Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials.

INTRODUCTION: Insulin degludec (degludec) is a basal insulin with an ultra-long, stable action profile and reduced pharmacodynamic variability. Seven phase 3a trials compared degludec with insulin glargine (glargine). Patient-level meta-analyses were performed to obtain a comprehensive overview of differences between the insulin preparations, possible because consistent outcome definitions were utilized. METHODS: Three categories of trials were analyzed: basal-bolus-treated type 1 diabetes mellitus (T1DMB/B), insulin-naïve type 2 diabetes mellitus (T2DMinsulin-naïve), and basal-bolus-treated T2DM (T2DMB/B). Regression models were adjusted for baseline characteristics. Endpoints analyzed were glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), insulin dose and hypoglycemic rates analyzed in mutually exclusive groups: non-severe nocturnal, non-severe daytime, and severe. RESULTS: As with previous treat-to-target trials, reductions in HbA1c were similar between degludec and glargine. Reductions in FPG were significantly greater with degludec in T1DMB/B and T2DMinsulin-naïve. Total daily insulin dose was significantly lower with degludec in T1DMB/B and T2DMinsulin-naïve. Estimated hypoglycemia rate ratios for degludec/glargine were as follows for T1DMB/B, T2DMinsulin-naïve and T2DMB/B, respectively: non-severe nocturnal 0.83, 0.64, 0.75 (all P < 0.05); non-severe daytime 1.14 [not significant (ns)], 0.89 (ns), and 0.83 (P < 0.05). Rate ratios for severe events were 1.12 (ns) (T1DMB/B); 0.14 (P < 0.05) (T2DMinsulin-naïve); and not analyzed (T2DMB/B) due to too few events. CONCLUSIONS: Compared with glargine, degludec is associated with equivalent HbA1c control and significantly lower nocturnal hypoglycemia rates. In T1DMB/B and T2DMinsulin-naïve, degludec is also associated with significantly greater reductions in FPG and lower total doses of insulin versus glargine.

Understanding the economic burden of nonsevere nocturnal hypoglycemic events: impact on work productivity, disease management, and resource utilization.

OBJECTIVE: Nonsevere hypoglycemic events are common and may occur in one-third of persons with diabetes as often as several times a week. This study's objective was to examine the economic burden of nonsevere nocturnal hypoglycemic events (NSNHEs). METHODS: A 20-minute Web-based survey, with items derived from the literature, expert input, and patient interviews, assessing the impact of NSNHEs was administered in nine countries to 18 years and older patients with self-reported diabetes having an NSNHE in the past month. RESULTS: A total of 20,212 persons were screened, with 2,108 respondents meeting criteria and included in the analysis sample. The cost of lost work productivity per NSNHE was estimated to be between $10.21 (Germany) and $28.13 (the United Kingdom), representing 3.3 to 7.5 hours of lost work time per event. A reduction in work productivity (presenteeism) was also reported. Compared with respondents' usual blood sugar monitoring practice, on average, 3.6 ± 6.6 extra tests were conducted in the week following the event at a cost of approximately $87.1 per year. Additional costs were also incurred for doctor visits as well as medical care required because of falls or injuries incurred during the NSNHE for an annual cost of $2,111.3 per person per year. When taking into consideration the multiple impacts of NSNHEs for the total sample and the frequency that these events occur, the resulting total annual economic burden was $288,000 or $127 per person per event. CONCLUSIONS: NSNHEs have serious consequences for patients. Greater attention to treatments that reduce NSNHEs can have a major impact on reducing the economic burden of diabetes.

Non-severe nocturnal hypoglycemic events: experience and impacts on patient functioning and well-being.

