Abstract 4367416: GLP-1 Receptor Agonists and Mortality Outcomes in Patients with Left Ventricular Assist Devices: A Propensity-Matched Cohort Study from the TriNetX Global Network

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.

Randomized clinical trials have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause significant weight loss and reduce cardiovascular events in patients with type 2 diabetes (T2D). Black patients have a disproportionate burden of obesity and cardiovascular disease and have a higher rate of cardiovascular-related mortality. Racial and ethnic disparities in health outcomes are largely attributable to the pervasiveness of structural racism, and patients who are marginalized by racism have less access to novel therapeutics. To evaluate GLP-1 RA uptake among a commercially insured population of patients with T2D; identify associations of race, ethnicity, sex, and socioeconomic status with GLP-1 RA use; and specifically examine its use among the subgroup of patients with atherosclerotic cardiovascular disease (ASCVD) because of the known benefit of GLP-1 RA use for this population. This was a retrospective cohort analysis using data from OptumInsight Clinformatics Data Mart of commercially insured adult patients with T2D (with or without ASCVD) in the US. Data from October 1, 2015, to June 31, 2019, were included, and the analyses were performed in July 2020. We estimated multivariable logistic regression models to identify the association of race, ethnicity, sex, and socioeconomic status with GLP-1 RA use. A prescription for a GLP-1 RA. Of the 1 180 260 patients with T2D (median [IQR] age, 69 [59-76] years; 50.3% female; 57.7% White), 90 934 (7.7%) were treated with GLP-1 RA during the study period. From 2015 to 2019, the percentage of T2D patients treated with an GLP-1 RA increased from 3.2% to 10.7%. Among patients with T2D and ASCVD, use also increased but remained low (2.8%-9.4%). In multivariable analyses, lower rates of GLP-1 RA use were found among Asian (aOR, 0.59; 95% CI, 0.56-0.62), Black (adjusted odds ratio [aOR] 0.81; 95% CI, 0.79-0.83), and Hispanic (aOR, 0.91; 95% CI, 0.88-0.93) patients with T2D. Female sex (aOR, 1.22; 95% CI, 1.20-1.24) and higher zip code-linked median household incomes (>$100 000 [OR, 1.13; 95% CI, 1.11-1.16] and $50 000-$99 999 [OR, 1.07; 95% CI, 1.05-1.09] vs <$50 000) were associated with higher GLP-1 RA use. These results were similar to those found among patients with ASCVD. In this cohort study of US patients with T2D, GLP-1 RA use increased, but remained low overall for treatment of T2D, particularly among patients with ASCVD who are likely to derive the most benefit. Asian, Black, and Hispanic patients and those with low income were less likely to receive treatment with a GLP-1 RA. Strategies to lower barriers to GLP-1 RA use, such as lower cost, are needed to prevent the widening of well-documented inequities in cardiovascular disease outcomes in the US.

