Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide.

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus.

Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets.

Simultaneous activation of the incretin G-protein-coupled receptors (GPCRs) via unimolecular dual-receptor agonists (UDRA) has emerged as a new therapeutic approach for type 2 diabetes. Recent studies also advocate triple agonism with molecules also capable of binding the glucagon receptor. In this scoping review, we discuss the cellular mechanisms of action (MOA) underlying the actions of these novel and therapeutically important classes of peptide receptor agonists. Clinical efficacy studies of several UDRAs have demonstrated favorable results both as monotherapies and when combined with approved hypoglycemics. Although the additive insulinotropic effects of dual glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic peptide receptor (GIPR) agonism were anticipated based on the known actions of either glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP) alone, the additional benefits from GCGR were largely unexpected. Whether additional synergistic or antagonistic interactions among these G-protein receptor signaling pathways arise from simultaneous stimulation is not known. The signaling pathways affected by dual- and tri-agonism require more trenchant investigation before a comprehensive understanding of the cellular MOA. This knowledge will be essential for understanding the chronic efficacy and safety of these treatments.

AWARE A novel web application to rapidly assess cardiovascular risk in type 2 diabetes mellitus.

AIM: To describe the development of the AWARE App, a novel web application for the rapid assessment of cardiovascular risk in Type 2 Diabetes Mellitus (T2DM) patients. We also tested the feasibility of using this App in clinical practice. METHODS: Based on 2019 European Society of Cardiology/European Association for the Study of Diabetes criteria for cardiovascular risk stratification in T2DM, the AWARE App classifies patients into very high (VHCVR), high (HCVR) and moderate (MCVR) cardiovascular risk categories. In this retrospective clinical study, we employed the App to assess the cardiovascular risk of T2DM patients, while also collecting data about current glycaemic control and pharmacological treatment. RESULTS: 2243 T2DM consecutive patients were evaluated. 72.2% of the patients were VHCVR, 8.9% were HCVR, 0.8% were MCVR while 18.2% did not fit into any of the risk categories and were classified as "moderate-to-high" (MHCVR). Compared with the other groups, patients with VHCVD were more frequently ≥ 65 years old (68.9%), with a longer disease duration (≥ 10 years [56.8%]), a history of cardiovascular disease (41.4%), organ damage (35.5%) and a higher numbers of cardiovascular risk factors. Patients with MHCVD generally had disease duration < 10 years (96%), younger age (50-60 years [55%]), no history of cardiovascular disease, no organ damage, and 1-2 cardiovascular risk factors (89%). Novel drugs such as Glucagon Like Peptyde 1 Receptor Agonists or Sodium-Glucose Linked Transporter 2 inhibitors were prescribed only to 26.3% of the patients with VHCVR and to 24.7% of those with HCVR. Glycaemic control was unsatisfactory in this patients population (HbA1c 7.5 ± 3.4% [58.7 ± 13.4 mmol/mol]). CONCLUSIONS: The AWARE App proved to be a practical tool for cardiovascular risk stratification of T2DM patients in real-world clinical practice.

Once-weekly semaglutide use in patients with type 2 diabetes: Real-world data from the SURE Italy observational study.

AIMS: SURE Italy, a multicentre, prospective, open-label, observational, real-world study, investigated once-weekly semaglutide in patients with type 2 diabetes (T2D) in routine clinical practice. MATERIALS AND METHODS: Adults with T2D and ≥1 documented glycated haemoglobin (HbA1c) level within 12 weeks of semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Other endpoints included changes in body weight, waist circumference and patient-reported outcomes, and the proportion of patients achieving HbA1c <7.0% or <6.5%, weight loss ≥5% and a post-hoc composite endpoint (HbA1c reduction of ≥1%-point and weight loss ≥5%). These endpoints were reported for patients on semaglutide at EOS [effectiveness analysis set (EAS)]. Safety data were reported in the full analysis set. RESULTS: Of 579 patients who initiated semaglutide (full analysis set), 491 completed the study on treatment (EAS). Mean baseline HbA1c was 8.0%, and 20.7% (120 of 579) of patients had HbA1c <7.0%. Mean semaglutide dose at EOS was 0.66 ± 0.28 mg. In the EAS, mean HbA1c and body weight decreased by 1.1%-point (95% confidence interval 1.20, 1.05; P < .0001) and 4.2 kg (95% confidence interval 4.63, 3.67; P < .0001), respectively. At EOS, 61.7% and 40.8% of patients achieved HbA1c <7.0% and <6.5%, respectively, 40.5% achieved weight loss ≥5% and 25.3% achieved the post-hoc composite endpoint. Patient-reported outcomes improved from baseline to EOS. No new safety concerns were identified. CONCLUSIONS: In routine clinical practice in Italy, patients with T2D treated with once-weekly semaglutide for 30 weeks achieved clinically significant improvements in HbA1c, body weight and other outcomes.