PURPOSE: Non-severe nocturnal hypoglycemic events (NSNHEs) are hypoglycemic events that occur during sleep but do not require medical assistance from another individual. This study was conducted to better understand the NSNHEs as patients actually experience them in their daily life, and how they impacted functioning and well-being. METHODS: Nine focus groups were held in four countries with diabetics (Type 1 and Type 2) who had experienced an NSNHE within the previous month: France (2 groups); Germany (2 groups); United Kingdom (2 groups); and United States (3 groups). These groups were audio-taped, translated to English where applicable, and analyzed thematically. RESULTS: Seventy-eight people with diabetes participated in the focus groups: 41 (53 %) were female and 37 (47 %) were male; 24 (31 %) had Type 1 diabetes, and 54 (69 %) had Type 2 diabetes. Participant reports were grouped into several major themes: next day effects, symptoms, sleep impacts, social impacts, corrective action, practical management, feelings about NSNHEs, and work impacts. CONCLUSIONS: People with both Type 1 and Type 2 diabetes experience NSNHEs. The range of impact on these patients is wide, from very mild to severe with a majority of participants experiencing strong impacts that limit their daily functioning. This finding suggests that NSNHEs are more impactful than previously believed.

Cost of Self-Monitoring of Blood Glucose in Canada among Patients on an Insulin Regimen for Diabetes.

INTRODUCTION: People with diabetes are at a higher risk of developing a variety of medical conditions relative to those without diabetes, resulting in increased healthcare costs. Self-monitoring of blood glucose (SMBG) is accepted as a recommended element of effective diabetes self-management. However, little is known about the real-world frequency and actual expenditures associated with SMBG, as well as the impact of SMBG costs relative to the cost of diabetes treatments. The primary objective is to evaluate the real-world utilization and costs of SMBG tests in Canada among insulin-treated diabetes patients during a 12-month follow-up period. METHODS: A retrospective cohort study was conducted using the IMS Brogan Inc. Drug Plan database from July 1, 2006 through June 30, 2010. Total costs during the 12-month follow-up period were assessed, focusing on blood glucose (BG) testing strip costs, insulin therapy costs, and costs associated with oral antidiabetics medications. All prevalent patients with two or more prescriptions for insulin between January 1, 2007 and December 31, 2009 were initially included in the analysis, the first prescription serving as their index date. Depending on the insulin type(s) used, patients were subcategorized into one of four insulin regimen groups (basal, bolus, premix, or basal-bolus). RESULTS: Among an initial sample of patients with two or more claims for insulin between January 1, 2007 and December 31, 2009, 142,551 met the aforementioned inclusion and exclusion criteria. An overall mean utilization of pharmacy-based blood glucose testing of approximately 1,094 strips per person per year was observed, with an average cost per testing strip of Canadian $0.79. SMBG treatment costs for insulin users ($860), specifically those associated with prescription testing strips, totaled 41.6% of the average annual pharmacy costs of diabetes-related prescriptions ($2,068). CONCLUSION: This study shows that SMBG accounts for approximately 40% of the total diabetes-related pharmacy costs for insulin users.

The impact of non-severe hypoglycemic events on daytime function and diabetes management among adults with type 1 and type 2 diabetes.

OBJECTIVES: To describe daytime non-severe hypoglycemic events (NSHEs), assess their impact on patient functioning and diabetes self-management, and examine if these impacts differ by diabetes type or country. METHODS: Internet survey to adults with diabetes in the US, UK, Germany, and France. RESULTS: Of 6756 screened respondents, 2439 reported a daytime NSHE in the past month. NSHEs occurred while active (e.g., running errands) (45.1%), 29.6% while not active (e.g., watching TV), and 23.8% at work. On average, it took half a day to respond and recover from NSHE. Respondents monitored their glucose 5.7 extra times on average over the following week. On the day of event, type 1 respondents tested significantly more often than type 2 (p<0.05). Type 2 were less likely to confirm NSHE with glucose test (p<0.001). Following NSHE, 12.6% of respondents reduced total insulin by an average of 7.6 units (SD=8.3). Total units and days with reduced dosing was significantly less, whilst number of additional glucose tests and time to recover was significantly longer if NSHE occurred at work (p<0.001). Type 1 decreased insulin doses more often (p<0.001); however, type 2 decreased a greater number of units (p<0.01). Compared with other countries, US respondents were more likely to eat a light or full meal and respondents in France took significantly longer than all other countries to recognize (p<0.05), respond to (p<0.001), and recover from (p<0.001) NSHE, used significantly more monitoring tests the day of (p<0.05) and over the subsequent week (p<0.001), and decreased their normal insulin dose more (p<0.001). Limitations of the study include potential recall bias and selection bias. CONCLUSIONS: NSHEs are associated with a significant impact on patient functioning and diabetes management.