BackgroundThe rising prevalence of obesity and type 2 diabetes mellitus (T2DM) among patients undergoing total joint arthroplasty (TJA) presents a significant clinical challenge, increasing the risk of postoperative complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a potential perioperative optimization strategy, but their impact on TJA outcomes remains debated. This systematic review was conducted to synthesize the evidence on the risks and benefits of GLP-1 RA use in adult patients undergoing primary TJA—specifically, total hip arthroplasty (THA), total knee arthroplasty (TKA), and total shoulder arthroplasty (TSA).MethodsA systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Scopus, and Web of Science databases were searched from their inception to June 16, 2025, for studies comparing postoperative outcomes in adult patients undergoing primary total joint arthroplasty (TJA) and using GLP-1 RAs versus a control group. Data on study characteristics, patient demographics, and postoperative outcomes were extracted. Due to significant heterogeneity and overlap in data sources, a narrative synthesis rather than meta-analysis of the findings was conducted. Study quality was assessed using the Newcastle–Ottawa Scale (NOS).ResultsFifteen retrospective cohort studies involving an aggregate total of 318,143 patients (114,365 THA, 125,505 TKA, 78,273 TSA) were included, with 56,132 receiving GLP-1 RAs. In THA and TKA, GLP-1 RAs use was associated with a reduced risk of periprosthetic joint infection (PJI) (e.g., 1.6% vs. 2.9% at 2 years for THA) and lower 90-day readmission rates (e.g., 1.1% vs. 2.0% for TKA and 1.6% vs. 2.0% for THA). When analyzed by exposure timing, the reduced PJI risk was most consistent in studies that defined GLP-1 RA use in the immediate perioperative period. Reported mean length of stay (LOS) was generally similar or slightly shorter among GLP-1 RA users compared to controls. Multiple studies reported either a reduction or no significant difference in the risk of 90-day emergency department visits. The short-term revision rates and dislocations were infrequent and did not differ significantly between groups in most of the included studies. In the TSA, evidence was inconsistent, with reduced odds of 90-day surgical site infection (SSI) (OR 0.25) in one study; however, no clear trend was observed. Gastrointestinal side effects and conflicting systemic risks were noted across procedures.ConclusionCurrent observational data suggest that perioperative GLP-1 RA use in patients undergoing total hip or knee arthroplasty is not associated with a consistent increase in short-term revision rates and may be associated with a reduced risk of postoperative infection. Evidence regarding TSA remains inconclusive. However, given the retrospective nature of the evidence, substantial overlap in data sources, heterogeneity in exposure definitions, and short-term follow-up, these findings should be considered hypothesis-generating. Future prospective, randomized controlled trials with standardized exposure definitions and longer follow-up are required to confirm these associations and establish causality.Supplementary InformationThe online version contains supplementary material available at 10.1186/s42836-026-00375-w.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective medications for the treatment of type 2 diabetes and obesity. Pharmacological studies in rodents support an association between the use of GLP-1 RAs and the development of medullary thyroid cancer (MTC) resulting in a black box warning for these agents in patients at risk for this condition. Yet, the association between GLP-1 RAs and non-MTC remains controversial. Excessive worry about unproven thyroid cancer risk might lead to underutilizing GLP-1 RAs in patients who could otherwise experience substantial benefits. Unwarranted concerns about thyroid cancer could lead to unnecessary thyroid cancer screening and harms from overdiagnosis. Summary: The body of evidence assessing the association between GLP-1 RA use and thyroid cancer spans a wide range of methodologies, including basic and translational research investigating biological plausibility; randomized trials assessing clinical efficacy and providing the strongest evidence for causality; observational studies providing real-life outcome evaluation in larger populations but with limited evaluation of covariates or dependable outcome definitions; and pharmacovigilance studies that provide postmarketing assessments of a safety signal but do not address causality. There is biological plausibility supporting an association between GLP-1 RA and MTC in rodents, which is less clear for non-MTC in humans. Clinical evidence from randomized trials and associated meta-analysis suggest thyroid cancer as a rare event making effect estimates imprecise but without conclusive and consistent evidence of increase risk in those receiving GLP-1 RA. Observational studies at higher risk of bias also show low event rates for thyroid cancer, with effect estimates that are inconsistent among different studies. Pharmacovigilance studies consistently show a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RA. Conclusions: Evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA. Observational studies at higher risk of bias yield inconsistent results. Overall there is no conclusive evidence of elevated thyroid cancer risk. These findings can help clinicians when addressing patient's concerns about a potential yet unproven link between GLP-1 RA therapy and thyroid cancer.