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Objective: Hypoglycemia (HG) occurs in up to 60% of patients with diabetes mellitus (DM) each year. We assessed a HG alert tool in an electronic health record system, and determined its effect on clinical practice and outcomes. Methods: The tool applied a statistical model, yielding patient-specific information about HG risk. We randomized outpatient primary-care providers (PCPs) to see or not see the alerts. Patients were assigned to study group according to the first PCP seen during four months. We assessed prescriptions, testing, and HG. Variables were compared by multinomial, logistic, or linear model. ClinicalTrials.gov ID: NCT04177147 (registered on 22 November 2019). Results: Patients ( N = 3350) visited 123 intervention PCPs; 3395 patients visited 220 control PCPs. Intervention PCPs were shown 18,645 alerts (mean of 152 per PCP). Patients' mean age was 55 years, with 61% female, 49% black, and 49% Medicaid recipients. Mean baseline A1c and body mass index were similar between groups. During follow-up, the number of A1c and glucose tests, and number of new, refilled, changed, or discontinued insulin prescriptions, were highest for patients with highest risk. Per 100 patients on average, the intervention group had fewer sulfonylurea refills (6 vs. 8; p < .05) and outpatient encounters (470 vs. 502; p < .05), though the change in encounters was not significant. Frequency of HG events was unchanged. Conclusions: Informing PCPs about risk of HG led to fewer sulfonylurea refills and visits. Longer-term studies are needed to assess potential for long-term benefits.

Objective: Hypoglycemia occurs in 20-60% of patients with diabetes mellitus. Identifying at-risk patients can facilitate interventions to lower risk. We sought to develop a hypoglycemia prediction model. Methods: In this retrospective cohort study, urban adults prescribed a diabetes drug between 2004 and 2013 were identified. Demographic and clinical data were extracted from an electronic medical record (EMR). Laboratory tests, diagnostic codes and natural language processing (NLP) identified hypoglycemia. We compared multiple logistic regression, classification and regression trees (CART), and random forest. Models were evaluated on an independent test set or through cross-validation. Results: The 38,780 patients had mean age 57 years; 56% were female, 40% African-American and 39% uninsured. Hypoglycemia occurred in 8128 (539 identified only by NLP). In logistic regression, factors positively associated with hypoglycemia included infection, non-long-acting insulin, dementia and recent hypoglycemia. Negatively associated factors included long-acting insulin plus sulfonylurea, and age 75 or older. The models' area under curve was similar (logistic regression, 89%; CART, 88%; random forest, 90%, with ten-fold cross-validation). Conclusions: NLP improved identification of hypoglycemia. Non-long-acting insulin was an important risk factor. Decreased risk with age may reflect treatment or diminished awareness of hypoglycemia. More complex models did not improve prediction.

Aims: TECOS, a cardiovascular safety trial (ClinicalTrials.gov identifier: NCT00790205) involving 14 671 patients with type 2 diabetes and cardiovascular disease, demonstrated that sitagliptin was non-inferior to placebo for the primary composite cardiovascular outcome when added to best usual care. This study tested hypotheses that medical resource use and costs differed between these 2 treatment strategies., Materials and Methods: Information concerning medical resource use was collected on case report forms throughout the trial and was valued using US costs for: Medicare payments for hospitalizations, medical procedures and outpatient visits, and wholesale acquisition costs (WAC) for diabetes-related medications. Hierarchical generalized linear models were used to compare resource use and US costs, accounting for variable intercountry practice patterns. Sensitivity analyses included resource valuation using English costs for a UK perspective., Results: There were no significant differences in hospitalizations, inpatient days, medical procedures, or outpatient visits during follow-up (mean and median 3.0 years in both groups). Hospitalization rates appeared to diverge after 2 years, with lower rates among sitagliptin-treated vs placebo patients after 2.5 years (relative rate, 0.90 [95% CI, 0.83-0.97]; P = .01). Mean medical costs, exclusive of study medication, were 11 937 USD in the sitagliptin arm and 12 409 USD in the placebo arm (P = .06). Mean sitagliptin costs based on undiscounted WAC were 9978 USD per patient. Differential UK total costs including study drug costs were smaller (911 GBP), primarily because of lower mean costs for sitagliptin (1072 GBP)., Conclusions: Lower hospitalization rates across time with sitagliptin slightly offset sitagliptin treatment costs over 3 years in type 2 diabetes patients at high risk for cardiovascular events., (© 2018 John Wiley & Sons Ltd.)

Aims: To analyse the prevalence of severe hypoglycaemia in patients with type 2 diabetes (T2DM) treated with antihyperglycaemic agents (AHA) and requiring emergency room (ER) assistance, and to analyse the prevalence according to type of AHA therapy., Methods: The present study, the Hypoglycaemia In Portugal Observational Study-Emergency Room (HIPOS-ER), was a cross-sectional, observational, multicentre, nationwide study, with specific hypoglycaemia source data collection., Results: Within the study period, a total of 425 706 admissions were recorded in the ERs of participating hospitals. The prevalence of severe hypoglycaemic episodes in patients with T2DM was 0.074%. In all, 238 patients were included, more than half of whom were on insulin-based therapy (55.0%) and a third of whom (31.5%) were on oral secretagogue-based therapy. In 61.2% of patients primary care was the main diabetes care setting. The median patient age was 77.5 years and the mean duration of diabetes was 19 years. Missing a meal or low carbohydrate meal content was the most frequent cause of hypoglycaemia (55.9%) and the most frequent triggers for seeking emergency assistance were pre-syncope (19.2%) and transient loss of consciousness (17.4%). A total of 44.1% of patients were hospitalized for a median of 5.1 days. Patients in the secretagogue group were admitted to hospital more often than patients in the insulin group (70.7% vs 29.0%; P < .001). Nine patients died., Conclusions: These findings confirm that severe hypoglycaemia in patients with T2DM requiring ER assistance occurs mainly in those on insulin- and secretagogue-based therapies and is associated with a significant medical burden. Antidiabetic therapy should be individualized to minimize the risk of severe iatrogenic hypoglycaemia, and any intervention to this end should always involve primary care stakeholders., (© 2017 John Wiley & Sons Ltd.)

