Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting - results of the 1 year follow-up of the prospective DiaRegis registry.

BACKGROUND: DPP-4 inhibitors (DPP4-I) have been shown to provide non-inferior glycaemic control compared with sulfonylureas (SU), but result in a reduction of body weight and a significantly lower risk of hypoglycaemia in patients with type 2 diabetes. We aimed to validate these results in a large real-world sample of patients participating in the prospective DiaRegis registry and to assess prognostic implications. METHODS: DiaRegis included 3810 patients with type 2 diabetes in which antidiabetic therapy was intensified. We defined two patient subgroups, the first receiving either a DPP4-I or SU on top of prior metformin monotherapy and the second containing patients out of subgroup 1 with unaltered treatment for 1 year. RESULTS: After enrolment 884 patients with prior metformin monotherapy received a dual combination of metformin with either DPP4-I (n = 628; 71%) or SU (n = 256; 29%). Patient characteristics, blood glucose and blood pressure control as well as comorbidity burden were virtually identical. There were neither significant differences in the change of HbA1c over the 12 months treatment period nor in the reduction of body weight, but fasting (p = 0.033) and postprandial glucose levels (p = 0.01) were significantly lower in those receiving DPP4-I. Hypoglycaemia was significantly less frequent in patients receiving DPP4-I (OR 0.32; 95% CI 0.19-0.54). Qualitative changes were robust for subgroup 2 (except of fasting plasma glucose). Patients receiving DPP4-I had significantly less stroke/transitory ischaemic attack (0.2 vs. 2.0; p < 0.05) during the 1 year follow-up, whereas other vascular events (coronary artery bypass graft, percutaneous coronary intervention) were borderline significant. CONCLUSIONS: The present results confirm prior randomised controlled trial results in patients with type 2 diabetes from real world clinical practice demonstrating that DPP4-I on top of prior metformin monotherapy result in similar HbA1c reductions within 12 months but a significant reduction in hypoglycaemia compared with sulfonylurea added to metformin. The reduction in vascular events observed has to be verified in larger cohorts.

Aliskiren for the treatment of essential hypertension under real-life practice conditions: design and baseline data of the prospective 3A registry.

BACKGROUND: The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in-class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions. METHODS: The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen. RESULTS: Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non-RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non-RAS; p < 0.0001). CONCLUSIONS: In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting.

[Comorbidity, hypoglycaemia and appropriate selection of antidiabetic pharmacotherapy in diabetic patients with heart failure in clinical practice in Germany. Results of the DiaRegis registry].

BACKGROUND: Patients with type 2 diabetes and heart failure are considered to be at high risk for hypoglycaemic complications. There is a considerable uncertainty with respect to the appropriate choice of antidiabetic pharmacotherapy in patients with type 2 diabetes and comorbid heart failure. Little is known about comorbidity, hypoglycaemia rates and selected pharmacotherapy in diabetic patients with heart failure in clinical practice. METHODS: DiaRegis is a prospective registry in Germany including 3,810 patients with type 2 diabetes receiving antidiabetic treatment with oral mono or oral dual combination therapy in 2009/2010. Only patients for which adjustment of pharmacotherapy (including the introduction of insulin and GLP-1 analogues) was deemed necessary were enrolled. We examined the differences in comorbidity, hypoglycaemia and choice of anti-diabetic pharmacotherapy between diabetics with and without clinical heart failure in clinical practice in Germany. RESULTS: For 3,746 patients, data on the presence of heart failure were available, median (IQR) age 65.9 (57.6-72.8) years and 46.8% were female. Patients with heart failure (n = 370; 9.9%) were older, had a higher BMI, were less physically active, and had more cardiovascular risk factors and a substantial comorbidity. Glycaemic control was comparable between groups. Of the patients with heart failure, 76.8% received metformin, 32.7% sulfonylureas, 2.2% glucosidase inhibitors, 4.3% glinides, 6.2% glitazones and 7.3% DPP-4 inhibitors at baseline before adjustment of therapy. In multivariate analyses, patients with heart failure received less metformin (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.43-0.79) and sulfonylureas (OR 0.70, 95%CI 0.52-0.95) but not thiazolidinediones (OR 1.22, 95%CI 0.82-1.81) or other antidiabetic drugs. Hypoglycaemia was considerably more frequent in diabetic patients with heart failure than in those without (OR 1.96, 95%CI 1.47-2.61). CONCLUSION: Patients with type 2 diabetes and heart failure had a substantially increased comorbidity burden compared to patients without heart failure. They more often suffered from episodes of hypoglycaemia, especially those requiring medical assistance. The diagnosis of heart failure did not impact the choice of antidiabetic pharmacotherapy in patients with type 2 diabetes. There was no differential use of thiazolidinediones despite evidence discouraging their use in patients with heart failure.