SGLT2-inhibitors are effective and safe in the elderly: The SOLD study.

BACKGROUND AND AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) may have important benefits for the elderly with type 2 diabetes (T2D), however some safety concerns still limit their use in patients over 70 years of age. The SOLD study (SGLT2i in Older Diabetic patients) is a multicenter study, aimed to evaluate the effectiveness and safety of SGLT2i in the older diabetic patients in a real-life setting. MATERIALS AND METHODS: We analyzed a population of 739 adults (mean age 75.4 ± 3.9 years, M/F 420/319) with T2D, which started a SGLT2i-based treatment after the age of 70, with at least one year of follow-up. Data were collected at baseline, at 6 and 12 months of follow-up. RESULTS: SGLT2i (37.5% Empagliflozin, 35.7% Dapagliflozin, 26.1% Canagliflozin, 0.7% Ertugliflozin) were an add-on therapy to Metformin in 88.6%, to basal insulin in 36.1% and to other antidiabetic drugs in 29.6% of cases. 565 subjects completed the follow up, while 174 (23.5%) discontinued treatment due to adverse events which were SGLT2i related. A statistically significant reduction of glycated hemoglobin (baseline vs 12 months: 7.8 ± 1.1 vs 7.1 ± 0.8%, p < 0.001) and body mass index values (baseline vs 12 months: 29.2 ± 4.7 vs 28.1 ± 4.5 kg/m2, p < 0.001) were evident during follow-up. Overall, estimated glomerular filtration rate remained stable over time, with significant reduction of urinary albumin excretion. In the subgroup of patients which were ≥ 80 years, a significant improvement in glycated hemoglobin values without renal function alterations was evident. Overall discontinuation rate during the follow-up period was different across age groups, being urinary tract infections and worsening of renal function the most common cause. CONCLUSION: SGLT2i are well-tolerated and safe in the elderly and appear as an effective therapeutic option, though some caution is also suggested, especially in more fragile subjects.

Dapagliflozin acutely improves kidney function in type 2 diabetes mellitus. The PRECARE study.

Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (-0.6 ± 1.8%) as well as in BMI (-1.5 ± 5.2 kg/m2). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D.

The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists.

In the last few years, a great interest has emerged in investigating the pleiotropic effects of Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs). While GLP-1RAs ability to lower plasma glucose and to induce weight loss has allowed them to be approved for the treatment of diabetes and obesity, consistent evidences from in vitro studies and preclinical models suggested that GLP-1RAs have anti-inflammatory properties and that may modulate the immune-system. Notably, such anti-inflammatory effects target different pathways in different tissues, underling the broad spectrum of GLP-1RAs actions. This review examines some of the currently proposed molecular mechanisms of GLP-1RAs actions and explores their potential benefits in reducing inflammatory responses, which may well suggest a future therapeutic use of GLP-1RAs in new indications.

Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (i) reduce cardiovascular and renal events in patients with and without type 2 diabetes (T2D). However, the underlying mechanisms are debated. Low-grade inflammation (LGI) is a key driver of vascular complications, suggested to be attenuated by SGLT-2i in animal models. Based on a specific working hypothesis, here we investigated the net effect of SGLT-2i on LGI in patients with T2D and the possible underlying mechanism. We enrolled patients with T2D treated either with a stable therapy with SGLT-2i or with other glucose-lowering drugs (GLD) (n = 43 per group after matching for a range of pro-inflammatory variables), and tested hs-CRP and interleukin (IL)-6 as primary variables of interest. Patients treated with SGLT-2i had lower circulating levels of IL-6, a prototypical marker of LGI, but also of uric acid and fasting insulin, compared with patients treated with other GLD. Then, to explore whether uric acid and insulin might mediate the effect of SGLT-2i on IL-6, we tested physiologically pertinent doses of these two molecules (i.e. 0.5 mM uric acid and 1 nM insulin) in two in vitro models of LGI, i.e. monocytes (THP-1) treated with LPS and endothelial cells (HUVEC) exposed to hyperglycaemia. Results from in vitro models supported a pro-inflammatory role for uric acid and its combination with insulin in monocytes and for uric acid alone in hyperglycaemia-stimulated endothelial cells. On the contrary, we observed no drug-intrinsic, anti-inflammatory effect for dapagliflozin, empagliflozin, and canagliflozin in the same models. Overall, these results suggest that SGLT-2i possess a tangible activity against LGI, an effect possibly mediated by their ability to lower uric acid and insulin concentrations and that juxtaposes other proposed mechanisms in explaining the observed benefit of this class on cardiovascular and renal endpoints.

Immunogenicity and Safety of SARS-CoV-2 mRNA Vaccines in a Cohort of Patients With Type 1 Diabetes.

Patients with type 1 diabetes (T1D) may develop severe outcomes during coronavirus disease 2019 (COVID-19), but their ability to generate an immune response against the SARS-CoV-2 mRNA vaccines remains to be established. We evaluated the safety, immunogenicity, and glycometabolic effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in patients with T1D. A total of 375 patients (326 with T1D and 49 subjects without diabetes) who received two doses of the SARS-CoV-2 mRNA vaccines (mRNA-1273, BNT162b2) between March and April 2021 at ASST Fatebenefratelli Sacco were included in this monocentric observational study. Local and systemic adverse events were reported in both groups after SARS-CoV-2 mRNA vaccination, without statistical differences between them. While both patients with T1D and subjects without diabetes exhibited a parallel increase in anti-SARS-CoV-2 spike titers after vaccination, the majority of patients with T1D (70% and 78%, respectively) did not show any increase in the SARS-CoV-2-specific cytotoxic response compared with the robust increase observed in all subjects without diabetes. A reduced secretion of the T-cell-related cytokines interleukin-2 and tumor necrosis factor-α in vaccinated patients with T1D was also observed. No glycometabolic alterations were evident in patients with T1D using continuous glucose monitoring during follow-up. Administration of the SARS-CoV-2 mRNA vaccine is associated with an impaired cellular SARS-CoV-2-specific cytotoxic immune response in patients with T1D.

Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01).

Introduction: Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D). Methods: This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated. Results: Overall, 594 patients (97% GLP-1RA naïve) were identified (mean age 63.9 ± 9.5 years, 58.7% men, diabetes duration 11.4 ± 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDL-cholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001). Discussion: The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of ß-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D.

Obesity Is Strongly Associated With Low Testosterone and Reduced Penis Growth During Development.

CONTEXT: Growth of male genitalia represents an important marker of sexual development. Testicle size is the primary measure and little is known regards penile length changes during puberty. OBJECTIVE: This work aims to assess penis growth and testosterone levels in obese vs normal-weight children and adolescents, to evaluate a possible influence of obesity on genital development in boys, and to establish a new method for measuring penis length that allows comparison of normal-weight and overweight boys. METHODS: We assessed anthropometric and genital development in 1130 boys from birth to age 20 years. Testosterone levels were also measured. A new method for penile length measurement was employed to minimize errors when comparing obese and nonobese children. Penis length was measured with a gentle, painless, straight positioning on a centimetric ruler without stretching, which is doable from the first years of life until the end of adolescence. RESULTS: Penis length and testosterone are strongly related in children during puberty. Penile length growth is significantly decreased (by about 10%) in obese boys when compared to normal-weight boys, with concomitantly reduced testosterone levels, across puberal phases. CONCLUSION: Childhood obesity represents an important determinant of lower testosterone level and reduced penis development. A new method should be employed to improve penis measurement in normal-weight and overweight/obese boys. The possible significance of these observations for adult genital development and reproductive potential will require large longitudinal studies.

Anti-diabetic drugs and weight loss in patients with type 2 diabetes.