Cost-effectiveness of switching patients with type 2 diabetes from insulin glargine to insulin detemir in Chinese setting: a health economic model based on the PREDICTIVE study.

OBJECTIVES: To evaluate the long-term cost-effectiveness of switching from insulin glargine (IGla) to insulin detemir (IDet) in patients with type 2 diabetes in the setting of Chinese secondary and tertiary hospitals. METHODS: A published and validated computer simulation model of diabetes (the Center for Outcomes Research model) was used to make the long-term (30 years) projection of health economic outcomes. Patient demographic information and clinical end points were derived from a subgroup analysis of the Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation (PREDICTIVE) study. Baseline risk factors and racial characteristic data were obtained from Chinese cohort studies. The diabetes management and complications costs were obtained from Chinese published data and adjusted to 2010 values by using the Chinese consumer price index. An annual discounting rate of 3% was used for both health and cost outcomes, and one-way sensitivities analysis was performed, which illustrated that the results were robust. RESULTS: Conversion to IDet from IGla was projected to improve patient life expectancy by 0.06 year and 0.48 quality-adjusted life-years. Drug costs and management costs of diabetes mellitus were increased by US$368 (US$17,466 vs. US$17,097) and US$31 (US$5464 vs. US$5433), respectively. However, the costs of complications, including cerebrovascular disease, renal complications, ulcer/amputation/neuropathy, eye complications, and hypoglycemia events, were reduced by US$819 (US$21,294 vs. US$22,114), resulting in a total direct medical cost saving of US$420 when converting to IDet. CONCLUSIONS: Conversion to IDet from an IGla regimen improved life expectancy and was a cost-saving treatment approach in a Chinese setting.

Cost of self-monitoring of blood glucose in the United States among patients on an insulin regimen for diabetes.

BACKGROUND: People with diabetes are at an increased risk of developing numerous complications, resulting in increased health care expenditures, economic burden, and higher mortality. For patients using an insulin pump or multiple insulin injections, self-monitoring of blood glucose (SMBG) is recognized as a core component of effective diabetes self-management. However, little is known about the real-world frequency and true costs associated with SMBG as a percentage of an insulin regimen in the United States. OBJECTIVE: To evaluate SMBG frequency, SMBG-related costs (including blood glucose test strips and testing supplies), and insulin therapy costs among insulin-dependent patients with diabetes and at least 1 pharmacy claim for blood glucose testing strips during a 12-month follow-up period. METHODS: A retrospective database analysis was conducted using the IMS LifeLink Health Plan Claims database to capture the frequency and costs associated with SMBG in relation to a specific insulin regimen, and SMBG expenditure compared with other treatment costs. The study employed a retrospective cohort analysis of patients with 2 or more claims for insulin between January 1, 2007, and June 30, 2009, with the first such claim representing the index date. All patients were required to have 6 months of pre-index continuous enrollment (pre-index period) and 12 months of post-index continuous enrollment (follow-up period). Patients were also required to have a diagnosis of diabetes in the pre-index period and to have no gaps of more than 90 days between consecutive insulin claims during the 360-day follow-up period. Patients without at least 1 pharmacy claim for blood glucose testing strips during the 12-month follow-up period and patients with pharmacy claims with extreme values (greater than 1,500 strips) were excluded. Depending on the insulin types used within the 30 days immediately following their index date, patients were subcategorized into 1 of 4 insulin regimen groups (basal, bolus, premixed, or basal-bolus). Patients' frequency of blood glucose testing was measured throughout their 12-month post-index follow-up period through analysis of clinical codes found on pharmacy claims. Quantity supplied fields on pharmacy claims were used to calculate total tests utilized over the follow-up period (e.g., 50 test strips dispensed=50 tests assumed). Insulin-related costs were also evaluated for the 12-month follow-up period. RESULTS: Among an initial sample of 373,946 patients with at least 2 claims for insulin between January 1, 2007, and June 30, 2009, 45,555 patients (12.2%) formed the final overall cohort who met the inclusion and exclusion criteria. SMBG-related pharmacy costs accounted for 27% of the insulin-and SMBG-related treatment costs for insulin users with an average $772 per patient in prescription testing strips and supplies versus $2,078 for insulin prescriptions and supplies. With an overall mean utilization for pharmacy-based SMBG testing of 764.3 strips per year, the average cost per testing strip was $0.98. Annual SMBG costs were 24.5% of total insulin and SMBG-related pharmacy costs for the basal insulin group compared with 35.8% for bolus, 21.0% for premixed, and 26.4% for basal-bolus. CONCLUSION: For insulin users with at least 1 pharmacy claim for glucose test strips, SMBG-related costs accounted for about one-fourth of total insulin and SMBG-related pharmacy costs.