Aims: Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and weight gain, and thus might counteract the benefits of intensive glucose control. We quantify the association of cardiovascular disease (CVD) outcomes with hypoglycaemia and weight gain among patients with type 2 diabetes treated with sulfonylureas., Materials and Methods: This cohort study included patients from January 2009 through December 2014 who were selected from within a deidentified nationwide electronic health records repository, including multiple provider networks and electronic medical records systems. Hypoglycaemia measures from structured data fields and free text clinical notes were categorized as serious or non-serious. Covariate adjusted Poisson regression analysis was used to assess the association between frequency of hypoglycaemia (by severity), or magnitude of weight change, and incidence of acute myocardial infarction (AMI), congestive heart failure (CHF) and stroke., Results: Among 143 635 eligible patients, we observed 5669 cases of AMI, 14 109 incident cases of CHF and 7017 cases of stroke. Overall incidence rates were 1.53, 4.26 and 1.92 per 100 person-years for AMI, CHF and stroke, respectively. The associations between overall hypoglycaemia and each of the CVD outcomes were positive, with stronger associations observed for serious hypoglycaemia and attenuated or null associations observed for non-serious hypoglycaemia. Weight change exhibited a U-shaped association with increased risks associated with both weight loss and weight gain relative to stable weight., Conclusions: This study provides evidence of increased CVD risk associated with hypoglycaemia, especially with serious hypoglycaemia events. While associations were attenuated with non-serious hypoglycaemia, the results were suggestive of a potential increased risk., (© 2017 John Wiley & Sons Ltd.)

