Temporal changes in the incidence and predictors of severe hypoglycaemia in type 2 diabetes: The Fremantle Diabetes Study.

AIM: To determine the incidence of severe hypoglycaemia and its predictors in community-based patients with type 2 diabetes studied between 2008 and 2013 compared with those in a cohort of patients with type 2 diabetes from the same geographical area assessed a decade earlier. METHODS: We studied 1551 participants (mean age 65.7 years, 51.9% men) with type 2 diabetes from the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). Severe hypoglycaemia was ascertained as that requiring ambulance attendance, emergency department services and/or hospitalization. Cox proportional hazards modelling was used to determine predictors of a first episode of severe hypoglycaemia, and negative binomial regression was used to identify predictors of frequency. RESULTS: Sixty-three participants (4.1%) experienced 83 episodes, representing an incidence of 1.34/100 participant-years (95% confidence interval [CI] 1.08 to 1.67; vs 1.67/100 participant-years [95% CI 1.31-2.13] in the Fremantle Diabetes Study Phase I [FDS1]; P = 0.18). Those experiencing severe hypoglycaemia experienced one to four episodes in both cohorts. The independent predictors of incident severe hypoglycaemia in the FDS2 were: older age; higher educational attainment; alcohol consumption; current smoking; sulphonylurea/insulin treatment; prior severe hypoglycaemia; renal impairment; and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). The same variables except smoking were associated with frequency of severe hypoglycaemia. Most of these risk factors paralleled those in the FDS1, but current smoking and plasma NT-proBNP were novel. CONCLUSIONS: The incidence and frequency of severe hypoglycaemia did not change between the Fremantle Diabetes Study phases but novel risk factors, including plasma NT-proBNP, were observed in the FDS2.

A multinational observational study assessing insulin use: Understanding the determinants associated with progression of therapy.

AIMS: To describe global patterns of insulin treatment and to assess the impact of patient, provider, health system and economic influences on treatment decisions for patients with insulin-treated type 2 diabetes (T2D). METHODS: This prospective cohort study of insulin-treated patients with T2D was conducted across 18 countries categorized as high, upper-middle or lower-middle income regions. Information collected from patients included knowledge of diabetes, experiences and interactions with their healthcare provider. Physician information included specialty, practice size, availability of diabetes support services, volume of diabetes patients treated and time spent per patient. Physicians determined an individualized haemoglobin A1c (HbA1c) target for each patient by the start of the study. Changes in T2D therapies and HbA1c were recorded for 2 years. RESULTS: Complete treatment data were available for 2528 patients. Median age was 61 years and median duration of diabetes was 11.4 years. Changes to treatment regimen occurred in 90.0% of patients, but changes were less common in countries with a higher economic status (P < 0.001). Most treatment changes involved insulin, with changes in dose the most common. Overall predictors of change in insulin therapy included younger age, use of any insulin regimen other than basal only, higher mean baseline HbA1c and longer duration of T2D. HbA1c levels remained constant regardless of regional economic status. At baseline, 20.6% of patients were at their HbA1c target; at 2 years this was 26.8%. CONCLUSIONS: Among insulin-treated patients with T2D, treatment changes were common; however, only approximately one-fourth of individuals achieved their HbA1c target.

The relationship between intensification of blood glucose-lowering therapies, health status and quality of life in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To determine whether therapeutic intensification in type 2 diabetes influences health status and quality of life (QoL). METHODS: We studied 930 participants in the longitudinal observational Fremantle Diabetes Study Phase II (mean age 65.3 years, 53.8% males, median diabetes duration 8.0 years) with valid data from baseline assessment and two biennial reviews (4 years of follow-up) between 2008 and 2015. The main outcome measures were the Short Form-12 version 2 physical and mental health composite scores (PCS, MCS) and the average weighted impact (AWI) score from the Audit of Diabetes Dependent QoL. RESULTS: There were reductions in PCS at Year 4 compared with baseline and Year 2 in patients on stable diet-based management (n = 160), oral glucose-lowering medication (OGLM; n = 387), and insulin with/without OGLM (n = 168; P < 0.05), but no statistically significant temporal changes in MCS/AWI. Insulin-treated patients had the lowest PCS, MCS and AWI compared to the other two subgroups at each time-point (P ≤ 0.012). In participants initiating OGLM (n = 84) or insulin (n = 85), there were no differences in PCS, MCS or AWI at the biennial assessments either side of these therapeutic changes (P ≥ 0.08). CONCLUSIONS: These real-life data show that treatment intensification, including insulin initiation, does not impact adversely on patient well-being in community-based type 2 diabetes. Since insulin use at entry was associated with longer diabetes duration, worse glycaemic control, and a greater risk of chronic complications, the burden of disease rather than treatment modality appears the primary determinant of health status and QoL.

