Patterns and trends of utilization of incretin-based medicines between 2008 and 2014 in three Italian geographic areas.

BACKGROUND: The incretin-based medicines GLP1 analogues (GLP1a) and dipeptidyl peptidase-4 inhibitors (DPP4i) are hypoglycaemic agents licensed for the treatment of type 2 diabetes mellitus (T2DM). Although these drugs possess comparable efficacy and low risk of hypoglycaemia, differences in terms of route of administration (subcutaneous versus oral), effect on body weight and gastrointestinal tolerabily can impact their actual use in clinical practice. This study aimed to describe the real-world utilization of incretin-based medicines in the Italian clinical practice. METHODS: A multi-database, population-based, descriptive, cohort study was performed using administrative data collected between 2008 and 2014 from three Italian geographic areas. Subjects aged ≥18 were selected. New users were defined as those with ≥1 dispensing of GLP1a or DPP4i during the year of interest and none in the past. Trends of cumulative annual incidence of use in the general adult population were observed. New users of GLP1a or DPP4i were respectively described in terms of demographic characteristics and use of antidiabetic drugs during 1 year before and after the first incretin dispensing. RESULTS: The overall study population included 4,943,952 subjects. A total of 7357 new users of GLP1a and 41,907 of DPP4i were identified during the study period. Incidence of use increased between 2008 (0.2‰ for both GLP1a and DPP4i) and 2011 (GLP1a = 0.6‰; DPP4i = 2.5‰) and slightly decreased thereafter. In 2014, 61% of new GLP1a users received once-daily liraglutide while 52% of new DPP4i users received metformin/DPP4i in fixed-dose. The percentage of new DPP4i users older than 65 years of age increased from 30.9 to 62.6% during the study period. Around 12% of new users had not received any antidiabetic before starting an incretin. CONCLUSIONS: During the study period, DPP4i rapidly became the most prescribed incretin-based medicine, particularly among older new user. The choice of the specific incretin-based medicine at first prescription appeared to be directed towards those with higher convenience of use (e.g. oral DPP4i rather than subcutaneous GLP1a, once-daily liraglutide rather than twice-daily exenatide). The non-negligibile use of incretin-based medicines as first-line pharmacotherapy for T2DM warrants further effectiveness and safety evaluations to better define their place in therapy.

Expert opinion of nephrologists about the effectiveness of low-protein diet in different stages of chronic kidney disease (CKD).

No clinical trials have specifically explored the benefits of low-protein diet in patients with different stages of chronic kidney disease (CKD) 3B. In the absence of RCTs, expert opinion may be a valid surrogate to estimate treatment effectiveness. A questionnaire-based survey of a large sample of nephrologists from Southern Italy was conducted to explore benefits of low-protein diet (LPD) in delaying dialysis entry in different CKD stages. For the case vignettes describing eight different patient profiles with various CKD stages, nephrologists reported expected benefits as time delay of dialysis entry. Information was collected through questionnaires filled by 88 nephrologists from different Southern Italian hospitals. On average, nephrologists estimated the highest delay in starting dialysis due to LPD in stages 3B (15 months) and 3A (14 months), and the lowest for 5 stage (3 months). According to opinion of a large sample of Southern Italian nephrologists, low-protein diet may be more efficacious if started in CKD stage 3B than 4 and 5.

Pharmacokinetics of new oral anticoagulants: implications for use in routine care.

INTRODUCTION: Since 2008, new oral anticoagulants (NOACs) have been approved for the prevention of venous thromboembolism (VTE) in patients receiving hip or knee replacement surgery, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), treatment of deep vein thrombosis (DVT), and pulmonary embolism (PE). Premarketing randomized clinical trials (RCTs) of NOACs demonstrated their non-inferiority in terms of efficacy vs. warfarin (traditional oral anticoagulant - TOA), with lower risk of serious adverse drug reactions, especially cerebral hemorrhages. In clinical practice, pharmacokinetic aspects of NOACs have to be carefully taken into account to optimize the benefit-risk profile of these drugs. Areas covered: An overview of major issues related to pharmacokinetics of NOACs, such as drug-drug interactions, over- and underdosage in special populations (e.g. elderly, underweight, and chronic kidney disease patients), and impact on adherence and persistence to NOACs therapy and ultimately clinical outcomes in real-world setting, is provided. Expert opinion: NOACs have been proven to be a better option than traditional anticoagulants due to better tolerability and ease of use. However, given specific pharmacokinetic characteristics, NOAC therapy has to be carefully tailored and monitored in relation to patient characteristics with the final goal of maximizing benefits and minimizing risks.

The Management of Diabetes Mellitus in Patients with Chronic Kidney Disease: A Population-Based Study in Southern Italy.

BACKGROUND AND OBJECTIVES: Diabetes mellitus in patients with chronic kidney disease (CKD) is known as diabetic kidney disease (DKD). Pharmacological management of DKD is challenging due to reduced renal excretion of some antidiabetic drugs. The aim of this population-based study was to explore antidiabetic drug use in DKD patients from Southern Italy. METHODS: The Arianna database from Caserta Local Health Unit was used. Diabetic patients with incident CKD [first diagnosis date: index date (ID)] were identified by searching for specific ICD9-CM codes among hospital discharge diagnoses/procedures and/or indication of use associated with drug prescriptions. To evaluate any change in the use of antidiabetic drugs after the CKD diagnosis, the prevalence of antidiabetic drug use among DKD patients was calculated within 1 year prior to/after ID and after dialysis entry. A Kaplan-Meier analysis was used to assess the time to discontinuation of antidiabetic drugs after CKD diagnosis. The frequency of antidiabetic drugs contraindicated in renal disease in DKD patients was measured. RESULTS: Overall, 725 diabetic patients (mean age 72.8 ± 11.4 years) had incident CKD from 2006 to 2011. The use of combination antidiabetic drugs, biguanides and sulphonamides decreased by approximately 10, 7 and 5%, respectively, after the ID. The use of insulins increased by 10% after the ID and by 20% after entry into dialysis. The use of antidiabetic drugs not contraindicated in CKD decreased marginally after the diagnosis of CKD. CONCLUSION: In a general practice of Southern Italy the management of diabetes mellitus changed only marginally in newly diagnosed CKD patients, suggesting a therapeutic inertia on the part of prescribers.