Impact of nocturnal hypoglycemic events on diabetes management, sleep quality, and next-day function: results from a four-country survey.

OBJECTIVES: Non-severe nocturnal hypoglycemic events (NSNHEs) may have a major impact on patients. The objective was to determine how NSNHEs affect diabetes management, sleep quality, functioning, and to assess if these impacts differ by diabetes type or country. METHODS: An internet survey to adults with diabetes in the US, UK, Germany, and France. RESULTS: Of 6756 screened respondents, 1086 reported an NSNHE in the past month. For this last event, respondents with type 2 required significantly more time than type 1 to recognize and respond to the event (1.5 vs 1.1 hours), 25.7% (T1) and 18.5% (T2) decreased their normal insulin dose due to their most recent NSNHE. All respondents were likely to take 1-2 additional self-monitored blood glucose measurements on the day following. NSNHEs were associated with a high proportion of respondents contacting a healthcare professional (18.6% T1, 27.8% T2) reporting they could not return to sleep at night (13.3% T1, 13.4% T2), and tiredness on the day following the event (71.2% for both). Of the respondents working for pay, 18.4% T1 and 28.1% T2 reported being absent from work due to the NSNHE, and a substantial proportion of respondents (8.7% T1, 14.4% T2) also reported missing a meeting or work appointment or not finishing a task on time. Compared with other countries, respondents from France may experience a more substantial impact on diabetes management and daily functioning following an NSNHE. Potential limitations in this study include recall and selection bias; however, these biases are not believed to have impacted findings in any meaningful way. CONCLUSIONS: NSNHEs are associated with a substantial impact on diabetes management, sleep quality, and next-day functioning.

The impact of non-severe hypoglycemic events on work productivity and diabetes management.

OBJECTIVES: Hypoglycemia is a common complication of treatment with certain diabetes drugs. Non-severe hypoglycemic events (NSHEs) occur more frequently than severe events and account for the majority of total events. The objective of this multi-country study was to identify how NSHEs in a working population affect productivity, costs, and self-management behaviors. METHODS: A 20-minute survey assessing the impact of NSHEs was administered via the Internet to individuals (≥ 18 years of age) with self-reported diabetes in the United States, United Kingdom, Germany, and France. The analysis sample consisted of all respondents who reported an NSHE in the past month. Topics included: reasons for, duration of, and impact of NSHE(s) on productivity and diabetes self-management. RESULTS: A total of 1404 respondents were included in this analysis. Lost productivity was estimated to range from $15.26 to $93.47 (USD) per NSHE, representing 8.3 to 15.9 hours of lost work time per month. Among individuals reporting an NSHE at work (n = 972), 18.3% missed work for an average of 9.9 hours (SD 8.4). Among respondents experiencing an NSHE outside working hours (including nocturnal), 22.7% arrived late for work or missed a full day. Productivity loss was highest for NSHEs occurring during sleep, with an average of 14.7 (SD 11.6) working hours lost. In the week following the NSHE, respondents required an average of 5.6 extra blood glucose test strips. Among respondents using insulin, 25% decreased their insulin dose following the NSHE. CONCLUSIONS: NSHEs are associated with substantial economic consequences for employers and patients. Greater attention to treatments that reduce NSHEs could have a major, positive impact on lost work productivity and overall diabetes management.

Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs.