Temporal changes in glycaemic thresholds for treatment intensification in type 2 diabetes in an urban Australian setting: the Fremantle Diabetes Study.

BACKGROUND: Pharmacotherapy and supportive care for diabetes in Australia are improving, with potential beneficial effects on therapeutic procrastination. AIM: To determine whether glycaemic thresholds for therapeutic intensification in type 2 diabetes changed over the 15 years between phases of the community-based Fremantle Diabetes Study (FDS). METHODS: We studied 531 Phase 1 participants (mean age 62.4 years, 54.2% males, median diabetes duration 3.0 years) with valid data from baseline assessment and five subsequent annual reviews between 1993 and 2001 and 930 Phase 2 participants (mean age 65.3 years, 53.8% males, median diabetes duration 8.0 years) with valid data from baseline and two subsequent biennial reviews between 2008 and 2015. The main outcome measure was HbA1c at assessments before and after change in blood glucose-lowering therapy (average 6 months in Phase 1, 12 months in Phase 2). RESULTS: Ninety-seven participants in Phase 1 and 84 in Phase 2 progressed from diet-based management to oral hypoglycaemic agents (OHA) and 45 and 85 participants, respectively, progressed from diet/OHA to insulin. The median HbA1c was 7.5% (58 mmol/mol) and 6.9% (52 mmol/mol) before OHA initiation in Phases 1 and 2, respectively, and 9.1% (76 mmol/mol) and 7.8% (62 mmol/mol), respectively, before insulin initiation. There were median HbA1c falls of 0.3% (3 mmol/mol) and 1.5% (16 mmol/mol) after OHA and insulin initiation in Phase 1, but no statistically significant changes in Phase 2. CONCLUSIONS: HbA1c thresholds triggering treatment intensification fell between FDS phases, suggesting a more proactive approach to management of glycaemia over time.

Exploring the role of the patient-physician relationship on insulin adherence and clinical outcomes in type 2 diabetes: Insights from the MOSAIc study.

BACKGROUND: The 2-year prospective MOSAIc (Multinational Observational Study assessing Insulin use: understanding the challenges associated with progression of therapy) study is investigating whether patient-, physician-, and health system-related factors affect outcomes in patients with type 2 diabetes (T2D). This baseline subanalysis investigated how aspects of the patient-physician relationship are associated with diabetes-related distress, insulin adherence, and glycemic control. METHODS: Patients with T2D taking insulin for ≥3 months were recruited at primary care and specialty practice sites in 18 countries. Physicians provided usual care. Clinical history and most recent HbA1c values were collected; patients were surveyed regarding their perception of physician interactions, diabetes-related distress level, and insulin adherence. RESULTS: The analysis population comprised 4341 patients. Four (of six) domains showed a significant relationship with total diabetes-related distress (P < 0.01). Poor insulin adherence was associated with greater diabetes-related distress (adjusted odds ratio [aOR] 1.14; 95% confidence interval [CI] 1.06-1.22), higher Discrimination (aOR 1.13; 95% CI 1.02-1.27) and Hurried Communication (aOR 1.35; 95% CI 1.20-1.53) scores, and a lower Explained Results score (aOR 0.86; 95% CI 0.77-0.97). Poor insulin adherence was associated with a 0.43% increase in HbA1c, whereas a 1-unit increase in total diabetes-related distress and Hurried Communication scores was associated with a 0.171% and 0.145% increase in HbA1c, respectively. CONCLUSIONS: Patients distressed about living with T2D, and dissatisfied with aspects of their interactions with physicians, exhibited poor insulin adherence. Perceived physician inattention and lack of engagement (and diabetes-related distress) directly affect insulin adherence and glycemic control.

