Real World Use of Antidiabetic Drugs in the Years 2011-2017: A Population-Based Study from Southern Italy.

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. The availability of new antidiabetic drugs (ADs) has led to complex treatment patterns and to changes in the patterns of specific drug utilization. The aim of this population-based study was to describe the pattern of antidiabetic drugs (ADs) use in Southern Italy in the years 2011-2017, in relation to the updated type 2 diabetes mellitus (T2DM) therapy guidelines. A retrospective cohort study was conducted on T2DM patients using data from the Palermo Local Health Unit (LHU) claims database and diabetologist registry. The first-line treatment was investigated and incident treatments were identified and characterized at baseline in terms of demographics, complications, comorbidities, concomitant drugs and clinical parameters. Persistence to AD treatment was also evaluated. During the study period, one-third of first ever ADs users started the treatment with ADs other than metformin, in contrast to guideline recommendations. Among 151,711 incident AD treatments, the male to female ratio was 1.0 and the median age was 66 (57-75) years. More than half (55.0%) of incident treatments discontinued the therapy during the first year of treatment. In Italy, general practitioners (GPs) can only prescribe first-generation ADs, while the prescription of more recently marketed ADs, such as GLP-1RA, DPP4i and SGLT2i, is restricted to diabetologists only, based on a therapeutic plan. The role of GPs in the management of T2DM in Italy should be re-evaluated.

A clinical audit: diagnostic and epidemiological evaluation of the adrenal incidentaloma.

BACKGROUND: Audit is a clinical instrument of government characterized by a whole process of evaluation inter pares to improve medical behaviors in the clinical practice. Different endocrinopathies are underestimated in the clinical and diagnostics practice but they can be a real problem in patients admitted in the departments of Internal Medicine. The adrenal incidentaloma is an accidental discovery with an incidence equal to 4% in radiologic studies but it's rarely considereted in the internal disorders. In the departments of Internal Medicine are hospitalized each year approximately 1450,000 patients and 58,000 about them show a surrenalic lesion identified with CT or MRI as Adrenal Incidentaloma. METHODS: Through a search in the radiological archives, were reviewed all abdominal CT performed in the year 2012 in 8 departments of Internal Medicine of 8 Italian public hospitals. They also examined all medical records of these patients to value clinical management of the adrenal masses and the real incidence of the adrenal incidentaloma. RESULTS: Distribution of pathological results show an important incidence about adrenal incidentaloma in Italian patients although this pathology is represented as a rare disease and its clinical and economic burden are significant. Many questions remain unanswered as the association between duration and severity of the disease, morbidity and how the dimensions affecting it. These results need to be supported by important studies with long follow-up to realize an easy diagnosis. CONCLUSIONS: The results of this audit confirm the real incidence of this pathology in the internistic patients and the final target is to implement changes about therapeutic diagnostic pathway of the hospital patients in the internal medicine departments.

[Collaborative synergy in the management of diabetic patients with acute coronary syndrome]. / Sinergia collaborativa nella gestione del paziente diabetico con recente sindrome coronarica acuta.

BACKGROUND: An increasing amount of evidence confirms that abnormalities in glucose metabolism are associated with cardiovascular morbidity and mortality in acute coronary syndromes (ACS). The in-hospital management of hyperglycemic diabetic patients with ACS is complex, and the traditional clinical-organizational approaches show a high degree of heterogeneity nationwide in Italy. METHODS: The current survey (March 2016-January 2017), carried out through the Delphi method, was focused on some management issues to verify the modalities/possibilities of resolution in daily clinical practice. In addition to the 12 members of the Board, who defined the web-based questionnaire and coordinated the various stages of the process, 66 specialists, cardiologists or diabetologists, were involved in 6 Italian Regions (Lombardy, Tuscany, Lazio, Friuli-Venezia Giulia, Puglia and Sicily). Three iterative rounds of evaluation of the 24 statements included in the questionnaire were scheduled. For each statement, the median evaluation value and the degree of convergence of the Panel of specialists were determined. RESULTS AND CONCLUSIONS: The final analysis reveals two key aspects with a broad convergence of opinions: (i) the need, since admission to hospital, of a close collaboration between cardiologists and diabetologists in the assistance of high-risk patients; and (ii) the opportunity of a specific diagnostic therapeutic care pathway extended to post-discharge management, where the role of the general practitioner should be adequately emphasized.

