Dataset Information

Glucagon-Like Peptide-1 Receptor Agonists and Hepatic Decompensation Events in Patients With Cirrhosis and Diabetes.

ABSTRACT:

Background & aims

The study sought to compare the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in reducing decompensation events, among patients with cirrhosis and type 2 diabetes.

Methods

This population-based, retrospective cohort study included patients with type 2 diabetes and cirrhosis, in a commercial healthcare database (IBM MarketScan). We constructed 3 pairwise, 1:1 propensity score (PS)-matched cohorts of adults initiating GLP-1RAs or a comparator medication (ie, DPP-4 inhibitors [2006-2020], sulfonylurea [2005-2020], or SGLT-2 inhibitors [2013-2020]). Patients were followed in an as-treated approach for decompensation events (ie, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, or esophageal variceal hemorrhage). Within each PS-matched cohort, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), controlling for >90 baseline characteristics.

Results

Over 132 days of median follow-up (interquartile range, 73-290 days), PS-matched rates of any decompensation were significantly lower among GLP-1RA initiators, versus DPP-4 inhibitor initiators (105.2 vs 144.0 per 1000 person-years [PY]; HR, 0.68; 95% CI, 0.53-0.88; n = 1431 pairs), and versus sulfonylureas (97.3 vs 144.0 per 1000 PY; HR, 0.64; 95% CI, 0.48-0.84; n = 1246 pairs). Similar, inverse associations were found for individual decompensation events, including ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome (HR, 0.66; 95% CI, 0.45-0.97; and HR, 0.66; 95% CI, 0.46-0.94, respectively); esophageal variceal hemorrhage (HR, 0.62 [95% CI, 0.41-0.92; and HR, 0.59; 95% CI, 0.37-0.92, respectively); and hepatic encephalopathy (HR, 0.76; 95% CI, 0.55-1.06; and HR, 0.60; 95% CI, 0.39-0.92, respectively). Results persisted in subgroups of patients with and without previously decompensated cirrhosis. In contrast, decompensation rates were similar when GLP-1RAs and SGLT-2 inhibitors were directly compared (103.5 vs 112.8 per 1000 PY; HR, 0.89; 95% CI, 0.62-1.28).

Conclusions

Among cirrhotic patients with type 2 diabetes, we find high rates of decompensation, consistent with previous reports; these rates were substantially lower among GLP-1RA initiators compared with DPP-4 inhibitors or sulfonylureas.

SUBMITTER: Simon TG

PROVIDER: S-EPMC8743301 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Glucagon-Like Peptide-1 Receptor Agonists and Hepatic Decompensation Events in Patients With Cirrhosis and Diabetes.

Simon Tracey G TG Patorno Elisabetta E Schneeweiss Sebastian S

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20210710 6

<h4>Background & aims</h4>The study sought to compare the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in reducing decompensation events, among patients with cirrhosis and type 2 diabetes.<h4>Methods</h4>This population-based, retrospective cohort study included patients with type 2 diabetes and cirrhosis, in a commercial healthcare database (IBM MarketSca ...[more]

PMID: 34256144

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Project description:BackgroundGlucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored.PurposeThis study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement.MethodsA cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE).ResultsAmong 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m2. GLP-1RAs' new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE.ConclusionGiven to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

Project description:ImportanceConcerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RA) may increase the risk of pancreatic cancer.ObjectiveTo investigate the association of GLP-1RA treatment with pancreatic cancer incidence over 9 years of follow-up.Design, setting, and participantsIn this population-based historical cohort study, adult patients (aged 21 to 89 years) with type 2 diabetes insured by Clalit Healthcare Services, the largest state-mandated health organization in Israel, were followed up from 2009, when GLP-1RA became available in Israel, until pancreatic cancer diagnosis, death, reaching age 90 years, or end of follow-up (December 2017). Data were analyzed from June 2022 to November 2023.ExposuresTreatment with GLP-1RA was compared with basal insulin.Main outcome and measuresPancreatic cancer incidence was compared according to weighted cumulative exposures to GLP-1RA and to basal insulin in a Cox model implemented in discrete time, with time origin at 2 years after diabetes diagnosis, adjusting for confounding. In sensitivity analyses, propensity score-matched pair new-user design and prevalent new-user design were used for the comparison. Because of risk for reverse-causation bias, results in the fifth to seventh year after medication were emphasized.ResultsDuring a cumulative follow-up of 3 290 439 person-years of 543 595 adults with a mean (SD) age of 59.9 (12.8) years (277 502 women [51%]) with incident diabetes, 1665 patients received pancreatic cancer diagnoses. In total, 33 377 patients (6.1%) used GLP-1RA and 106 849 (19.7%) used basal insulin. The estimated hazard ratio (HR) for pancreatic cancer associated with incremental use of 1 defined daily dose per day of GLP-1RA compared with basal insulin in the fifth to seventh year previously (all other characteristics, including age, sex, ethnic background, sociodemographic status, baseline body mass index, smoking history, history of pancreatitis, other glucose-lowering medications treatment history, and length of diabetes, being equal) was 0.50 (95% CI, 0.15-1.71). The new-user and prevalent new-user designs showed HRs from the fifth year onwards following initiation of GLP-1RA vs basal insulin of 0.52 (95 % CI, 0.19-1.41) and 0.75 (95 % CI, 0.37-1.53), respectively.Conclusions and relevanceIn this historical cohort study of adults with type 2 diabetes, no support for an increased pancreatic cancer incidence over 7 years following start of GLP-1RA treatment was found. However, monitoring for pancreatic cancer risk beyond 7 years following initiation of therapy is still required.Trial registrationClinicalTrials.gov Identifier: NCT02072902.

Project description:ImportanceThirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear.ObjectiveTo compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin.Design, setting, and participantsThis retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024.ExposuresPrescription of GLP-1RAs, insulins, or metformin.Main outcomes and measuresIncident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates.ResultsIn the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87).Conclusions and relevanceIn this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.

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Dataset Information

Glucagon-Like Peptide-1 Receptor Agonists and Hepatic Decompensation Events in Patients With Cirrhosis and Diabetes.

Background & aims

Methods

Results

Conclusions

Publications

Glucagon-Like Peptide-1 Receptor Agonists and Hepatic Decompensation Events in Patients With Cirrhosis and Diabetes.

Similar Datasets

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