Negative Consequences of Removing GLP-1 RA Obesity Coverage: A Cross-Sectional Cohort Comparison Study.

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a class of antidiabetic drugs developed over the past 15 years. GLP-1, a gastrointestinal peptide hormone that contributes to the postprandial “incretin effect”, stimulates glucose-dependent insulin secretion. The incretin effect is greatly diminished in type 2 diabetes, but can be restored by GLP-1RAs. These drugs also exert other GLP-1 effects, including reducing glucagon secretion, delaying gastric emptying, reducing food intake, improving cardiac ventricular function, and lowering blood pressure. Short-acting GLP-1RAs are administered once daily (lixisenatide) or twice daily (exenatide); long-acting GLP 1RAs are administered once daily (liraglutide) or once weekly (slow-release exenatide, dulaglutide, albiglutide). All GLP-1RAs significantly reduce glycated hemoglobin (HbA1c) in patients with type 2 diabetes whose glycemic control is inadequate with oral antidiabetic drugs. Compared with other antidiabetic medications, GLP-1RAs provide better glycemic control with the additional benefit of weight loss. Within this class, long-acting GLP-1RAs are more efficacious than short-acting GLP-1RAs, with similar or lower risk of hypoglycemia and lower incidence of gastrointestinal adverse effects. Head-to-head trials and a network meta-analysis suggest that once daily liraglutide is the most effective GLP-1RA in reducing HbA1c. Dulaglutide is the only once-weekly GLP 1RA demonstrated to be noninferior to liraglutide. The once-weekly GLP-1RAs offer additional advantages to patients, including fewer injections and easy-to-use, single-dose pen devices. Despite the relatively recent development of GLP-1RAs, international diabetes guidelines recognize the benefits of this class of drugs and recommend them as a treatment option for patients with type 2 diabetes.

Evolution of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

PDB52 - A Comparison of Patient Characteristics Between Glp-1 Ra and Insulin Initiators in China

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for weight and glycemic control and may have immunomodulatory effects relevant to cancer therapy. A recent study by Santos et al. (J Clin Oncol. 2025;43(16)_suppl:1115) found that GLP-1 RA use was significantly associated with lower pathologic complete response (pCR) rates in Triple Negative Breast cancer patients (TNBC) undergoing neoadjuvant chemoimmunotherapy (30.8% vs 64.4%, p=0.001). Given the high prevalence of obesity and predominance of Hispanic patients at our center, we sought to evaluate this relationship in our population. Methods: We conducted a retrospective analysis of stage II-III TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (KEYNOTE-522 regimen) between January 2018 and June 2025 at UT Health San Antonio Mays Cancer Center, which serves a predominantly Hispanic population with high rates of obesity. The KEYNOTE-522 regimen consisted of neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin or epirubicin and cyclophosphamide, with pembrolizumab continued postoperatively. Clinical data collected included age, BMI, race/ethnicity, GLP-1 RA use, and pCR status (ypT0/Tis ypN0). Associations with pCR were assessed. Results: Seventy-seven patients were included; 16.7% (n=13) received GLP-1 RAs. Median BMI was 29.5 for users vs 30.0 for non-users. The cohort was 61.5% Hispanic, 16.7% non-Hispanic White, 5.1% Asian, and 5.1% non-Hispanic Black. pCR rates were similar between groups: 46.2% in GLP-1 users vs 51.6% in non-users (OR 0.81; p=0.77). BMI showed no association with pCR (p=0.95). Race/ethnicity was significantly associated with pCR (p<0.001), with Asian patients achieving a 100% pCR rate. Conclusions: In co ntrast to findings by Santos et al., GLP-1 RA use was not associated with decreased pCR rates in our predominantly Hispanic, high-BMI TNBC cohort. These results suggest that GLP-1’s effect on treatment response may vary across patient populations. Given the limited sample size of this study, a larger multi-center analysis will be critical to more definitively assess the relationship between GLP-1 use and pCR outcomes in diverse TNBC populations. Citation Format: D. Urueta PortilloS. HaddadE. KaserA. BaigR. BanwaitM. Mazo Canola. Revisiting the GLP-1-pCR Link in TNBC: Contrasting Outcomes in a High-BMI, Majority-Hispanic Cohort [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD8-09.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have shown efficacy for reducing cardiovascular morbidity and mortality in patients with diabetes mellitus (DM), but conflicting evidence exists regarding their impact on cardiac arrhythmias. Whereas some studies suggested a possible association between GLP-1RA use and arrhythmogenesis, other studies suggested decreased association with atrial fibrillation (AF). Overall, large-scale real-world data evaluating risk of AF in association with GLP-1RAs are lacking. Objective: To compare risk of incident AF after initiation of GLP1-RA vs Dipeptidyl peptidase-4 inhibitors (DPP4i), as active comparators, in patients with DM. Methods: This retrospective propensity score-matched cohort study was conducted within the Veterans Health Administration from fiscal years 2006 to 2021. The study included U.S. veterans aged 35 years or older who initiated either GLP1-RA or DPP4i prescriptions. The primary outcome assessed was a composite outcome of atrial fibrillation (AF), defined as a diagnosis of AF/flutter based on administrative codes or undergoing an AF procedure. Results: Out of 116,235 GLP1-RA users and 217,668 DPP4i users, we propensity score-matched 80,948 pairs, on 88 characteristics, including demographics, comorbidities, vital signs, cardiovascular risk score, healthcare utilization, DM control, laboratory investigation, and medications. Composite outcome of AF was similar in GLP-1RA group (4.1%) and DPP4i group (4.3%); odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.01. Secondary analyses stratified by medication use duration showed no significant differences in composite AF risk (P>0.05). Notably, individuals achieving weight loss of 2%, 5%, or 10% of baseline body weight had significantly lower AF incidence, whereas no significant differences were observed in those with no weight loss or weight gain (OR 0.99, 95% CI 0.91-1.07). Conclusions: Use of GLP1-RA in patients with DM was not associated with a decreased risk of AF when compared with the use of DPP4i. In the subgroup analysis, significantly lower AF risk was seen in the GLP-1 RA group who achieved weight loss vs. DPP4i and this highlights weight loss as a potential modifier of cardiovascular outcomes in DM.