Exenatide once-weekly improves metabolic parameters, endothelial dysfunction and carotid intima-media thickness in patients with type-2 diabetes: An 8-month prospective study.

AIM: To evaluate the effect of exenatide long acting release (LAR) on carotid intima-media thickness (IMT) and endothelial function in patients with type 2 diabetes mellitus. METHODS: Sixty subjects with type 2 diabetes mellitus were treated with exenatide LAR as add-on to stable doses of metformin for 8 months in an open label study. Anthropometric variables, lipid profile and glycemic parameters were assessed by routine analysis. Carotid IMT by Doppler ultrasound and endothelial function by flow-mediated dilation of the brachial artery were also assessed. RESULTS: Exenatide significantly improved fasting glycaemia (from 8.8 ±â€¯2.8 to 7.3 ±â€¯2.2 mmol/L, p < 0.0001), HbA1c (from 8.0 ±â€¯0.4 to 6.9 ±â€¯1.1%, p < 0.0001), body mass index (from 33 ±â€¯9 to 31 ±â€¯6 kg/m2, p = 0.0348) and waist circumference (from 109 ±â€¯13 to 106 ±â€¯13 cm, p = 0.0105). There was a significant improvement of the lipid profile, except in triglyceride level where no changes were observed. Carotid IMT and flow-mediated dilation were also improved (from 0.98 ±â€¯0.14 to 0.87 ±â€¯0.15 mm and from 5.8 ±â€¯1.3 to 6.8 ±â€¯1.7%, respectively; p < 0.0001 for both). CONCLUSIONS: Treatment with exenatide LAR led to improved cardio-metabolic parameters, including carotid IMT and flow-mediated dilation, independently of glucometabolic control. These results may help to explain, at least in part, the cardiovascular safety of exenatide LAR, as recently reported in cardiovascular outcome trials.

Efficacy and Renal Safety of Dapagliflozin in Patients with Type 2 Diabetes Mellitus Also Receiving Metformin: A Real-Life Experience.

INTRODUCTION: This study aimed at evaluating the efficacy and safety of dapagliflozin in patients with type 2 diabetes (T2D) who also received metformin in clinical practice in Italy. METHODS: This was a retrospective observational study and it included data from patients who received dapagliflozin 10 mg once daily in conjunction with metformin for 12 months (DAPA + MET). In those with inadequate glycemic control, insulin or glimepiride was added after 30 days (DAPA + MET + other glucose-lowering drugs). Efficacy assessments included glycosylated hemoglobin (HbA1c) levels at 6 and 12 months, as well as body mass index (BMI) and lipid parameters at 12 months. Safety was also assessed. RESULTS: Data on 66 patients were included. In both groups, HbA1c was significantly reduced at 6 and 12 months compared with baseline and significant reductions in HbA1c were observed at 12 months compared with 6 months. Over the 12-month treatment period, dapagliflozin significantly reduced BMI in both groups. No significant changes in lipid parameters were observed in either group and no detrimental effects on renal function were detected. CONCLUSIONS: Dapagliflozin is effective and safe in patients with T2D also receiving metformin. Glycemic control was already achieved with dapagliflozin + metformin, and add-on therapy was not associated with further improvements.

Long-Term Effectiveness of Liraglutide for Treatment of Type 2 Diabetes in a Real-Life Setting: A 24-Month, Multicenter, Non-interventional, Retrospective Study.

INTRODUCTION: The aim of the study was to evaluate whether the reduction in glycated hemoglobin (HbA1c) observed in clinical trials with liraglutide in type 2 diabetes (T2D) could be attained in routine clinical practice. METHODS: ReaL was a multicenter, non-interventional, observational, retrospective, longitudinal study on the effectiveness of liraglutide, a human glucagon-like peptide-1 analog, in individuals with T2D treated in daily practice in Italy. Between 26 March and 16 November 2015, data were taken from clinical records of patients aged ≥ 18 years with treatment follow-up data of up to 24 months and who received their first prescription of liraglutide in 2011. RESULTS: A total of 1723 patients were included in the analysis. At baseline, mean age was 58.9 years, duration of diabetes was 9.6 years, and HbA1c was 8.3%. At 12 months, 36.1% of patients were prescribed the maximum 1.8 mg dose; 43.5% [95% confidence interval (CI): 40.9; 46.2] of patients attained the primary outcome of a reduction in HbA1c of ≥ 1% point at 12 months. At 24 months, 40.9% (95% CI 38.1; 43.7) of patients had attained the HbA1c target of ≤ 7%. Additionally, body weight significantly decreased by 3.4 kg (95% CI - 3.6; - 3.1, p < 0.0001). CONCLUSION: In this observational study conducted in routine clinical practice for up to 2 years, treatment with liraglutide improved HbA1c and reduced body weight in a similar fashion to that observed under randomized clinical trial conditions. The data support the use of liraglutide as an effective treatment for T2D in clinical practice. FUNDING: Novo Nordisk S.p.A. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02255266.

Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study.

BACKGROUND: Liraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM. METHODS: We performed an 18-month prospective, real-world study. All subjects had T2DM and the MetS based on the AHA/NHLBI criteria. Subjects with a history of a major CV event were excluded. One hundred-twenty-one subjects (71 men and 50 women; mean age: 62 ± 9 years) with T2DM and the MetS, who were naïve to incretin-based therapies and treated with metformin only, were included. Liraglutide (1.2 mg/day) was added to metformin (1500-3000 mg/day) for the entire study. Fasting plasma samples for metabolic parameters were collected and carotid-intima media thickness (cIMT) was assessed by B-mode real-time ultrasound at baseline and every 6 months thereafter. RESULTS: There was a significant reduction in waist circumference, body mass index, fasting glycemia, HbA1c, total- and LDL-cholesterol, triglycerides, and cIMT during the 18-month follow-up. Correlation analysis showed a significant association between changes in cIMT and triglycerides (r = 0.362; p < 0.0001). The MetS prevalence significantly reduced during the study, and the 26% of subjects no longer fulfilled the criteria for the MetS after 18 months. CONCLUSIONS: Liraglutide improves cardio-metabolic risk factors in subjects with the MetS in a real-world study. Trial Registration ClinicalTrials.gov: NCT01715428.

The effectiveness and durability of an early insulin pump therapy in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: This study evaluated the predictors of effectiveness and durability of insulin pump therapy in children and adolescents who have initiated continuous subcutaneous insulin infusion (CSII) within 2 years after the diagnosis of type 1 diabetes mellitus (T1DM). SUBJECTS AND METHODS: The charts of individuals with T1DM using insulin pumps who were treated at our center were reviewed, including subjects with age at onset of <22 years, interval between onset and insulin pump commencement (interval onset-commencement) of <2 years, use of pumps of >1 year, and use of glucose sensors for <4 weeks/year. The primary end point was the mean glycosylated hemoglobin (HbA1c) value (MHbA1c) throughout the follow-up. RESULTS: From 684 patients treated with insulin pumps, 119 met the inclusion criteria, and 113 were selected for statistical analysis (60 females; age at diabetes onset, 8.9±5.6 years [mean±SD]; follow-up, 4.0±1.8 years; range, 1-8 years; baseline HbA1c, 9.3±1.8%). Only the interval onset-commencement was a linear predictor of the MHbA1c (P=0.01; R(2)=0.089). A significant reduction of the mean yearly HbA1c from baseline throughout all the follow-up was observed (P<0.001). Categorizing the sample into four quartiles on the basis of an increasing interval onset-commencement resulted in levels of MHbA1c significantly lower in the first and second quartiles in comparison with the fourth quartile (7.6±0.8% and 7.8±1.0%, respectively, versus 8.5±0.8%; P<0.001 and P=0.004, respectively). CONCLUSIONS: The present study suggests that early pump commencement in children and adolescents with T1DM provides lower and more durable HbA1c values than a late commencement. It is possible that an early pump commencement could prolong the honeymoon phase, but we cannot confirm or exclude this hypothesis because the lack of data about C-peptide levels during the follow-up.

Comparison of TSH Levels with Liquid Formulation Versus Tablet Formulations of Levothyroxine in the Treatment of Adult Hypothyroidism.

