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Improved clinical outcomes in adults with sickle cell disease and diabetes treated with metformin

key information

source: American Society of Hematology

year: 2017

authors: Sherif M. Badawy, Amanda B. Payne, Sundar S. Shrestha, Scott D. Grosse


Complications of sickle cell disease (SCD) include pain episodes, chronic anemia, cardiopulmonary disease, and long-term end-organ damage. Hydroxyurea is efficacious in preventing these complications by increasing fetal hemoglobin levels (HbF); however, adherence is limited. Metformin, a Food and Drug Administration-approved drug used for type-2 diabetes mellitus (DM), was recently found to induce HbF through upregulation of FOXO3 and gamma-globin expression. However, the relation of metformin utilization to clinical outcomes and healthcare utilization in adults with SCD and DM has not been studied.

Objectives: Our specific aims were to 1) estimate the prevalence of DM in a cohort of adult patients with SCD and 2) assess the association of metformin with clinical outcomes and healthcare utilization in this population. We hypothesized that adults with SCD and DM on metformin have less frequent SCD-related complication and lower utilization of hospital care for those complications.

Methods: We analyzed subjects with SCD and DM ≥18 years of age from the Truven Health MarketScan® Multi-State Medicaid Database from 2009-2015 with continuous enrollment of ≥365 days. Subjects with SCD and DM were identified through the presence of ≥1 inpatient or ≥2 outpatient disease-specific billing codes or ≥1 outpatient DM code and ≥1 DM-related drug claim. Subjects with drug claims for insulin, hydroxyurea, or iron chelation were excluded. Metformin use was defined as having ≥1 metformin-related drug claim in the study period. Outcomes included annual rates of all-cause inpatient hospitalizations, SCD-related hospitalizations, all-cause emergency department (ED) visits, SCD-related ED visits, vaso-occlusive episodes (VOE), strokes, acute chest syndrome (ACS) episodes, avascular necrosis (AVN) events, and gallstone events. Outcomes were identified based on claims records after the subject’s first DM diagnosis record in the dataset. Clinical events among metformin users and non-users were compared using chi square tests. Rate ratios (RR) comparing annual rates of clinical events among metformin users to non-users were estimated using negative binomial regression, controlling for age, sex, and claims-data-defined Charlson Comorbidity Index (CCI) score.

organisation: Northwestern University Feinberg School of Medicine, Chicago; Ann & Robert Lurie Chilren's Hospital, Chicago, IL; Centers for Disease Control and Prevention, Atlanta, GA

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