Exercise in the management of type 2 diabetes mellitus: what are the benefits and how does it work?

In this article, we examine the results from meta-analyses of studies that have focused on the effects of supervised exercise in patients with established type 2 diabetes mellitus. Exercise has been clearly demonstrated to have benefits on blood glucose control (average reduction of glycated hemoglobin, 0.6%) and cardiovascular risk factors. These benefits are observed independently of any change in body mass index and fat mass, and are also seen in older populations. Multiple mechanisms are involved, and the improved insulin-sensitizing effect of exercise training is not restricted to muscle but extends to hepatic and adipose tissue. However, while the benefits of exercise in type 2 diabetes management are undisputable, it is not as easy to draw correlations between clinical benefit and the amount of physical activity included in daily life. Recent studies have shown encouraging results with moderate increases in physical activity, which are feasible for most patients and are sufficient to induce sustained positive changes for 2 years. Thus, the benefits of structured and supervised exercise in patients with type 2 diabetes have been consistently demonstrated. Currently, the primary challenge is to determine how long-term increased physical activity can be durably implemented in a patient's daily life.

Penetration rates of new pharmaceutical products in Europe: A comparative study of several classes recently launched in type-2 diabetes.

BACKGROUND: Different countries have their own systems for evaluating new medicines, and they make decisions as to when and how each new medicine is adopted. PURPOSE: To compare the rate of uptake of new diabetes medicines (dipeptidyl peptidase-4 inhibitors [DPP-4Is], glucagon-like peptide-1 receptor agonists [GLP1-RAs], and sodium-glucose co-transporter-2 inhibitors [SGLT2Is]) in the five most populated European countries. METHODS: The monthly volume of sales of antidiabetic drugs was extracted for each country from the IQVIA™ MIDAS® database for the period 2007 to 2016 and the defined daily doses (DDDs) were calculated. For each new drug, market shares were expressed as a percentage of the total market of non-insulin antidiabetic agents. RESULTS: Sharp differences were observed between the countries. Overall, the highest and fastest rates of uptake were seen for Germany and Spain, compared to lower rates for the UK and Italy. This was especially marked for DPP-4Is, where the market share reached over 30% of non-insulin antidiabetic drugs in Germany and Spain, compared to around 10% in the UK and Italy. In France, there was an initial rapid uptake, which stabilized at around 20% after three years. Rates of uptake were lower for the other drugs, with the GLP1-RAs reaching a market share of 2.5-4.5% in Germany, Spain and France, compared to less than 2.5% in the UK and Italy. The SGLT2Is reached a market share of 5-8% in Spain and Germany, compared to less than 4% in the UK and Italy, and they were not launched at all in France in March 2020. CONCLUSION: The differences in the uptake of new antidiabetic drugs may reflect different methods for assessing and introducing new medicines, as well as cultural factors. The uptake of the new medicines would appear to be more cautious in the UK and Italy, perhaps due to concerns about cost-effectiveness, whereas in Germany and Spain, and possibly also France, a new medicine's potential benefits may be prioritized.

Cost of Managing Type 2 Diabetes Before and After Initiating Dipeptidyl Peptidase 4 Inhibitor Treatment: A Longitudinal Study Using a French Public Health Insurance Database.

INTRODUCTION: Diabetes is a growing epidemic that imposes a substantial economic burden on healthcare systems. This study aimed to evaluate the cost of managing type 2 diabetes (T2D) with dipeptidyl peptidase 4 inhibitors (DPP4Is) using real-world data. METHOD: This longitudinal study used data from the French EGB (Echantillon Généraliste des Bénéficiaires) database. The annual average direct healthcare cost of treating patients with T2D was calculated 3 years prior and 3 years after initiation of DPP4I therapy. Actual total ambulatory and hospital care expenditure for the 3 years after DPP4I initiation was compared to projected costs. The distribution of costs across all care modalities was assessed over the 6-year period. RESULTS: Ambulatory and hospital care expenditure data for 919 patients with T2D starting DPP4I therapy alone or in combination in 2013 were analyzed. A total of 526 patients (57.2%) were still being treated with DPP4I 3 years after DPP4I initiation. Regardless of the treatment regimen, the ambulatory and hospital care costs increased above projected costs in the first year following DPP4I initiation, and then declined during the second and third years to levels in line with or below projected values for patients using DPP4Is as an add-on therapy. The increase in total expenditure in the first year following DPP4I initiation and the subsequent decline in costs in the second and third years were both associated with general trends in consumption across all aspects of patient care. CONCLUSION: Despite an initial increase in healthcare expenditure, concomitant with reevaluation of patient care, this study showed that initiation of DPP4Is as an add-on therapy in French patients with T2D was associated with care expenditure that was in line or below predicted values within the 3 years following treatment initiation. Additional studies are required to evaluate the economic impact of the long-term treatment benefits.