THE CARIES MANAGEMENT SYSTEM: UPDATING COST-EFFECTIVENESS WITH 4-YEAR POSTTRIAL DATA.

OBJECTIVES: Long-term follow-up of the Caries Management System (CMS) protocol demonstrated that regular monitoring and noninvasive management of dental caries is effective in reducing the number of caries-related events over a 7-year period. This analysis complements the authors' original economic evaluation of the CMS by re-evaluating the per-protocol cost-effectiveness of the CMS approach. METHODS: An individual patient-simulation Markov model was developed previously, based on 3-year randomized-controlled trial (RCT) data, to simulate the incidence and progression of dental caries, and resultant interventions, and to evaluate the lifetime cost-effectiveness of the CMS versus standard dental care from the Australian private dental practitioner perspective (in which the baseline age distribution was similar to that of the Australian population). The 4-year posttrial follow-up data are used to re-evaluate the long-term cost-effectiveness of the CMS in a more real-life setting. RESULTS: The reduction in caries risk was maintained among those practices within which the CMS protocols were adhered to. The per-protocol model appears to be reasonably accurate at predicting the risk of restorative events in the posttrial follow-up period. The per-protocol lifetime cost per restorative event avoided is AUD1,980 (USD1,409; 1 AUD = 0.71 USD). CONCLUSIONS: The current analysis confirms that the CMS approach is both effective, when the protocols are adhered to appropriately, and cost-effective compared with standard care in the Australian private practice setting.

Evaluation of a patient self-directed mealtime insulin titration algorithm: a US payer perspective.

Objective To model the potential economic impact of implementing the AUTONOMY once daily (Q1D) patient self-titration mealtime insulin dosing algorithm vs standard of care (SOC) among a population of patients with Type 2 diabetes living in the US. Methods Three validated models were used in this analysis: The Treatment Transitions Model (TTM) was used to generate the primary results, while both the Archimedes (AM) and IMS Core Diabetes Models (IMS) were used to test the veracity of the primary results produced by TTM. Models used data from a 'real world' representative sample of patients (2012 US National Health and Nutrition Examination Survey) that matched the characteristics of US patients enrolled in the randomized controlled trial 'AUTONOMY' cohort. The base-case time horizon was 10 years. Results The modeling results from TTM demonstrated that total costs in the base-case were reduced by $1732, with savings predicted to occur as early as year 1. Results from the three models were consistent, showing a reduction in total costs for all sensitivity analyses. Limitations Data from short-term clinical trials were used to develop long-term projections. The nature of such extrapolation leads to increased uncertainty. Conclusion The results from all three models indicate that the AUTONOMY Q1D algorithm has the potential to abate total costs as early as the first year.

A qualitative examination of the content validity of the EQ-5D-5L in patients with type 2 diabetes.

BACKGROUND: The EQ-5D is frequently used to derive utilities for patients with type 2 diabetes (T2D). Despite widely available quantitative psychometric data on the EQ-5D, little is known about content validity in this population. Thus, the purpose of this qualitative study was to examine content validity of the EQ-5D in patients with T2D. METHODS: Patients with T2D in the UK completed concept elicitation interviews, followed by administration of the EQ-5D-5L and cognitive interviewing focused on the instrument's relevance, clarity, and comprehensiveness. RESULTS: A total of 25 participants completed interviews (52.0 % male; mean age = 53.5 years). Approximately half (52 %) reported that the EQ-5D-5L was relevant to their experience with T2D. When asked if each individual item was relevant to their experience with T2D, responses varied widely (24.0 % said the self-care item was relevant; 68.0 % said the anxiety/depression item was relevant). Participants frequently said items were not relevant to themselves, but could be relevant to patients with more severe diabetes. Most participants (92.0 %) reported that T2D and/or its treatment/monitoring requirements had an impact on their quality of life that was not captured by the EQ-5D-5L. Common missing concepts included food awareness/restriction (n = 13, 52.0 %); activities (n = 11, 44.0 %); emotional functioning other than depression/anxiety (n = 8, 32.0 %); and social/relationship functioning (n = 8, 32.0 %). CONCLUSIONS: The results highlight strengths and potential limitations of the EQ-5D-5L, including missing content that could be important for some patients with T2D. Suggestions for addressing limitations are provided.