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medication that is highly effective at treating Type 2 diabetes (T2D) due to its glucose-lowering ability. Although people with T2D treated with basal insulin may use both GLP-1 RA and Freestyle Libre (FSL) glucose monitors, the impact of FSL utilization on glycemic outcomes in the presence of GLP-1 RAs has not been widely studied. We conducted a retrospective cohort study using linked databases of FSL glucose values and Inovalon Insights insurance claims. Patients were ≥18 yrs old, diagnosed with T2D, initiated FSL between November 2017 and March 2022, and treated with basal insulin and GLP-1 RAs. FSL use and GLP-1 RA adherence were calculated using proportion of days covered (PDC) over 12-months from the index date (date of FSL initiation). Consistent FSL and adherent GLP-1 RA use were defined as PDC ≥0.8. Glucose management indicator (GMI) and % time in range (TIR) were calculated at baseline, 6-, and 12-months post index, and change in glycemic metrics from baseline to 12-months were assessed using paired t tests. A total of 2141 individuals met the inclusion criteria. Among consistent FSL users (56%), GMI and TIR did not change significantly from baseline to 12-months. However, among inconsistent FSL users (44%), changes were statistically significant overall: GMI increased by 0.27% (p&amp;lt;0.001) and TIR decreased by 3.94% (p&amp;lt;0.001). Subgroup analysis showed that regardless of GLP-1 RA adherence, inconsistent FSL users still had statistically significant worsening in GMI (nonadherent: 0.30%, p&amp;lt;0.001; adherent: 0.22%, p=0.006) and TIR (nonadherent: -3.70%, p&amp;lt;0.001; adherent: -4.34%, p=0.001). This study shows that frequent use of FSL plays a pivotal role in glucose management among people with T2D treated with basal insulin and GLP-1 RAs, where consistent FSL use is associated with sustained glycemic control, and inconsistent FSL use is associated with worsened glycemic outcomes. Disclosure E. Huang: Employee; Abbott. K. Kao: Employee; Abbott. L. Brandner: Employee; Abbott. A. Bindal: Employee; Abbott.

Type 2 diabetes mellitus (T2DM) is an independent risk factor for osteoporosis, increasing the risk of fractures and poor prognosis. Recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may play a protective role in bone metabolism. However, limited evidence exists on their effect on osteoporosis incidence in T2DM patients. This study aimed to evaluate the association between GLP-1 RA use and osteoporosis risk in a real-world cohort of elderly T2DM patients. This retrospective cohort study utilized electronic medical records (EMRs) from Tangdu Hospital, Xi'an, China, between January 1, 2012, and December 31, 2023. Patients with T2DM who had at least two clinical visits annually and no prior osteoporosis diagnosis (ICD-10: M80-M82) at baseline were included. The primary outcome was the incidence of osteoporosis during follow-up. Cox proportional hazards models were used to evaluate the association between GLP-1 RA use and osteoporosis risk, adjusting for age, sex, BMI, blood pressure, lipid profile, renal function, osteocalcin, vitamin D levels, HbA1c, statin use, antihypertensive medication use, and smoking status. Subgroup analyses were conducted to assess potential effect modifications. A total of 1,845 patients with T2DM were included, of whom 676 (36.6%) developed osteoporosis during follow-up. Among the 256 patients who received GLP-1 RAs, the incidence of osteoporosis was significantly lower than in those who did not receive GLP-1 RAs (P < 0.01). In the fully adjusted Cox model, GLP-1 RA use was associated with a significantly reduced risk of osteoporosis compared to non-users (hazard ratio [HR] = 0.69, 95% confidence interval [CI] =0.45-0.84, P < 0.05). Subgroup analyses indicated that the protective effect of GLP-1 RAs was consistent across age, sex, BMI, smoking status, and antihypertensive medication use (P for interaction > 0.05). In patients with T2DM, patients with treatment of GLP-1 RAs resulted in lower risks of osteoporosis than those without treatment of GLP-1 RAs. These findings support the potential bone-protective effects of GLP-1 RAs but further randomized controlled trials (RCTs) or large-scale database analyses are needed to confirm these observations and guide clinical recommendations.