IntroductionAlthough insulin remains the recommended treatment in type 2 diabetes for hyperglycemia with catabolic symptoms, it is also the generally recommended treatment for persistent hyperglycemia or hemoglobin A1c (HbA1c) values above 10% 1 . Recent data has suggested that glucagon like peptide 1 receptor agonists (GLP-1RAs) are also powerful at glucose lowering while additionally offering extra-glycemic benefits such as weight loss with minimal risk of hypoglycemia. Unfortunately, data on initial use of GLP-1RA is limited in patients with very high hemoglobin A1cs. Our objective was to evaluate outcomes in patients with type 2 diabetes and a baseline HbA1c of 10% or greater treated with GLP-1RAs instead of insulin.MethodsThis study is a small retrospective case series of insulin-naïve patients with uncontrolled type 2 diabetes who were prescribed an injectable GLP-1RA. Patients included had a baseline hemoglobin A1c ≥ 10% without signs of catabolism (weight loss, ketosis, significant polyuria), a minimum of one follow-up visit after initiating GLP-1RA, and at least one HbA1c measurement within six months of initiating treatment. Patients were excluded if they had previously been on insulin or a GLP-1RA in the past 1 year. The primary endpoint was change in HbA1c after 3-6 months of GLP-1 RA use.ResultsOf the patients initially screened, 7 patients fulfilled criteria and were included in the final analysis. The age range was 45-73 with 4 female patients and 3 male patients. The number of years patients had been diagnosed with type 2 diabetes ranged from 0 to 13 with 1 patient having newly diagnosed diabetes not previously on medications. Of the 6 patients who were on medical treatment at baseline, 3 patients were on monotherapy with either metformin or a sulfonylurea and 3 patients were on 2-4 oral hypoglycemic agents. Patients were continued on their initial medication regimen with the exception of DPP-4 inhibitors which were stopped at the time of GLP-1RA initiation. Mean baseline HbA1c prior to initiation of GLP-1RA was 11.9%. Following 3-6 months of GLP-1RA use, mean HbA1c significantly improved to 7.5% (p value= 0. 0005). All patients showed improvement of HbA1c in response to GLP-1RA initiation (mean HbA1c reduction = 4.4, minimum = 1.9, maximum = 7.5). All patients remained on GLP-1RA without significant side effects.ConclusionIn this limited case series of patients with HbA1c ≥ 10%, GLP-1RAs were well tolerated and resulted in significant improvement in HbA1c. Our results suggest that GLP-1RAs should be considered as an alternative treatment option to insulin in non-catabolic patients with very high hemoglobin A1cs.

