Reduced risks of colorectal cancer with GLP-1RAs in type 2 diabetes: A nationwide cohort study using a target trial emulation framework.

To explore the modifying effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO-DKD and FIGARO-DKD. Patients with T2D and CKD treated with optimized renin-angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin-to-creatinine ratio (UACR), and safety were analysed by GLP-1RA use. Of 13 026 patients, 944 (7.2%) used GLP-1RAs at baseline. Finerenone reduced the risk of the cardiovascular composite outcome (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.52-1.11 with GLP-1RA; HR 0.87, 95% CI 0.79-0.96 without GLP-1RA; P-interaction=0.63) and the kidney composite outcome (HR 0.82, 95% CI 0.45-1.48 with GLP-1RA; HR 0.77, 95% CI 0.67-0.89 without GLP-1RA; P-interaction=0.79) irrespective of baseline GLP-1RA use. Reduction in UACR with finerenone at Month 4 was -38% in patients with baseline GLP-1RA use compared with -31% in those without GLP-1RA use (P-interaction=0.03). Overall safety and incidence of hyperkalaemia were similar, irrespective of GLP-1RA use. The cardiorenal benefits of finerenone on composite cardiovascular and kidney outcomes and UACR reduction in patients with CKD and T2D appear to be maintained, regardless of GLP-1RA use. Subsequent studies are needed to investigate any potential benefit of this combination.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have cardioprotective and kidney-protective benefits among patients with type 2 diabetes (T2D). We sought to determine whether GLP-1RA use improves cardiovascular (CV) and kidney outcomes among patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN). We emulated a pragmatic target trial to evaluate the impact of GLP-1RA vs. comparator hypoglycemic agents, dipeptidyl peptidase 4 inhibitors (DPP4i), on CV and kidney outcomes among patients with SLE and T2D using a large, US multi-center electronic health record database. We used propensity score overlap weighting to emulate randomization between treatment groups. Outcomes included major adverse cardiovascular events, venous thrombosis (VTE), kidney disease progression (eGFR decline ≥ 30% or new-onset end-stage kidney disease), and all-cause mortality. We used Cox regression to compare hazard ratios (HR) based on the weighted populations. In a secondary analysis, we only included patients with LN. There were 910 and 1004 initiators of GLP-1RA and DPP4i, respectively, including 267 and 324 patients with LN, respectively. Baseline covariates were balanced after propensity score overlap weighting. The risks of MACE (HR 0.66 [95% CI 0.48-0.91]), VTE (HR 0.49 [0.24-0.97]), kidney disease progression (HR 0.77 [0.60-0.98]), and all-cause mortality (HR 0.26 [CI 0.10-0.68]) were lower with GLP-1RA vs. DPP4i use. GLP-1RA use was similarly associated with lower risks of MACE and kidney disease progression among patients with LN. We found lower risks of adverse CV and kidney outcomes and mortality with GLP-1RA use compared with DPP4i use among patients with lupus and T2D.

Glucagon-Like Peptide-1 Receptor Agonists and Dementia Risk Reduction in Older Adults With Type 2 Diabetes: A Retrospective Cohort Study.

ObjectiveTo determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.DesignPopulation based...

Objective: To determine the prevalence of sodium-glucose contransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1RA) use among adults with type 2 diabetes (T2D) in the United States. Methods: We studied adults with T2D and eGFR ≥30mL/min/1.73m2 who participated in the National Health and Nutrition Examination Survey (NHANES) , focusing on the 2017-2020 examination cycle. We tested prevalence of SGLT2i and GLP1RA use among subgroups based on demographic variables and relevant comorbidities, including chronic kidney disease (CKD) , congestive heart failure (CHF) , and atherosclerotic cardiovascular disease (ASCVD) . We compared use of SGLT2i and GLP1RA to other glucose-lowering medications and assessed trends from prior NHANES cycles. Results: Among 1,375 participants studied in 2017-2020, mean age was 60 years, 46% were women, 13% self-identified as non-Hispanic Black, 10% self-identified as Mexican American, 37% had CKD, 8.5% had CHF, and 23% had ASCVD. The prevalence of SGLT2i and GLP1RA use was 5.8% and 4.4%, respectively. SGLT2i were used by 7.2% of adults with CKD or CHF, and GLP1RA were used by 3.5% of adults with ASCVD. Differences in SGLT2i or GLP1RA use were observed by age, race, ethnicity, and health insurance status. Biguanides, sulfonylureas, DPP-4 inhibitors, and insulin were used more frequently than SGLT2i or GLP1RA. Overall, prevalence of SGLT2i but not GLP1RA use increased significantly from 2013-2014 to 2017-2020. Conclusions: SGLT2i and GLP1RA use is low among adults with T2D, including among those with strong indications. Enhanced implementation of these agents is crucial to improving kidney and cardiovascular outcomes and mitigating health disparities in T2D. Disclosure C.Limonte: None. Y.Hall: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. L.Zelnick: None. Funding This work was supported by an unrestricted fund from the Northwest Kidney Centers. CPL was funded by NIDDK grant T32DK007467 and the American Kidney Fund Clinical Scientist in Nephrology grant program. Additional funding was provided by R01DK126373, R01DK125084, R01DK088762.