Aims: Accurate measures of hypoglycemia within electronic health records (EHR) can facilitate clinical population management and research. We quantify the occurrence of serious and mild-to-moderate hypoglycemia in a large EHR database in the US, comparing estimates based only on structured data to those from structured data and natural language processing (NLP) of clinical notes., Methods: This cohort study included patients with type 2 diabetes identified from January 2009 through March 2014. We compared estimates of occurrence of hypoglycemia derived from diagnostic codes to those recorded within clinical notes and classified via NLP. Measures of hypoglycemia from only structured data (ICD-9 Algorithm), only note mentions (NLP Algorithm), and either structured data or notes (Combined Algorithm) were compared with estimates of the period prevalence, incidence rate, and event rate of hypoglycemia, overall and by seriousness., Results: Of the 844,683 eligible patients, 119,695 had at least one recorded hypoglycemic event identified with ICD-9 or NLP. The period prevalence of hypoglycemia was 12.4%, 25.1%, and 32.2% for the ICD-9 Algorithm, NLP Algorithm, and Combined Algorithm, respectively. There were 6128 apparent non-serious events utilizing the ICD-9 Algorithm, which increased to 152,987 non-serious events within the Combined Algorithm., Conclusions: Ascertainment of events from clinical notes more than doubled the completeness of hypoglycemia capture overall relative to measures from structured data, and increased capture of non-serious events more than 20-fold. The structured data and clinical notes are complementary within the EHR, and both need to be considered in order to fully assess the occurrence of hypoglycemia., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: To compare the change in urinary albumin to creatinine ratio (UACR) in type 2 diabetes (T2DM) patients with albuminuria who initiate sitagliptin to those who initiate a sulfonylurea (SU) as add-on to metformin monotherapy., Method: A cohort of T2DM patients with albuminuria (UACR >30mg/g) who initiated sitagliptin or SU as add-on dual therapy to metformin between 2008 and 2014 was extracted from the computerized medical records of a large managed care organization in Israel. Patients with albuminuria and UACR measurements available at treatment initiation and 120-365days afterwards were included. Propensity scores were calculated based on 17 factors, including demography, comorbidities, baseline levels of HbA1c, UACR, BMI, eGFR, and ACE/ARB use, and patients were matched in a 1:1 ratio. Changes in UACR were compared between the matched pairs using generalized estimating equations., Results: A total of 282 eligible pairs (sitagliptin:SU) were identified. During a mean follow-up of 9months, median UACR changes were -35% (IQR=-73% to 5%) and -31% (IQR=-72% to 21%) in the sitagliptin and SU groups, respectively. Mean absolute HbA1c reductions among sitagliptin and SU groups were 0.9% and 1.0%, respectively. The magnitude of UACR reduction generally increased with greater magnitude of HbA1c reduction in both treatment groups. However, after controlling for HbA1c reduction and the interaction between HbA1c reduction and UACR reduction, sitagliptin users demonstrated a trend toward an increased likelihood of UACR reduction compared to SU users (odds ratio=1.20; 95% confidence interval: 0.99-1.47, P=0.063)., Conclusion: Our results suggest that both sitagliptin and SU reduce albuminuria as an add-on therapy to metformin, but that sitagliptin may provide greater reductions in albuminuria independent of glycemic control when compared to SU. Larger population studies are required to further explore this., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The American Diabetes Association (ADA) recommends metformin to treat individuals diagnosed with type 2 diabetes and recommends that hemoglobin A1c (HbA1c) be maintained below or around 7%. If the HbA1c target is not achieved or maintained by metformin monotherapy at maximal tolerated dose over 3 to 6 months, treatment modification with addition of a second oral antihyperglycemic agent or by initiating insulin is recommended. Despite the importance of attaining and maintaining HbA1c goals, actual treatment behavior may not follow ADA guidelines to add a second oral agent or to initiate insulin as expected even considering that individual patient's needs are taken into account when treatment decisions are made., Objective: To evaluate treatment addition for metformin monotherapy users with suboptimal glycemic control and associated factors., Methods: A retrospective health care claims study identified 7,109 subjects aged 18 to 89 years, treated for type 2 diabetes with an HbA1c > 7% following at least 60 days of continuous metformin monotherapy. Subjects were required to have 12 months continuous enrollment with the health plan before and after the index lab date. Pharmacological treatment additions after the HbA1c lab result and time to treatment addition were evaluated. A logistic regression model was used to evaluate the patient characteristics and comorbidities associated with the treatment addition., Results: Thirty-eight percent of study subjects had evidence of addition of a second antidiabetic medication to primary metformin monotherapy, 57.5% remained on metformin monotherapy, and 4.5% discontinued metformin altogether. A logistic regression model found age inversely related to treatment addition: age 45-64 versus 18-44 (OR = 0.77, 95% CI = 0.59-0.99) and age 65-89 versus 18-44 (OR = 0.57, 95% CI = 0.43-0.74). HbA1c was positively related to treatment addition: > 8%-9% versus > 7%-8% (OR = 2.31, 95% CI = 2.00-2.67); > 9%-10% versus > 7%-8% (OR = 2.88, 95% CI = 2.32-3.58); and > 10% versus > 7%-8% (OR = 3.54, 95% CI = 2.92-4.28). Evidence of ophthalmic disorder was not related to treatment addition (P = 0.056), but evidence of hypertension (OR = 1.56, 95% CI = 1.28-1.89); hyperlipidemia (OR = 1.28, 95% CI = 1.05-1.55); other cardiovascular diseases (OR = 1.30, 95% CI = 1.16-1.45); obesity (OR = 1.21, 95% CI = 1.08-1.36); and renal disease (OR = 1.35, 95% CI = 1.21-1.51) were associated., Conclusions: The majority of the metformin monotherapy users with suboptimal glycemic control did not initiate add-on therapy as recommended by guidelines, and prolonged time on metformin monotherapy demonstrated clinical inertia in real-world clinical practice. Several factors were associated with this delay including older age, lower index HbA1c, and lack of evidence of certain comorbidities.

Introduction: Hypoglycemia is an acute complication of diabetes that increases morbidity, mortality and disease costs. We aim to estimate healthcare resource consumption and costs associated with severe hypoglycemia using the societal perspective., Methods: A cross-sectional, observational, nationwide, multicenter, hospital-based study was conducted in seven centers of Portuguese mainland with a 1-year enrolment period. Unit costs were extracted from official/public data sources. Patient-level data were used to quantify healthcare resource use related to emergency transportation, emergency-department care and hospitalization. Productivity loss was calculated based on the Human Capital Approach., Results: The study enrolled 238 Type-2 diabetic patients and the proportion of hypoglycemic episodes among all emergency events during the study period was 0.075% (95% CI: 0.067-0.083%). Mean patient age was 76 years and 57.6% were female. At time of the emergency department admission, 55% of patients were using insulin, 31.5% were being treated with secretagogues, 6.7% were on a combination of both, and 6.7% were on other oral antihyperglycemic agents. Estimated mean costs in the emergency department were: emergency transportation €33, medication €4, laboratory workup €56, other exams €72, physician and nurse time €30 and €13, respectively. Mean hospitalization cost was €1271. Indirect cost averaged €15. Overall cost per hypoglycemic episode averaged €1493 (standard deviation: €2962; range: €34-26,818). Patients treated with secretagogues had the highest rates of hospitalizations and mean costs., Conclusion: We conclude that severe hypoglycemic events represent a substantial cost for society and in particular for the hospitals of the National Health Service.