Introduction and Objective: There is a lack of evidence regarding the impact of GLP-1 receptor agonist (GLP-1RA) use on survival among cancer survivors with type 2 diabetes (T2D). Methods: Using 2013-2020 national Medicare Claims data, we identified older adults with T2D who coexist with one of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer) for at least one year (n=28,232). We further identified new users of GLP-1 RA, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and dipeptidyl peptidase 4 inhibitors (DPP4i) and followed up with them until death or 12/31/2020. We used 1:1 propensity score matching to control for potential confounding at baseline and Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for mortality risk. Results: In the GLP-1 RA vs. SGLT2i cohort (n=2553 pair), GLP-1RA users had a similar mortality risk with SGLT2i users (HR, 1.03 [95%CI, 0.85-1.23]). In the GLP-1 RA vs. DPP4i cohort (n=2564 matched pairs), GLP-1RA was associated with a lower risk of mortality compared to DPP4i users (HR, 0.60 [95%CI, 0.51-0.70]). Figure 1 presents the Kaplan-Meier plots of cumulative incidence of mortality. Conclusion: GLP-1RA might be associated with improved survival compared to DPP4i among cancer survivors with T2D. Disclosure Y. Lu: None. H. Dai: None. H. Tang: None. W.T. Donahoo: None. T.J. George: Consultant; BillionToOne, Nihon Medi-Physics, Kahr Medical, Avammune Therapeutics, Exact Sciences, Summit Therapeutics, Arbele. Y. Guo: None. J. Guo: None. J. Bian: None.

Disclosure: A. Rivadeneira: None. M. Walker: None. R. Gallop: None. A. Amaro: Advisory Board Member; Self; Novo Nordisk. Research Investigator; Self; Eli Lilly & Company, Novo Nordisk. Background: Obesity prevalence worldwide is increasing. By 2030, almost one-fourth of US population will have severe obesity (BMI >35 mg/kg2). Bariatric surgery (BS) is an effective intervention for weight loss (WL) in patients with severe obesity; weight regain (WR) remains a concern. Over one-third of patients will regain more than 25% of total WL. GLP-1 receptor agonists (GLP1RA) have been effective for WL in patients with obesity. Effectiveness and safety of liraglutide and semaglutide in patients with WR after BS were observed in several retrospective studies. The difference in response to GLP1RA in patients with and without a history of bariatric surgery has not been assessed. Objectives: We aimed to retrospectively compare amount of WL and time to nadir in BMI matched individuals with history of WR following BS and without history of surgery treated with GLP1RA. Methods: Retrospective matched cohort study of the patients referred to Penn Metabolic Medicine (PMM) clinic for non-surgical weight management. We analyzed 63 patients with history of RYGB or VSG seen between 8/2015-8/2021 for WR and who received GLP1RA. BMI matched non-surgical (NS) cohort (N=60) treated with GLP1RA was built from the PMM patients of the same period for comparison. Results: Mean weight on presentation at PMM in surgical group (SG) was 273.1 lbs, (BMI 43.5 kg/m2), and in non-surgical one (NS) 264.9 lbs (BMI 43.3 kg/m2). Nadir weight after initiation of GLP1RA in SG 241.1 lbs and controls 244 lbs, with percentage WL of 11.8% in SG and 7.86% in NS controls (p-value 0.0081). Mean time to nadir weight after initiation of GLP1RA was 17.2 months for SG, and 9.2 months in NS controls (p-value <0.0001). Discussion: When treated with GLP1RA, patients with post-bariatric WR lost on average 12% of their weight and achieved nadir around 17 months. Weight matched NS controls lost less weight and entered a plateau phase faster, suggesting enhanced GLP1RA efficacy after bariatric surgery. Significant WL response to GLP1RA was similar in RYGB and VSG groups, supporting previously demonstrated GLP1RA efficacy for post-bariatric WR. Larger prospective trials are needed for confirmation. Reports suggest both RYGB and VSG increase postprandial GLP-1. Proposed WR mechanisms include hormonal changes, nutritional non-adherence, physical inactivity and maladaptive eating. Hormonal mechanisms include increase in ghrelin, decrease in GLP-1 and peptide YY, post-bariatric hypoglycemia and other pathways. Further studies are needed to elucidate the mechanism of enhanced GLP-1 RA efficacy in patients with WR after BS. The limitations of our study include a retrospective nature, modest sample size and the choice of GLP1RA limited to liraglutide, exenatide and semaglutide and guided by the subjects’ insurance plans. In the future, dual incretins will need to be studied in patients with WR after bariatric surgery. Presentation: Friday, June 16, 2023

