Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial. METHODS: A systematic review of the literature (PubMed, Cochrane Library Central Register of Controlled Trials [CENTRAL] and https://clinicaltrials.gov), including all RCTs vs placebo published up to May 2015 and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), published June 2015, was performed. Primary endpoints were all-cause mortality and death from cardiovascular causes; secondary endpoints were macrovascular and microvascular events. Safety endpoints were acute pancreatitis, pancreatic cancer, serious adverse events and severe hypoglycaemia. RESULTS: A total of 36 double-blind RCTs were included, allowing analyses of 54,664 patients. There were no significant differences in all-cause mortality (RR=1.03, 95% confidence interval [CI]=0.95-1.12), cardiovascular mortality (RR=1.02, 95% CI=0.92-1.12), myocardial infarction (RR=0.98, 95% CI=0.89-1.08), strokes (RR=1.02, 95% CI=0.88-1.17), renal failure (RR=1.06, 95% CI=0.88-1.27), severe hypoglycaemia (RR=1.14, 95% CI=0.95-1.36) and pancreatic cancer (RR=0.54, 95% CI=0.28-1.04) with the use of DPP-4Is. However, DDP-4Is were associated with an increased risk of heart failure (RR=1.13, 95% CI=1.01-1.26) and of acute pancreatitis (RR=1.57, 95% CI=1.03-2.39). CONCLUSION: There is no significant evidence of short-term efficacy of DPP-4Is on either morbidity/mortality or macro-/microvascular complications in T2D. However, there are warning signs concerning heart failure and acute pancreatitis. This suggests a great need for additional relevant studies in future.

[Prevention of venous thromboembolic events by fondaparinux 2.5 mg in general practice. ArchiMed Ville]. / Utilisation du fondaparinux 2,5 mg pour la prévention des évènements thromboemboliques veineux en médecine générale. ArchiMed Ville.

OBJECTIVE: To evaluate the mean duration of treatment course with fondaparinux 2.5 mg (ARIXTRA(®)) in the setting of ambulatory general medicine, with respect to its indication in thromboprophylaxis for medically ill patients and to describe the population treated. METHODS: Observational, prospective, national, multicenter, pharmaco-epidemiological study, performed in France, at the request of the Transparency Commission (a division of the French Health Regulatory Authority). The general practitioners had to include the first three adult patients, considered as patients at high risk of venous thromboembolic events and immobilized for acute medical illness, treated with initiation of thromboprophylaxis by fondaparinux 2.5 mg. RESULTS: Two hundred and seventeen general practitioners included 840 patients. The mean age of patients was 63.6±18.1 years, and 63% of patients (n=520/831) were females. The real total administration duration of the treatment by fondaparinux 2.5 mg was known for 797 patients and was 15.8±12.4 days on average (range: 1-90 days, median: 10 days). In 40% of patients, the duration ranged from 6 to 14 days [duration consistent with the summary of product characteristics (SmPC)]. Among the 834 patients analyzed, 569 (68%) suffered from at least one acute illness and had at least one risk factor for venous thromboembolism (VTE). The indication did fully comply with the summary of product characteristics of fondaparinux 2.5 mg in 52% of the patients (n=434/834 patients). CONCLUSION: The results of the ArchiMed study support that the thromboprophylaxis treatment with fondaparinux 2.5 mg in ambulatory general medicine, and the associated medical conditions were usually consistent with the SmPC or guidelines. However, a difference was found for the duration and the initial indication, in situations that may be regarded as presenting a risk by the prescriber.

[Prevention of venous thromboembolic events by fondaparinux 2.5mg in patients hospitalized for an acute medical illness. ArchiMed Study]. / Prévention des évènements thromboemboliques veineux par fondaparinux 2,5mg chez des patients hospitalisés pour une affection médicale aiguë. Étude ArchiMed. ArchiMed hôpital - étude observationnelle d'usage du fondaparinux 2,5mg en vie réelle ; 718 patients inclus par 107 pharmaciens hospitaliers.