BACKGROUND: The clinical goal in the treatment of diabetes is to achieve good glycemic control. Tight glycemic control achieved with intensive glucose lowering treatment reduces the risk of long-term micro- and macro-vascular complications of diabetes, resulting in an improvement in quality-of-life for the patient and decreased healthcare costs. The positive impact of good glycemic control is, however, counterbalanced by the negative impact of an increased incidence of hypoglycemia. METHODS: A search of PubMed was conducted to identify published literature on the impact of hypoglycemia, both on patient quality-of-life and associated costs to the healthcare system and society. RESULTS: In people with type 1 or type 2 diabetes, hypoglycemia is associated with a reduction in quality-of-life, increased fear and anxiety, reduced productivity, and increased healthcare costs. Fear of hypoglycemia may promote compensatory behaviors in order to avoid hypoglycemia, such as decreased insulin doses, resulting in poor glycemic control and an increased risk of serious health consequences. Every non-severe event may be associated with a utility loss in the range of 0.0033-0.0052 over 1 year, further contributing to the negative impact. LIMITATIONS: This review is intended to provide an overview of hypoglycemia in diabetes and its impact on patients and society, and consequently it is not a comprehensive evaluation of all studies reporting hypoglycemic episodes. CONCLUSION: To provide the best possible care for patients and a cost-effective treatment strategy for healthcare decision-makers, a treatment that provides good glycemic control with a limited risk of hypoglycemia would be a welcome addition to diabetes management options.

Healthcare costs of fast-acting insulin analogues versus short-acting human insulin for Danish patients with type 2 diabetes on a basal-bolus regimen.

AIMS: Fast-acting insulin analogues (FAIAs) reduce hypoglycaemia and improve administration flexibility compared with short-acting human insulin (SHI). This analysis examines whether these benefits translate into cost offsets when comparing the total treatment costs for FAIA versus SHI used as basal-bolus therapy for treating type 2 diabetes (T2D). METHODS: Registry data covering the Danish population including demographic variables, prescription, hospital and primary care data formed the basis for analysis. To capture patients on basal-bolus therapy only, inclusion criteria were ≥2 prescriptions of either long-acting insulin analogues (LAIAs) or neutral protamine Hagedorn (NPH) insulin (basal component), and ≥2 prescriptions for either an FAIA or SHI (bolus component) during the inclusion period (1 January-31 December 2005). Patients using LAIAs (n = 521) or NPH (n = 2695) were analysed separately. Within each basal cohort, patients using FAIAs or SHI were matched regarding observable variables using propensity scores. Healthcare costs were analysed for a follow-up period (maximum 2 years post-inclusion). RESULTS: Within each cohort, matching produced groups with similar observed covariates. Overall direct healthcare costs in the LAIA cohort were €4183 and €5289 for FAIA and SHI, respectively. In the NPH cohort, costs were €4940 and €4699 for FAIA and SHI, respectively. For both basal cohorts, cost differences between FAIA and SHI were not statistically significant. LIMITATIONS: As the propensity score model cannot account for unobserved variables, conclusions of causality cannot be made. Moreover, exclusion of indirect costs and application of hospital contact charges accrued in the discharge year only may result in an underestimation of overall healthcare costs. CONCLUSION: Using matched cohorts, treating patients with T2D using basal-bolus regimens containing FAIAs was no more costly to the Danish healthcare system than regimens using SHI. FAIAs provide a flexible administration and optimal glucose control for a similar cost.

Examining the ability to detect change using the TRIM-Diabetes and TRIM-Diabetes Device measures.

PURPOSE: Responsiveness is defined as the ability of an instrument to accurately detect change when it has occurred and is an essential psychometric property of a patient-reported outcomes (PRO) measure to understand and interpret study findings. This study examined the responsiveness of 2 Treatment Related Impact Measures (TRIMs): The TRIM-Diabetes (TRIM-D) and TRIM-Diabetes Device (TRIM-DD) as well as confirmed their measurement models in a randomized controlled trial (RCT) design. METHODS: The data were collected in a multi-center, randomized, open-label (2 × 12 week), cross-over study of two prefilled pens in subjects with type 1 or type 2 diabetes, age 18 or older. Internal and external responsiveness were examined. To confirm the measurement model identified in the previous study, the Bentler comparative fit index (CFI) and internal consistency for the RCT sample scores were examined and compared. RESULTS: Based on a priori criteria, tests of responsiveness were confirmed with patients having significant improvements over time ranging from 2.7 (Psychological Health) to 11.1 (Treatment Burden) (P < 0.01) (effect sizes ranging from 0.2 to 0.8). The previous measurement model factor structure was confirmed (CFI ranging from 0.8 to 1.0), and internal consistency of the TRIMs was similar to the developmental findings. CONCLUSIONS: The total score as well as all domain scores of the TRIMs was significantly responsive over time, thus acceptable internal and external responsiveness of TRIM-D and TRIM-DD are concluded. To date, all validation evidence supports the use of these two measures in future clinical trials.

