Letter to the Editor Regarding "Association of Glucagon-like Peptide-1 Receptor Agonist Use with Complications Following Thoracic and/or Lumbar Spinal Fusion for Degenerative Spine Disease": A BMI-Stratified Retrospective Study.

Retrospective Cohort. Spinal fusions are common interventions for degenerative spine disease (DSD), with increasing utilization in obese and metabolic syndrome populations. Glucagon-like peptide-1 (GLP-1) receptor agonists (RA), widely adopted for diabetes and weight management, may offer systemic benefits that exert a parallel influence on surgical outcomes. We aimed to evaluate whether preoperative GLP-1 RA use influences 90-day medical and 2- and 10-year surgical complications following thoracic and/or lumbar spinal fusion for DSD, stratified by BMI. Using a national claims database (2010-2023), we identified patients undergoing thoracic and/or lumbar spinal fusion for degenerative conditions. GLP-1 RA users within 6 months pre-op were 4:1 matched to controls by age, sex, and CCI across six BMI strata. Outcomes included 90-day medical and 2- and 10-year surgical complications (e.g., revisions for infection, pseudoarthrosis, and mechanical failure). Chi-square, t-tests, and Cox models were used for statistical analysis. Among 291,677 patients, 19,232 GLP-1 RA users were matched to 76,778 controls. Ninety-day medical complications-such as infection, pneumonia, thromboembolism, sepsis, stroke, and UTI-were significantly reduced in GLP-1 RA users across BMI categories ≥25. Two-year surgical complications were lower among GLP-1 RA users in BMI 35-39.9 (1.1% vs. 1.6%, P=0.007 for pseudarthrosis-related revision; 0.8% vs. 1.2%, P=0.038 for mechanical failure) and ≥40 groups. At 10 years, GLP-1 RA use was associated with significantly reduced risk of revision in the 25.0-29.9 (HR 0.79, P=0.046) BMI group. Revision due to pseudarthrosis was reduced in BMI 35.0-39.9 (HR 0.69, P=0.014) and ≥40.0 (HR 0.73, P=0.041), while revision for mechanical failure was lower in BMI 35.0-39.9 (HR 0.65, P=0.013) and ≥40.0 (HR 0.57, P=0.003). GLP-1 RA use was linked with reduced perioperative and long-term surgical complications in patients undergoing thoracic and/or lumbar fusions for degenerative spine disease, particularly in those with BMI ≥25. This risk reduction may be attributed to weight loss and/or the systemic metabolic, inflammatory, and vascular benefits of these medications.

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.

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.

Prevalence of SGLT2i and GLP1RA use among US adults with type 2 diabetes

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.

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.

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.

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...

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.

Obesity in women of childbearing age disrupts lipid metabolism in pregnancy. This study aims to evaluate the impact of prepregnancy glucagon-like peptide-1 receptor agonist (GLP-1RA) use on lipid metabolism during pregnancy. A retrospective case-control study with 42 participants was employed to analyze the impact of prepregnancy GLP-1RA use on lipid metabolism during pregnancy in women with obesity. An animal study involved 60 virgin female Sprague Dawley rats fed a normal diet or a high-fat diet (HFD) for 8 weeks, with the latter diet divided into HFD + saline, HFD + liraglutide, and HFD + semaglutide for 4 weeks. Rats were mated and then sacrificed on gestational day 21. Clinically, prepregnancy GLP-1RA use reduced prepregnancy BMI, gestational weight gain, ratio with first-trimester metabolic dysfunction-associated steatotic liver disease, and triglyceride levels during pregnancy. In animals, GLP-1RA improved plasma fibroblast growth factor 21 (FGF21), adiponectin, triglyceride levels, and leptin in midgestation. During late gestation, compared with the HFD group, the GLP-1RA groups exhibited improved liver lipid deposition, increased fatty acid oxidation and lipolysis genes, decreased lipogenesis genes, and increased extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor γ (PPAR-γ) and AMP-activated protein kinase (AMPK)/NAD-dependent protein deacetylase sirtuin-1 (SIRT1) pathways in liver; in the visceral adipose, the GLP-1RA groups showed increased lipolysis genes, decreased lipogenesis genes, and increased phosphorylated to total fibroblast growth factor receptor 1 (FGFR1) with activated ERK/PPAR-γ pathways. Prepregnancy GLP-1RA use improves maternal lipid metabolism during pregnancy, potentially involving elevated liver-secreted FGF21. This study offers a new strategy for treating lipid metabolic disorders in pregnancy.