OPADIA Study: Is a Patient Questionnaire Useful for Enhancing Physician-Patient Shared Decision Making on Physical Activity Micro-objectives in Diabetes?

INTRODUCTION: Regular physical activity (PA) is recommended by all type 2 diabetes mellitus (T2DM) management guidelines. The OPADIA study aimed to determine whether using a specific patient questionnaire (Optima-PA©) could help T2DM patients increase their PA by leading to better physician-patient communication and improved levels of shared decision making concerning Specific, Measurable, Acceptable, Realistic, Timely (SMART)-PA micro-objectives. METHODS: Physicians participating in this multicentre, prospective, randomised, real-life study were allocated to a standard group (T2DM patients managed according to usual clinical practice, n = 24) or the OPTIMA-PA group (additional use of the questionnaire, n = 30). The main outcome was the percentage of inclusion visits ending with the setting up of at least one SMART-PA micro-objective. Other outcomes were the impact of the OPTIMA-PA questionnaire on patient perceptions of shared decision making (ENTRED questionnaire) and the impact of the OPTIMA-PA questionnaire and establishing SMART-PA micro-objectives as well as patient-perceived physician empathy (ENTRED questionnaire) and GP aptitude for patient-centredness (SEPCQ scores) on patient PA levels over a 3-month period (IPAQ-SF scores). RESULTS: One hundred twenty-two patients were included in the standard group and 134 in the OPTIMA-PA group. Unexpectedly, more inclusion visits ended with SMART-PA micro-objectives being set up in the standard group (p < 0.001): 81.1% (n = 99/122) versus 59.7% (n = 80/134). However, fewer patients in the OPTIMA-PA group felt that GPs made decisions alone (32% versus 60%; p < 0.0001). Positive correlations were also observed between GP patient-centredness and patient-perceived GP empathy or increased patient PA over the study period. CONCLUSION: Although the OPTIMA-PA questionnaire did not directly promote setting up of SMART-PA micro-objectives in T2DM patients, the OPADIA study demonstrated that this tool was effective at improving patient-physician relationships by increasing patient involvement in therapeutic decision making. Our study also highlighted the importance of GP aptitude for patient-centredness for improving PA in T2DM patients.

Patient perceptions and understanding of treatment instructions for ovarian stimulation during infertility treatment.

The impact of patient-physician communication and levels of understanding of treatment on patient knowledge and compliance has been studied in patients undergoing their first cycle of infertility treatment. This observational, real-life, longitudinal study involved 488 patients from 28 infertility centres in France. Data on communication quality, understanding of treatment instructions, patient knowledge and compliance to treatment protocol were collected through questionnaires administered before treatment initiation (V1) and at oocyte retrieval (V2). At V1, patients were very satisfied with their levels of understanding of the injection and monitoring schedules, the information given by the medical team, and the way of receiving instructions, with average ratings on a scale of 0-100% of > 75%. They rated their understanding of possible treatment side-effects as satisfactory (average score 71.1%). Gaps in patient knowledge about their treatment, revealed by discrepancies between physician and patient reports, were observed in 20.5% of patients (n = 79/386), and most commonly resulted from confusion about the units and dose of gonadotropin. Anxiety about performing self-injections and a lack of confidence in their ability to self-inject correctly were each observed in approximately one-third of patients. Patient self-assessment of compliance at V2 revealed that 27% of patients (n = 83/305) did not comply with or had doubts about the injection schedule or dose injected. Meanwhile physicians reported high levels of patient compliance (94.3%; n = 350/371). In conclusion, even when patient-physician relationships appear to be satisfactory, patient miscomprehension and non-compliance during infertility treatment may be underestimated. Further interventions are required to improve these outcomes.