Aim: To assess time to insulin initiation among patients with type 2 diabetes mellitus (T2DM) treated with sitagliptin versus sulphonylurea as add-on to metformin., Methods: This retrospective cohort study used GE Centricity electronic medical records and included patients aged ≥18 years with continuous medical records and an initial prescription of sitagliptin or sulphonylurea (index date) with metformin for ≥90 days during 2006-2013. Sitagliptin and sulphonylurea users were matched 1 : 1 using propensity score matching, and differences in insulin initiation were assessed using Kaplan-Meier curves and Cox regression. We used conditional logistic regression to examine the likelihood of insulin use 1-6 years after the index date for each year., Results: Propensity score matching produced 3864 matched pairs. Kaplan-Meier analysis showed that sitagliptin users had a lower risk of insulin initiation compared with sulphonylurea users (p = 0.003), with 26.6% of sitagliptin users initiating insulin versus 34.1% of sulphonylurea users over 6 years. This finding remained significant after adjusting for baseline characteristics (hazard ratio 0.76, 95% confidence interval 0.65-0.90). Conditional logistic regression analyses confirmed that sitagliptin users were less likely to initiate insulin compared with sulphonylurea users [odds ratios for years 1-6: 0.77, 0.79, 0.81, 0.57, 0.29 and 0.75, respectively (p < 0.05 for years 4 and 5)]., Conclusions: In this real-world matched cohort study, patients with T2DM treated with sitagliptin had a significantly lower risk of insulin initiation compared with patients treated with sulphonylurea, both as add-on to metformin., (© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

To evaluate adherence to oral antihyperglycemic monotherapy, we conducted a retrospective cohort study of a UK clinical database. The mean proportion of days covered was 73.5%, and 60.1% of patients were adherent. Younger age and fewer concomitant medications were negatively associated with the likelihood of being adherent., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To estimate overall rates of adherence, persistence, and discontinuation for patients with type 2 diabetes mellitus (T2DM) prescribed oral antihyperglycemic agents (OAHAs) by combining results of published studies., Research Design and Methods: A systematic literature review was conducted to identify articles published in English over the last 10 years evaluating the use of OAHAs for the treatment of T2DM. Databases searched included PubMed/MEDLINE, EMBASE, and the Cochrane Library. Seventy studies reporting adherence, persistence or discontinuation were identified by two independent reviewers and 40 reported relevant endpoints for the analysis. Outcomes included: (1) mean adherence defined as the average medication possession ratio (MPR); (2) proportion of adherent patients (MPR ≥ 80%); (3) discontinuation; and (4) persistence. Adherence and persistence were reported in observational studies only. Discontinuation was examined separately in randomized controlled trials (RCTs) and observational studies. Meta-analyses were conducted using both fixed and random effects models. When meta-analysis was not appropriate for a given outcome, descriptive statistics were provided., Results: The pooled mean MPR (95% confidence interval [CI]) was 75.3% (68.8%-81.7%; n = 13) and the proportion of adherent patients (95% CI) was 67.9% (59.6%-76.3%; n = 12). The discontinuation rate (95% CI) in RCTs was 31.8% (17.0%-46.7%; n = 7). Persistence and discontinuation were not assessed via meta-analysis for observational studies due to the limited number of available studies and differences in outcome definitions. In these studies, persistence estimates ranged from 41.0% to 81.1%, with a mean (95% CI) of 56.2% (46.1%-66.3%; n = 6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% CI) of 31.4% (17.6%-45.3%; n = 6)., Limitations: Limitations include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity., Conclusion: The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

Objective: To assess the time from the first observed diagnosis of type 2 diabetes (T2DM) to initiation of an oral antihyperglycemic agent (OAHA) and statin., Methods: In a retrospective US cohort study using the GE electronic medical record database, patients ≥18 years were included if they had a T2DM diagnosis between January 1, 2004 and December 31, 2005 (index period), had a last pre-index HbA1c value ≥7%, and had not received antihyperglycemic agents within one year prior to diagnosis (index date). Patients were eligible for statin therapy but not on a statin within one year before the index date. Patients had medical records for one year prior to (baseline) and two years after (follow up) diagnosis., Results: Of the 2254 eligible patients, 58% were male, mean age was 58 years, mean HbA1c was 8.5%, and mean LDL cholesterol was 115 mg/dL (2.97 mmol/L) at baseline. Additionally, 21% of patients had pre-existing overt cardiovascular disease, 40% had dyslipidemia, 37% were obese, and 11% were smokers. During follow-up, 66.1% and 41.9% of patients initiated an OAHA and a statin, respectively. Among the treated patients, median time from the first observed diabetes diagnosis to therapy initiation was 3 months (interquartile range: 1, 9) for OAHAs and 6 months (2, 13) for statins., Limitations: Treatment initiation with injectable antihyperglycemic agents and/or non-statin lipid-modifying therapies as well as contraindications to OAHAs or statins were not assessed, therefore their impact on our study results cannot be determined. Laboratory measurements were not available for every patient and thus many patients were excluded from the analysis., Conclusion: Treatment initiation with OAHAs and/or statins was suboptimal in patients with T2DM who were treatment eligible and previously untreated with OAHAs and statins. Of those treated, patients initiated treatment with an OAHA more often and earlier than with a statin.