OBJECTIVE: To evaluate the average duration of in-hospital treatment with fondaparinux 2.5mg prescribed for venous thromboprophylaxis in acutely ill medical patients and to describe the treatment population. METHODS: Prospective, observational, national, multicentre, epidemiological study, performed in France at the request of the Transparency Commission of the French National Health Authority (Haute Autorité de Santé). This is part of a larger study program that also included a study with similar design in the general practice setting. The hospital practice part of the study was conducted by hospital pharmacists who were asked to include the first 15 adult subjects hospitalized in a non-surgical ward for whom fondaparinux 2.5mg was initiated for prophylaxis. RESULTS: Fifty-three pharmacists (49.5%) included a total of 718 patients. The average age was 71 ± 16 years (47%<75 years old); 54% were women. For 41% of patients, duration of fondaparinux 2.5mg administration ranged from 6 to 14 days. Eighty-five percent of patients had at least one acute illness related to the prescription of fondaparinux 2.5mg for thromboprophylaxis. Ten percent of the population had at least one risk factor listed on the Case Report Form. Characteristics of patients from the hospital practice study differ from those included in the general practice part of the ArchiMed Study program. CONCLUSION: The hospital practice part of the ArchiMed Study, which is similar to "audits of practices", shows that the real-life conditions of prescription of fondaparinux 2.5mg in patients hospitalized are generally in line with guidelines with respect to indication for thromboprophylaxis in acute medical illness.

High prevalence of COPD symptoms in the general population contrasting with low awareness of the disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is underdiagnosed because of limited disease awareness with trivialization of the symptoms in the general population. METHODS: A survey was conducted in a representative sample (n=2758) of individuals older than 40 years of age in the general population of France. Respiratory symptoms and knowledge about COPD were assessed in individuals with or at risk for COPD (n=860, 31% of the sample). RESULTS: In the overall sample, 40% of individuals had a Medical Research Council dyspnea grade of 1 or more but only 9% spontaneously reported shortness of breath. Of these 9%, 72% reported limitations to their daily activities but only 14% believed they had severe lung disease. In the overall sample, only 220 (8%) individuals knew the term COPD and only 66% associated the term COPD with respiratory disease. CONCLUSIONS: Despite a large proportion of individuals at risk for COPD or having COPD and a high prevalence of breathlessness, awareness of respiratory symptoms and knowledge of COPD were limited. These findings indicate a need for educating the general population about COPD.

[The gap between the high impact and low awareness of COPD in the population]. / Sujets à risque de BPCO en population générale: disproportion entre la fréquence des symptômes, leur perception et la connaissance de la maladie.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is markedly under-diagnosed, which may relate to under-reporting of symptoms and poor awareness of the disease. METHODS: A survey was conducted in a sample of the French general population aged 40-75 years (n=2758) to assess respiratory symptoms and level of knowledge of the disease in subjects with or at-risk of COPD (n=860, 31%). RESULTS: The high frequency of dyspnoea (MRC dyspnoea grade > or =1: 40%) contrasted with that of subjects spontaneously reporting respiratory problems (9%). Among these, 72% reported limitations in daily-life activities but only 14% considered that they were severely affected by their respiratory status. A very low proportion of subjects knew the term COPD (8%) and only 66% of these associated COPD with a respiratory disease. CONCLUSIONS: There is a wide gap between the high number of subjects at risk of COPD in the general population and the frequency of breathlessness in these subjects on one hand, and the poor knowledge of the disease, poor perception of symptoms, and under-diagnosis and under-use of spirometry on the other. Increasing awareness of COPD in the population is needed.

Abdominal obesity is associated with ineffective control of cardiovascular risk factors in primary care in France.

AIM: Insufficient control of cardiovascular risk factors is observed in primary care. The goal of the present study was to evaluate the association of abdominal obesity with achievement of treatment targets for HbA(1c), LDL cholesterol, triglycerides, HDL cholesterol and blood pressure in primary care. METHODS: In this cross-sectional observational epidemiological study, primary-care practitioners completed a questionnaire covering demographic and socioeconomic data, medical history, drug treatment, and clinical and biological characteristics for 3351 patients (1630 men and 1721 women). Therapeutic targets were HbA(1c) <7%, LDL cholesterol <1.6g/L, triglycerides <1.5 g/L and SBP/DBP <140/90 mmHg. Multivariate analyses were performed to assess the relationship between waist circumference and a lack of cardiovascular risk-factor control. RESULTS: The patients' mean ages were 58+/-14 years and 55+/-16 years for men and women, respectively. A large waist circumference was positively and significantly (P<0.0001 for all) associated with diabetes, hypercholesterolaemia, hypertriglyceridaemia, low HDL cholesterol and hypertension. The prevalence of patients not achieving therapeutic targets increased across waist-circumference quartiles. For treated patients, the odds ratios (95% CI) (adjusted for age, gender, education, smoking status and medical specialty) for not achieving treatment targets were 17.6 (2.2-142) for triglycerides, 2.8 (1.3-6.1) for HbA(1c) and 1.4 (0.9-2.0) for blood pressure on comparisons with extreme quartiles of waist-circumference distribution. CONCLUSION: In primary care, a lack of control of triglycerides, HbA(1c) and, to a lesser extent, blood pressure increases with waist circumference independently of confounders. This suggests that abdominal obesity is associated of poor results in the treatment of diabetes and hypertriglyceridaemia.