Prediction of unplanned hospital admissions in older community dwellers using the 6-item Brief Geriatric Assessment: Results from REPERAGE, an observational prospective population-based cohort study.

BACKGROUND: The 6-item Brief Geriatric Assessment (BGA) provides a priori risk stratification of incident hospital health adverse events, but it has not been used yet to assess the risk of unplanned hospital admission for older patients in primary care. This study aims to examine the association between the a priori risk stratification levels of the 6-item BGA performed by general practitioners (GPs) and incident unplanned hospital admissions in older community patients. METHODS: Based on an observational prospective cohort design, 668 participants (mean age 84.7 ± 3.9 years; 64.7% female) were recruited by their GPs during an index primary care visit. The 6-item BGA was completed at baseline and provided an a priori risk stratification in three levels (low, moderate, high). Incident unplanned hospital admissions were recorded during a 6-month follow-up. RESULTS: The incidence of unplanned hospital admissions increased with the risk level of the 6-item BGA stratification, the highest prevalence (35.3%) being reported with the high-risk level (P = 0.001). The risk of unplanned hospital admission at the high-risk level was significant (crude odds ratio (OR) = 5.48, P = 0.001 and fully adjusted OR = 3.71, P = 0.032, crude hazard ratio (HR) = 4.20; P = 0.002 and fully adjusted HR = 2.81; P = 0.035). The Kaplan-Meier's distributions of incident unplanned hospital admissions differed significantly between the three risk levels (P-value = 0.002). Participants with a high-risk level were more frequently admitted to hospital than those at a low-risk level (P = 0.001). Criteria performances of all risk levels were poor, except the specificity of the high-risk level, which was 98.2%. CONCLUSIONS: The a priori 6-item BGA risk stratification was significantly associated with incident unplanned hospital admissions in primary care older patients. However, except for the specificity of the high-risk level, its criteria performances were poor, suggesting that this tool is unsuitable for screening older patients in primary care settings at risk of unplanned hospital admission.

Impact of a Community Pharmacist-Delivered Information Program on the Follow-up of Type-2 Diabetic Patients: A Cluster Randomized Controlled Study.

INTRODUCTION: Low-quality communication between patients and care providers and limited patient knowledge of the disease and the therapy are important factors associated with poor glycemic control in patients with type 2 diabetes. We conducted a multicenter study to determine whether structured and tailored information delivered by pharmacists to type 2 diabetic patients could improve patient treatment adherence, hemoglobin A1c (HbA1c) levels and knowledge about diabetes. METHODS: One hundred seventy-four pharmacies were randomized to deliver an educational program on diet, drug treatment, disease and complications during three 30-min interviews over a 6-month period, or to provide no intervention, to type 2 diabetic patients treated with oral antidiabetic agents. Medication adherence was assessed by measuring the medication possession ratio and diabetes control by collecting HbA1c values. Levels of patient treatment self-management and disease knowledge were assessed using self-questionnaires. RESULTS: Three hundred seventy-seven patients were analyzed. The medication possession ratio, already very high at baseline in the intervention (94.8%) and control (92.3%) groups, did not vary significantly after 6 months with no difference between the two groups. Significant decreases in HbA1c were observed in both groups at 6 months (p < 0.001) and 12 months (p < 0.01), with significantly greater changes from baseline in the intervention group than in the control group at 6 months (- 0.5% vs. - 0.2%, p = 0.0047) and 12 months (- 0.6% vs. - 0.2%, p = 0.0057). Patients in the intervention group showed greater improvement in their ability to self-manage treatment (+ 4.86 vs. + 1.58, p = 0.0014) and in the extent of their knowledge about diabetes (+ 0.6 vs. + 0.2, p < 0.01) at 6 months versus baseline compared with the control group. CONCLUSION: Tailored information provided by the pharmacist to patients with type 2 diabetes did not significantly improve the already high adherence rates, but was associated with a significant decrease in HbA1c and an improvement of patient knowledge about diabetes. TRIAL REGISTRATION: ISRCTN33776525. FUNDING: MSD France.

Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial.