Objective: To assess the impact of hypoglycemia on clinical outcomes among hospitalized, insulin-treated patients., Methods: In a retrospective study, hospitalizations in 2005-2007 were identified from a US inpatient electronic medical records database. All encounters for insulin-treated patients with valid blood glucose measurement were included, except for those with a length of stay <24 hours or >30 days. In an encounter-based analysis, associations between hypoglycemic (glucose ≤70 mg/dL) or severe hypoglycemic (glucose ≤50 mg/dL) episodes and inpatient mortality, ischemic events, neurologic complications, and length of stay were evaluated., Results: Among 107,312 admissions, hypoglycemia occurred in 21,561 (20%) and severe hypoglycemia in 7539 (7%). Inpatient mortality occurred in 6.5% of hospitalizations with hypoglycemia and 3.8% of those without (p < 0.001). Inpatient mortality occurred in 7.6% of hospitalizations with a severe hypoglycemic event. Ischemic events (8.1 vs. 8.0%) and neurologic complications (3.8 vs. 3.7%) were similar in hospitalizations with and without a hypoglycemic event, respectively. In multivariate logistic regression analyses adjusting for age, gender, and selected comorbidities, hypoglycemia was associated with a significant increase in inpatient mortality risk (adjusted odds ratio (OR) = 1.66 [95% CI: 1.55, 1.78]). Similar results were observed with severe hypoglycemia (adjusted OR = 1.44 [1.38, 1.52]). Length of stay was increased in hospitalizations with hypoglycemia (median [interquartile range]: 8.2 days [4.9, 13.9] vs. 5.2 days [3.1, 8.3]; p < 0.0001)., Limitations: Due to the nature of the data source, some data of interest were not available, including insulin dose and dose regimen, outpatient medical histories (including diabetes history), pre-hospitalization medications, and cause of death., Conclusions: Hypoglycemia was common among hospitalized patients receiving insulin and, while a direct causal relationship cannot be assumed, was associated with an increased risk of inpatient mortality and increased length of hospital stay. Hypoglycemia is an undesirable event and efforts to minimize in-hospital hypoglycemic events are warranted across the spectrum of hospitalized patients.

Objectives: To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA(1c)) and medication adherence., Methods: A systematic literature review and meta-analysis were performed to compare the HbA(1c) response and medication adherence between the two drug regimens. Selected articles were limited to studies that compared equivalent drug components within FDC and CDT. Searches used PubMed, Embase, Web of Knowledge, and Cochrane databases. The search results were independently screened and reviewed by two authors (SH, KI). Of the 1246 identified abstracts, 152 articles were reviewed, and ten met the inclusion criteria. Results were extracted and pooled in a meta-analysis, using a random-effects model. Cohort comparisons were described as mean differences (MDs) with 95% confidence intervals (CIs)., Results: The ten articles that met the inclusion criteria had a total study size of 70,573 patients. Four articles reported HbA(1c) results, which had a total of five cohort comparisons of FDC and CDT use. The meta-analysis revealed a significantly greater HbA(1c) reduction with FDC (MD = -0.53% [95% CI: -0.78, -0.28]; p < 0.0001). Eight studies evaluated medication adherence (measured as medication possession ratio [MPR]). Of the eight studies reporting MPR results, a total of 12 cohort comparisons were made and were further divided into three subgroups based on comparison types. Five comparisons described MPR for FDC versus CDT cohorts, with significantly higher MPR with FDC (MD = 8.6% [95% CI: 1.6, 15.6]; p = 0.0162]). Four comparisons examined patients who switched from monotherapy to FDC or CDT, with higher MPR for patients who switched to FDC (MD = 7.7% [95% CI: 5.7, 9.6]; p < 0.0001). Three comparisons described results for patients who switched from CDT to FDC or stayed on CDT, with higher MPR for patients who switched to FDC (MD = 5.0% [95% CI: 3.1, 6.8]; p < 0.0001)., Limitations: A limited number of published studies were available for this meta-analysis and all of those included were observational studies. There was heterogeneity between studies in the statistical methods used to control for confounding variables and differing population characteristics., Conclusions: In a meta-analysis, use of FDCs with antihyperglycemic agents was associated with lower HbA(1c) and higher MPR values compared to CDT use in patients with type 2 diabetes.

Aim: To compare the time from initial diagnosis to initiation with oral antihyperglycaemic treatment in younger versus older patients with type 2 diabetes, and to evaluate factors associated with initiating treatment., Methods: This was a retrospective US cohort study with a 2-year follow-up period after diagnosis of type 2 diabetes. Using the General Electric Healthcare's Clinical Data Services electronic medical record database, eligible patients included those aged ≥30 years at initial diagnosis of type 2 diabetes between January 2003 and December 2005. In the 2-year period following diagnosis, the time to the first prescription of an oral antihyperglycaemic agent was compared between younger (30-64 years) and older (≥65 years) patients. Factors associated with time to treatment with an oral antihyperglycaemic agent were examined using Cox proportional hazards regression., Results: Of the 10 743 patients with newly diagnosed type 2 diabetes, 43% were ≥65 years old. The mean age at diagnosis was 73 years for older patients and 52 years for younger patients. Compared to younger patients, a greater proportion of older patients had a baseline haemoglobin A1c (HbA1c) value <7% (38 vs. 32%; p < 0.001). In the 2-year follow-up period, a significantly greater proportion of younger patients (59%) received oral antihyperglycaemic treatment compared to older patients (44%; p < 0.001). The median time between diagnosis and initiating treatment with an oral antihyperglycaemic agent was 350 days for younger patients and >2 years for older patients. After adjusting for covariates, older patients had a greater risk of not receiving treatment with oral antihyperglycaemic therapy than younger patients [adjusted hazard ratio = 0.82 (95% confidence interval: 0.75, 0.90)]., Conclusions: In patients with newly diagnosed type 2 diabetes, the time to initiation of oral antihyperglycaemic therapy was significantly longer in older patients (≥65 years old) than younger patients (<65 years)., (© 2011 Blackwell Publishing Ltd.)