Background: Glucagon-like peptide receptor agonists (GLP-1 RAs) are associated with delayed gastric emptying and may increase the risk of aspiration due to retained gastric contents. There are no guidelines on peri-endoscopic use of GLP-1 RAs, and real-world outcomes in an ambulatory setting remain unknown. This study reports real-world data from an ambulatory center associated with a large tertiary hospital. Methods: A retrospective review of electronic medical records was conducted for patients who underwent esophagogastroduodenoscopy (EGD) at a hospital-based outpatient center from January to June 2023. Exclusions included non-elective procedures, current opioid use, altered foregut anatomy, and known gastroparesis. All patients were on GLP-1 RAs before endoscopy and followed standard fasting protocols. Adverse event rates were recorded, and patients were divided into cohorts based on GLP-1 RA use. Univariate and multivariate regression analyses identified risk factors for food retention and complications. Results: A total of 1438 patients underwent elective EGD during the study period. Among the 1046 patients included, 73 (7%) were on GLP-1 RAs. The procedure was aborted in four patients (0.4%) due to gastric food retention, with two (50%) on GLP-1 RAs. Independent risk factors for food retention included GLP-1 RA use (OR: 9.19; 95% CI: 2.73–30.8; p = 0.0003) and diabetes (OR 5.6; 95% CI: 1.72–18.2; p = 0.004). Tirzepatide showed the strongest association (p = 0.0056). Factors that did not impact food retention included A1c, BMI, and gender. Protective factors were age (OR 0.96; 95% CI: 0.93–0.99; p = 0.02) and same-day colonoscopy (OR 0.18; 95% CI: 0.06–0.58; p = 0.003). Conclusions: GLP-1 RA use in diabetics increases the risk of retained gastric contents during elective EGD, particularly with tirzepatide, without increasing aspiration risk. Patients undergoing simultaneous colonoscopy had a lower risk of retained gastric contents. Further studies are needed to evaluate the impact of GLP-1 RAs on gastric food retention and procedural risk.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective drugs for the treatment of type 2 diabetes mellitus and the management of obesity. Although these medications are generally safe, concerns have emerged regarding the possible link between GLP-1 RA use and thyroid cancer, particularly medullary thyroid carcinoma. This systematic review and meta-analysis aimed to investigate the association between GLP-1 RA use and the risk of all types of thyroid cancer. Materials and Methods: A systematic search was performed using Embase, PubMed/Medline, the US Clinical Trials Registry, and Google Scholar up to July 2024 for randomized controlled trials (RCTs) on GLP-1 RAs in diabetic or overweight/obese adults with at least 24 weeks of treatment and reported thyroid cancer incidence. A random-effects meta-analysis model was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) of the risk of thyroid cancer in the GLP-1 RA group compared to control groups. Assessments of subgroup analyses and publication bias were also performed. Results: Of the 44 RCTs in the meta-analysis, which involved 84,472 study participants, there was no significant association between the use of GLP-1 RAs and thyroid cancer when compared to control groups (OR = 1.11; 95% CI = 0.74–1.69). In the subgroup analysis based on the comparators, population, and type of GLP-1 RAs, no significant association was found to be associated with the risk of thyroid cancer. Conclusion: The analysis showed no increased risk of thyroid cancer with GLP-1 RAs use. However, large-scale, long-term studies are necessary given the very low incidence of thyroid cancer and variations in the duration of treatment.