Measuring the health status burden in hemodialysis patients using the SF-36® health survey.

PURPOSE: The SF-36, a generic measure of 8 domains of health-related quality of life (HRQOL), has been widely used to examine HRQOL of end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). The current study synthesizes existing literature to examine which SF-36 domains capture the largest burden in this patient population. METHODS: A literature search of published studies that presented descriptive statistics for baseline SF-36 scale scores from HD patients was conducted. Disease burden was estimated by comparing HD patients' SF-36 scores to those from either a control group or a general population normative sample taken from the same country. For each study, Cohen d effect sizes for between-sample differences were calculated for each scale. RESULTS: Twenty-six articles that matched set criteria were identified. Estimation of differences between HD patients and comparison groups showed that the SF-36 physical functioning scale yielded the largest weighted mean effect size across studies (d = 1.46), followed by the general health (d = 1.29) and role physical (d = 1.21) scales. CONCLUSIONS: Among the eight domains of the SF-36, physical functioning, general health, and role physical scales best captured disease burden for HD patients. The disease burden negatively impacts physical HRQOL more strongly than mental HRQOL.

Real-life dosage and clinical efficacy of biphasic insulin preparations in patients with type 2 diabetes.

INTRODUCTION: This retrospective study used data from a primary care database to compare two insulin products in routine clinical practice for the treatment of type 2 diabetes in the UK. PATIENTS AND METHODS: Records were analyzed for patients with type 2 diabetes who had been initiated on biphasic insulin aspart 30 (BIAsp30) (n=632) or biphasic isophane human insulin 30 (BHI30) (n=762) and who had a glycated hemoglobin (HbA1(c)) measurement at baseline (up to 6 months before the index date) and end of study (6-12 months after index date). Regression analyses were used to test for a statistically significant interaction between reduction in HbA1(c) from baseline to end of study and the log-transformed average daily dose (logADD) of insulin. RESULTS: With BIAsp30 a significantly lower dose of insulin (47.74 insulin units [IU]/day vs. 66.63 IU/day, P<0.0001) was required to obtain a similar HbA1(c) reduction (1.71%-point vs. 1.55%-point, P=0.24). To achieve an additional reduction of 0.1 percentage points in HbA1(c) (eg, reduction from 9% to 7.9% HbA1(c) instead of from 9% to 8%), the dose of BIAsp30 would need to be increased by a factor of 1.15. For BHI30, a greater increase in dose would be needed to achieve the same additional HbA1(c) reduction (dose increase by a factor of 1.74). CONCLUSION: Clinically meaningful reductions in HbA1(c) can be achieved at lower insulin doses with BIAsp30 treatment than with BHI30. Lower insulin doses may have important implications for medication costs.

Patient treatment satisfaction after switching to NovoMix® 30 (BIAsp 30) in the IMPROVE™ study: an analysis of the influence of prior and current treatment factors.