Objectives: To compare compliance and persistence with statin and oral antihyperglycemic therapies in patients with type 2 diabetes who received concomitant therapy., Study Design: Retrospective cohort study using a large US commercial claims database., Methods: Patients with type 2 diabetes and dispensed prescriptions for both statin and oral antihyperglycemic therapies on the same date in 2006 (index date = first date of such dispensing) were included in the analysis (N = 52,414). Patients were required to have continuous enrollment in the database for 1 year prior to (baseline) and 2 years after (follow-up) index date. The 2-year medication possession ratio (MPR) was compared between statin and oral antihyperglycemic therapy. For the persistence analysis, treatment discontinuation was defined by a gap >30 days between the last date of supply from previous dispensing and subsequent refill. The likelihood of discontinuation of statin versus oral antihyperglycemic therapy was estimated by fitting a robust Cox proportional hazards regression model, adjusted for baseline variables., Results: The 2-year MPR was 70% for statin and 78% for oral antihyperglycemic therapy (P <.0001). The proportion of patients with a 2-year MPR >80% was 52% for statin and 63% for oral antihyperglycemic therapy (P <.0001). The median time to discontinuation of statin was significantly shorter compared with oral antihyperglycemic therapy (284 vs 495 days, P <.001). There was a greater risk to discontinue statin than oral antihyperglycemic therapy (adjusted hazard ratio: 1.47 [95% confidence interval 1.45-1.48])., Conclusions: Compliance and persistence with statin therapy significantly lagged behind oral antihyperglycemic therapy in patients with type 2 diabetes who were treated concomitantly with both therapies.

Aims: To compare the incidence of symptomatic hypoglycaemia in fasting Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan., Methods: Patients with type 2 diabetes (age ≥ 18 years) who were treated with a stable dose of a sulphonylurea with or without metformin for at least 3 months prior to screening, who had an HbA(1c) < 10% and who expressed their intention to daytime fast during Ramadan were eligible for this open-label study. Patients were randomised in a 1 : 1 ratio to either switch to sitagliptin 100 mg qd or to remain on their prestudy sulphonylurea. Patients completed daily diary cards to document information on hypoglycaemic symptoms and complications. The primary end-point was the overall incidence of symptomatic hypoglycaemia recorded during Ramadan., Results: Of the 1066 patients randomised, 1021 (n = 507 for sitagliptin and n = 514 for sulphonylurea) returned at least one completed diary card and were included in the analysis. The proportion of patients who recorded one or more symptomatic hypoglycaemic events during Ramadan was lower in the sitagliptin group (6.7%) compared with the sulphonylurea group (13.2%). The risk of symptomatic hypoglycaemia was significantly decreased with sitagliptin relative to sulphonylurea treatment (Mantel-Haenszel relative risk ratio [95% CI] = 0.51 [0.34, 0.75]; p < 0.001). There were no reported events that required medical assistance (i.e. visits to physician or emergency room or hospitalisations) or were considered severe (i.e. events that caused loss of consciousness, seizure, coma or physical injury) during Ramadan., Conclusions: In Muslim patients with type 2 diabetes who observed the fast during Ramadan, switching to a sitagliptin-based regimen decreased the risk of hypoglycaemia compared with remaining on a sulphonylurea-based regimen. The incidence of hypoglycaemia was lower with gliclazide relative to the other sulphonylurea agents and similar to that observed with sitagliptin., (© 2011 Blackwell Publishing Ltd.)

Aim: To evaluate the time to and factors associated with treatment intensification in patients with type 2 diabetes who failed metformin monotherapy., Methods: In a retrospective analysis using a large US electronic medical record database, eligible patients included those with type 2 diabetes and an HbA(1c) of ≥7.0% or at least two fasting blood glucose levels of ≥126 mg/dl while on metformin monotherapy for at least 6 months within the period of 1 January 1997 to 31 December 2008. Time to treatment intensification was calculated as the time between index date (date on which HbA(1c) ≥ 7% after metformin monotherapy for at least 6 months) and first prescription for additional antihyperglycaemic agent during follow-up period. All patients were required to have data for at least 12 months prior to and following the index date. A Cox proportional hazards model was employed to determine patient baseline characteristics associated with time to treatment intensification., Results: Of the 12 566 patients identified, mean age at index date was 63 years and 51% were female. Mean index HbA(1c) was 8.0% overall, with 66, 19 and 15% of patients having an index HbA(1c) of 7 to <8%, 8 to <9% and ≥9%, respectively. Median time to treatment intensification was 14.0 months overall and 19.0, 8.7 and 4.5 months for patients with index HbA(1c) of 7 to <8%, 8 to <9% and ≥9%, respectively. Factors associated with treatment intensification included higher index HbA(1c) , younger age, higher Charlson co-morbidity index, metformin daily dose ≥ 1500 mg and later index date (all p < 0.05)., Conclusions: In US clinical practice, median time to receive additional antihyperglycaemic medication is more than 1 year for patients with type 2 diabetes who failed metformin monotherapy., (© 2011 Blackwell Publishing Ltd.)