Geographic patterns in patient demographics and insulin use in 18 countries, a global perspective from the multinational observational study assessing insulin use: understanding the challenges associated with progression of therapy (MOSAIc).

BACKGROUND: Among patients with type 2 diabetes, insulin intensification to achieve glycemic targets occurs less often than clinically indicated. Barriers to intensification are not well understood. We present patients' baseline characteristics from MOSAIc, a study investigating patient-, physician-, and healthcare environment-based factors affecting insulin intensification and subsequent health outcomes. METHODS: MOSAIc is a longitudinal, observational study following patients' diabetes care in 18 countries: United Arab Emirates (UAE), Argentina, Brazil, Canada, China, Germany, India, Israel, Italy, Japan, Mexico, Russia, Saudi Arabia, South Korea, Spain, Turkey, United Kingdom, United States. Eligible patients are age ≥ 18, have type 2 diabetes, and have used insulin for ≥ 3 months with/without other antidiabetic medications. Extensive baseline demographic, clinical, and psychosocial data are collected at baseline and regular intervals during the 24-month follow-up. We conducted descriptive analyses of baseline data. RESULTS: Four thousand three hundred forty one patients met eligibility criteria. Patients received their type 2 diabetes diagnosis 12 ± 8 years prior to baseline visit, yet patients in developing countries were younger than in developed countries (e.g., UAE, 55 ± 10; Germany = 70 ± 10). Saudi Arabians had the highest HbA1c values (9.0 ± 2.2) and Germany (7.5 ± 1.4) among the lowest. Most patients in 5 (28%) of the 18 countries did not use an oral antidiabetic drug. Over half of patients in fourteen (78 %) countries exclusively used basal insulin; most Indian and Chinese patients exclusively used mixed insulin. CONCLUSIONS: MOSAIc's baseline data highlight differences in patient characteristics across countries. These patterns, along with physician and healthcare environment differences, may contribute to the likelihood of insulin intensification and subsequent clinical outcomes.

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study.

AIM: Describe the characteristics of patients initiating human regular U-500 insulin (U-500R) and their subsequent glycemic control in a real-world setting. METHODS: US Humedica electronic health record system data (July 2007-September 2011) were used to identify patients with diabetes aged ≥18 years with ≥1 records for U-500R prescriptions, 6 months of preindex data, 12 months following first use of U-500R, and at least one glycated hemoglobin (HbA1c) value in both preindex and postindex periods. Paired t tests were used to measure the change in HbA1c from preindex to postindex periods (last or most recent values) and hypoglycemia. RESULTS: Among patients initiating U-500R (N=445), 96.9% had type 2 diabetes with mean age 57 years and mean body mass index 40.4 kg/m(2). Postindex prescriptions were written for U-500R alone (47.0%, group A) and concomitant U-500R/U-100 insulins (53.0%, group B). Concomitant oral antihyperglycemic agents (AHAs) and non-insulin injectable AHAs were used by 43.4% and 14.6% of patients, respectively. Following initiation of U-500R, mean HbA1c improved 0.68% in all patients (p<0.0001 compared with baseline), but the decrease in HbA1c did not differ significantly between groups (A: 0.78%; B: 0.60%). Overall, hypoglycemic events, largely captured in the outpatient setting, increased in incidence from 6.7% to 11.9% (p≤0.0001) and from 0.23 to 0.39 events/patient/year, an increase of 0.16 (p=0.003), from preindex to postindex. CONCLUSIONS: This real-world outcomes analysis demonstrates that U-500R initiation is associated with a clinically meaningful improvement in glycemic control over the subsequent 12-month period with modest increase in incidence and rate of hypoglycemia.

Economic impact of severe and non-severe hypoglycemia in patients with Type 1 and Type 2 diabetes in the United States.

