Dataset Information

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use.

ABSTRACT:

Aims

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.

Materials and methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Rossing P

PROVIDER: S-EPMC10092103 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use.

Rossing Peter P Agarwal Rajiv R Anker Stefan D SD Filippatos Gerasimos G Pitt Bertram B Ruilope Luis M LM Fonseca Vivian V Umpierrez Guillermo E GE Caramori Maria Luiza ML Joseph Amer A Lambelet Marc M Lawatscheck Robert R Bakris George L GL

Diabetes, obesity & metabolism 20221102 2

<h4>Aims</h4>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.<h4>Materials and methods</h4>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 (cardi ...[more]

PMID: 36193847

Similar Datasets

Project description:ImportanceGlucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood.ObjectiveTo assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors.Design, setting, and participantsThis retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021.ExposuresTreatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors.Main outcomes and measuresAll-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups.ResultsOf 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction).Conclusions and relevanceTreatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.

Project description:ImportanceGlucagon-like peptide-1 receptor agonist (GLP-1 RA) use is rapidly increasing in the US, driven by its expanded approval for weight management in addition to hyperglycemia management in patients with type 2 diabetes. The perioperative safety of these medications, particularly with aspiration risk under anesthesia, is uncertain.ObjectiveTo assess the association between GLP-1 RA use and prevalence of increased residual gastric content (RGC), a major risk factor for aspiration under anesthesia, using gastric ultrasonography.Design, setting, and participantsThis cross-sectional study prospectively enrolled patients from a large, tertiary, university-affiliated hospital from June 6 through July 12, 2023. Participants followed preprocedural fasting guidelines before an elective procedure under anesthesia. Patients with altered gastric anatomy (eg, from previous gastric surgery), pregnancy, recent trauma (<1 month), or an inability to lie in the right lateral decubitus position for gastric ultrasonography were excluded.ExposureUse of a once-weekly GLP-1 RA.Main outcomes and measuresThe primary outcome was the presence of increased RGC, defined by the presence of solids, thick liquids, or more than 1.5 mL/kg of clear liquids on gastric ultrasonography. Analysis was adjusted for confounders using augmented inverse probability of treatment weighting, a propensity score-based technique. Secondarily, the association between the duration of drug interruption and the prevalence of increased RGC was explored.ResultsAmong the 124 participants (median age, 56 years [IQR, 46-65 years]; 75 [60%] female), the prevalence of increased RGC was 56% (35 of 62) in patients with GLP-1 RA use (exposure group) compared with 19% (12 of 62) in patients who were not taking a GLP-1 RA drug (control group). After adjustment for confounding, GLP-1 RA use was associated with a 30.5% (95% CI, 9.9%-51.2%) higher prevalence of increased RGC (adjusted prevalence ratio, 2.48; 95% CI, 1.23-4.97). There was no association between the duration of GLP-1 RA interruption and the prevalence of increased RGC (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14).Conclusions and relevanceUse of a GLP-1 RA was independently associated with increased RGC on preprocedural gastric ultrasonography. The findings suggest that the preprocedural fasting duration suggested by current guidelines may be inadequate in this group of patients at increased risk of aspiration under anesthesia.

Project description:ImportanceRandomized 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.ObjectivesTo 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.Design setting and participantsThis 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.Main outcome and measureA prescription for a GLP-1 RA.ResultsOf 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.Conclusions and relevanceIn 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.

Dataset Information

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use.

Aims

Materials and methods

Results

Conclusions

Publications

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets