Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes

BACKGROUND: The aim of the study was to evaluate the effect of delay in treatment intensification (IT; clinical inertia) in conjunction with glycaemic burden on the risk of macrovascular events (CVE) in type 2 diabetes (T2DM) patients. METHODS: A retrospective cohort study was carried out using United Kingdom Clinical Practice Research Datalink, including T2DM patients diagnosed from 1990 with follow-up data available until 2012. RESULTS: In the cohort of 105,477 patients mean HbA1c was 8.1% (65 mmol/mol) at diagnosis, 11% had a history of cardiovascular disease, and 7.1% experienced at least one CVE during 5.3 years of median follow-up. In patients with HbA1c consistently above 7/7.5% (53/58 mmol/mol, n = 23,101/11,281) during 2 years post diagnosis, 26/22% never received any IT. Compared to patients with HbA1c <7% (<53 mmol/mol), in patients with HbA1c ≥7% (≥53 mmol/mol), a 1 year delay in receiving IT was associated with significantly increased risk of MI, stroke, HF and composite CVE by 67% (HR CI: 1.39, 2.01), 51% (HR CI: 1.25, 1.83), 64% (HR CI: 1.40, 1.91) and 62% (HR CI: 1.46, 1.80) respectively. One year delay in IT in interaction with HbA1c above 7.5% (58 mmol/mol) was also associated with similar increased risk of CVE. CONCLUSIONS: Among patients with newly diagnosed T2DM, 22% remained under poor glycaemic control over 2 years, and 26% never received IT. Delay in IT by 1 year in conjunction with poor glycaemic control significantly increased the risk of MI, HF, stroke and composite CVE

Assessment of channeling bias among initiators of glucose-lowering drugs: A UK cohort study

Mikkel Z Ankarfeldt,1,2 Brian L Thorsted,1 Rolf HH Groenwold,2,3 Erpur Adalsteinsson,1 M Sanni Ali,2&ndash;4 Olaf H Klungel2,3 1Novo Nordisk A/S, Bagsvaerd, Denmark; 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; 3Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, the Netherlands; 4Nuffield Department of Orthopaedics, Rheumatology, Musculoskeletal Sciences, University of Oxford, Oxford, UK Background: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding).Aim: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea.Methods: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included. Analyses were stratified by years since first prescription of GLP-1 and DPP-4i, respectively. The characteristics of GLP-1 versus insulin and DPP-4i versus sulfonylurea initiators were compared over time. After propensity score matching, the relative effectiveness regarding 6-month changes in glycated hemoglobin (HbA1c) and body weight was estimated.Results: In total, 8,398 GLP-1, 14,807 insulin, 24,481 DPP-4i, and 33,505 sulfonylurea initiators were identified. No major channeling was observed. Considerable overlap in distributions of characteristics allowed for propensity score-matched analyses. Relative effectiveness was similar across time. The overall relative effect of GLP-1 versus insulin showed no difference for HbA1c and relative increase in body weight (3.57 kg [95% confidence interval {CI}: 3.21, 3.92]) for insulin. The overall relative effect of DPP-4i versus sulfonylurea showed relative decrease in HbA1c (&ndash;0.34% [95% CI: &ndash;0.38, &ndash;0.30]) and increase in body weight (1.58 kg [95% CI: 1.38, 1.78]) for sulfonylurea.Conclusion: No major channeling was identified in the investigated glucose-lowering drugs. Relative effectiveness could be estimated already in the first year after launch and was consistent in the years thereafter. Keywords: channelling bias, channeling bias, glucose-lowering drugs, DPP-4i, GLP-1, type 2 diabetes, observational study, relative effectivenes

Assessment of channeling bias among initiators of glucose-lowering drugs: A UK cohort study [Corrigendum]