PURPOSE: Understanding treatment satisfaction (TS) for diabetes is increasingly important as treatment options increase. This study examines treatment satisfaction with NovoMix® 30 in an observational study in patients with type 2 diabetes. METHODS: The DiabMedSat assesses Overall, Treatment Burden, Symptom and Efficacy Treatment Satisfaction. The impact of type of pretreatment variables on TS was examined by ANOVA at baseline and week 26. Satisfaction at week 26 was examined by t-test and effect size. Linear regression models examined impact of prior treatment factors (age, gender, duration of diabetes, type of prior treatment and diabetes-related comorbidities) and current treatment factors (weight gain, hypoglycemic events, reaching therapeutic goal) on TS. RESULTS: The data set comprised 17,488 persons. Prior treatment with insulin had a more positive impact on baseline satisfaction. At week 26, there were no differences between type of prior treatment groups in Overall, Symptoms and Burden TS. Current treatment with NovoMix 30 significantly improved TS. Regression analyses examining the combined effect of pretreatment factors and current treatment factors found that all factors except for age-impacted TS although the domains impacted varied. CONCLUSIONS: Patients treated with NovoMix 30 reported improved treatment satisfaction, and the improvement is considered clinically meaningful to patients.

Cost-effectiveness of somatropin for the treatment of short children born small for gestational age.

BACKGROUND: Short children born small for gestational age (SGA) may be at increased risk for long-term morbidity and reduced health-related quality of life (HRQoL) due to their short stature. Normalization of height in childhood and adolescence is possible in such children via the use of the recombinant human growth hormone somatropin. OBJECTIVE: The aim of this study was to determine whether somatropin was a cost-effective treatment option in short children born SGA. METHODS: A decision analytic model was constructed to calculate the cost-effectiveness of somatropin treatment versus no treatment over the lifetime of a short individual born SGA, from the perspective of the UK National Health Service (NHS). The model was based on patient-level data from a multicenter, double-blind, randomized controlled trial that reported the effects of somatropin on final (adult) height in short children born SGA. Health care resource and drug costs associated with each of the treatment arms were considered, and published utility scores were used to calculate improvement in HRQoL. The model calculated incremental costs and incremental quality-adjusted life-years (QALYs) associated with somatropin treatment compared with no treatment. Cost-effectiveness was expressed as incremental cost per QALY and cost per centimeter of height gained. RESULTS: Over a patient's lifetime, somatropin (0.033 mg/kg/d) treatment was associated with a height gain of 16.12 cm and a cost per centimeter of height gained of pound4359 compared with no treatment. The incremental cost of somatropin treatment was pound70,263, with a QALY gain of 2.95, resulting in an incremental cost per QALY of pound23,807-below the widely accepted cost-effectiveness threshold in the United Kingdom of pound30,000. CONCLUSION: In this model, somatropin was a cost-effective treatment option for short children born SGA from the perspective of the UK NHS.

Glycemic control and long-acting insulin analog utilization in patients with type 2 diabetes.

INTRODUCTION: The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands. METHODS: Insulin-naïve patients with T2D, starting treatment with IDet or IGlar between January 1, 2004 and June 30, 2008, were selected from the PHARMO data network. Glycemic control (hemoglobin A1c [HbA1c]), target rates (HbA1c <7%), daily insulin dose, and weight gain were analyzed comparing IDet and IGlar for patients with available HbA1c levels both at baseline and at 1-year follow-up. Analysis of all eligible patients (AEP) and a subgroup of patients without treatment changes (WOTC) in the follow-up period were adjusted for patient characteristics, propensity scores, and baseline HbA1c. RESULTS: A total of 127 IDet users and 292 IGlar users were included in the WOTC analyses. The mean HbA1c dropped from 8.4%-8.6% at baseline to 7.4% after 1 year. Patients at HbA1c goal increased from 9% at baseline to 32% for IDet and 11% to 35% for IGlar, which was not significantly different (OR 0.75, 95% CI 0.46, 1.24). Weight gain (n=90) was less among IDet users (+0.4 kg) than among IGlar users (+1.1 kg), albeit not significant. The AEP analysis (252 IDet + 468 IGlar users) showed similar results with 33%-36% at goal (OR 0.81, 95% CI 0.57, 1.16), and median daily insulin doses of 25 IU/day (P=0.70). CONCLUSION: There was no significant difference between users of IDet and IGlar with respect to glycemic control and insulin dose in a real-life setting. The low proportion of patients on target at baseline may indicate that insulin therapy is initiated too late. Moreover, the observation that one-third of the patients reached HbA1c target at follow-up may indicate that basal insulin analogs are not titrated intensively enough.

Direct healthcare costs of patients with type 2 diabetes using long-acting insulin analogues or NPH insulin in a basal insulin-only regimen.