OBJECTIVE: To identify the direct and indirect costs of hypoglycemia in patients with Type 1 or Type 2 diabetes mellitus (DM) in the US setting. METHODS: A literature review was conducted to identify and review studies that reported data on the economic burden of hypoglycemia and the related medical resource consumption or productivity loss related to hypoglycemia in patients with Type 1 or Type 2 DM. Relevant information was collated in an economic model to assess the direct and indirect costs following severe and non-severe hypoglycemic events in Type 1 and Type 2 DM. RESULTS: Detailed evidence of the medical cost burden of hypoglycemic events was identified from 14 studies. For both Type 1 and Type 2 DM, episodes requiring assistance from a healthcare practitioner were identified as particularly costly and amounted to $1161 per episode (direct costs) compared with episode costs of $66 and $11 for events requiring third-party (non-medical) assistance and events managed by self-treatment, respectively. Indirect costs associated with severe hypoglycemia requiring non-medical assistance, severe hypoglycemia requiring medical assistance, and non-severe hypoglycemia were predicted to be $242, $160, and $11 for patients with Type 1 diabetes and $579, $176, and $11 for patients with Type 2 diabetes, respectively. CONCLUSION: Both severe and non-severe hypoglycemia incur substantial healthcare costs. Failure to account for these costs may under-estimate the value of management strategies that minimize hypoglycemia risk.

Factors associated with increased healthcare costs in Medicare Advantage patients with type 2 diabetes enrolled in a large representative health insurance plan in the US.

AIM: The objective of this study was to apply quantile regression (QR) methodology to a population from a large representative health insurance plan with known skewed healthcare utilization attributes, co-morbidities, and costs in order to identify predictors of increased healthcare costs. Further, this study provides comparison of the results to those obtained using ordinary least squares (OLS) regression methodology. METHODS: Members diagnosed with Type 2 Diabetes and with 24 months of continuous enrollment were included. Baseline patient demographic, clinical, consumer/behavioural, and cost characteristics were quantified. Quantile regression was used to model the relationship between the baseline characteristics and total healthcare costs during the follow-up 12 month period. RESULTS: The sample included 83,705 patients (mean age = 70.6 years, 48% male) residing primarily in the southern US (78.1%); 81.2% of subjects were on oral-only anti-diabetic therapy. Co-morbid conditions included nephropathy (43.5%), peripheral artery disease (26.4%), and retinopathy (18.0%). Variables with the strongest relationship with costs during the follow-up period included outpatient visits, ER visits, inpatient visits, and Diabetes Complications Severity Index score during the baseline period. In the top cost quantiles, each additional glycohemoglobin (HbA1c) test was associated with cost savings ($1400 in the 98th percentile). Stage 4 and Stage 5 chronic kidney disease were associated with an incremental cost increase of $33,131 and $106,975 relative to Stage 1 or no CKD in the 98th percentile ($US). CONCLUSIONS: These results demonstrate that QR provides additional insight compared to traditional OLS regression modeling, and may be more useful for informing resource allocation to patients most likely to benefit from interventions. This study highlights that the impact of clinical and demographic characteristics on the economic burden of the disease vary across the continuum of healthcare costs. Understanding factors that drive costs on an individual patient level provide important insights that will help in ameliorating the clinical, humanistic, and economic burden of diabetes.

The evaluation of clinical and cost outcomes associated with earlier initiation of insulin in patients with type 2 diabetes mellitus.

