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Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.

ABSTRACT: We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control.We identified 13,238 veterans who initiated sulfonylurea or metformin treatment (2000–2007) with a baseline estimated glomerular filtration rate (eGFR) >60?mL/minute, and followed them until a study event occurred, non-persistence on treatment, loss of follow-up, or end of the study. The composite outcome was a sustained decline from baseline eGFR of ?25%, end-stage renal disease, or death. We estimated the association of cumulative measurements of potential mediators including BMI, SBP, and glycated hemoglobin on the study outcome. We determined if controlling for these time-varying covariates accounted for the differences in outcome between sulfonylurea and metformin initiators.Compared to sulfonylurea use, metformin use was associated with a lower risk for renal function decline or death [adjusted hazard ratio (aHR) 0.82, 95% confidence interval 0.70, 0.97]. This protective association remained significant [aHR 0.83 (0.70–0.98)] when accounting for the cumulative time-varying measurements of the three mediators of interest.Metformin initiation was associated with a lower risk of kidney function decline or death compared to sulfonylureas, which which appeared to be independent of changes in BMI, SBP, and glycated hemoglobin over time.

SUBMITTER: Hung AM

PROVIDER: S-EPMC4887572 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.

Hung Adriana M AM Roumie Christianne L CL Greevy Robert A RA Liu Xulei X Grijalva Carlos G CG Murff Harvey J HJ Griffin Marie R MR

Pharmacoepidemiology and drug safety 20130601 6

<h4>Background and objective</h4>We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control.<h4>Methods</h4>We identified 13,2 ...[more]

PMID: 23592561

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Project description:ImportanceBefore 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown.ObjectiveTo compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea.Design, setting, and participantsRetrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174 882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women or ≥1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016).ExposuresNew users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function.Main outcomes and measuresMACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death.ResultsThere were 67 749 metformin and 28 976 sulfonylurea persistent monotherapy users; the weighted cohort included 24 679 metformin and 24 799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48 497 men [98%]; and 40 476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use.Conclusions and relevanceAmong patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.

Project description:IntroductionENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years. This economic analysis of ENDURE aimed to quantify the relationship between increased glycemic durability and cost-effectiveness of alogliptin in the UK clinical setting, and communicate its sustained glycemic benefit in economic terms.MethodsUsing baseline characteristics and treatment effects from the ENDURE trial population, between-group cost-effectiveness analyses compared the combined use of metformin and alogliptin (MET + ALO12.5/25) in patients with inadequately controlled T2DM, as an alternative to metformin and SU (MET + SU). In scenario analyses, an intragroup cost-effectiveness analysis compared MET + ALO12.5/25 with MET + SU; a between-group cost-effectiveness analysis also compared MET + ALO12.5/25 versus MET + SU within a subpopulation of patients who achieved HbA1c control (<7.5%) at 2 years on study drug.ResultsCompared with baseline profiles of patients, combination therapies with alogliptin or SU were associated with improvements in length and quality of life and were cost-effective at established norms. Despite increased drug acquisition costs, alogliptin at 12.5 mg and 25 mg doses resulted in greater predicted lifetime quality-adjusted life year (QALY) gains with associated incremental cost-effectiveness ratios (ICERs) of £10,959/QALY and £7217/QALY compared to SU, respectively.ConclusionThe ENDURE trial and the present cost-effectiveness analysis found that the glycemic durability of alogliptin therapy was associated with improved long-term patient outcomes, QALY gains, and ICERs that were cost-effective when evaluated against standard threshold values. Alogliptin therefore represents a cost-effective treatment alternative to SU as add-on therapy to metformin in patients with poorly managed T2DM.FundingTakeda Development Centre Europe Ltd.

Dataset Information

Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.

Publications

Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.

Similar Datasets

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