BackgroundTo evaluate the association between Glucagon-like peptide-1 receptor agonists (GLP-1RA) use and the risk of acute diabetes complications among adults with type 1 diabetes (T1D) who were eligible for anti-obesity medication (AOM) treatment.MethodsWe employed a target trial emulation using EHR data from the OneFlorida+ network (2014–2024) to investigate the association between GLP-1RA initiation and acute diabetes complications among adults with T1D. Eligible participants were adults with a diagnosis of T1D and who met clinical criteria for AOM treatment. GLP-1RA initiators were 1:1 matched to non-initiators using time-conditional propensity scores. The primary outcome was the occurrence of diabetic ketoacidosis (DKA). Secondary outcomes included severe hypoglycemia, all-cause hospitalizations, and emergency department (ED) visits. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We applied a causal learning approach to explore heterogeneous treatment effects.FindingsThe matched cohort included 651 GLP-1RA users and 651 non-users. For GLP-1RA users and non-users, the incidence rates were 13.5 vs. 21.8 per 1,000 person-years for DKA. Compared to non-users, GLP-1RA use was not significantly associated with incidence of DKA (HR 0.62 [95%CI 0.33–1.17]) or severe hypoglycemia (HR 0.52 [95%CI 0.17–1.55]); notably, GLP-1RA use was significantly associated with fewer hospitalizations (HR 0.74 [95%CI 0.62–0.90]) and ED visits (HR 0.73 [95%CI 0.57–0.92]).InterpretationAmong adults with T1D and obesity, GLP-1RA use was not associated with an increased risk of DKA or severe hypoglycemia but was linked to fewer ED visits and hospitalizations.FundingThe study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) R01DK133465.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) 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 versus comparator hypoglycemic agents, dipeptidyl peptidase 4 inhibitors (DPP4i), on CV and kidney outcomes among patients with SLE and T2D using a large, US multicenter electronic health record database. We used propensity score overlap weighting to emulate randomization among treatment groups. Outcomes included major adverse CV events, venous thromboembolism (VTE), kidney disease progression (estimated glomerular filtration rate 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 1,004 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 major adverse cardiac events (MACEs; hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.48-0.91), VTE (HR 0.49, 95% CI 0.24-0.97), kidney disease progression (HR 0.77, 95% CI 0.60-0.98), and all-cause mortality (HR 0.26, 95% CI 0.10-0.68) were lower with GLP-1RA versus 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.

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.

Of the 808,000 US dialysis patients, 60% have diabetes and are eligible for glucagon-like peptide-1 (GLP-1) receptor agonists. Safety and outcomes in this population is unknown. We sought to examine GLP-1 receptor agonist real-world safety, efficacy, and weight loss in people with diabetes on dialysis. In this observational national cohort study (2013-2021), we identified adults with type 2 diabetes on dialysis. The exposure of interest was GLP-1 receptor agonist use. Body mass index (BMI) change after dialysis initiation was quantified among patients with two measurements (N=6,474). Extended Cox models with inverse probability of treatment weights (censoring for kidney transplant waitlisting) were used to quantify all-cause mortality associated with GLP-1 receptor agonists. Specific safety outcomes (acute pancreatitis, biliary complications, medullary thyroid cancer, diabetic retinopathy) were assessed. The study included 151,649 incident dialysis patients with type 2 diabetes. Mean BMI and weight change among GLP-1 receptor agonist users were greater than that among non-users (-1.47 versus -0.61 kg/m2; -4.03 versus -1.47 kg; P<0.001 for both). The mortality incidence rate was lower among GLP-1 receptor agonist users (219.0 versus 279.5 cases/1,000 person-years; P<0.001). GLP-1 receptor agonist use was associated with a 23% lower risk of mortality (adjusted hazard ratio [aHR]: 0.77, 95% confidence interval [CI]:0.70-0.85; P<0.001); results were consistent among initiates with BMI≥30 kg/m2. GLP-1 receptor agonist use was associated with a 66% higher chance of waitlisting (aHR=1.66, 95%CI:1.28-2.13; P<0.001). There was an increased association with diabetic retinopathy (aHR=1.32, 95%CI:1.12-1.56; P=0.001), but not with any other safety outcomes. Inferences were consistent across multiple sensitivity analyses. GLP-1 receptor agonist use in patients with type 2 diabetes on dialysis was associated with weight loss, reduced mortality risk, and increased likelihood of kidney transplant waitlisting. These real-world data are the strongest evidence to date supporting GLP-1 receptor agonist use in this population.

Diabetic kidney disease (DKD), a devastating complication of diabetes, is one of the leading causes of end stage kidney disease (ESKD). Kidney transplantation provides superior outcomes for ESKD patients with type 2 diabetes, giving opportunities to be free from dialysis, but needs lifetime immunosuppressive medications to avoid graft kidney rejection. Post-transplant hyperglycemia, however, remains to be unsolved, because immunosuppressive agents, including glucocorticoids and calcineurin inhibitors, may result in impaired insulin secretion and sensitivity. Safe and promising anti-diabetic strategy is long-awaited among kidney transplant recipients (KTRs) with type 2 diabetes. Enormous evidence has accumulated that Glucagon-like peptide 1 (GLP-1) receptor agonists have potential to maintain kidney function as well as improve glucose tolerance in patients with DKD. The present study was designed to elucidate the association between GLP-1 receptor agonist use and better graft kidney function in KTRs with type 2 diabetes. Among KTRs with type 2 diabetes between 2012 and 2019, 73 with GLP-1 receptor agonist use and 73 without GLP-1 receptor use were identified in our center. After propensity matching, 50 KTRs were newly initiated with GLP-1 receptor agonist use or other antidiabetic medications. Baseline characteristics were well-balanced in the 2 groups. KTRs with GLP-1 receptor agonist use had greater kidney function 12 months after initiation of GLP-1 receptor agonists, compared to their counterpart KTRs without GLP-1 receptor agonists, according to estimated glomerular filtration ratio (p=0.01). Interestingly, transient decrease of body mass index was observed in KTRs with GLP-1 receptor agonist use during the 12 months. All GLP-1 receptor agonist-initiated KTRs were followed up through December 31, 2019. In conclusion, GLP-1 receptor agonist treatment was associated with better graft kidney function in KTRs with type 2 diabetes. Pharmacological GLP-1 receptor activation showed favorable tolerability and may alleviate graft kidney damage in KTRs with type 2 diabetes.