In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes. This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor agonist exposure. The Gray test was performed to detect the difference in cumulative incidence functions for progression by GLP-1 receptor agonist use status. The association between time-varying GLP-1 receptor agonist use and progression was estimated through multivariable-adjusted hazard ratio using a stratified Fine-Gray distribution hazard model, with death as a competing event and stratum for the matched patient triad. Our matched cohort included 1097 individuals with MGUS who had ever used GLP-1 receptor agonists and the matched 2194 patients who had never used GLP-1 receptor agonists. Overall, 2.6% of individuals progressed in the GLP-1 receptor agonist ever use group compared with 5.0% in the GLP-1 receptor agonist never use group. Cumulative incidence functions were statistically significantly different between the exposed and unexposed groups (P = .02). GLP-1 receptor agonist use vs no use was associated with decreased progression to multiple myeloma (hazard ratio = 0.45, 95% confidence interval = 0.22 to 0.93, P = .03). For patients with diabetes and MGUS, GLP-1 receptor agonist use is associated with a 55% reduction in risk of progression from MGUS to multiple myeloma compared with no use.

Introduction: In patients with type 2 diabetes (T2D) at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been shown to reduce major adverse cardiovascular events. However, patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been largely excluded from randomized trials. Hypothesis: We investigated whether GLP1-RA use is associated with improved one-year cardiovascular outcomes in patients with T2D undergoing TAVI. Methods: We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with T2D who underwent TAVI between 2015 and 2023 were included and stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). The primary outcome was a composite of all-cause mortality or hospitalization at 1 year. Secondary outcomes included acute heart failure (HF) exacerbation, acute myocardial infarction (AMI), cardiac arrest, and ischemic stroke. Outcomes were assessed from 1 month to 1 year after TAVI. Survival probabilities were estimated using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Results: Among 20,454 patients with T2D undergoing TAVI from 2015-2023, 937 received GLP1-RAs. After PSM, 930 patients were included in each cohort, with a mean age of 73 years and 37% female. The mean follow-up duration was 342 days for GLP1-RA users and 325 days for non-users. GLP1-RA cohort exhibited a higher 1-year survival probability (93.8%) compared to non-users (89.5%) (HR 0.573 [95% CI, 0.410-0.801]; p=0.001). GLP1-RA use was also associated lower rates of all-cause hospitalization (HR 0.762 [95% CI, 0.652-0.891]; p=0.001), acute HF exacerbation (HR 0.687 [95% CI, 0.566-0.834]; p<0.001), and cardiac arrest (HR 0.452 [95% CI, 0.213-0.960]; p=0.034). No differences were observed in AMI (HR 1.033 [95% CI, 0.750-1.423]; p=0.844), or ischemic stroke (HR 0.875 [95% CI, 0.659-1.162]; p=0.356). Conclusions: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiovascular outcomes, including reductions in acute HF exacerbation, all-cause hospitalization, and cardiac arrest. These findings highlight the need for prospective clinical trials to confirm these results.