BACKGROUND: The treatment for patients with type 2 diabetes mellitus (T2DM) follows a stepwise progression. As a treatment loses its effectiveness, it is typically replaced with a more complex and frequently more costly treatment. Eventually this progression leads to the use of basal insulin typically with concomitant treatments (e.g., metformin, a GLP-1 RA [glucagon-like peptide-1 receptor agonist], a TZD [thiazolidinedione] or a DPP-4i [dipeptidyl peptidase 4 inhibitor]) and, ultimately, to basal-bolus insulin in some forms. As the cost of oral antidiabetics (OADs) and noninsulin injectables have approached, and in some cases exceeded, the cost of insulin, we reexamined the placement of insulin in T2DM treatment progression. Our hypothesis was that earlier use of insulin produces clinical and cost benefits due to its superior efficacy and treatment scalability at an acceptable cost when considered over a 5-year period. OBJECTIVES: To (a) estimate clinical and payer cost outcomes of initiating insulin treatment for patients with T2DM earlier in their treatment progression and (b) estimate clinical and payer cost outcomes resulting from delays in escalating treatment for T2DM when indicated by patient hemoglobin A1c levels. METHODS: We developed a Monte Carlo microsimulation model to estimate patients reaching target A1c, diabetes-related complications, mortality, and associated costs under various treatment strategies for newly diagnosed patients with T2DM. Treatment efficacies were modeled from results of randomized clinical trials, including the time and rate of A1c drift. A typical treatment progression was selected based on the American Diabetes Association and the European Association for the Study of Diabetes guidelines as the standard of care (SOC). Two treatment approaches were evaluated: two-stage insulin (basal plus antidiabetics followed by biphasic plus metformin) and single-stage insulin (biphasic plus metformin). For each approach, we analyzed multiple strategies. For each analysis, treatment steps were sequentially and cumulatively removed from the SOC until only the insulin steps remained. Delays in escalating treatment were evaluated by increasing the minimum time on a treatment within each strategy. The analysis time frame was 5 years. RESULTS: Relative to SOC, the two-stage insulin approach resulted in 0.10% to 1.79% more patients achieving target A1c (<7.0%), at incremental costs of $95 to $3,267. (The ranges are due to the different strategies within the approach.) With the single-stage approach, 0.50% to 2.63% more patients achieved the target A1c compared with SOC at an incremental cost of -$1,642 to $1,177. Major diabetes-related complications were reduced by 0.38% to 17.46% using the two-stage approach and 0.72% to 25.92% using the single-stage approach. Severe hypoglycemia increased by 17.97% to 60.43% using the two-stage approach and 6.44% to 68.87% using the single-stage approach. In the base case scenario, the minimum time on a specific treatment was 3 months. When the minimum time on each treatment was increased to 12 months (i.e., delayed), patients reaching A1c targets were reduced by 57%, complications increased by 13% to 76%, and mortality increased by 8% over 5 years when compared with the base case for the SOC. However, severe hypoglycemic events were reduced by 83%. CONCLUSIONS: As insulin was advanced earlier in therapy in the two-stage and single-stage approaches, patients reaching their A1c targets increased, severe hypoglycemic events increased, and diabetes-related complications and mortality decreased. Cost savings were estimated for 3 (of 4) strategies in the single-stage approach. Delays in treatment escalation substantially reduced patients reaching target A1c levels and increased the occurrence of major nonhypoglycemic diabetic complications. With the exception of substantial increases in severe hypoglycemic events, earlier use of insulin mitigates the clinical consequences of these delays.

Treatment patterns among older patients with type 2 diabetes in the United States: a retrospective cohort study.

BACKGROUND: The American Diabetes Association consensus statement on the treatment of type 2 diabetes mellitus (T2DM) in older patients highlights the need for treatment pattern and effectiveness data from real-world settings and populations. This retrospective cohort study assessed the relative frequency of use of four commonly prescribed antihyperglycemia treatments for T2DM and quantified their effectiveness up to 2 years post-initiation. SUBJECTS AND METHODS: Within a large, U.S.-based, electronic health record database, we investigated usage of insulin, sulfonylureas, glucagon-like peptide-1(GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with T2DM, focusing on those ≥65 years old, although younger patients were included for comparative purposes. RESULTS: Inclusion criteria were met by 77,440 patients. Mean baseline glycosylated hemoglobin (HbA1c) levels for patients ≥65 years old varied among treatments: insulin (7.7% [61 mmol/mol]; n=3,311), sulfonylureas (7.0% [53 mmol/mol]; n=5,706), GLP-1 receptor agonists (7.1% [54 mmol/mol]; n=260), and DPP-4 inhibitors (7.1% [54 mmol/mol]; n=1,096). Older patients demonstrated good glycemic control at therapy initiation and were prescribed glucose-lowering agents at lower HbA1c values compared with younger patients. A large proportion of older patients were prescribed sulfonylureas (56%) and insulin (34%) compared with GLP-1 receptor agonists (3.4%) and DPP-4 inhibitors (12%), despite the associated risk of hypoglycemia. CONCLUSIONS: Patients initiating insulin and sulfonylureas demonstrated more sustained glycemic control compared with GLP-1 receptor agonists and DPP-4 inhibitors. A majority of older patients with T2DM was initiated on sulfonylureas and insulin at relatively low levels of HbA1c, a practice not entirely consistent with the recommendations of published guidelines.

