Fracture risk in patients with type 2 diabetes under different antidiabetic treatment regimens: a retrospective database analysis in primary care.

AIM: Type 2 diabetes is associated with an increased risk of fractures. There are a few studies on the effects of diabetes treatment on fracture risk. The aim was to investigate the fracture risk related to various types of insulin therapy in primary care practices. METHODS: Data from 105,960 type 2 diabetes patients from 1,072 general and internal medicine practices in Germany were retrospectively analyzed (Disease Analyzer database; 01/2000-12/2013). Fracture risk of the following therapies was compared using multivariate logistic regression models adjusting for age, sex, diabetes care, comorbidity, and glycemic control (HbAlc): 1) incident insulin therapy versus oral antidiabetic drugs, 2) basal-supported oral therapy versus supplementary insulin therapy versus conventional insulin therapy, and 3) insulin glargine versus insulin detemir versus NPH insulin. RESULTS: There was a lower odds of having incident fractures in the oral antidiabetic drug group compared to incident insulin users, although not significant (odds ratio [OR]; 95% confidence interval: 0.87; 0.72-1.06). There were increased odds for conventional insulin therapy (OR: 1.59; 95% CI [confidence interval] 0.89-2.84) and supplementary insulin therapy (OR: 1.20; 0.63-2.27) compared to basal-supported oral therapy, which was not significant as well. Overall, there was no significant difference in fracture risk for basal insulins (glargine, detemir, NPH insulin). After a treatment duration ≥2 years, insulin glargine showed a lower odds of having ≥1 fracture compared to NPH users (OR: 0.78; 0.65-0.95) (detemir vs NPH insulin: OR: 1.03; 0.79-1.36). CONCLUSION: Long-standing therapy with insulin glargine was associated with a lower odds of having any fractures compared to NPH insulin. Further studies are required to investigate whether the lower chance is due to a reduced frequency of hypoglycemia.

Predictors of early discontinuation of basal insulin therapy in type 2 diabetes in primary care.

AIMS: To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care. METHODS: A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity. RESULTS: Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were ≥1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation. CONCLUSIONS: Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment.

Comparison of basal insulin therapies with regard to the risk of acute myocardial infarction in patients with type 2 diabetes: an observational cohort study.

AIMS: To assess the risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus treated with long-acting insulin analogues in comparison with other basal insulin therapy. METHODS: We used German insurance claims data from the years 2004-2009 to conduct a study in a retrospective cohort of patients with type 2 diabetes. Naïve insulin users were defined as patients who had an insulin-free history before the first prescription of long-acting analogue insulin, human NPH insulin or premixed insulin and who were pretreated with oral antidiabetic drugs. Adjusted hazard ratios (HRs) of AMI and corresponding 95% confidence intervals (CIs) were calculated using sex-stratified Cox models. Propensity-score-matched analyses were conducted as sensitivity analyses. RESULTS: We identified 21,501 new insulin users. Patients treated with premixed insulin were older than patients treated with analogue or NPH insulin (mean age 70.7 vs. 64.1 and 61.6 years, respectively) and had more comorbidities. Regarding the risk of AMI, adjusted HRs showed no statistically significant difference between NPH and analogue insulin (HR 0.94, 95% CI 0.74-1.19), but a higher risk for premixed than for analogue insulin (HR 1.27, 95% CI 1.02-1.58). Contrary to the primary analysis, the propensity-score-matched analysis did not show an increased risk for premixed insulin. CONCLUSIONS: In contrast to a former database study, no difference was observed for the risk of AMI between long-acting analogue and NPH insulin in this study. Neither long-acting analogue insulin nor premixed insulin appears to be associated with AMI in patients with type 2 diabetes.

Risk of diabetic foot ulceration during treatment with insulin glargine and NPH insulin.