Objectives: To determine the incidence of hypoglycaemia during Ramadan in Muslim subjects with type 2 diabetes treated with a sulphonylurea., Methods: In an observational study, eligible subjects were Muslims with type 2 diabetes (age ≥18 years) who were treated with glimepiride, gliclazide, or glibenclamide with or without metformin and who expressed their intention to fast during Ramadan in 2009. Subjects were recruited by clinicians in India, Malaysia, Israel, the United Arab Emirates (UAE), and Saudi Arabia. Each day during Ramadan, patients completed diary cards, which collected information regarding hypoglycaemic symptoms and complications, time from last meal and from last medication, self-monitored blood glucose measurements, and need for assistance. The overall incidence of symptomatic hypoglycaemia recorded during Ramadan was the primary endpoint of interest., Results: Of the enrolled subjects (N = 1397), 1378 returned their diary cards at study end and were included in the analysis. Overall, 89% of subjects who expressed their intention to fast prior to Ramadan reported that they observed the fast during Ramadan. A total of 271 subjects (19.7%) experienced one or more symptomatic hypoglycaemic events during Ramadan, with incidences of 25.6%, 16.8%, and 14.0% observed in subjects treated with glibenclamide, glimepiride, and gliclazide, respectively. By country, the highest incidence of hypoglycaemia was reported by subjects from Israel (40%) followed by those from Malaysia (24%), the UAE (18%), India (13%), and Saudi Arabia (10%). The overall incidence of severe hypoglycaemic events (i.e., events requiring medical or non-medical assistance) was 6.7%, with the highest incidence occurring in the glibenclamide group., Limitations: This was an observational study and as such subjects were not randomised to treatments. While baseline measures appeared comparable, it is possible that differences in measured and unmeasured patient characteristics (e.g., measures of glycaemic control) could partially explain these results. Lastly, no inferential testing was performed on the comparisons between sulphonylurea types and/or countries., Conclusions: In this five-country observational study, nearly 20% of sulphonylurea-treated Muslim subjects with type 2 diabetes experienced symptomatic hypoglycaemia while fasting during Ramadan, with variations across sulphonylureas and countries.

Aim: To examine and to quantify the impact of concurrent macrovascular co-morbidities (MVC) on healthcare resource utilization among patients with type 2 diabetes mellitus (T2DM) in Europe., Methods: This is a matched cohort study based on the Real-Life Effectiveness and Care Patterns of Diabetes Management study, a multicentre, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, UK, Norway, Finland, Germany and Poland. Included patients were aged > or =30 years at time of diagnosis of T2DM who added a sulfonylurea or a PPARgamma agonist to failing metformin monotherapy (index date) and had concurrent MVC (cases). A control cohort with T2DM but without concurrent MVC was identified using 1:1 propensity score matching. Logit models were used to identify the relationship between concurrent MVC and the likelihood of emergency room admission, receiving medical/surgical procedures, and hospitalization during the study period after controlling for baseline demographics, clinical information and baseline treatment. Negative binomial models were used to predict the number of office visits and length of hospital stay per year attributable to the concurrent MVC., Results: Relative to controls, patients with MVC were significantly more likely to have emergency department admissions [odds ratio (OR) 2.69; 95% CI: 1.56-4.65], receiving medical/surgical procedures (OR 2.57; 95% CI: 1.56-4.21) and hospitalizations (OR 2.58; 95% CI: 1.64-4.07) after controlling for other predictors. Similarly, MVC were associated with 1.49 additional office visits per year (p = 0.036) and 0.32 days of hospital stay per year (p = 0.023)., Conclusions: Within a seven-country European sample, this study showed that T2DM patients with MVC were more likely to use healthcare resources compared with T2DM patients without MVC.

Aims: This study examined the relationship of baseline characteristics and medication use in patients with type 2 diabetes who were prescribed sitagliptin versus other oral antihyperglycemic agents in clinical practice settings in the United States., Methods: The General Electric Healthcare's Clinical Data Services electronic medical record (EMR) database, covering 12 million US patients of all ages from 49 states, was used to identify patients with type 2 diabetes, aged >or=30 years, who received their first sitagliptin, metformin, sulfonylurea, or thiazolidinedione prescription between October 2006 and June 2008 (index period) as part of new mono-, dual, or triple therapy regimens. Patient demographics, diagnoses, prescriptions, and laboratory results were extracted for the 12-month period (baseline) prior to the index date (i.e., date of first prescription). Data were stratified by mono-, dual, or triple therapy and compared between sitagliptin regimens and non-sitagliptin regimens with other oral agents (metformin, sulfonylureas, or thiazolidinediones). Adjusted logistic regression analyses were used to estimate odds ratios (OR) associated with prescribing sitagliptin versus other oral monotherapy in relation to patient baseline characteristics., Results: Among 41,836 patients new to oral monotherapy, 876 (2.1%) received sitagliptin. Compared to patients initiating non-sitagliptin monotherapy, patients on sitagliptin monotherapy were older (64 vs. 60 years) and had lower body mass index (33 kg/m(2) vs. 34 kg/m(2)), higher serum creatinine (1.2 vs. 1.0 mg/dL), higher prevalence of chronic renal disease (7.2% vs. 1.9%), greater use of lipid-lowering agents (42% vs. 38%), and higher prevalence of cardiovascular conditions (CVD: 12.7% vs. 8.3%) and microvascular complications (MVD: 13.4% vs. 5.8%) (all p < 0.05). Of 22,683 patients new to dual therapy, 1885 (8.3%) were on sitagliptin regimens. Relative to patients on non-sitagliptin dual therapy regimens, patients prescribed sitagliptin as part of dual therapy regimens were older and had higher serum creatinine, higher prevalence of CVD, MVD, or chronic renal disease, and greater use of lipid-lowering and antihypertensive agents (all p < 0.05). Among 9967 patients new to triple therapy, 2828 (28.4%) were on triple therapy regimens with sitagliptin. Relative to patients on non-sitagliptin triple therapy regimens, patients on sitagliptin as part of triple therapy regimens were older, and had higher serum creatinine and greater use of antihypertensive or lipid-lowering agents (all p < 0.05). Adjusted logistic regression showed that significant predictors of being prescribed sitagliptin monotherapy were older age (OR 1.01, 95% CI 1.00, 1.02), higher HbA(1c) level (OR 1.10, 95% CI 1.04, 1.17), higher serum creatinine level (OR 1.22, 95% CI 1.08, 1.39), presence of MVD (OR 1.50, 95% CI 1.08, 2.09), and presence of chronic renal disease (OR 2.22, 95% CI 1.41, 3.49)., Limitations: Diabetes care delivered by non-participating physicians is not captured in the GE CDS EMR database and, therefore, the prevalence of the diseases identified based on ICD-9 diagnosis/procedure and CPT codes provided in the Appendix may be underestimated. Duration of diabetes was not consistently recorded and some measures were not available., Conclusion: Patients with type 2 diabetes who were prescribed sitagliptin regimens in clinical practice were older and more likely to have pre-existing co-morbid conditions compared to patients receiving non-sitagliptin regimens with other common oral antihyperglycemic agents. These findings have important implications for observational studies in that estimated clinical and health outcome measures may be biased due to channeling of patients to different therapies based on different baseline characteristics.