OBJECTIVE: To compare the efficacy and tolerability of vildagliptin and rosiglitazone during a 24-week treatment in drug-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, active-controlled, parallel-group, multicenter study of 24-week treatment with vildagliptin (100 mg daily, given as equally divided doses; n = 519) or rosiglitazone (8 mg daily, given as a once-daily dose; n = 267). RESULTS: Monotherapy with vildagliptin and rosiglitazone decreased A1C (baseline = 8.7%) to a similar extent during the 24-week treatment, with most of the A1C reduction achieved by weeks 12 and 16, respectively. At end point, vildagliptin was as effective as rosiglitazone, improving A1C by -1.1 +/- 0.1% (P < 0.001) and -1.3 +/- 0.1% (P < 0.001), respectively, meeting the statistical criterion for noninferiority (upper-limit 95% CI for between-treatment difference < or =0.4%). Fasting plasma glucose decreased more with rosiglitazone (-2.3 mmol/l) than with vildagliptin (-1.3 mmol/l). Body weight did not change in vildagliptin-treated patients (-0.3 +/- 0.2 kg) but increased in rosiglitazone-treated patients (+1.6 +/- 0.3 kg, P < 0.001 vs. vildagliptin). Relative to rosiglitazone, vildagliptin significantly decreased triglycerides, total cholesterol, and LDL, non-HDL, and total-to-HDL cholesterol (-9 to -16%, all P < or = 0.01) but produced a smaller increase in HDL cholesterol (+4 vs. +9%, P = 0.003). The proportion of patients experiencing an adverse event was 61.4 vs. 64.0% in patients receiving vildagliptin and rosiglitazone, respectively. Only one mild hypoglycemic episode was experienced by one patient in each treatment group, while the incidence of edema was greater with rosiglitazone (4.1%) than vildagliptin (2.1%). CONCLUSIONS: Vildagliptin is an effective and well-tolerated treatment option in patients with type 2 diabetes, demonstrating similar glycemic reductions as rosiglitazone but without weight gain.

Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet.

Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-4), orally active, that improves glycemic control in patients with type 2 diabetes (T2DM) primarily by enhancing pancreatic (alpha and beta) islet function. Thus vildagliptin has been shown both to improve insulin secretion and to suppress the inappropriate glucagon secretion seen in patients with T2DM. Vildagliptin reduces HbA(1c) when given as monotherapy, without weight gain and with minimal hypoglycemia, or in combination with the most commonly prescribed classes of oral hypoglycemic drugs: metformin, a sulfonylurea, a thiazolidinedione, or insulin. Metformin, with a different mode of action not addressing beta-cell dysfunction, has been used for about 50 years and still represents the universal first line therapy of all guidelines. However, given the multiple pathophysiological abnormalities in T2DM and the progressive nature of the disease, intensification of therapy with combinations is typically required over time. Recent guidelines imply that patients will require pharmacologic combinations much earlier to attain and sustain the increasingly stringent glycemic targets, with careful drug selection to avoid unwanted adverse events, especially hypoglycemia. The combination of metformin and vildagliptin offers advantages when compared to currently used combinations with additive efficacy and complimentary mechanisms of action, since it does not increase the risk of hypoglycemia and does not promote weight gain. Therefore, by specifically combining these agents in a single tablet, there is considerable potential to achieve better blood glucose control and to improve compliance to therapy.

Direct Medical Costs of Type 2 Diabetes in France: An Insurance Claims Database Analysis.

OBJECTIVES: Our objects was to estimate the direct healthcare costs of type 2 diabetes mellitus (T2DM) in France in 2013. METHODS: Data were drawn from a random sample of ≈600,000 patients registered in the French national health insurances database, which covers 90% of the French population. An algorithm was used to select patients with T2DM. Direct healthcare costs from a collective perspective were derived from the database and compared with those from a control group to estimate the cost of diabetes and related comorbidities. Overall direct costs were also compared according to the diabetes therapies used throughout the year 2013. RESULTS: Cost analysis was available for a sample of 25,987 patients with T2DM (mean age 67.5 ± standard deviation 12.5; 53.9% male) matched with a control group of 76,406 individuals without diabetes. Overall per patient per year medical expenditures were €6506 ± 10,106 in the T2DM group as compared with €3668 ± 6954 in the control group. The cost difference between the two groups was €2838 per patient per year, mainly due to hospitalizations, medication and nursing care costs. Total per capita annual costs were lowest for patients receiving metformin monotherapy (€4153 ± 6170) and highest for those receiving insulin (€12,890). However, apart from patients receiving insulin, costs did not differ markedly across the different oral treatment patterns. CONCLUSION: Extrapolating these results to the whole T2DM population in France, total direct costs of diagnosed T2DM in 2013 was estimated at over €8.5 billion. This estimate highlights the substantial economic burden of this condition on society.

Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes.

UNLABELLED: This 24-week, double-blind, randomized, multicenter, placebo-controlled, parallel-group study performed in 354 drug-naïve patients with type 2 diabetes (T2DM) assessed efficacy and tolerability of vildagliptin (50mg qd, 50mg bid, or 100mg qd). The primary assessment was change from baseline to endpoint in hemoglobin A1c (A1C), comparing vildagliptin to placebo by ANCOVA. Baseline A1C averaged 8.4% and the between-treatment difference (vildagliptin-placebo) in adjusted mean change (AMDelta) in A1C was -0.5+/-0.2% (P=0.011), -0.7+/-0.2% (P<0.001), and -0.9+/-0.2% (P<0.001) in patients receiving vildagliptin 50 mg qd, 50 mg bid, or 100 mg qd, respectively. Baseline FPG averaged 10.5 mmol/L; the between-treatment difference in AMDelta FPG was -0.6+/-0.4 mmol/L in patients receiving vildagliptin 50mg qd and -1.3+/-0.4 mmol/L (P=0.001) in both groups receiving 100mg daily. Relative to baseline, body weight did not change significantly in any of the three vildagliptin groups and decreased by 1.4+/-0.4 kg in the placebo group. Adverse events (AEs) occurred with similar frequency in each group: 55.8%, 59.3%, 59.3%, and 57.6% of patients receiving vildagliptin 50 mg qd, 50 mg bid, 100 mg qd, or placebo, respectively, experienced an AE. No confirmed hypoglycemia was reported. CONCLUSION: Vildagliptin is effective and well-tolerated in drug-naïve patients with T2DM and 100 mg vildagliptin provides similar clinical benefit whether given as single or in divided doses.

Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes.

OBJECTIVE: To define the threshold for excess glucose variability (GV), one of the main features of dysglycemia in diabetes. RESEARCH DESIGN AND METHODS: A total of 376 persons with diabetes investigated at the University Hospital of Montpellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groups-groups 1, 2a, 2b, and 3 (n = 82, 28, 65, and 79, respectively)-according to treatment: 1) diet and/or insulin sensitizers alone; 2) oral therapy including an insulinotropic agent, dipeptidyl peptidase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or 3) insulin. Group 4 included 122 persons with type 1 diabetes. Percentage coefficient of variation for glucose (%CV = [(SD of glucose)/(mean glucose)] × 100) and frequencies of hypoglycemia (interstitial glucose <56 mg/dL [3.1 mmol/L]) were computed. RESULTS: Percentages of CV (median [interquartile range]; %) increased significantly (P < 0.0001) from group 1 (18.1 [15.2-23.9]) to group 4 (37.2 [31.0-42.3]). In group 1, the upper limit of %CV, which served as reference for defining excess GV, was 36%. Percentages of patients with %CVs above this threshold in groups 2a, 2b, 3, and 4 were 0, 12.3, 19.0, and 55.7%, respectively. Hypoglycemia was more frequent in group 2b (P < 0.01) and groups 3 and 4 (P < 0.0001) when subjects with a %CV >36% were compared with those with %CV ≤36%. CONCLUSIONS: A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypoglycemia is significantly increased, especially in insulin-treated subjects.

Breaking Barriers to Effective Type 2 Diabetes Management: Findings from the use of the OPTIMA© Questionnaire in Clinical Practice.