10508 Background: The use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) has substantially expended given their remarkable benefits in managing obesity. Yet, their impact on long-term cancer risk remains unclear, with existing real-world evidence being limited and yielding conflicting results. Methods: This retrospective cohort study followed a target trial emulation design using 2014–2024 OneFlorida+ electronic health records (EHR) data. Adults (≥18 years) eligible for anti-obesity medications (AOMs) and without a cancer history were included. We compared GLP-RA users vs. non-users, with 1:1 propensity score matching applied to balance baseline factors between the two groups. The primary outcomes include the incidence of 16 obesity-associated cancers (liver, thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, meningioma, esophageal adenocarcinoma, gallbladder, upper stomach, ovarian, multiple myeloma, and prostate), assessed over a follow-up period of up to 10 years. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and cumulative incidences were estimated using Kaplan-Meier analyses. Results: After matching, 43,317 GLP-1RA users were compared with 43,315 non-users. The incidence rates of the 16 cancers were 20.5 versus 23.6 per 1,000 person-years, respectively, indicating a significantly lower overall cancer risk among GLP-1RA users (HR, 0.83 [95% CI, 0.76–0.91]) compared to non-users. In particular, GLP-1RA use was associated with a reduced risk of endometrial cancer (HR, 0.75 [95% CI, 0.57–0.99]), ovarian cancer (HR, 0.53 [95% CI, 0.29–0.96]), meningioma (HR, 0.69 [95% CI, 0.48–0.97]), and esophageal adenocarcinoma (HR, 0.34 [95% CI, 0.12–0.94]). However, GLP-1RA users showed a trend toward an increased risk of kidney cancer (HR, 1.38 [95% CI, 0.99–1.93]), particularly among the younger adults (≤65 years) and overweight patients (BMI 27–29.9). Conclusions: In this large cohort of real-world obesity population with and without diabetes, GLP-1RA use was associated with an overall reduction in obesity-related cancer risk, as well as lower risks of several specific cancers. However, a potential elevated risk of kidney cancer, especially in younger or moderately obese individuals, highlights the need for targeted surveillance and longer-term follow-up to clarify the underlying mechanisms and clinical implications of these findings.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors improve hyperglycemia, and SGLT2 inhibitors and GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACEs) among individuals with type 2 diabetes. It is not clear whether efficacy varies by age or sex. To assess whether age or sex are associated with differences in the efficacy of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP4 inhibitors. The MEDLINE and Embase databases and US and Chinese clinical trial registries were searched for articles published from inception to November 2022; in August 2024, the search was updated to capture the trial results. Two reviewers screened for randomized clinical trials of SGLT2 inhibitors, GLP-1 receptor agonists, or DPP4 inhibitors vs a placebo or active comparator in adults with type 2 diabetes. Individual participant data and aggregate data were used to estimate age × treatment interactions and sex × treatment interactions in multilevel network meta-regression models. Hemoglobin A1c (HbA1c) and MACEs. Of the 601 eligible trials identified (592 trials with 309 503 participants reported HbA1c; mean age, 58.9 [SD, 10.8] years; 42.3% were female and 23 trials with 168 489 participants reported MACEs; mean age, 64.0 [SD, 8.6] years; 35.3% were female), individual participant data were obtained for 103 trials (103 reported HbA1c and 6 reported MACEs). The use of SGLT2 inhibitors (vs placebo) was associated with less HbA1c lowering with increasing age for monotherapy (absolute reduction [AR], 0.24% [95% credible interval {CrI}, 0.10% to 0.38%] per 30-year increment in age), for dual therapy (AR, 0.17% [95% CrI, 0.10% to 0.24%]), and for triple therapy (AR, 0.25% [95% CrI, 0.20% to 0.30%]). The use of GLP-1 receptor agonists was associated with greater HbA1c lowering with increasing age for monotherapy (AR, -0.18% [95% CrI, -0.31% to -0.05%] per 30-year increment in age) and for dual therapy (AR, -0.24% [95% CrI, -0.40% to -0.07%]), but not for triple therapy (AR, 0.04% [95% CrI, -0.02% to 0.11%]). The use of DPP4 inhibitors was associated with slightly better HbA1c lowering in older people for dual therapy (AR, -0.09% [95% CrI, -0.15% to -0.03%] per 30-year increment in age), but not for monotherapy (AR, -0.08% [95% CrI, -0.18% to 0.01%]) or triple therapy (AR, -0.01% [95% CrI, -0.06% to 0.05%]). The relative reduction in MACEs with use of SGLT2 inhibitors was greater in older vs younger participants per 30-year increment in age (hazard ratio, 0.76 [95% CrI, 0.62 to 0.93]), and the relative reduction in MACEs with use of GLP-1 receptor agonists was less in older vs younger participants (hazard ratio, 1.47 [95% CrI, 1.07 to 2.02]). There was no consistent evidence for sex × treatment interactions with use of SGLT2 inhibitors and GLP-1 receptor agonists. The SGLT2 inhibitors and GLP-1 receptor agonists were associated with lower risk of MACEs. Analysis of age × treatment interactions suggested that SGLT2 inhibitors were more cardioprotective in older than in younger people despite smaller reductions in HbA1c; GLP-1 receptor agonists were more cardioprotective in younger people.