Type 2 diabetes mellitus (T2D) is associated with an increased burden of neuropsychiatric disorders, including cognitive decline, affective disorders, and substance use disorders. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for glycemic control and weight reduction, have been hypothesized to confer neuroprotective and psychotropic benefits via central and peripheral mechanisms. However, evidence across individual studies remains inconsistent. We conducted a systematic review and meta-analysis (PROSPERO CRD420251025534) of randomized controlled trials (RCTs) and observational studies assessing the effect of GLP-1 RAs on neuropsychiatric outcomes. Searches were performed in MEDLINE, SCOPUS, CENTRAL, and Web of Science up to 30th October 2025. Eligible comparators included placebo, standard care, or alternative glucose-lowering agents. Data were synthesized using random-effects models, and risk of bias was assessed using RoB2 and ROBINS-I. Evidence certainty was graded using GRADE methodology. From 10,037 records, 82 studies were included. GLP-1 RAs were associated with a reduced risk of idiopathic Parkinson's disease (PD) (pooled HR 0.70, 95% CI: 0.53-0.92, I2 = 38%) but no improvements in motor symptoms in established PD (MDS-UPDRS Part III off-medication: mean difference -3.29, 95% CI: -7.84, 1.26, I2 = 80%). No consistent improvements in non-motor symptoms, quality of life, or dyskinesia scores were seen. GLP-1 RAs were associated with a reduced risk of cannabis use disorder (pooled HR 0.55, 95% CI: 0.39-0.77, I2 = 71%) but showed no significant effect on opioid use disorder (pooled HR 0.61, 95% CI: 0.24-1.52, I2 = 91%). Liraglutide reduced binge frequency in binge eating disorder (mean difference -1.28, 95% CI: -1.67, -0.89, I2 = 53%) compared to placebo. In observational studies versus non-user controls, GLP-1 RA use was associated with a lower reported risk of suicidality (pooled OR 0.34, 95% CI: 0.18-0.63, I2 = 99%), but no such association was seen with Semaglutide alone (pooled OR 0.71, 95% CI: 0.29-1.73, I2 = 99%), active-comparator studies (pooled HR 0.96, 95% CI: 0.81-1.15, I2=0%) or RCTs (pooled RR 1.13, 95% CI: 0.53-2.41, I2=0%). No associations were observed for depression or anxiety. For dementia, findings were mixed: no benefit versus SGLT2 inhibitors (pooled RR 1.07, 95% CI: 0.73-1.56, I2 = 78%), but there was a reduced risk of Alzheimer's disease when compared to unmatched or non-exposed controls (pooled RR 0.37, 95% CI: 0.14-0.96, I2 = 98%). Certainty of evidence ranged from moderate to very low. Current evidence, largely of low to very low certainty, suggests potential selective neuropsychiatric associations of GLP-1 RAs, particularly in Parkinson's disease risk reduction and binge eating disorder. Benefits for dementia risk reduction were observed primarily in comparisons with non-exposed or DPP4i, whereas no advantage was seen versus other active comparators, such as SGLT2 inhibitors. Our findings should be interpreted as hypothesis-generating due to significant heterogeneity and wide confidence intervals, indicating imprecision. Longer-term studies with neuropsychiatric outcomes as the primary endpoint are required.

Aims/hypothesisWhether sodium–glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs.MethodsWe designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained.ResultsThe numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs.Conclusions/interpretationAt current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.Graphical abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control and promote weight loss but may increase gastric residue, raising concerns during esophagogastroduodenoscopy (EGD). African American patients remain underrepresented in research on these agents. We performed a retrospective cohort study at a single tertiary referral center, including adults (≥ 18 years) undergoing elective EGD. Participants were divided into two groups based on documented GLP-1 RA use within 7 days of EGD versus no use. Outcomes included the presence of residual gastric contents, procedure abortion due to gastric residue, procedural bleeding, and post-procedural hospitalization. We applied multiple imputation for missing data and entropy balancing for covariate adjustment, reporting odds ratios (OR) and 95% confidence intervals (CI). Among 1408 participants, 270 used GLP-1 RAs. Compared to non-users, GLP-1 RA users had a higher mean body mass index (33 vs. 30 kg/m2) and hemoglobin A1c (7.43% vs. 6.54%). In the adjusted analysis, GLP-1 RA treatment was not significantly associated with increased gastric content (OR, 1.52; 95% CI, 0.58-3.99; p = 0.395) or other procedural complications. Conversely, GLP-1 RA use was linked to lower post-procedural hospitalization rates (OR, 0.19; 95% CI, 0.06-0.58; p = 0.004). In this predominantly African American cohort, recent GLP-1 RA therapy did not significantly elevate intra-procedural risk or necessitate procedure abortion. These findings suggest that routine discontinuation of GLP-1 RAs prior to EGD may not be universally required, especially for patients benefiting from improved metabolic control. Larger prospective studies are warranted to inform guideline updates for diverse patient populations.