BACKGROUND: The OPTIMA© (MSD, Courbevoie, France) questionnaire was developed to promote shared decisions and the set-up of specific micro-objectives in clinical practice by optimizing communication between type 2 diabetes (T2DM) patients and their physicians. The present study aimed to assess OPTIMA in clinical practice. METHODS: A cross-sectional multicenter observational study was conducted in France from 2012 to 2014. During routine consultation, patients completed one of the five modules of the OPTIMA questionnaire (Physical activity, Diet, Treatment, Knowledge of the disease or Self-monitoring of blood glucose). The rate of SMART (specific, measurable, acceptable, realistic, timely) micro-objective set-up following the use of the questionnaire was assessed. Data on how patients felt about their diabetes management (beliefs concerning actions, how easy they were to do and how often they were done in practice) were gathered. Finally, patients' and physicians' opinions on OPTIMA were assessed using the PRAgmatic Content and face validity Test (PRAC-Test© (Mapi, Lyon, France) evaluation questionnaire. RESULTS: Overall, 807 patients were included by 186 physicians. While 92.7 % of consultations led to the set-up of a micro-objective, only 22.3 % were SMART micro-objectives: Physical activity module (34.3 %), Diet module (9.6 %), Treatment module (16.4 %), Knowledge of the disease module (25.2 %), and self-monitoring of blood glucose module (29.5 %). Among patients completing the Physical activity module, 79.0 % reported that they believed physical activity was useful, 35.0 % that it was easy, and 25.8 % that they regularly practised it. PRAC-Test results showed that OPTIMA was a useful and easy-to-use questionnaire that promotes communication between physicians and their patients according to 92.8 % of patients and 69.4 % of physicians. CONCLUSION: The OPTIMA questionnaire facilitates communication between patients and their physicians and promotes the set-up of micro-objectives concerning T2DM management. The Physical activity module was the most likely of the five modules in the questionnaire to lead to the set-up of SMART micro-objectives. FUNDING: MSD France.

Comparison of efficacy and safety assessment of fluvastatin in patients <65 years versus > or =65 years of age.

This pooled analysis of 30 completed clinical trials assessed the efficacy and safety of fluvastatin in patients <65 (n = 8,037) and patients > or =65 years of age (n = 3,717). The results demonstrated that in patients > or =65 years of age, lipid changes with fluvastatin therapy are equivalent to or slightly better than those observed in patients <65 years of age. Treatment with fluvastatin produced a significantly lower incidence of major cardiovascular clinical end points (major adverse cardiac events [MACEs]) and an increase in the time to a first MACE in the older population. The incidence of adverse events, particularly those of concern with statin therapy, was similar between the placebo- and fluvastatin-treated patients and between the different age groups. In conclusion, data derived from the pooled analysis with fluvastatin demonstrate that cardiovascular events are reduced in older high-risk patients to a greater extent compared with younger patients. Furthermore, this pooled analysis supports the use of fluvastatin to lower cholesterol levels in older high-risk patients.

Hypoglycemia hospitalization frequency in patients with type 2 diabetes mellitus: a comparison of dipeptidyl peptidase 4 inhibitors and insulin secretagogues using the French health insurance database.

AIM: We aimed to compare the frequency of severe hypoglycemia leading to hospitalization (HH) and emergency visits (EV) for any cause in patients with type 2 diabetes mellitus exposed to dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4-i) versus those exposed to insulin secretagogues (IS; sulfonylureas or glinides). METHODS: Data were extracted from the EGB (Echantillon Généraliste des Bénéficiaires) database, comprising a representative sample of ~1% of patients registered in the French National Health Insurance System (~600,000 patients). Type 2 diabetes mellitus patients exposed to regimens containing either a DPP4-i (excluding treatment with IS, insulin, or glucagon-like peptide 1 analog) or IS (excluding treatment with insulin and any incretin therapy) between 2009 and 2012 were selected. HH and EV during the exposure periods were identified in both cohorts. A similar analysis was conducted considering vildagliptin alone versus IS. Comparative analyses adjusting for covariates within the model (subjects matched for key characteristics) and using multinomial regression models were performed. RESULTS: Overall, 7,152 patients exposed to any DPP4-i and 1,440 patients exposed to vildagliptin were compared to 10,019 patients exposed to IS. Eight patients (0.11%) from the DPP4-i cohort and none from the vildagliptin cohort (0.0%) were hospitalized for hypoglycemia versus 130 patients (1.30%) from the IS cohort (138 hospitalizations) (P=0.02 and P<0.0001, respectively). Crude rates of HH/1,000 patient-years were 1.4 (95% CI: 0.7; 2.4) in the DPP4-i cohort, 0.0 in the vildagliptin cohort (95% CI: 0.0; 4.0), versus 5.6 (95% CI, 4.7; 6.6) in the IS cohort (P<0.0001). After adjustments, rates per 1,000 patient-years of HH were 1.4 (95% CI: 0.7; 2.4) with DPP4-i versus 7.5 (95% CI: 6.0; 9.2) with IS (P<0.0001), and 0.0 (95% CI: 0.0; 4.0) with vildagliptin versus 13.6 (95% CI: 10.4; 17.5) with IS (P<0.0001). Adjusted EV rates were also significantly lower with all DPP4-i or with vildagliptin, as compared to IS (P<0.0001). Consistent results were found when considering only treatment initiations for all compared cohorts. CONCLUSION: HH and EV were significantly less frequent in patients exposed to any DPP4-i or to vildagliptin versus IS. These real-life data should be considered in the benefit/risk evaluation of the drugs.