Introduction: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and T2D in the FIDELIO-DKD and FIGARO-DKD studies. In FIDELIO-DKD the effects of finerenone on kidney and CV outcomes were consistent irrespective of glucagon-like peptide-1 receptor agonist (GLP-1RA) use, but analyses were better powered to evaluate change in urine albumin-to-creatinine ratio (UACR) . Here, we extend these analyses to patients in both studies (FIDELITY analysis) , thus encompassing a larger population with broader inclusion criteria. Methods: Patients with T2D and CKD (UACR ≥30-<300 mg/g and eGFR ≥25-≤90 mL/min/1.73 m2, or UACR ≥300-≤5000 mg/g and eGFR ≥25 mL/min/1.73 m2) , treated with optimized renin-angiotensin system blockade, were randomized to finerenone or placebo. The effects of finerenone on CV (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained ≥57% eGFR decline, or renal death) composite outcomes, and on UACR at month 4, were analyzed by GLP-1RA use. Results: Of 13026 patients, 944 (7.2%) received GLP-1RAs at baseline. Results were consistent irrespective of GLP-1RA use at baseline for the CV composite outcome (hazard ratio [HR] 0.76; 95% CI 0.52-1.with GLP-1RA; HR 0.87, 95% CI 0.79-0.96 without GLP-1RA; p-interaction 0.63) , and the kidney composite outcome (HR 0.82; 95% CI 0.45-1.48 with GLP-1RA; HR 0.77, 95% CI 0.67-0.89 without GLP-1RA; p-interaction 0.79) . A greater reduction in UACR was observed with finerenone in patients taking GLP-1RA at baseline (placebo-corrected change -38% with GLP-1RA and -31% without GLP-1RA use; p-interaction 0.03) . Incidence of hyperkalemia was similarly increased with finerenone irrespective of GLP-1RA use at baseline. Conclusion: The benefits of finerenone on composite CV and kidney outcomes in patients with CKD and T2D are not modified by GLP-1RA use at baseline, with an increased effect observed for UACR reduction, suggesting a different mechanism of reduction in albuminuria. Disclosure P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. P.Viswanathan: Employee; Bayer AG. R.Lawatscheck: None. A.Joseph: Employee; Bayer AG. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. S.Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. G.Filippatos: Other Relationship; Amgen Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. L.M.Ruilope: Consultant; Bayer AG. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. L.Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG. M.Lambelet: Other Relationship; Bayer AG.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status. The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas. The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are antidiabetic agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxane-induced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation (TTE) using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity score matched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 (International Classification of Diseases, Tenth Revision) codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540 258 patients with 270 129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs 7.6 events per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.73-0.83). This was similar for pulmonary embolism (2.9 vs 3.8 events per 1000 patient-years; HR, 0.74; 95% CI, 0.68-0.82) and deep vein thrombosis (3.9 vs 4.7 events per 1000 patient-years; HR, 0.81; 95% CI, 0.75-0.88). In this propensity score-matched, TTE study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at 1 year compared with patients who received DPP4i.

Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have demonstrated cardiorenal benefits in patients with type 2 diabetes, but their effectiveness in patients with MGUS remains unexplored. To assess the effectiveness of GLP-1 RAs for primary prevention of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with MGUS and diabetes. This retrospective cohort study used a propensity score-matched analysis of data from the TriNetX Global Database, encompassing patients diagnosed with diabetes and MGUS between January 1, 2018, and January 13, 2023. Patients with prior heart failure (HF), ischemic heart disease, coronary revascularization, or stroke or transient ischemic attack before MGUS diagnosis were excluded. The cohort was divided into 2 groups: GLP-1 RA users and nonusers at baseline. After 1:1 propensity score matching, GLP-1 RA users and nonusers were compared up to 5 years from the MGUS diagnosis date. Data analyses were completed January 19, 2025. GLP-1 RA use within 1 year before MGUS diagnosis. The primary end point was MACCE, defined as a composite of all-cause mortality, new-onset HF, acute coronary syndrome, and stroke or transient ischemic attack. Secondary end points included individual MACCE components, decompensated HF, and acute kidney injury or end-stage kidney disease. A total of 4871 patients with MGUS (mean [SD] age, 68.9 [10.1] years; 2366 [48.5%] male) were included (473 GLP-1 RA users and 4398 non-users). A total of 460 users were matched to 460 nonusers, with balanced characteristics (mean [SD] age, 65.0 [10.6] vs 65.1 [11.0] years; 229 [49.7%] male vs 234 [50.8%] male), including 14 patients (3.0%) vs 13 patients (2.8%) identifying as Asian, 8 (21.3%) vs 92 (20.0%) as Black or African American, 25 patients (5.4%) vs 20 patients (4.3%) as Hispanic or Latino, and 243 patients (52.8%) vs 250 patients (54.3%) as White. GLP-1 RA use was associated with a significantly lower risk of MACCE (hazard ratio [HR], 0.75; 95% CI, 0.60-0.93). Significant reductions were also observed in all-cause mortality (HR, 0.57; 95% CI, 0.37-0.87), new-onset HF (HR, 0.69; 95% CI, 0.54-0.90), decompensated HF (HR, 0.60; 95% CI, 0.43-0.84), and acute kidney injury or end-stage kidney disease (HR, 0.73; 95% CI, 0.57-0.92). The findings of this cohort study of GLP-1 RA use vs no use in patients with MGUS and diabetes suggest the potential of GLP-1 RA for primary prevention of MACCE. These findings warrant further investigation in prospective randomized trials.

Time to Follow the Evidence: Glycemic Control and Cardiovascular Benefits of New Diabetes Medications

Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction. Using data from nationwide registers in Sweden, Denmark, and Norway, 2013-2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors). Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6-2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96-1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4-1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69-1.01). In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.