[One-year follow-up in real clinical practice conditions of type 2 diabetic patients treated with rosiglitazone: the Avantage study]. / Suivi sur un an dans les conditions de pratique courante d'une cohorte de patients diabétiques de type 2 traités par rosiglitazone: l'étude Avantage.

The Avandia, tolérance à grande échelle (Avantage) study was an observational study conducted in a large cohort of type 2 diabetic patients (T2D) followed for 12 months. Its aim was to assess in real clinical practice conditions, the tolerability of rosiglitazone, an oral antidiabetic agent of the new thiazolidinedione ("glitazone") class, available in France since May 2002. Study was carried out from December 2002 to January 2005. To be included, T2D seen during the inclusion period should start the rosiglitazone treatment (within eight days prior to 15 days after) in agreement with therapeutic indications and drug datasheet information in force at that time. Patient characteristics, clinical and biological data and adverse events (AE) during the 12-month follow-up were recorded. Among the 3845 T2D enrolled from January to November 2003, 3580 constituted the analyzed population (at least one documented rosiglitazone intake). At inclusion, mean age (+/-S.D.) was 62+/-11 years, 52% were male, mean BMI was 29.9+/-5.3kg/m2 and mean HbA1c was 8.5+/-1.4%. Ongoing antidiabetic treatments were mainly a monotherapy (46% of patients, metformin or a sulfonylurea) or a bitherapy (in 47%). Main reasons to prescribe rosiglitazone were insufficient control of diabetes (91% of patients), associated or not with a poor tolerance to the ongoing oral antidiabetic treatment at inclusion (in 29%) and/or with a contraindication to metformin (in 4%). Two thousand four hundred and twenty-four patients (71%) completed the 12-month follow-up. Along the study, 514 T2D (14%) experienced at least one AE, judged related to the treatment in the physician's opinion for 377 patients (11%). Two hundred and fifteen patients dropped out from the study due to AE. AE notified in more than 1% of patients were: weight gain (n=100 patients; 3% of the cohort), nausea (n=57; 2%), edema (n=55; 2%) and anemia (n=40; 1%). A seriousness criteria was reported for 105 patients (3% of the cohort), including 18 (<1%) heart failure. Mean HbA1c level decreased from 8.5+/-1.4% at inclusion to 7.8+/-1.6% at study end. Mean value of the main lipid parameters remained stable. Mean systolic blood pressure (BP) decreased from 137+/-13 to 135+/-12mmHg and diastolic BP from 79+/-8 to 78+/-8mmHg. Mean weight was 82+/-15kg at inclusion and 83+/-17kg at study end (NS), mean waist circumference was not significantly modified. In conclusion, the observational Avantage study, conducted in a large cohort of type 2 diabetic patients treated with rosiglitazone in clinical practice conditions and followed-up for 12 months, confirmed the results of controlled double blind clincal studies, with a clinical and biological tolerability in accordance with the known AE profile and a beneficial effect on metabolic control and arterial blood pressure.

A prospective observational study of a cohort of outpatients with an acute medical event and reduced mobility: incidence of symptomatic thromboembolism and description of thromboprophylaxis practices.

OBJECTIVES: The study was performed to determine the incidence of symptomatic venous thromboembolism in outpatients with an acute medical event causing temporary reduced mobility. Risk factors for venous thromboembolism and thromboprophylaxis practices were also studied. DESIGN: This was a prospective, observational, multicentre, cohort study. SETTING: General practitioners randomly selected from a registry of 25,000 active representative doctors in France including eligible outpatients. SUBJECTS: Outpatients aged at least 40 years anticipated to have reduced mobility for at least 48 h due to an acute medical event were eligible. INTERVENTIONS: None required. MAIN OUTCOME MEASURES: Symptomatic deep-vein thrombosis and pulmonary embolism at 3 weeks were the main study end-points. RESULTS: Overall, 16,532 evaluable patients of mean age 71 years were recruited between October 2002 and June 2003 by 2895 doctors. The main acute medical events leading to reduced mobility were infection, acute rheumatism and falls without fracture. The incidence rates (95% confidence interval) of symptomatic deep-vein thrombosis and pulmonary embolism were 1% (0.84-1.14) and 0.20% (0.13-0.27) respectively. Venous insufficiency in legs, cancer, and a personal or family history of venous thromboembolism were independent risk factors for venous thromboembolism. Pharmacological thromboprophylaxis was initiated in 35.0% (n=5782) of the patients. The principal driver of prescription was a personal history of venous thromboembolism. CONCLUSIONS: The risk of symptomatic venous thromboembolism in outpatients with reduced mobility for medical reasons is close to that reported in medical and surgical inpatients. This risk and the potential need for thromboprophylaxis should be taken into account by primary care doctors.