GLP-1 receptor agonist use in elective lumbar spine surgery: Reduced pseudarthrosis rates and favorable safety profile.

Data concerning glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on risk of ischemic optic neuropathy (ION) are conflicting. We synthesize current evidence of GLP-1 RAs on risk of optic nerve or vision-threatening events from randomized controlled trials (RCTs) in patients with type 2 diabetes or cardiometabolic diseases. A total of 83,288 participants with type 2 diabetes/cardiometabolic diseases from 20 published RCTs were analyzed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RCTs investigating GLP-1 RAs for type 2 diabetes/cardiometabolic disease populations and reported optic nerve or vision-related adverse events were assessed. Primary outcome was a composite of optic nerve and/or vision-threatening serious adverse events, including ION, ocular ischemic syndrome, papilledema, blindness, blurred vision, visual impairment, and reduced visual acuity. Odds ratios (ORs) were derived. Type 2 diabetes occurred in 76.4% of participants. Over mean follow-up duration of 2.97 years (estimated cumulative exposure of 240,334 patient-years), GLP-1 RA use was not associated with increased risk of primary end point (OR 1.20, 95% CI 0.73-1.97, I2 = 0%). Prespecified individual adverse events, including ION (OR 1.50, 95% CI 0.49-4.63), and vision loss/disturbance events (OR 1.08, 95% CI 0.60-1.94) were not significantly associated with GLP-1 RA use. RCTs reported vision-threatening events as adverse events rather than as prespecified outcomes. Based on a large number of patients who contributed to a meta-analysis of RCTs involving participants with type 2 diabetes and cardiometabolic disease, GLP-1 RAs were not associated with an increased risk of optic nerve/vision-threatening events.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are extensively used in treating diabetes and obesity, yet little is known about the long-term ocular effects of systemic prolonged exposure. To evaluate the risk of developing neovascular age-related macular degeneration (nAMD) associated with the use of GLP-1 RAs in patients with diabetes. This population-based, retrospective cohort study was conducted from January 2020 to November 2023, with a follow-up period of 3 years. Data analysis was performed from August 2024 to October 2024. The investigators used comprehensive administrative health and demographic data from patients in Ontario, Canada, which were collected by the Institute for Clinical Evaluative Sciences in the context of a universal public health care system. Inclusion criteria were patients aged 66 years or older with a diagnosis of diabetes and a minimum follow-up period of 12 months following initial diabetes diagnosis. Patients with incomplete Ontario Health Insurance Plan or Ontario Drug Benefit data or patients exposed to GLP-1 RA for less than 6 months were excluded. Of 1 119 517 eligible patients, a 1:2 matched cohort of 139 002 patients was created, including 46 334 patients who were exposed to GLP-1 RAs and 92 668 unexposed matched patients. Systemic comorbidities that were associated with any kind of AMD and socioeconomic status were used to calculate propensity scores. GLP-1 RA use for 6 months or longer. The primary outcome was the incidence and time to event of nAMD during the follow-up period. Among 139 002 matched patients, mean (SD) patient age was 66.2 (7.5) years, and 64 775 patients (46.6%) were women. The incidence of nAMD was higher among the exposed cohort than among the unexposed cohort. Cox proportional hazard models, both unadjusted (crude) and adjusted, estimated hazard ratios for nAMD development of greater than 2.0 among patients exposed to GLP-1 RAs (exposed, 0.2% vs unexposed, 0.1%; difference, 0.1%; crude: HR, 2.11; 95% CI, 1.58-2.82; adjusted: HR, 2.21; 95% CI, 1.65-2.96). In this cohort study, the use of GLP-1 RAs among patients with diabetes was associated with a 2-fold higher risk of incident nAMD development than among similar patients with diabetes who did not receive a GLP-1 RA. Further research is needed to elucidate the exact pathophysiological mechanisms involved and to understand the trade-offs between the benefits and risks of GLP-1 RAs.

Comparative risk of infections with GLP-1 receptor agonists versus SGLT2 inhibitors in patients with advanced chronic kidney disease and type 2 diabetes.