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.

Fragestellung: Insulin degludec (IDeg) ist ein neues Basalinsulin mit einem flachen und langem pharmakokinetischen Profil und weniger Hypoglykämien verglichen mit Insulin glargin (IGlar). Bisher wurde wenig über Dauer und Folgen von Hypoglykämien publiziert.

In this post-hoc meta-analysis, we examined whether severe hypoglycemia impacts HRQoL in insulin-treated patients with type 1 (T1D) and type 2 diabetes (T2D). All open-label, randomized, treat-to-target phase 3a trials (26 or 52 weeks) in which once-daily insulin degludec and insulin glargine were given and HRQoL recorded (T1D: 1 trial; T2D: 5 trials) were eligible for inclusion. Severe hypoglycemia was defined as episodes requiring assistance. HRQoL was assessed at baseline and end of trial via the Short Form 36 (SF-36; v2) questionnaire. Scores for patients who experienced 1 or more episodes of severe hypoglycemia and those who experienced no severe hypoglycemia were compared using ANCOVA. 11.9% (74/621) of T1D patients had at least 1 episode of severe hypoglycemia vs. 1.7% (57/3346) of T2D patients. For both T1D and T2D, patients reporting severe hypoglycemia had a significantly lower (worse) social functioning score (Table). Severe hypoglycemia was also associated with a significantly lower role-physical score in T1D (borderline significant in T2D), and mental health and general health scores in T2D. All other SF-36 scores were lower for patients with severe hypoglycemia (not significant). In conclusion, severe hypoglycemia had a pronounced negative impact on multiple domains of SF-36 in insulin-treated patients with T1D and T2D. These findings highlight the need to minimize hypoglycemia in all forms of diabetes.TableTreatment contrastTreatment contrastSubdomainT1DT2DSubdomainT1DT2DPhysical functioning–0.80 [–2.35; 0.74]–1.18 [–3.37; 1.01]Vitality–0.78 [–2.74; 1.18]–1.12 [–3.36; 1.13]Role-physical–2.16 [–3.88; –0.44]∗–2.19 [–4.39; 0.00]Social functioning–2.30 [–4.27; –0.34]∗–2.69 [–4.99; –0.38]∗Bodily pain–0.86 [–3.15; 1.43]–0.73 [–3.26; 1.79]Role-emotional–0.26 [–2.33; 1.82]–0.92 [–3.54; 1.70]General health–1.60 [–3.41; 0.20]–2.65 [–4.61; –0.70]∗Mental health–1.07 [–3.10; 0.96]–2.39 [–4.73; –0.05]∗Physical component summary–1.51 [–3.04; 0.02]–1.52 [–3.38; 0.33]Mental component summary–0.81 [–2.93; 1.31]–1.74 [–4.05; 0.58]Treatment contrast: patients experiencing severe hypoglycemia–patients who did not experience severe hypoglycemia.∗ p<0.05% Open table in a new tab Treatment contrast: patients experiencing severe hypoglycemia–patients who did not experience severe hypoglycemia. ∗ p<0.05%

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.

Insulin degludec (IDeg) is a new-generation, ultra-long-acting basal insulin with a flat, stable pharmacokinetic profile and a low rate of hypoglycemia. This meta-analysis comprised 3 treat-to-target, open-label, non-inferiority trials (26 to 52 weeks' duration) comparing IDeg and insulin glargine (IGlar) in 1925 insulin-naïve patients with type 2 diabetes on a basal insulin-only regimen. Patients were interviewed to discuss their hypoglycemic events at each visit; if >1 event was reported, only the last event was analyzed to minimize recall bias. The interview captured time to recognize event, duration of event, recovery time, any contact with healthcare professionals (HCPs) and impact on usual activities; 6,065 events were analyzed using an ANOVA model controlling for covariates. Across these trials, rates of overall confirmed hypoglycemia (plasma glucose <3.1 mmol/L or severe requiring assistance) were significantly lower for IDeg vs. IGlar (rate ratio 0.83, 95% CI: [0.70; 0.98]). There were no statistical differences in the characteristics of a hypoglycemic event between IDeg and IGlar for any of the parameters tested. Time to recognize: 7.2 min for both IDeg and IGlar. Duration: 26.4 vs. 28.2 min for IDeg vs. IGlar. Recovery time: 34.2 vs. 32.4 min for IDeg vs. IGlar. After an event, 9.2% (IDeg) vs. 10.2% (IGlar) contacted a HCP. Rates of confirmed hypoglycemia were 17% lower with IDeg vs. IGlar and there were no differences in recovery time, impact on daily activities or use of healthcare resources. The ultra-long-acting profile of IDeg did not affect the duration or impact of a hypoglycemic event vs. IGlar.

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.

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.

Hypoglycemia is a common side-effect of treatment with certain diabetes drugs. Non-Severe Nocturnal Hypoglycemic Events (NSNHE) occur more frequently than severe events. The objective of this study was to identify how NSNHEs in a Canadian diabetes population affect disease self-management and disease-related costs.

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.

Abstract 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.

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.

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.

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.

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.

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.

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.

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.