Occupation and malignant lymphoma: a population based case control study in Germany.

AIMS: To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study. METHODS: Male and female patients with malignant lymphoma (n = 710) aged 18-80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack-years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. RESULTS: The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers. CONCLUSIONS: The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma.

Ambulatory blood pressure monitoring: is it mandatory for blood pressure control in treated hypertensive patients?: prospective observational study.

OBJECTIVE: Twenty-four hour ambulatory blood pressure (ABP) is superior to office blood pressure (BP) in predicting cardiovascular events. However, its use to optimise BP control in treated hypertensive patients is less well examined. DESIGN AND METHOD: In this observational study conducted in 899 general practitioners' offices, 4078 hypertensive patients with uncontrolled office BP were included. Antihypertensive therapy was intensified and after 1 year office BP and 24-hour ABP were measured to categorise patients according to the ESC/ESH 2007 guidelines. RESULTS: In this cohort (mean office BP 156/90 mmHg, mean ABP 146/85 mmHg), 2059 out of 4078 patients (50.5%) had controlled office BP (<140/90 mmHg) at 1 year examination. Of these apparently controlled patients (N=2059), 1339 (65.8%) had 24-hour ABP ≥ 130/80 mmHg, indicating masked hypertension (32.9% of all treated patients). In the prespecified subgroups the prevalence of masked hypertension was the following: diabetes 28.2%, CVD 29.1%, and CKD 32.1%. White coat hypertension (24h-ABP<130/80 mmHg and office BP ≥ 140/90 mmHg) was found in 12.4% (N=233) of patients with elevated office BP (6.1% of all treated patients), and in 5.7% of the diabetic subgroup, 5.6% CVD and 7.1% CKD. Discrepancies in BP categorisation between office BP and 24-hour ABP were high; all subjects 52.8%, diabetes 50.0%, CVD 49.0% and CKD 50.4%. CONCLUSION: In hypertensive patients on therapy, 2 out of 3 with apparently controlled office BP had masked hypertension, suggesting a more aggressive therapy, and 1 out of 8 with elevated office BP had white coat hypertension potentially falsely forcing physicians to intensify therapy. The 3A Registry is listed under clinicaltrials.gov, NCT01454583.

Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk.

Interactions between environment and immune system play an essential role in the aetiology of immunopathologies, including lymphomas. Toll-like receptors (TLR) belong to a group of pattern recognition receptors, with importance for innate immune response and inflammatory processes. Interleukin-10 (IL-10) is a key regulatory cytokine and has been implicated in lymphomagenesis. Functional polymorphisms in these inflammation-associated genes may affect the susceptibility towards lymphoma. To test this hypothesis, we have genotyped DNA of 710 lymphoma cases and 710 controls within the context of a population-based epidemiological study for 11 functionally important single-nucleotide polymorphisms in TLR1, -2, -4, -5, -9, IL10 and IL10 receptor (IL10RA). The IL10RA Ser138Gly variant was underrepresented among lymphoma cases (odds ratio (OR)=0.81, 95 per cent confidence interval (95% CI)=0.65-1.02), mainly owing to an inverse association with Hodgkin's lymphoma (HL). The TLR2 -16933T>A variant was associated with a 2.8-fold increased risk of follicular lymphoma (95% CI=1.43-5.59) and a decreased risk of chronic lymphocytic leukaemia (OR=0.61, 95% CI=0.38-0.95). Furthermore, the TLR4 Asp299Gly variant was positively associated with the risk of mucosa-associated lymphoid tissue lymphoma (OR=2.76, 95% CI=1.12-6.81) and HL (OR=1.80, 95% CI=0.99-3.26). In conclusion, this study suggests an effect of polymorphisms in factors of the innate immune response in the aetiology of some lymphoma subtypes.