Frequency and causes of hospitalization in older compared to younger adults with type 2 diabetes in the United States: a retrospective, claims-based analysis.

AIMS: This study assessed the frequency and most common causes of hospitalization in older compared to younger adults with type 2 diabetes mellitus (T2DM) in the US. METHODS: A retrospective study utilizing data from a nationally representative insurance claim database included patients who were diagnosed or treated for diabetes during or prior to the defined study period and who experienced hospitalization with or without re-hospitalization. RESULTS: Among 887,182 patients with T2DM, 31% were ≥ 65 years old and nearly 1 in 4 (23.5%) were hospitalized during the observation period. Only 2.3% of first hospitalizations were determined to be diabetes-related, and these events were most commonly associated with a history of pre-study hospitalization and increasing age. Hypoglycemia was a common cause for T2DM-related hospitalizations (22.9%), and older patients demonstrated a higher proportion of hypoglycemia-related hospitalizations (age ≥ 65 years: 38.3% vs. age < 65 years: 11.4%). Survival analysis predicting readmission within 6 months after first hospitalization showed that primary factors associated with first readmissions were history of prior hospitalization, malignancy, insulin use, and presence of pre-existing liver or renal disease. CONCLUSIONS: Hospitalization is common in patients with diagnosed diabetes, and nearly 1 in 4 diabetes-related hospital admissions were due to hypoglycemia. While the overall rate of hypoglycemia-associated admission was low, the age-specific rate was nearly 2.5-fold higher in older adults (≥ 65 years), affirming the need to carefully assess the potential benefit/risk of diabetes medications in those ≥ 65 years of age.

Healthcare costs and adherence associated with human regular U-500 versus high-dose U-100 insulin in patients with diabetes.

OBJECTIVE: Describe the characteristics, costs, and adherence of patients receiving human regular U-500 insulin (U-500R) compared with those of patients receiving high-dose (≥150 units/day) U-100 insulin. METHODS: Data from Truven Health MarketScan Research Databases, July 1, 2008, through December 31, 2010, were used. The U-100 cohort received ≥150 units/day of U-100 insulin for ≥31 days during the first 60 days after the index date. The U-500R cohort received ≥2 prescriptions of U-500R after the index date. Analyses were performed on propensity-matched cohorts. The changes in annualized costs were compared between the 2 cohorts using paired t tests. Adherence was assessed by the proportion of days covered (PDC) and compared using a 2-sample t test. Glycemic efficacy data were not available in this database. RESULTS: There were 1,044 U-500R-treated patients (19.1% with type 1 diabetes [T1D]) and 11,520 U-100-treated patients (23.8% with T1D) identified, from which 1,039 matched pairs were obtained. The mean decrease of $1,290 in annual pharmacy costs for the U-500R cohort was significantly different from the mean increase of $2,586 for the U-100 cohort (P<.001; 95% confidence interval, -$4,345 to -$3,422). More U-500R patients experienced hypoglycemia (17.3% vs. 11.8%; P<.001), but the hypoglycemia rate per person and related costs were not significantly different between cohorts. Finally, the mean 12-month PDC was 65.0% for U-500R versus 47.6% for U-100 patients (P<.0001). CONCLUSION: Compared with treatment with ≥150 units/day of U-100 insulin, treatment with U-500R was associated with decreases in pharmacy costs, a higher percentage of patients experiencing hypoglycemia, and greater treatment adherence.

Efficacy and safety of insulin lispro in geriatric patients with type 2 diabetes: a retrospective analysis of seven randomized controlled clinical trials.