OBJECTIVE: To evaluate the effect of the long-acting basal insulin analog glargine compared with neutral protamine Hagedorn (NPH) insulin on the incidence of diabetic foot ulceration (DFU) in patients with diabetes in Germany. METHOD: A retrospective cohort study was performed using a representative German database (IMS Disease Analyzer) of patients with type 2 diabetes, who started a basal insulin therapy with either insulin glargine or NPH insulin, between July 2000 and September 2007, and continued this therapy for at least 24 months, and whose data were continuously documented.The occurrence of DFU was recorded beginning in the third year after therapy initiation and Kaplan-Meier curves were generated and compared using log-rank tests. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for the incidence of DFU. RESULTS: Patients who fulfilled the inclusion criteria (n=23 395) had started either on insulin glargine (n=9638) or on NPH insulin (n= 13 757).After adjustment for demographic and clinical variables, it was demonstrated that the relative risk to diabetes patients of developing DFS is 64% lower with insulin glargine than with NPH insulin therapy (HR=0.6 I; p=0.0405). CONCLUSION: The results suggest that, compared with NPH insulin, insulin glargine therapy significantly reduces the risk of DFS in patients with diabetes under real life conditions. Prospective long-term trials are needed to confirm these secondary data analysis results. DECLARATION OF INTEREST: There were no external sources of funding for this study.The authors have no conflicts of interest to declare.

Different persistence on initial basal supported oral therapy in Type 2 diabetics is associated with unequal distributions of insulin treatment regimens under real-life conditions in Germany.

OBJECTIVES: Results from a representative German database and from two German health services research studies revealed an unequal distribution between basal supported oral therapy (BOT) and basal-bolus therapy (ICT) regimens in Type 2 diabetics treated with either insulin glargine (GLA) or human insulin (Neutral Protamine Hagedorn; NPH). This study assesses whether this unequal distribution could be caused by a different persistence on the initial BOT regimen. METHODS: A Markov model was developed simulating the transition from BOT to ICT during a treatment course of 10 years. Data on persistence with BOT were obtained from the IMS® Disease Analyzer database. The model cohort consisted of German statutorily insured Type 2 diabetics starting a BOT either with insulin glargine or NPH insulin at a ratio of 1 : 1. RESULTS: The number of Type 2 diabetics who switched from BOT to ICT differed between the two groups: After 2 years, 53% of glargine-treated patients and 31% of NPH-treated patients continued the BOT. After 6.5 years, all NPH-treated patients had switched to ICT. However, complete transition to ICT of glargine-treated patients occurred 1.75 years later. In the first quarter of Year 3, the model simulation resulted in BOT : ICT ratios comparable to those found in the real-world settings for GLA- and NPH-treated patients. CONCLUSIONS: The simulation indicates that the persistence on the initial basal supported oral therapy is associated with the resulting BOT : ICT ratio. Therefore, the unequal distribution between BOT and ICT of Type 2 diabetics treated with either insulin glargine or NPH insulin might be caused by different persistence on the initial BOT regimen.

Comparison of one-year costs of type 2 diabetes treatment with insulin glargine or insulin detemir in a basal supported oral therapy (BOT) in Germany.

OBJECTIVE: A one-year cost analysis comparing basal insulin analogues glargine (IG, Lantus) versus detemir (ID, Levemir) in combination with oral antidiabetic drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes patients in Germany based on the results of a randomized controlled clinical trial (RCT). The trial demonstrated equivalent treatment efficacy. MATERIALS AND METHODS: Total direct diabetes treatment costs were estimated from the perspective of the German statutory health insurance (SHI) for the time horizon of one-year. Simulated resources included medication (insulin, oral antidiabetic drugs) and consumable items (needles, blood glucose test strips and lancets). Initial and final insulin doses per kg body weight and proportion of patients with once/twice daily insulin injection were taken from the above mentioned RCT. Unit costs were taken from official German price lists and sources. Deterministic-(DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs were performed to test robustness of the results. RESULTS: Average annual treatment costs per patient (base case) were euro 849 for glargine and euro 1,334 for detemir resulting in cost savings of euro 486 per patient per year (36%). Costs of insulins were euro 469 (IG) and euro 746 (ID). Costs of consumable items amounted at euro 380 (IG) and euro 588 (ID) respectively. Sensitivity analyses confirmed the findings in favor of insulin glargine. PSA results found cost savings ranging from euro 429 to euro 608 (5th/95th percentiles). CONCLUSIONS: The current model estimated that insulin glargine was associated with lower annual treatment costs of euro 486 (36%) compared to the use of insulin detemir while the same glycemic control is expected to be achieved.

