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Hanefeld M.,TU Dresden | Duetting E.,Novartis | Bramlage P.,Institute For Pharmakologie Und Praventive Medizin
Cardiovascular Diabetology | Year: 2013

Background: Hypoglycaemia has been associated with increased cardiovascular (CV) risk and mortality in a number of recent multicentre trials, but the mechanistic links driving this association remain ill defined. This review aims to summarize the available data on how hypoglycaemia may affect CV risk in patients with diabetes.Methods: This was a systematic review of available mechanistic and clinical studies on the relationship between hypoglycaemia and cardiovascular risk. Study outcomes were compiled from relevant articles, and factors contributing to hypoglycaemia-mediated CVD and its complications are discussed.Results: Six recent comprehensive clinical trials have reinforced the critical importance of understanding the link between hypoglycaemia and the CV system. In addition, 88 studies have indicated that hypoglycaemia mechanistically contributes to CV risk by increasing thrombotic tendency, causing abnormal cardiac repolarization, inducing inflammation, and contributing to the development of atherosclerosis. These hypoglycaemia-associated risk factors are conducive to events such as unstable angina, non-fatal and fatal myocardial infarction, sudden death, and stroke in patients with diabetes.Conclusions: Emerging data suggest that there is an impact of hypoglycaemia on CV function and mechanistic link is multifactorial. Further research will be needed to ascertain the full impact of hypoglycaemia on the CV system and its complications. © 2013 Hanefeld et al.; licensee BioMed Central Ltd.

Forst T.,Profil Institute Mainz | Bramlage P.,Institute For Pharmakologie Und Praventive Medizin
Expert Opinion on Pharmacotherapy | Year: 2014

Introduction: Dipeptidyl peptidase-4 inhibitors increase circulating levels of glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide regulating glucose-dependent insulin secretion. In addition, GLP-1 suppresses glucagon secretion, delays gastric emptying and increases satiety. The combination of vildagliptin with the biguanide metformin is of particular interest because of its complementary mode of action, addressing insulin resistance, alpha-and beta cell function in the islet of the pancreas. Areas covered: Because of the abundance of data supporting the use of vildagliptin alone and in combination with metformin, the present paper aims at giving an overview on the current evidence for its use in patients with type 2 diabetes mellitus. Expert opinion: The data suggest that vildagliptin offers similar glycemic control compared to sulfonylureas and thiazolidinediones, while having the benefit of being associated with fewer cases of hypoglycemia and less body weight gain. There is increasing evidence that compared with sulfonylureas, vildagliptin has favorable effects on pancreatic alpha-and beta-cell function. Vildagliptin in combination with metformin, improve glycemic control with a favorable safety and tolerability profile, making it an attractive therapeutic option in patients where metformin monotherapy alone is not sufficient. © 2014 Informa UK, Ltd.

Bramlage P.,Institute For Pharmakologie Und Praventive Medizin | Gitt A.K.,University of Heidelberg | Binz C.,Bristol Myers Squibb | Krekler M.,Bristol Myers Squibb | And 3 more authors.
Cardiovascular Diabetology | Year: 2012

Background: We aimed at identifying variables predicting hypoglycemia in elderly type 2 diabetic patients and the relation to HbA1c values achieved.Design: Prospective, observational registry in 3810 patients in primary care. Comparison of patients in different age tertiles: with an age < 60 (young, n=1,253), age 60 to < 70 (middle aged, n=1,184) to those ≥ 70 years (elderly, n=1,373). Odds Ratios (OR) with 95% confidence intervals (CI) were determined from univariable and multivariable regression analyses.Results: Elderly patients had a later diabetes diagnosis, a longer diabetes duration, better glucose control and more frequent co-morbid disease conditions. Overall 10.7% of patients experienced any severity hypoglycemia within the last 12 months prior to inclusion. Higher rates of hypoglycemia were observed in the elderly than in the young after adjusting for differences in HbA1c, fasting and post-prandial blood glucose (OR 1.68; 95%CI 1.16-2.45). This was particularly true for hypoglycemic episodes without specific symptoms (OR 1.74; 95%CI 1.05-2.89). In a multivariate model stroke / transitory ischemic attack, the presence of heart failure, clinically relevant depression, sulfonylurea use and blood glucose self-measurement were associated with hypoglycemic events.Conclusion: Elderly patients are at an increased risk of hypoglycemia even at comparable glycemic control. Therefore identified variables associated with hypoglycemia in the elderly such as heart failure, clinically relevant depression, the use of sulfonylurea help to optimize the balance between glucose control and low levels of hypoglycemia. Asymptomatic hypoglycemia should not be disregarded as irrelevant but considered as a sign of possible hypoglycemia associated autonomic failure. © 2012 Bramlage et al.; licensee BioMed Central Ltd.