BACKGROUND AND AIMS: Glycemic control in geriatric patients with type 2 diabetes (T2DM) remains clinically challenging. The objective of this study was to compare the safety and efficacy of insulin lispro in patients C65 years (geriatric) to those\65 years (non-geriatric), using a metaanalysis of randomized controlled clinical trials (RCT). METHODS: This is a retrospective analysis of predefined endpoints from an integrated database of seven RCTs of T2DM patients treated with insulin lispro. The primary efficacy measure tested the non-inferiority of insulin lispro (geriatric vs. non-geriatric; non-inferiority margin 0.4 %) in terms of hemoglobin A1c (HbA1c) change from baseline to Month 3 (N = 1,525), with change from baseline to Month 6 as a supportive analysis (N = 885). Changes in HbA1c from baseline were evaluated with an analysis of covariance model. Secondary measures included incidence and rate of hypoglycemia, and incidence of cardiovascular events. RESULTS: Mean change in HbA1c from baseline to Month 3 was similar for geriatric (-0.97 %) and non-geriatric patients (-1.05 %); least-square (LS) mean difference (95 % CI) was 0.02 % (-0.11, 0.15 %; p = 0.756). Similar results were observed in patients treated up to Month 6; LS mean difference (95 % CI) was 0.07 % (-0.12, 0.26 %; p = 0.490). Decrease in HbA1c from baseline to Months 3 and 6 was non-inferior in geriatric compared with non-geriatric patients. There were no significant differences in the incidence and the rate of hypoglycemia, incidence of cardiovascular events, or other serious adverse events including malignancy, post-baseline between the two cohorts. CONCLUSION: Key measures of efficacy and safety in geriatric patients with T2DM were not significantly different from non-geriatric patients when utilizing insulin lispro. Insulin lispro may be considered a safe and efficacious therapeutic option for the management of T2DM in geriatric patients.

Efficacy and safety of insulin lispro in obese patients with type 2 diabetes: a retrospective metaanalysis of 7 randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of insulin lispro in the treatment of patients with type 2 diabetes (T2DM) who had a body mass index (BMI) ≥30 kg/m2 (obese) compared with patients with BMIs <30 kg/m2 (nonobese). METHODS: A retrospective analysis of predefined end-points from 7 randomized clinical trials of T2DM patients treated with insulin lispro was performed. The primary efficacy measure was to assess the noninferiority of insulin lispro in obese patients versus nonobese patients as measured by the change in hemoglobin A1C (HbA1c) from baseline to Month 3 (n = 1,518), using a noninferiority margin of 0.4%. The secondary measures included overall hypoglycemia incidence and event rates and relative change in body weight. RESULTS: Mean changes in HbA1c from baseline (9.06% for obese and 8.92% for nonobese) to Month 3 were similar for obese patients (-1.03%) and nonobese (-1.02%), with a least squares (LS) mean difference (95% confidence interval [CI]) of -0.05% (-0.17%, 0.07%; P = .384). The overall incidence of hypoglycemia (53% vs. 63%; P<.001) and rate of hypoglycemia (0.93 vs. 1.76 events per 30 days; P<.001) was significantly lower in obese patients compared with nonobese patients. The 2 BMI cohorts did not demonstrate a significant difference in mean percent changes in body weights (LS mean difference = 0.4% [-0.2%, 0.9%]; P = .202). CONCLUSION: Obese patients with T2DM treated with insulin lispro were able to achieve the same level of glycemic control as their nonobese counterparts, with some evidence supporting a reduced risk of hypoglycemia.

Patterns and trends in insulin intensification among patients with type 2 diabetes: a systematic review.

Type 2 diabetes (T2DM) diagnoses are skyrocketing, making treatment of this disease an increasing focus of primary care visits. Guidelines recommend insulin intensification over time to achieve HbA1c targets. We conducted a systematic review regarding patterns and trends of insulin intensification and barriers to intensification. Providers across primary and specialty care settings often did not intensify insulin regimens despite patients' clinical status. Even among progressed patients, HbA1c values remained high. The paucity of available studies prevented a comprehensive understanding of patterns and trends in insulin intensification. Such information is needed to assess the quality of pharmacologic care for patients with T2DM.