Background: Although there is a growing body of evidence showing that patients with type 2 diabetes mellitus (T2DM) have poor glycemic control in general, it is not clear whether T2DM patients with pre-existing cardiovascular diseases (CVD) are more or less likely to have good glycemic control than patients without pre-existing CVD. Our aim was to examine the degree of glycemic control among T2DM patients in Europe with and without pre-existing CVD., Methods: This is a matched cohort study based on a multi-center, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, United Kingdom, Norway, Finland, Germany, and Poland. Included patients were aged >= 30 years at time of diagnosis of T2DM, had added a SU or a PPARgamma agonist to failing metformin monotherapy (index date) and had pre-existing CVD (cases). A control cohort with T2DM without pre-existing CVD was identified using 1:1 propensity score matching. With difference-in-difference approach, logistic and linear regression analyses were applied to identify differences in glycemic control by CVD during the follow up period, after controlling for baseline demographics, clinical information, and concurrent anti-hyperglycemic medication use., Results: The percentage of case patients with adequate glycemic control relative to control patients during the 1st, 2nd, 3rd, and 4th years after the index date was 19.9 vs. 26.5, 16.8 vs. 26.5, 18.8 vs. 28.3, and 16.8 vs. 23.5 respectively. Cases were significantly less likely to have adequate glycemic control (odds ratio: 0.62; 95% confidence interval: 0.46-0.82) than controls after adjusting for baseline differences, secular trend, and other potential confounding covariates., Conclusions: T2DM patients with pre-existing CVD tended to have poorer glycemic control than those without pre-existing CVD, all other factors being equal. It suggests that clinicians may need to pay more attention to glycemic control among T2DM patients with CVD.

Introduction: Sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and exenatide, an injectable glucagon-like peptide-1 receptor agonist, are incretin-based therapies for the treatment of type 2 diabetes. This study examined differences in baseline characteristics between patients with type 2 diabetes initiating sitagliptin vs. exenatide treatment in clinical practice settings in the US., Methods: The General Electric Healthcare's Clinical Data Services electronic medical records database, covering 12 million US patients of all ages from 49 states, was used to identify patients with type 2 diabetes, aged > or =30 years, who received their first sitagliptin or exenatide prescription between October 1, 2006 and June 30, 2008 (index period). Patient's medical records, including demographics, diagnoses, procedures, prescriptions, and laboratory results were extracted for the 12-month period (baseline) prior to the date of the first prescription of sitagliptin or exenatide (ie, the index date). Patient baseline profiles were stratified by mono-, dual, or triple therapy and compared between regimens with sitagliptin or exenatide., Results: A total of 9543 patients initiated therapy with sitagliptin (n=5589) or exenatide (n=3954) during the index period. For those initiating monotherapy, 876 patients initiated sitagliptin and 476 initiated exenatide. Compared with patients initiating exenatide at baseline, patients on sitagliptin were older (64 vs. 55 years), more likely to be men (45% vs. 35%), and less likely to be obese (60% vs. 87%), and had higher hemoglobin A(1c) (HbA(1c); 7.1% vs. 6.9%), a higher serum creatinine (1.2 mg/dL vs. 1.0 mg/dL), and a higher prevalence of pre-existing cardiovascular complications or microvascular conditions (all P<0.01 for sitagliptin vs. exenatide). For dual therapy, 1885 were prescribed sitagliptin and 1392 were prescribed exenatide. For triple therapy, 2828 were prescribed sitagliptin and 2086 were prescribed exenatide. The observed patient profile differences with dual and triple therapy were generally consistent with those observed with monotherapy., Conclusion: In a clinical practice setting, there are differences in the baseline characteristics of patients with type 2 diabetes who are prescribed sitagliptin relative to those prescribed exenatide. These findings have important implications for conclusions drawn from observational studies using medical record or claim databases, as estimated clinical and health outcomes measures may be biased due to channeling of patients to different therapies based on different baseline characteristics.