Background: GLP-1 RAs are an incretin-based, injectable, therapeutic option for the treatment of T2D. However, there are limited data related to patients’ adherence to, or discontinuation of, GLP-1 RA therapy in the real-world. Methods: Using the Optum Research Database (2010-2016), we conducted a retrospective cohort study of U.S. T2D patients ≥ 18 years initiating GLP-1 RAs as monotherapy or as dual therapy with metformin to evaluate GLP-1 RA adherence and discontinuation. GLP-1 RA adherence was assessed using the proportion of days covered (PDC) among all GLP-1 RA initiators with two or more prescription fills. Discontinuation was defined as any GLP-1 RA therapy gap >90 days after end of days of supply from medication fill during follow-up. Multivariable logistic regression was used to evaluate factors associated with non-adherence and discontinuation. Results: Of 4,791 patients included, 42% were female and median age was 56 years. The proportion of patients characterized as non-adherent (PDC <80%) was 49.1% within 1 year. The proportion of patients who discontinued therapy was 47.7% within 1 year. Factors associated with poor adherence/discontinuation within 1 year included male sex, older age, Southern geographic region, and Medicare insurance. Conclusion: A substantial proportion of U.S. T2D patients are non-adherent to GLP-1 RA therapy and nearly half of patients discontinue GLP-1 RA therapy within a year. Further investigation on the impact of adherence on real-world effectiveness, including weight loss and HbA1c, is warranted. Disclosure T. Weiss: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.D. Carr: Employee; Self; Merck & Co., Inc. Speaker's Bureau; Spouse/Partner; Eli Lilly and Company, Merck & Co., Inc. A.P. Mishra: None. L. Yang: Employee; Self; Bristol-Myers Squibb Company, Merck & Co., Inc. S. Rajpathak: None.

Glucagon-like peptide-1 receptor agonist use and clinical outcomes after lung transplantation: A single-center cohort study.

PDB25 The Cost-Effectiveness of ORAL Semaglutide in Patients Treated with Currently Available GLP-1 Receptor Agonists - a UK Perspective

<i>Objective:</i> There is mounting evidence regarding the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) and glucagon like peptide-1 receptor agonists (GLP-1RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their utilization. <p> </p> <p><i>Research Design and Methods:</i> We used the nationwide Veterans Affairs (VA) healthcare system dataset from January 1, 2020 to December 31, 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1RA and the facility-level variation in their utilization. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1RA in patients with ASCVD and T2DM. </p> <p> </p> <p><i>Results:</i> Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received SGLT2i while 8.0% of patients received GLP-1RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10<sup>th</sup>-90<sup>th</sup> percentile) facility-level rates were 14.92% (9.31%-22.50%) for SGLT2i and 10.88% (4.44%-17.07%) for GLP-1RA. There was significant facility level variation among SGLT2-Is utilization - MRR<sub>unadjusted</sub> (95% CI):1.41 (1.35-1.47) and MRR<sub>adjusted</sub> (95% CI): 1.55 (1.46 – 1.63). Similar facility level variation was observed for utilization of GLP-1 RA – MRR<sub>unadjusted</sub> (95% CI):1.34 (1.29-1.38) and MRR<sub>adjusted </sub>(95% CI): 1.78 (1.65 – 1.90).</p> <p> </p> <p><i>Conclusions:</i> Overall utilization rates of SGLT2i and GLP-1RA among eligible patients are low with significantly higher residual facility-level variation in utilization of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients. </p>

<i>Objective:</i> There is mounting evidence regarding the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) and glucagon like peptide-1 receptor agonists (GLP-1RAs) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their utilization. <p> </p> <p><i>Research Design and Methods:</i> We used the nationwide Veterans Affairs (VA) healthcare system dataset from January 1, 2020 to December 31, 2020 and included patients with established ASCVD and T2DM. Among these patients, we assessed the use of SGLT2i and GLP-1RA and the facility-level variation in their utilization. Facility-level variation was computed using median rate ratios (MRR), a measure of likelihood that two random facilities differ in use of SGLT2i and GLP-1RA in patients with ASCVD and T2DM. </p> <p> </p> <p><i>Results:</i> Among 537,980 patients with ASCVD and T2DM across 130 VA facilities, 11.2% of patients received SGLT2i while 8.0% of patients received GLP-1RA. Patients receiving these cardioprotective glucose-lowering drug classes were on average younger and had a higher proportion of non-Hispanic Whites. Overall, median (10<sup>th</sup>-90<sup>th</sup> percentile) facility-level rates were 14.92% (9.31%-22.50%) for SGLT2i and 10.88% (4.44%-17.07%) for GLP-1RA. There was significant facility level variation among SGLT2-Is utilization - MRR<sub>unadjusted</sub> (95% CI):1.41 (1.35-1.47) and MRR<sub>adjusted</sub> (95% CI): 1.55 (1.46 – 1.63). Similar facility level variation was observed for utilization of GLP-1 RA – MRR<sub>unadjusted</sub> (95% CI):1.34 (1.29-1.38) and MRR<sub>adjusted </sub>(95% CI): 1.78 (1.65 – 1.90).</p> <p> </p> <p><i>Conclusions:</i> Overall utilization rates of SGLT2i and GLP-1RA among eligible patients are low with significantly higher residual facility-level variation in utilization of these drug classes. Our results suggest opportunities to optimize their use to prevent future adverse cardiovascular events among these patients. </p>

