Dataset Information

Within-Sulfonylurea-Class Evaluation of Time to Intensification with Insulin (ZODIAC-43).

ABSTRACT:

Background

Previous studies have shown that many within-class differences exist between sulfonylureas (SUs), however, whether differences exist regarding the time it takes between initiating an SU and the need to intensify treatment with insulin is unclear. The aim of this study was investigate the relationships between the three frequently used sulphonylureas, prescribed as dual therapy next to metformin, and the time needed to treatment intensification with either insulin or oral triple therapy in patients with type 2 diabetes mellitus.

Methods

Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) is a prospective observational cohort study set in primary care in the Netherlands. Annually collected data on diabetes medication and clinical variables within ZODIAC are used to evaluate the primary outcome, time to insulin and secondary outcome, time to either insulin or triple oral therapy. For statistical analysis a time-dependent cox proportional hazard model was used.

Results

3507 patients were included in the analysis, with a mean age of 61 (SD 11.4) and a median HbA1c of 6.8% [IQR 6.4-7.4] (50.8 mmol/mol [IQR 46.4-57.4]).The hazard ratio (HR) for the primary endpoint was 1.10 (95% CI 0.78-1.54) for metformin/glimepiride and 0.93 (95% CI 0.67-1.30) for metformin/tolbutamide with metformin/gliclazide as reference group. The HR for the secondary outcome was 1.04 (95% CI 0.78-1.40) and 0.85 (95% CI 0.64-1.13), respectively.

Conclusion

In this large Dutch primary care cohort, new users of neither gliclazide, glimepiride nor tolbutamide as dual therapy with metformin, resulted in differences in the time needed for further treatment intensification.

SUBMITTER: Schrijnders D

PROVIDER: S-EPMC4915672 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Within-Sulfonylurea-Class Evaluation of Time to Intensification with Insulin (ZODIAC-43).

Schrijnders Dennis D Hartog Laura C LC Kleefstra Nanne N Groenier Klaas H KH Landman Gijs W D GW Bilo Henk J G HJ

PloS one 20160621 6

<h4>Background</h4>Previous studies have shown that many within-class differences exist between sulfonylureas (SUs), however, whether differences exist regarding the time it takes between initiating an SU and the need to intensify treatment with insulin is unclear. The aim of this study was investigate the relationships between the three frequently used sulphonylureas, prescribed as dual therapy next to metformin, and the time needed to treatment intensification with either insulin or oral tripl ...[more]

PMID: 27327605

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Project description:BACKGROUND:Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication-including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)-can be added to achieve this. However, treatment effects of intensification with the medications on the risk of severe hypoglycemia (SH), cardiovascular disease (CVD), and all-cause mortality are uncertain. Study aim was to compare the risks of all-cause mortality, CVD, and SH among patients with T2DM on Met-SU dual therapy intensified with DPP4i, insulin, or TZD. METHODS AND FINDINGS:We analyzed a retrospective cohort data of 17,293 patients with T2DM who were free from CVD and on Met-SU dual therapy and who were intensified with DPP4i (n = 8,248), insulin (n = 6,395), or TZD (n = 2,650) from 2006 to 2017. Propensity-score weighting was used to balance out baseline covariates across groups. Hazard ratios (HRs) for all-cause mortality, CVD, and SH were assessed using Cox proportional hazard models. Mean age of all patients was 58.56 ± 11.41 years. All baseline covariates achieved a balance across the 3 groups. Over a mean follow-up period of 34 months with 49,299 person-years, cumulative incidences of all-cause mortality, SH, and CVD were 0.061, 0.119, and 0.074, respectively. Patients intensified with insulin had higher risk of all-cause mortality (HR = 2.648, 95% confidence interval [CI] 2.367-2.963, p < 0.001; 2.352, 95% CI 2.123-2.605, p < 0.001) than those intensified with TZD and DPP4i, respectively. Insulin users had the greatest risk of SH (HR = 1.198, 95% CI 1.071-1.340, p = 0.002; 1.496, 95% CI 1.342-1.668, p < 0.001) compared with TZD and DPP4i users, respectively. Comparing between TZDs and DPP4i, TZDs were associated with a higher risk of SH (HR = 1.249, 95% CI 1.099-1.419, p < 0.001) but not all-cause mortality (HR = 0.888, 95% CI 0.776-1.016, p = 0.084) or CVD (HR = 1.005, 95% CI 0.915-1.104, p = 0.925). Limitations of this study included the lack of data regarding lifestyle, drug adherence, time-varying factors, patients' motivation, and cost considerations. A limited duration of patients intensifying with TZD might also weaken the strength of study results. CONCLUSIONS:Our results indicated that, for patients with T2DM who are on Met-SU dual therapy, the addition of DPP4i was a preferred third-line medication among 3 options, with the lowest risks of mortality and SH and posing no increased risk for CVD events when compared to insulin and TZD. Intensification with insulin had the greatest risk of mortality and SH events.

Project description:BackgroundType 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited.ObjectiveTo compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin.DesignThis was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases.ParticipantsVeterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011.Main measuresThe association between insulin versus sulfonylurea?+?insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ? 65 years and estimated glomerular filtration rate ? 60 and < 60 ml/min.Key findingsThere were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea?+?insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings.ConclusionsCompared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.

Dataset Information

Within-Sulfonylurea-Class Evaluation of Time to Intensification with Insulin (ZODIAC-43).

Background

Methods

Results

Conclusion

Publications

Within-Sulfonylurea-Class Evaluation of Time to Intensification with Insulin (ZODIAC-43).

Similar Datasets

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