Rubenacker S.,Fachabteilung Chirurgie | Kaiser J.,Sanofi S.A. | Guschmann M.,Institute For Pharmakologie Und Praventive Medizin
Chirurg | Year: 2013

Venous thromboembolism and subsequent pulmonary embolism are frequent and sometimes fatal complications in patients after surgical interventions. To prevent thromboembolisms an effective prophylaxis is necessary and outpatients in particular need adequate compliance. The aim of the prospective non-interventional study COMFORT was to analyze 8,091 outpatients after surgical and orthopedic interventions with different risk profiles with respect to factors affecting patient compliance in a positive or negative way. The follow-up period was 14 days and 92. 5 % of the patients took the medication for the prescribed duration, 2. 1 % (n = 166) terminated the medication too early and no information was available for 5. 9 % (n = 442) of the patients. The reasons given for the premature termination of the injections were no more need for prophylaxis and end of medication by order of the physician due to mobilization or adverse events. Of the patients 73 % stated that the administartion was simple and without any problems and the majority of patients recognized injection as the administration mode of low molecular weight heparin to be the most important medication. The findings of this study can contribute to a better understanding of patient compliance. © 2013 Springer-Verlag Berlin Heidelberg.

Seufert J.,University Hospital Freiburg | Pegelow K.,Sanofi S.A. | Bramlage P.,Institute For Pharmakologie Und Praventive Medizin
Vascular Health and Risk Management | Year: 2013

Background: For patients with type 2 diabetes who are uncontrolled on a combination of two oral antidiabetic agents, addition of the long-acting basal insulin glargine is a well established treatment option. However, data on the efficacy and safety of a combination of metformin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin glargine are limited in real-world settings. Therefore, the aim of this study was to analyze blood glucose control, rates of hypoglycemia and body weight in a large cohort of patients with type 2 diabetes treated with this combination therapy in real practice. Methods: This noninterventional, multicenter, prospective, observational trial with a follow-up of 20 weeks enrolled insulin-naïve patients who had been on a stable fixed dose of metformin and a DPP-4 inhibitor for at least 3 months, and had a glycosylated hemoglobin (HbAlc) between 7.5% and 10%. Patients were selected at the investigators' discretion for initiation of insulin glargine at baseline. A total of 1, 483 patients were included, of whom 1, 262 were considered to be the efficacy set. Primary efficacy parameters were HbAlc and fasting plasma glucose. Secondary outcome measures included achievement of glycemic targets, body weight, rates of hypoglycemia, and other safety parameters, as well as resource consumption. Results: Upon initiation of insulin glargine, mean HbA1c decreased from 8.51% to 7.36% (-1.15%±0.91%; 95% confidence interval [CI] -1.20 to -1.10). An HbAlc level <6.5% was achieved in 8.2% of patients and a level <7.0% in 31.5%. Mean fasting plasma glucose decreased from 174±47 mg/dL to 127±31 mg/dL (-47.3±44.1 mg/dL; 95% CI -49.8 to -44.8). In 11.9% of patients, a fasting plasma glucose level <100 mg/dL was achieved. Bodyweight decreased on average by 0.98±3.90 kg (95% CI 1.19-0.76). Hypoglycemia (blood glucose ≤70 mg/dL) was observed in 29 patients (2.30%), of whom six (0.48%) had nocturnal hypoglycemia and four (0.32%) had documented severe events (blood glucose <56 mg/dL). Conclusion: The results of this observational study show that insulin glargine, when added to a fixed-dose combination of metformin and a DPP-4 inhibitor, resulted in a significant and clinically relevant improvement of glycemic control. Importantly, this intervention did not interfere with the action of the DPP-4 inhibitors, resulting in neutral effects on weight and low rates of hypoglycemia. We conclude that this treatment intensification approach may be useful, efficient, and safe in daily clinical practice for patients with type 2 diabetes. © 2013 Seufert et al.

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