Economic impact of compliance to treatment with antidiabetes medication in type 2 diabetes mellitus: a review paper.

OBJECTIVES: Suboptimal compliance and failure to persist with antidiabetes therapies are of potential economic significance. The present research aims to describe the impact of poor compliance and persistence with antidiabetes medications on the cost of healthcare or its components for patients with type 2 diabetes mellitus (T2DM). METHODS: Literature search was conducted in PubMed for relevant articles published in the period between 1 January 2000 and 30 April 2009. Thus, it is possible that relevant articles not listed in PubMed, but available in other databases are not included in the current review. Studies describing economic consequence of compliance and/or persistence with pharmaceutical antidiabetes treatment were identified. The variability in the studies reviewed was high, making it extremely difficult to make a comparison between them. RESULTS: Of 449 articles corresponding to the primary search algorithm, 12 studies (all conducted in USA) fulfilled the inclusion criteria regarding the economic impact of compliance and/or persistence with treatment on the overall cost of T2DM care or its components. Compliance was assessed via medication possession ratio (MPR) in ten studies, where it ranged from 0.52 to 0.93 depending on regimen. Persistence was assessed in one study. Mean total annual costs per T2DM patient varied between the studies, ranging from $4570 to $17338. In seven studies, medication compliance was inversely associated with total healthcare costs, while in four other studies inverse associations between medication compliance and hospitalisation costs were reported. In one study increased adherence did not change overall healthcare costs. CONCLUSIONS: Improved compliance may lead to reductions of the total healthcare costs in T2DM, Further research is needed in countries other than the US to assess impact of compliance and persistence to pharmacotherapy on T2DM costs in country-specific settings.

[Quality of life and treatment satisfaction in patients being treated with long-acting insulin analogues]. / Lebensqualität und Behandlungszufriedenheit unter Therapie mit langwirksamen Analoginsulinen.

BACKGROUND AND OBJECTIVES: The purpose of this study was to review studies reporting on quality of life and treatment satisfaction of patients with diabetes mellitus being treated with long-acting insulin analogues. MATERIAL AND METHODS: A systematic literature search was made of trials published between January 1, 2000 and June 28, 2007. Retrieved studies were analysed, using predefined inclusion criteria as well as methodological and quality aspects. RESULTS: Twelve studies were included, all of them dealing with insulin glargine as the trial drug or for comparison. With regard to treatment satisfaction, insulin glargine was superior in one head-to-head comparison with NPH (neutral protamine Hagedorn) and one head-to-head comparison with NPH as an add-on to oral glimepiride. There was no difference in comparisons with continuous subcutaneous insulin infusion (CSII), insulin aspart or exenatide. Regarding health related quality of life (HRQoL), insulin glargine was shown to be superior to rosiglitazone as an add-on to metformin and sulfonylurea. Again, there were no differences in comparisons with NPH, CSII or exenatide. CONCLUSION: There are only a limited number of high quality studies showing that insulin glargine is superior regarding treatment satisfaction and HRQoL of patients with diabetes mellitus. There are fewer publications with good evidence of patient-reported outcomes than those reporting well-established outcomes using HbA1c levels or the incidence of hypoglycaemia.

[LAPTOP trial--results of an health economics evaluation]. / LAPTOP-Studie--Ergebnisse einer gesundheitsökonomischen Analyse.

Based on the LAPTOP trial, a cost and a benefit assessment were undertaken. The cost analysis was performed as a desk-top evaluation using the cost minimization method. The benefit assessment was done as a simulation using the diabetes mellitus model (DMM). In each analysis either cost or benefit of treating diabetes mellitus with oral antidiabetic drug(s) supported by insulin glargine were compared to those with conventional insulin treatment using premixed insulin twice daily. The cost benefit analysis demonstrated that treatment with insulin glargine plus oral antidiabetics was less expensive than the conventional insulin treatment with premixed insulin. Furthermore, avoidance of diabetic complications was better with insulin glargine plus oral antidiabetics than with premixed insulin alone.