Ankarfeldt MZ, Thorsted BL, Groenwold RHH, et al. Clin Epidemiol. 2017;9:19&ndash;30.&nbsp;On page 23, Figure 1 Notes section was marked incorrectly. The correct Notes should read as follows:Figure 1 Propensity score over time for GLP-1 versus basal insulin initiators.Notes: Blue: insulin, red: GLP-1.Abbreviation: GLP-1, glucagon-like peptide-1 analogs.&nbsp;On page 24, Figure 2 Notes section was marked incorrectly. The correct Notes should read as follows:Figure 2 Propensity score over time for DPP-4i versus sulfonylurea initiators.Notes: Blue: sulfonylurea, red: DPP-4i.Abbreviation: DPP-4i, dipeptidyl peptidase-4 inhibitors.&nbsp;On Page 3 of Supplementary materials, Figure S2 caption was shown incorrectly. The correct caption should read as follows:Figure S2 Histograms of propensity score over time. Intention-to-treat and perprotocol cohorts of all identified initiators of GLP-1 and insulin, and DPP-4i and sulfonylurea, respectively. Blue: insulin and sulfonylurea initiators, respectively. Red: GLP-1 and DPP-4i initiators, respectively.&nbsp;Despite the above corrections, the interpretation of these figures in the published proof and the Supplementary materials was correct.&nbsp;Read the original articl

Selectivity of beta-blockers, cardiovascular and all-cause mortality in people with hypoglycaemia: an observational study

Background and Aims The association of beta-blockers and their selectivity with mortality and cardiovascular events in patients with and without hypoglycaemia is unknown. Methods and Results Insulin-treated patients with diabetes were identified within the UK CPRD database. All-cause deaths, cardiovascular events, and hypoglycaemic episodes were captured to assess the interaction between beta-blocker therapy and selectivity with hypoglycaemia. 13682 patients, of which 2036 (14.9%) with at least one hypoglycaemic episode, were included; 3148 deaths and 1235 cardiovascular events were recorded during a median of 2.3 and 4.7 years in patients with and without incident hypoglycaemia, respectively. Treatment with any beta-blocker was not associated with risk of death in both patients with and without hypoglycaemia, without significant interaction. Compared to no therapy, non-selective beta-blockers were associated with higher risk of death in patients without hypoglycaemia (hazard ratio (HR) 2.93 [1.26–6.83] in the fully adjusted model) but not in those with hypoglycaemia; interactions was not significant. For beta1-selective beta-blockers, there was no association with mortality in both patients with and without hypoglycaemia, without significant interaction. After missing data imputation, results were consistent for non-selective beta-blockers (HR in patients without hypoglycaemia 1.59 [1.22–2.08]) while indicated a reduced risk of death for beta1-selective beta-blockers in patients with hypoglycaemia (HR 0.76 [0.61–0.94]). Due to few cardiovascular events, complete-case analysis compared only any vs no beta-blocker therapy and indicated no associations with therapy or interaction by hypoglycaemia. Conclusion In patients with hypoglycaemic episodes, treatment with beta1-selective beta-blockers may potentially reduce the risk of death. These explorative findings and the potential role of confounding by indication need to be evaluated in other studies

Exposure to tetrachloroethylene in dry cleaning shops in the Nordic countries

Objectives: Tetrachloroethylene is the dominant solvent used in dry cleaning worldwide and many workers are potentially exposed. We report here on results of 1296 measurements of tetrachloroethylene undertaken in Nordic dry cleaning shops 1947–2001. Methods: We searched documents and files in the Nordic institutes of occupational health for air measurements of tetrachloroethylene. Repeated measurements from the same facility during a short time interval were registered only once using the time-weighted average. We registered also changes over time in occupational exposure limits (OELs) to tetrachloroethylene. Results: Only scattered measurements were available from the early years, and the exposure level seemed fairly stable up until the mid 1970s. The median exposure level was 20 p.p.m. in 1976 and decreased to 3 p.p.m. in 2000. Exposure levels in the four Nordic countries followed similar trends. In the late 1960s, the OELs varied between the Nordic countries from 30 to 100 p.p.m. Sweden was first to lower the limit, but limits gradually converged over time. At present, Denmark, Finland, and Sweden use 10 p.p.m., while Norway uses 6 p.p.m. Over time, the average observed exposure level was lower than the OEL in all countries, but in Denmark and Sweden, up to one-third of measured exposures exceeded the OEL. Overall, the stationary measurements for maintenance work showed 36 p.p.m., while the personal measurements showed 7.5 p.p.m. for dry cleaners and 6.25 p.p.m. for shop assistants. Conclusion: The Nordic data illustrate that it is possible over time to control chemical exposures even in an industry consisting of many small and scattered work places