Background: Atherosclerotic cardiovascular disease (ASCVD) frequently coexists with type 2 diabetes (T2D), amplifying morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RA) confer significant cardiovascular benefits and are recommended for patients with T2D and established ASCVD. However, real-world use may not reflect a complication-driven therapeutic approach. Methods: This retrospective study included adults with T2D and established ASCVD (prior myocardial infarction, ischemic stroke, transient ischemic attack, or symptomatic peripheral arterial disease) consecutively admitted to the internal medicine and cardiology departments of a tertiary hospital over a 60-day period. Pre-admission medication use, comorbidities, and laboratory parameters were recorded. Factors associated with GLP-1 RA use were assessed using logistic regression before and after 1:1 propensity score (PS) matching. Results: Among 202 eligible patients, 49 (24.3%) were treated with a GLP-1RA. GLP-1RA users were younger (71.9 vs. 77.8 years, p < 0.001), had lower hypertension prevalence (61.2% vs. 78.4%, p = 0.02), and were more frequently on insulin (69.4% vs. 25.5%, p < 0.001) and sodium-glucose cotransporter 2 inhibitors (55.1% vs. 28.1%, p = 0.001). After PS matching (48 pairs), demographic and comorbidity differences were attenuated, although insulin remained strongly associated with GLP-1RA therapy (Odds Ratio 11.85, p < 0.001). Neither cardiovascular disease burden-captured through the presence of multiple cardiovascular comorbidities-nor renal function were independently associated with GLP-1RA use after adjustment. Conclusions: In patients with T2D and established ASCVD, GLP-1RA use was more strongly associated with the intensity of glucose-lowering therapy-particularly insulin use-than with cardiovascular or renal risk profiles. These findings should be interpreted with caution given the retrospective observational design and the limited availability of glycated hemoglobin, anthropometry and diabetes duration data. However, they suggest that, in real-world clinical practice, GLP-1RA prescribing may remain predominantly glucose-centric rather than complication-driven, underscoring the need for improved implementation of contemporary diabetes guidelines.

The purpose of this paper is to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on stroke or heart disease in patients having chronic respiratory disease and diabetes (CD) with underlying diseases related to COVID-19. From 1998 to 2019, we adjusted competing risk by assessing the effect of GLP-1RAs on stroke or heart disease in a CD cohort after propensity matching based on the Taiwan National Health Insurance Research Database. We also used the time-dependent method to examine the results. GLP-1 RA and non-GLP-1 RA user groups included 15,801 patients (53% women and 46% men with a mean age of 52.6 ± 12.8 years). The time between the diagnoses of DM and the initial use of the GLP-1 RA among the stroke subcohort (<2000 days) was shorter than that of the heart disease subcohort (>2000 days) (all p-values < 0.05). The overall risks of stroke, ischemic, and hemorrhagic stroke were significantly lower in GLP-1 RA users than nonusers. The adjusted subhazard ratio (aSHR) was 0.76 [95% CI 0.65-0.90], 0.77 [95% CI 0.64-0.92], and 0.69 [95% CI 0.54-0.88] (p < 0.05 for all). Furthermore, a ≥351-day use had a significantly lower stroke risk than GLP-1 RA nonusers (aSHR 0.35 [95% CI 0.26-0.49]). The time-dependent method revealed the same result, such as lower stroke, and ischemic or hemorrhagic stroke risk. In contrast, the cardiac arrhythmia incidence was higher in GLP-1 RA users with an aSHR of 1.36 [95% CI 1.16-1.59]. However, this risk disappeared after the ≥351-day use with 1.21 (0.98, 1.68) aSHR. Longer GLP-1 RA use was associated with a decreased risk of ischemic or hemorrhagic stroke and the risk of cardiac arrhythmia disappears in a CD cohort. Both a shorter lag time use of the GLP-1 RA and a longer time use of GLP-1 RA were associated with a decreased risk of ischemic or hemorrhagic stroke in the CD cohort. The GLP-1 RA use in the early stage and optimal time use in the CD cohort may avoid the stroke risk.