Description of a New Predictive Modeling Approach That Correlates the Risk and Associated Cost of Well-Defined Diabetes-Related Complications With Changes in Glycated Hemoglobin (HbA1c).

The modeling approach described here is designed to support the development of spreadsheet-based simple predictive models. It is based on 3 pillars: association of the complications with HbA1c changes, incidence of the complications, and average cost per event of the complication. For each pillar, the goal of the analysis was (1) to find results for a large diversity of populations with a focus on countries/regions, diabetes type, age, diabetes duration, baseline HbA1c value, and gender; (2) to assess the range of incidences and associations previously reported. Unlike simple predictive models, which mostly are based on only 1 source of information for each of the pillars, we conducted a comprehensive, systematic literature review. Each source found was thoroughly reviewed and only sources meeting quality expectations were considered. The approach allows avoidance of unintended use of extreme data. The user can utilize (1) one of the found sources, (2) the found range as validation for the found figures, or (3) the average of all found publications for an expedited estimate. The modeling approach is intended for use in average insulin-treated diabetes populations in which the baseline HbA1c values are within an average range (6.5% to 11.5%); it is not intended for use in individuals or unique diabetes populations (eg, gestational diabetes). Because the modeling approach only considers diabetes-related complications that are positively associated with HbA1c decreases, the costs of negatively associated complications (eg, severe hypoglycemic events) must be calculated separately.

Systematic literature review of use of blood glucose monitoring in phase III clinical studies of insulin analogs.

BACKGROUND: Safe and effective insulin therapy for diabetes mellitus requires initial dose titration and regular adjustments based on blood glucose (BG) monitoring. Our objective was to explore the use of BG measurement in phase-III clinical studies of insulin analogs. These studies provide safety and efficacy information for regulatory authorities and are the basis for insulin analog regulatory approval. METHODS: A systematic review of phase-III studies of rapid-acting insulin analogs (insulin lispro, insulin aspart and insulin glulisine) and pre-mixed insulin analogs (biphasic insulin aspart and insulin lispro mix) was conducted. Studies were identified using manufacturers' databases. Search for reports was performed in Medline and registry of clinical trials (clinicaltrials.gov). The European Medicines Agency was contacted to provide Clinical Study Reports. RESULTS: Forty-five studies were included. Regular BG measurements were reported in 100 % of the studies and were performed by either self-monitoring of blood glucose (SMBG) alone in 84 %, laboratory alone in 7 %, and both SMBG and laboratory in 9 % of studies. In total, 93 % of the studies reported SMBG. Most studies (91 %) reported insulin therapy adjustments based on BG measurements. CONCLUSIONS: The findings suggest that BG monitoring and specifically SMBG are co-dependent technologies with insulin analogs. BG measurement is used in most phase-III registration studies for establishing safe and efficacious insulin administration and is recommended in the insulin labels. The indispensable role of SMBG in treatment of insulin-dependent patients should receive attention from health care payers to assess and reimburse SMBG along with insulin to avoid adverse events from inappropriate insulin administration and associated costs.

Use of an integrated strip-free blood glucose monitoring system increases frequency of self-monitoring and improves glycemic control: Results from the ExAct study.

AIMS: We investigated the impact of using an integrated, strip-free system compared to the use of single-strip systems on testing frequency and glycemic control in individuals with insulin-treated diabetes. METHODS: This multinational, comparative, cluster-randomized, observational study included 311 patients with type 1 and insulin-treated type 2 diabetes who were performing SMBG at suboptimal frequencies. Sites were cluster-randomized to "integrated strip-free" system (EXP group) or any "single-strip" system (CNL group). Testing frequency and HbA1c were measured at baseline, 12 weeks and 24 weeks. RESULTS: At week 24, the EXP group showed an increase in SMBG frequency from baseline of 4.17 tests/week (95% CI 2.76, 5.58) compared with an increase of 0.53 tests/week (95% CI -0.73, 1.79) among CNL patients, resulting in a between-group difference of 3.63 tests/week (p < 0.0002). Mixed-effects models for repeated measurements (MMRM) controlling for baseline frequency of testing, country and clinical site confirmed a higher SMBG testing frequency in the EXP group compared to the CNL group, with a between-group difference of 2.70 tests/week (p < 0.01). Univariate analysis showed greater HbA1c reductions in the EXP group than CNL group: -0.44% (95% CI -0.59, -0.29) vs. -0.13% (95% CI -0.27, 0.01), respectively, p < 0.0002. MMRM analyses confirmed these HbA1c reductions. A greater percentage of EXP than CNL patients achieved HbA1c reductions of ≥0.5%: 45.1% vs. 29.1%, respectively, p < 0.01. CONCLUSIONS: The use of an integrated, strip-free SMBG system improved testing adherence and was associated with improvements in glycemic control.

Risk and potential risk reduction in diabetes type 2 patients in Germany.

Avoiding serious complications such as stroke, myocardial infarction, and amputations in diabetes patients is the main interest of long-term treatment. Given the considerable prevalence of diabetes type 2 in industrialized countries this is a major public health concern as well as a burden to health care systems. The present study estimated the current risk of major complications occurring in the German diabetes type 2 population and explored the potential for further risk reduction. Risk reduction can be achieved when physiological and behavioral parameters (HbAlc, blood pressure, cholesterol level, body mass index, smoking) are set to target values recommended in guidelines. To estimate individual risk and potential risk reduction the multifactor disease model Mellibase was employed. Data were obtained from the German Health Survey of 1998, which includes a sample of 7,124 individuals representative of the German population. The survey shows a prevalence rate of 6.3% for diabetes type 2 in persons older than 35 years. The analyses reveal that the overall potential for risk reduction is moderate (e.g., the average reduction potential of the 10-year risk of stroke is 5.7%). A majority of parameter ranges found in the patient population are either already close to the recommended values (HbA1c), are not alarmingly higher than in the general population (blood pressure) or have little impact on risk reduction. In addition nonmodifiable risk factors such as duration of the illness and advanced age constrain possible improvements. However, there is a wide variation in the actual risk between individuals (e.g., the 10-year risk of stroke varies between 2.2% and 79.8%), and thus a wide variation in potential risk reduction (the risk reduction potential for stroke varies between 0% and 53.4%). Intensified treatment should therefore (a) focus on relevant subgroups of patients taking their risk reduction potential into account and (b) aim at improvement in the overall metabolic profile rather than concentrating on single risk factors.