"Mild dysglycemia" in type 2 diabetes: to be neglected or not?

"Mild dysglycemia" in type 2 diabetes can be defined by the range of HbA1c levels≥6.5% (48 mmol/mol) and<7% (53 mmol/mol), which corresponds to when the risk for vascular complications begins to increase. This "mild dysglycemia" is characterized by both a dawn phenomenon (a spontaneous blood glucose rise in the early morning) and an excess of post-prandial glucose excursions in the absence of abnormal elevation in basal glucose, especially during nocturnal periods. This represents an intermediary stage between pre-diabetes (HbA1c≥5.7%, 39 mmol/mol, and<6.5%, 48 mmol/mol) and those who begin to show a steadily progressive worsening in basal glucose (HbA1c≥7%, 53 mmol/mol). Should this relatively minor intermediate dysglycemic phase deserve more attention, that is the question. The now available incretin-based therapies, and more specifically the DPP-4 inhibitors provide the clinician with the possibility to reduce or eradicate both the dawn phenomenon and post-meal glucose excursions with minimal side effects. The availability of 24-h glycemic profiles in those with "mild dysglycemia" will help to describe their individual glycemic phenotype, based on which the early and appropriate life style changes and/or pharmacological interventions can be introduced.

Potential glycemic overtreatment in patients ≥75 years with type 2 diabetes mellitus and renal disease: experience from the observational OREDIA study.

BACKGROUND: Few data exist examining the management of elderly patients with type 2 diabetes mellitus and renal impairment (RI). This observational study assessed the therapeutic management of this fragile population. METHODS: Cross-sectional study: data from 980 diabetic patients ≥75 years with renal disease are presented. RESULTS: Patients had a mean age of 81 years (range 75-101) with long-standing diabetes (15.4 years) often complicated (half with macrovascular disease). Mean estimated glomerular filtration rate was 43 mL/min/1.73 m(2) and 20% had severe RI. Mean hemoglobin A1c was 7.4%. Anti-diabetic therapy was oral based for 51% of patients (60% ≥2 oral anti-diabetic drugs [OAD]) and insulin based for 49% (combined with OAD in 59%). OAD included metformin (47%), sulfonylureas (26%), glinides (19%), and DPP-4 inhibitors (31%). Treatments were adjusted to increasing RI, with less use of metformin, sulfonylureas, and DPP-4 inhibitors, and more glinides and insulin in severe RI. In all, 579 (60%) of these elderly patients with comorbidities had hemoglobin A1c <7.5% (mean 6.7%) while being intensively treated: 69% under insulin-secretagogues and/or insulin, putting them at high risk for severe hypoglycemia. Only one-fourth were under oral monotherapy. CONCLUSION: In clinical practice, a substantial proportion of elderly patients may be overtreated. RI is insufficiently taken into account when prescribing OAD.

Physical activity in patients with type 2 diabetes and hypertension--insights into motivations and barriers from the MOBILE study.