OBJECTIVE: A great number of factors can interfere with levothyroxine (LT4) tablet absorption, leading to increased serum thyroid-stimulating hormone (TSH) levels and, accordingly, to increased LT4 requirements. LT4 oral solution (LT4-OS) is a novel formulation with a pharmacokinetics profile different from those of tablets. The aim of this study was to retrospectively evaluate whether serum TSH levels were decreased after switching adult hypothyroid patients from the tablet to LT-OS. METHODS: We retrospectively evaluated 53 outpatients on LT4 replacement therapy (consumed within 1 hour before breakfast) who switched from LT4 tablets to LT4-OS without changing the daily dose. We compared preswitch TSH (TSH1) with TSH level 60 to 90 days after the switch (TSH2) and examined the clinical differences between the patients whose TSH did and did not drop after the switch. RESULTS: After the switch, TSH levels decreased from a median value of 3.04 (interquartile range [IQR] 1.75-6.80) to 2.30 (IQR 1.21-3.81) µIU/mL, and the difference was significant (P = .0034). We observed a TSH reduction (TSH2/TSH1 ratio <1) in 36/53 (67.9%) of patients; the median TSH2/TSH1 ratio was 0.71 (IQR 0.37-1.14). In the group of patients whose TSH dropped, we observed an increased frequency of factors interfering with LT4 absorption (P = .014). The median TSH2/TSH1 ratios were 0.50 (IQR 0.31-0.72) and 0.85 (IQR 0.65-1.36) for patients with and without interfering factors, respectively. CONCLUSION: Our study confirms that LT4-OS could have an increased absorption rate in comparison to LT4 tablets, especially in the presence of other factors interfering with LT4 absorption.

Prognostic accuracy of continuous glucose monitoring in the prediction of diabetes mellitus in children with incidental hyperglycemia: receiver operating characteristic analysis.

AIM: The purpose of this study is to evaluate continuous glucose monitoring (CGM) in predicting diabetes mellitus in children with incident hyperglycemia (IH) and negativity for some insular autoantibodies. SUBJECTS AND METHODS: Thirty-one autoantibody-negative children who presented at our center with IH underwent a baseline assessment and were followed up for 23.8 months (range, 6-48 months). At the end of the follow-up, we compared the receiver operating characteristic (ROC) areas under the curve (AUCs) of metabolic markers from 17 children who developed diabetes (Group A; n=17) and 14 children who did not develop diabetes (Group B; n=14). RESULTS: Only two oral glucose tolerance test (OGTT)-derived markers and three CGM-derived markers showed a good prognostic performance, with ROC AUCs indicating significant results (P<0.0001) for the following markers: 2-h glucose, OGTT (0.813; 95% confidence interval [CI] 0.621-0.954); AUC glucose, OGTT (0.832; 95% CI 0.611-0.950); CGM glucose measurement peak (0.803; 95% CI 0.621-0.923); percentage of CGM glucose measurements inside the range 70-125 mg/dL (0.866; 95% CI 0.695-0.961); and percentage of CGM measurements ≥126 mg/dL (0.889; 95% CI 0.724-0.973). The combination of the OGTT-derived markers did not increase the predictive value, but the combination of CGM markers with each other or with the OGTT markers yielded higher ROC AUCs (ranging from 0.828 to 0.945). CONCLUSIONS: This is the first study showing that CGM is useful in predicting diabetes mellitus in children with IH.

Brittle type 1 diabetes mellitus.

A small group of patients affected by type 1 diabetes mellitus is characterized by a severe instability of glycemic values with frequent and unpredictable hypoglycemic and/or ketoacidosis episodes which cannot be explained by errors of patients or diabetologists. The quality of life of these patients is dramatically compromised in particular because of the frequency of acute events, hospital recoveries and precocious appearance of chronic complications. This clinical condition has been defined as "brittle diabetes". A precise quantification of these patients is difficult because diagnostic criteria are still not well defined and it is often difficult to verify errors of patients in terms of inappropriate conduct with the pathology. Even more than the other kinds of diabetes, therapy is based on education, glycemic control, intensive therapy and strict interaction between physicians and patients. The introduction of insulin analogous, with either ultra-fast and ultra-slow action and the use of subcutaneous insulin pumps have significantly increased the possibility of treating the most of these cases. However, there is a minority of patients resistant to the therapy. In similar cases, pancreas or islet transplantation represents an effective therapeutic option entailing good expected outcomes. The main limiting factor of beta cell function replacement by transplantation is so far represented by the potentially severe side effects of the immunosuppression therapy necessary to avoid graft rejection and recurrence of autoimmunity.