Dataset Information

Association between clinical outcomes and metformin use in adults with sickle cell disease and diabetes mellitus.

ABSTRACT: Metformin was recently found to increase fetal hemoglobin, which is protective in sickle cell disease (SCD). We tested the hypothesis that, among adults with SCD and diabetes mellitus (DM), metformin use is associated with fewer adverse SCD clinical outcomes and lower health care utilization. This is a retrospective cohort study using the MarketScan Medicaid claims database for 2006 to 2016, comparing metformin users and nonusers. Patients on hydroxyurea, insulin, or iron chelation were excluded. Main outcomes included annual rates of all-cause inpatient encounters, all-cause emergency department (ED) encounters, inpatient and ED encounters with SCD codes, vaso-occlusive episodes (VOEs), strokes, acute chest syndrome (ACS), avascular necrosis (AVN), and gallstones. Of 457 adults (median age [interquartile range], 43 years [33-52 years]; 72% female), 142 (31%) were treated with metformin. Adjusted for age, sex, and Charlson Comorbidity Index, metformin users had significantly lower rate ratios of all-cause inpatient encounters (0.68; 95% confidence interval [CI], 0.52-0.88; P < .01), inpatient encounters with SCD codes (0.45; 95% CI, 0.30-0.66; P < .01), ED encounters with SCD codes (0.34; 95% CI, 0.21-0.54; P < .01), VOE (0.22; 95% CI, 0.12-0.41; P < .01), ACS (0.17; 95% CI, 0.05-0.60; P = .01), and AVN (0.30; 95% CI, 0.11-0.87; P = .03). A subgroup analysis of 54 enrollees preinitiation and postinitiation of metformin did not indicate significant changes in rates of clinical events. Metformin was associated with significantly fewer inpatient and ED SCD encounters in adults with SCD and DM; however, confounding of underlying SCD severity cannot be excluded.

SUBMITTER: Badawy SM

PROVIDER: S-EPMC6855104 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association between clinical outcomes and metformin use in adults with sickle cell disease and diabetes mellitus.

Badawy Sherif M SM Payne Amanda B AB

Blood advances 20191101 21

Metformin was recently found to increase fetal hemoglobin, which is protective in sickle cell disease (SCD). We tested the hypothesis that, among adults with SCD and diabetes mellitus (DM), metformin use is associated with fewer adverse SCD clinical outcomes and lower health care utilization. This is a retrospective cohort study using the MarketScan Medicaid claims database for 2006 to 2016, comparing metformin users and nonusers. Patients on hydroxyurea, insulin, or iron chelation were excluded ...[more]

PMID: 31698459

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Project description:ImportanceAdults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention.ObjectiveTo assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin.Design, setting, and participantsThis cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018.ExposuresPreoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure.Main outcomes and measuresAll-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score-matched cohort.ResultsAmong the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score-matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score-matched cohort, preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]) and hazard of readmission, with mortality as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding.Conclusions and relevanceThis study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.

Project description:Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma.We did a retrospective cohort study of patients registered in the US Veterans Health Administration database and diagnosed with MGUS between Oct 1, 1999, and Dec 31, 2009. We included patients (aged >18 years) with at least one International Classification of Diseases (9th revision) code for diabetes mellitus and one treatment for their diabetes before MGUS diagnosis. We reviewed patient-level clinical data to verify diagnoses and extract any available data for size of baseline M-protein and type of MGUS. We defined metformin users as patients with diabetes who were given metformin consistently for 4 years after their diabetes diagnosis and before multiple myeloma development, death, or censorship. Our primary outcome was time from MGUS diagnosis to multiple myeloma diagnosis. We used Kaplan-Meier curves and Cox models to analyse the association between metformin use and MGUS progression.We obtained data for 3287 patients, of whom 2003 (61%) were included in the final analytical cohort. Median follow-up was 69 months (IQR 49–96). 463 (23%) participants were metformin users and 1540 (77%) participants were non-users. 13 (3%) metformin users progressed to multiple myeloma compared with 74 (5%) non-users. After adjustment, metformin use was associated with a reduced risk of progression to multiple myeloma (hazard ratio 0·47, 95% CI 0·25–0·87).For patients with diabetes diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of progression of MGUS to multiple myeloma. Prospective studies are needed to establish whether this association is causal and whether these results can be extrapolated to non-diabetic individuals.Barnes-Jewish Hospital Foundation, National Institutes of Health, Agency for Healthcare Research and Quality, American Cancer Society.

Dataset Information

Association between clinical outcomes and metformin use in adults with sickle cell disease and diabetes mellitus.

Publications

Association between clinical outcomes and metformin use in adults with sickle cell disease and diabetes mellitus.

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