AIMS: To compare direct healthcare costs incurred by patients with type 2 diabetes in Denmark prescribed long-acting insulin analogues (LAIA) or intermediate-acting human insulin (NPH) in a basal-only regimen. METHODS: Demographic and socio-economic patient characteristics, hospital utilisation data, primary care visits, specialist physician visits and prescription data were extracted from registers covering the Danish population. Patients receiving basal insulin were identified during a 1-year inclusion period (2005) and allocated to a LAIA (n=303) or NPH group (n=8523). LAIA patients were then matched with NPH patients using propensity scores based on observable covariates. Annual direct healthcare costs were determined during a <2-year analysis period (2005-2006). RESULTS: Direct healthcare costs, including prescription costs, were equivalent between groups. However, while most cost items were similar between groups, ambulatory visit costs were significantly lower in LAIA-treated patients (p=0.03), whereas insulin pharmacy costs were significantly lower in NPH-treated patients (p<0.001). CONCLUSION: There was no difference in direct healthcare costs between patients using LAIAs or NPH insulin.

The cost-effectiveness of somatropin treatment for short children born small for gestational age (SGA) and children with growth hormone deficiency (GHD) in Sweden.

OBJECTIVE: Reduction in health-related quality of life is common in children born small for gestational age (SGA) or children with growth hormone deficiency (GHD). Growth hormone treatment with somatropin in these children leads to normalisation of height. The aim of this study was to determine whether somatropin is a cost-effective treatment option for short children born SGA and GHD children in Sweden. METHODS: A Markov decision-tree model was used to calculate the relative costs and health benefits associated with somatropin treatment over the lifetime of SGA and GHD children, compared with no treatment. The analysis was undertaken from a Swedish Health Service perspective. As quality-adjusted life-year (QALY) data were not obtained directly in the clinical studies, a degree of uncertainty is related to these results. Sensitivity analyses assessed the degree of uncertainty surrounding central parameters. RESULTS: For short children born SGA, somatropin treatment was associated with an additional 3.29 QALYs at an incremental cost of 792,489 SEK (Swedish Krona), compared with no treatment. For GHD, somatropin treatment resulted in 3.25 additional QALYs at an incremental cost of 391,291 SEK. This equates to an incremental cost per QALY of 240,831 SEK and 120,494 SEK for SGA and GHD, respectively, below a cost-effectiveness threshold of 500,000-600,000 SEK/QALY. CONCLUSIONS: Somatropin is a cost-effective treatment strategy in Sweden for children with GHD and SGA. To overcome present study limitations future clinical research should incorporate appropriate quality of life questionnaires.

Examining and interpreting responsiveness of the Diabetes Medication Satisfaction measure.

OBJECTIVE: Treatment satisfaction (TS) is an important patient reported outcome (PRO) in diabetes as it is correlated with outcomes necessary for optimal treatment (e.g., compliance, self-management behaviour). The objective of this study was to examine the responsiveness of the DiabMedSat, a disease-specific PRO measure, assessing Overall, Burden, Efficacy and Symptom TS. METHODS: The DiabMedSat was included in an open label, observational study of the safety and efficacy of biphasic insulin aspart 30 (NovoMix 30) in routine practice with type 2 diabetes. Responsiveness analyses, examining both internal and external responsiveness, were conducted and minimally important differences (MID) assessed. RESULTS: In 18,817 patients, all TS scores significantly improved after 26 weeks of treatment (p<0.001). The effect sizes for these changes were above 0.5 indicating that the ability to detect change was moderate-to-large in size. Significant differences were found for all TS scores comparing patients who met their HbA(1c) goal, who improved but did not meet goal and who did not improve (p<0.01), and for patients who experienced a minor hypoglycaemic event and those who did not (p<0.001). DiabMedSat scores were able to detect changes in patients' own global rating of satisfaction (MID ranging from 5.3 to 11.7) and in physician-rated satisfaction with patients' HbA(1c) improvement (MID ranging from 5.3 to 10.2). CONCLUSIONS: In the context of an observational study, the DiabMedSat has been shown to be highly responsive to change and can be considered as an acceptable PRO measure for TS in diabetes.