BACKGROUND: Although physical activity (PA) is key in the management of type 2 diabetes (T2DM) and hypertension, it is difficult to implement in practice. METHODS: Cross-sectional, observational study. Participating physicians were asked to recruit two active and four inactive patients, screened with the Ricci-Gagnon (RG) self-questionnaire (active if score ≥16). Patients subsequently completed the International Physical Activity Questionnaire. The objective was to assess the achievement of individualized glycated hemoglobin and blood pressure goals (<140/90 mmHg) in the active vs inactive cohort, to explore the correlates for meeting both targets by multivariate analysis, and to examine the barriers and motivations to engage in PA. RESULTS: About 1,766 patients were analyzed. Active (n=628) vs. inactive (n=1,138) patients were more often male, younger, less obese, had shorter durations of diabetes, fewer complications and other health issues, such as osteoarticular disorders (P<0.001 for all). Their diabetes and hypertension control was better and obtained despite a lower treatment burden. The biggest difference in PA between the active vs inactive patients was the percentage who declared engaging in regular leisure-type PA (97.9% vs. 9.6%), also reflected in the percentage with vigorous activities in International Physical Activity Questionnaire (59.5% vs. 9.6%). Target control was achieved by 33% of active and 19% of inactive patients (P<0.001). Active patients, those with fewer barriers to PA, with lower treatment burden, and with an active physician, were more likely to reach targets. The physician's role emerged in the motivations (reassurance on health issues, training on hypoglycemia risk, and prescription/monitoring of the PA by the physician). A negative self-image was the highest ranked barrier for the inactive patients, followed by lack of support and medical concerns. CONCLUSION: Physicians should consider PA prescription as seriously as any drug prescription, and take into account motivations and barriers to PA to tailor advice to patients' specific needs and reduce their perceived constraints.

Effects of baseline level of triglycerides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate, or gemfibrozil).

This analysis was conducted to evaluate the effect of baseline triglyceride levels on lipid and lipoprotein changes after treatment with the combination of fluvastatin and fibrates. The analysis involved pooling data from 10 studies that included 1,018 patients with either mixed hyperlipidemia or primary hypercholesterolemia. Patients received a combination of fluvastatin and a fibrate (bezafibrate, fenofibrate, or gemfibrozil) from 16 to 108 weeks. The combination of fluvastatin and a fibrate improved lipid profiles, with reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol that were dependent on baseline triglyceride levels. The greatest triglyceride reductions were observed in patients with high baseline triglyceride levels (> or =400 mg/dl) (41%, p <0.0001). The greatest LDL cholesterol and non-HDL cholesterol reductions occurred in patients with normal baseline triglyceride levels (<150 mg/dl) (35% and 33%, respectively; p <0.0001). The combined fluvastatin-fibrate therapy was well tolerated. Two patients (0.2%) (1 patient on fluvastatin 80 mg + gemfibrozil 1,200 mg and 1 patient on fluvastatin 20 mg + fenofibrate 200 mg) had creatine kinase levels > or =10 times the upper limit of normal, 11 patients (1.1%) had an elevation in alanine transaminase >3 times the upper limit of normal, and 7 patients (0.7%) had elevations in aspartate transaminase >3 times the upper limit of normal. Combined fluvastatin-fibrate therapy takes advantage of the complementary effects of the 2 agents, with the extent of triglyceride, LDL cholesterol, and non-HDL cholesterol lowering dependent on baseline triglyceride levels. The combination of fluvastatin and fibrates was well tolerated with no major safety concerns.

Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients.

The efficacy and safety of lipid-lowering agents in elderly individuals have not been extensively assessed. This population generally takes more drugs concurrently than middle-aged patients, and are therefore at higher risk of drug-drug interactions. This large-scale, randomized, double-blind, placebo-controlled study investigated the efficacy and safety of extended-release (XL) fluvastatin 80 mg once daily for up to 1 year in elderly patients with primary hypercholesterolemia. A total of 1229 patients (mean age, 75.5 years) were randomized. After 2 months of treatment, fluvastatin XL 80 mg significantly decreased plasma lipid levels from baseline compared with placebo; fluvastatin reduced total cholesterol by 25% compared with a decrease of 2.5% in the placebo group, low-density lipoprotein cholesterol was -33% vs. -2.5%, respectively, and triglycerides were -13.3% vs. 2.9%, respectively (p<0.00001). The safety profile of fluvastatin XL was similar to that of placebo. Fluvastatin XL 80 mg once daily was well tolerated and effectively managed plasma lipid profiles in a large cohort of elderly patients. These findings are consistent with data obtained previously in younger recipients of fluvastatin XL 80 mg, and reinforce the safety of fluvastatin in a population at high risk of drug-drug interactions.