Guideline Adherence and Associated Outcomes in the Treatment of Type 2 Diabetes Mellitus Patients With an Incident Cardiovascular Comorbidity: An Analysis Based on a Large German Claims Dataset.

INTRODUCTION: According to current guidelines, appropriate drug treatment is the backbone of the effective management of cardiovascular (CV) comorbidities in patients with type 2 diabetes mellitus (T2DM). The main objective of this study was to assess the degree of real-world adherence to these guideline recommendations and to identify whether poor guideline adherence is associated with worse clinical outcomes. METHODS: In this retrospective German claims data analysis (AOK PLUS dataset), patients with T2DM with an incident diagnosis (index date) of ischemic stroke, myocardial infarction, heart failure or coronary artery disease were observed for 12 months between 1 January 2014 and 31 December 2017. We assessed guideline adherence per observed CV disease combination at three levels: "green" if patients received prescriptions of all recommended medications with > 185 defined daily doses (DDDs) per observed patient-year; "yellow" if patients received at least two prescriptions of at least one of the recommended medications; and "red" if patients did not receive at least two prescriptions of at least one of the recommended medications. The impact of the assignment of a patient to one of these three levels on all-cause mortality and CV risk was analyzed based on multivariable Cox regression analyses and reported as adjusted hazard ratios (HRs). RESULTS: We identified 32,916 patients with T2DM with an incident CV comorbidity (mean age 75.0 years, 54.2% female, Charlson Comorbidity Index [CCI]: 5.5). Observed patients received at least 185 DDDs of the following medication classes in the 12 months before/after the index date: vitamin K antagonists (6%/6%); antiplatelet drugs (9%/27%); novel oral anticoagulants (3%/13%); diuretics (48%/54%); beta blockers (31%/35%); calcium-channel blockers (34%/32%); renin-angiotensin-aldosterone system inhibitors (69%/68%); and lipid-modifying agents (19%/37%). When post-index therapy was compared to guideline recommendations, the level of "guideline adherence" was classified as "green" for 14.4% of the patients, "yellow" for 75.2% and "red" for 10.5%. An assignment of "red" was associated with worse CV outcomes in all analyses. Regarding mortality, in addition to one additional year of age (hazard ratio [HR] 1.04), CCI (HR 1.17), use of insulins (HR 1.25), digitalis glycosides (HR 1.52) and diuretics (HR 1.32), non-adherence to guideline recommendations ("red": HR 6.79; "yellow": HR: 1.30) was a significant predictor for early death, while female gender (HR 0.79), the participation in a disease management program (HR 0.69) and the use of antidiabetics other than insulin (HR 0.74) were generally associated with a reduced risk. CONCLUSION: Only a minority of patients with T2DM and an incident CV comorbidity receive a treatment fully adherent with guideline recommendations. This may contribute to high mortality rates in this population in clinical practice.

Real-world clinical outcomes and costs in type 2 diabetes mellitus patients after initiation of insulin therapy: A German claims data analysis.

BACKGROUND: This study describes real-world treatment-related outcomes and healthcare costs of German type 2 diabetes mellitus (T2D) patients who initiated insulin therapy. METHODS: This retrospective analysis includes German claims data from 01/01/2012 until 31/12/2016. Identification of eligible patients took place between 01/01/2013 and 31/12/2015, allowing for at least 1 year of follow-up. Clinical outcomes, such as HbA1c values and body mass index, were observed in a subpopulation participating in a Disease Management Program. Healthcare expenditures were evaluated for the first year of therapy. RESULTS: Overall, 27,340 insulin starters with T2D were observed (mean age: 72.2 years, female: 51.4%). Treatment-related outcomes were evaluated in a subsample of 12,034 patients. Patients who started insulin combined with other antidiabetic drugs (ADs) achieved their HbA1c goals more frequently than patients on insulin monotherapy (+10.7 percentage points [pp] vs. +21.1 pp for insulin plus metformin). All-cause costs were by far highest among patients with insulin monotherapy (€ 12,283 per patient-year) compared with patients receiving a combined AD regimen (€ 9,947-10,509 per patient-year). CONCLUSIONS: Changes in HbA1c values were not in favor of insulin monotherapy, compared to regimens including other ADs. It was also associated with higher costs, suggesting that insulin alone is a suboptimal treatment.

