lt;0.01) were observed in the GLP-1 agonists group. Conclusion: The use of GLP-1 agonists in HCM was associated with improved cardiovascular outcomes. Future clinical trials are needed to validate these potential benefits.

» Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.» GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).» The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.» While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.» Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts.

Emotional eating in patients attending a specialist obesity treatment service

Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After the burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. Glucagon-like peptide-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on patients with burns is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management.

There have been conflicting reports concerning an increased risk of pancreatic cancer (PC) in new users of glucagon-like peptide-1 agonists (GLP-1As). We aimed to explore whether the use of GLP-1A is associated with an increased risk of PC. A multicenter, retrospective cohort study was conducted using TriNetX. Adult patients with diabetes and/or overweight and obesity who were newly treated with GLP-1A or metformin for the first time between 2006 and 2021 were matched 1:1 using propensity score matching. The risk of PC was estimated using a Cox proportional hazards model. A total of 492,760 patients were identified in the GLP-1A and 918,711 patients in the metformin group. After propensity score matching, both cohorts (370,490 each) were well matched. During follow-up, 351 patients in the GLP-1A and 956 on metformin developed PC after an exposure lag of 1 year. Glucagon-like peptide-1 agonists was associated with a significantly lower risk of PC (hazard ratio, 0.47; 95% confidence interval, 0.42-0.52). The use of GLP-1A in patients with obesity/diabetes is associated with a lower risk of PC compared with a similar cohort of patients using metformin. Our study findings reassure clinicians and patients with apprehensions about any possible association between GLP-1A and PC.

Background Recent research on Parkinson's disease (PD) therapy has highlighted glucagon-like peptide 1 (GLP-1) agonists as potential therapeutic agents. However, recent randomized controlled trials (RCTs) have shown mixed results regarding the use of this medication.Objective To perform a meta-analysis comparing GLP-1 agonists with placebo or standard PD treatment in adult PD patients.Methods We systematically searched the PubMed, Embase and Cochrane Central databases. The efficacy outcomes were assessed through the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). We also assessed adverse events. Dichotomous data were compared using the risk ratio (RR), and continuous endpoints were pooled using the mean difference (MD).Results We included 4 RCTs, with a total of 514 patients. In every study, the Hoehn and Yahr stage was < 3. The pooled analysis demonstrated that the use of GLP-1 agonists was not associated with an improvement in the scores on parts I, II, III, and IV of the MDS-UPDRS at 6 and 12 months of follow-up. Neither did quality of life (PDQ-39) show significant differences among the groups, and a higher risk of gastrointestinal adverse events and weight loss was observed with the use of GLP-1 agonists. A subgroup analysis further confirmed the lack of clinical benefits of the intervention regarding all of these efficacy outcomes, and the intervention also significantly reduced result heterogeneity.Conclusion In 1 year, GLP-1 agonists failed to improve motor and non-motor features of PD. Additional high-quality studies are needed to draw more robust conclusions about this treatment.