[Biochemical evaluation of the results of lipid regulating treatment in France]. / Evaluation biologique des résultats du traitement hypolipémiant en France. Etude SPOT.

The objective of the SPOT study (Study of Practice versus Objectives of Treatment) was the biochemical evaluation of the results of long term lipid regulating treatment in France, compared to the objectives defined by AFSSAPS (French regulatory agency for the safety of medical products) in 2000. A random sample of doctors was recruited in 21 French regions by the Regional Health Observation service. To be included in the SPOT study, the patients had to be on lipid regulating medication for at least six months and consent to biochemical evaluation following a consultation. A sample of 641 doctors examined 2,479 patients treated for 7 years on average. These middle aged patients (aged 63 +/- 11 years) were mostly taking statins (72%). They had an average total cholesterol level of 5.41 +/- 1.01 mmol/L (2.10 +/- 0.39 g/L). and LDL of 3.25 +/- 0.93 mmol/L (1.26 +/- 0.36 g/L), reflecting previous results and confirming the stability of their treatment. In primary prevention and in low risk subjects (with less than 2 associated risk factors), the AFSSAPS objectives were achieved in 95% of cases. In secondary prevention or in very high risk subjects (at least 3 associated risk factors 0), 35% of patients had LDL cholesterol greater than 3.4 mmol/L (1.30 g/L). The SPOT study, performed on subjects who had in theory been stabilised with lipid regulating medication, gave two conclusions: cardiovascular prevention with lipid regulating medication is improving in France, and the subjects at greatest risk attain the recommended objectives less often despite the expected benefit of treatment being higher.

[Causes of uncontrolled hypertension. DUO-HTA survey]. / Causes de non-contrôle de l'hypertension artérielle. Enquête DUO-HTA.

OBJECTIVES: To identify the socio-demographic, clinical, psycho-behavioural and therapeutic factors explaining uncontrolled blood pressure in a population of hypertensives in ambulatory practice. METHODS: The DUO-HTA survey is a national, cross-sectional, mirrored, observational study, from a representative sample of 347 general practitioners (MG) and 210 cardiologists, and a population of 2022 hypertensive patients followed by these doctors. The data were collected by means of questionnaires completed by the hypertensives and their doctors. RESULTS: The factors significantly discriminating patients for whom BP was controlled (C) from those patients whose BP was not controlled (NC) were an age less than 65 years, smoking, obesity, alcohol consumption, sedentary lifestyle and multiple anti-hypertensive treatment. On the psycho-behavioural front, the NC patients were more often anxious and irritable, claiming to lead a stressful life and for whom hypertension was often perceived as a "foreign entity" and a source of frustration and multiple deprivations. The factors discriminating the NC doctors from the C doctors were essentially psycho-behavioural, with the NC doctors considering the management of hypertension as being less gratifying, and hypertension as a condition with fluctuating progression, poorly understood and dramatized by patients. CONCLUSION: The DUO-HTA survey underlines the weight of reciprocal representation systems in hypertension for patients and their doctors, as well as the quality of the doctor-patient relationship in blood pressure control. It prompts the development of sensitisation actions for practitioners centered on improving the doctor-patient relationship.

[Arterial hypertension and anxiety in primary care]. / Hypertension artérielle et anxiété en soins primaires.

Various forms of hypertension and anxiety are two very frequent reasons for consultations in primary care. Prevalence of comorbidity HTA/anxiety is unknown in France. Practically, general practitioners meet sometime the association of both typical pathologies. More often, they wonder about the interpretation of high blood pressure figures with an anxious patient, and inversely about the responsibility of the hypertension (with the suite of phantasms) with the apparition of anxious symptoms. Both these last clinical situations are the more frequent in general practice. The global clinical approach, the listening, the time use as help for diagnosis, the use of personal patient's characteristics and his/her environment more often allow to distinguish and to propose an individual therapeutic strategy.