Real-world insulin therapy in German type 2 diabetes mellitus patients: patient characteristics, treatment patterns, and insulin dosage.

BACKGROUND: A substantial share of type 2 diabetes mellitus (T2DM) patients receive insulin. However, little is known about the real-world treatment patterns around insulin initiation. METHODS: This was a retrospective claims data analysis. T2DM patients who initiated an insulin therapy between 01/01/2013 and 31/12/2015 were identified in the German AOK PLUS dataset. For validation of results, additional data on a similar T2DM patient population were collected in a Germany-wide medical chart review. RESULTS: A total of 284,878 T2DM patients were identified. Of these, 27,340 (9.6%) initiated an insulin treatment during the inclusion period (mean age: 72.2 years; 51.4% female). Mean/median weight and BMI of patients with available clinical data was 85.8/84.0 kg (SD:18.9) and 30.6/29.8 kg/m2 (SD:6.1), respectively at baseline. Mean/median HbA1c-value at baseline was 8.4/8.0% (SD: 1.8). Most commonly prescribed antidiabetic drugs (AD) within 6 months before insulin initiation were metformin (MET; 54.0%), DPP-4 inhibitors (DPP-4i; 37.6%), and sulfonylureas (SU; 29.5%). As high as 23.2% of the patients did not receive any AD prescription within 6 months before insulin initiation. A total of 10,953 of above 27,340 insulin starters (40.1%) initiated their insulin therapy without concomitant ADs (insulin monotherapy); 43% of these patients did not receive any AD before insulin initiation. Of the remaining 16,387 patients (59.9%), 4070 patients (14.9%) received MET only as concomitant AD, 6385 (23.4%) received MET plus at least one further AD, and 5932 (21.7%) received at least one further AD excluding MET. Throughout the first year of treatment, prescribed insulin dosage increased over time, resulting in approximately 43.3-77.9 IUs per observed patient day after 12 months of insulin treatment. CONCLUSIONS: Characteristics of German T2DM patients initiating insulin deviate substantially from the average German population, especially in terms of weight. We identified an unexpectedly high number of patients without previous AD therapy receiving insulin monotherapy, which is not in line with the clinical guidelines.

Self-reported Hypoglycaemic Events in 2 430 Patients with Insulin-treated Diabetes in the German Sub-population of the HAT Study.

Data concerning true hypoglycaemic incidence in insulin-treated patients with diabetes in real-world clinical practice are lacking in Germany. The aim of this analysis was to determine the incidence of hypoglycaemia experienced by the German cohort of patients enrolled in the global Hypoglycaemia Assessment Tool (HAT) study. This was a non-interventional, 6-month retrospective and 4-week prospective study using self-assessment questionnaires and patient diaries assessing patients aged ≥18 years in Germany, with type 1 diabetes (T1D) (n=811) or type 2 diabetes (T2D) (n=1 619) treated with insulin for >12 months. The primary endpoint was the percentage of patients experiencing ≥1 hypoglycaemic event during the prospective observational period (4 weeks after baseline). Predictive and continuous factors (such as age, gender, duration of insulin use and HbA1c) contributing to hypoglycaemia risk were explored.During the prospective period, at least one hypoglycaemic event was reported by 81.3% of patients with T1D and 39.7% of patients with T2D, indicating that hypoglycaemia is a common acute complication among patients with insulin-treated diabetes. Severe hypoglycaemia was reported by 9.1% of patients with T1D and 5.4% of patients with T2D. Higher rates of any and severe hypoglycaemia were reported prospectively than retrospectively, regardless of diabetes type, indicating that patients retrospectively under-report hypoglycaemia. Prospective rates (events per patient-year) of any, nocturnal and severe hypoglycaemia were 80.3, 9.9 and 3.0 for T1D and 15.6, 2.4 and 1.1 for T2D, respectively. Given the potential for recall bias in retrospective reporting, this prospective assessment of hypoglycaemia appears more reliable than retrospective assessment. Trial number: NCT01696266.