INTRODUCTION: Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in patients with type 2 diabetes, but lifestyle-based weight loss strategies are not long-term effective. There is an increasing need to consider pharmacological approaches to assist weight loss in the so called diabesity syndrome. Aim of this review is to analyze the weight-loss effect of non-insulin glucose lowering drugs in patients with type 2 diabetes. MATERIAL AND METHODS: A systematic analysis of the literature on the effect of non-insulin glucose lowering drugs on weight loss in patients with type 2 diabetes was performed. For each class of drugs, the following parameters were analyzed: kilograms lost on average, effect on body mass index and body composition. RESULTS: Our results suggested that anti-diabetic drugs can be stratified into 3 groups based on their efficacy in weight loss: metformin, acarbose, empagliflozin and exenatide resulted in a in a mild weight loss (less than 3.2% of initial weight); canagliflozin, ertugliflozin, dapagliflozin and dulaglutide induces a moderate weight loss (between 3.2% and 5%); liraglutide, semaglutide and tirzepatide resulted in a strong weight loss (greater than 5%). CONCLUSIONS: This study shows that new anti-diabetic drugs, particularly GLP1-RA and Tirzepatide, are the most effective in inducing weight loss in patients with type 2 diabetes. Interestingly, exenatide appears to be the only GLP1-RA that induces a mild weight loss.

Telemedicine and urban diabetes during COVID-19 pandemic in Milano, Italy during lock-down: epidemiological and sociodemographic picture.

BACKGROUND: Since 2010, more than half of World population lives in Urban Environments. Urban Diabetes has arisen as a novel nosological entity in Medicine. Urbanization leads to the accrual of a number of factors increasing the vulnerability to diabetes mellitus and related diseases. Herein we report clinical-epidemiological data of the Milano Metropolitan Area in the contest of the Cities Changing Diabetes Program. Since the epidemiological picture was taken in January 2020, on the edge of COVID-19 outbreak in the Milano Metropolitan Area, a perspective addressing potential interactions between diabetes and obesity prevalence and COVID-19 outbreak, morbidity and mortality will be presented. To counteract lock-down isolation and, in general, social distancing a pilot study was conducted to assess the feasibility and efficacy of tele-monitoring via Flash Glucose control in a cohort of diabetic patients in ASST North Milano. METHODS: Data presented derive from 1. ISTAT (National Institute of Statistics of Italy), 2. Milano ATS web site (Health Agency of Metropolitan Milano Area), which entails five ASST (Health Agencies in the Territories). A pilot study was conducted in 65 screened diabetic patients (only 40 were enrolled in the study of those 36 were affected by type 2 diabetes and 4 were affected by type 1 diabetes) of ASST North Milano utilizing Flash Glucose Monitoring for 3 months (mean age 65 years, HbA1c 7,9%. Patients were subdivided in 3 groups using glycemic Variability Coefficient (VC): a. High risk, VC > 36, n. 8 patients; Intermediate risk 20 < VC < 36, n. 26 patients; Low risk VC < 20, n. 4 patients. The control group was constituted by 26 diabetic patients non utilizing Flash Glucose monitoring. RESULTS: In a total population of 3.227.264 (23% is over 65 y) there is an overall prevalence of 5.65% with a significant difference between Downtown ASST (5.31%) and peripheral ASST (ASST North Milano, 6.8%). Obesity and overweight account for a prevalence of 7.8% and 27.7%, respectively, in Milano Metropolitan Area. We found a linear relationship (R = 0.36) between prevalence of diabetes and aging index. Similarly, correlations between diabetes prevalence and both older people depending index and structural dependence index (R = 0.75 and R = 0.93, respectively), were found. A positive correlation (R = 0.46) with percent of unoccupied people and diabetes prevalence was also found. A reverse relationship between diabetes prevalence and University level instruction rate was finally identified (R = - 0.82). Our preliminary study demonstrated a reduction of Glycated Hemoglobin (p = 0.047) at 3 months follow-up during the lock-down period, indicating Flash Glucose Monitoring and remote control as a potential methodology for diabetes management during COVID-19 lock-down. HYPOTHESIS AND DISCUSSION: The increase in diabetes and obesity prevalence in Milano Metropolitan Area, which took place over 30 years, is related to several environmental factors. We hypothesize that some of those factors may have also determined the high incidence and virulence of COVID-19 in the Milano area. Health Agencies of Milano Metropolitan Area are presently taking care of diabetic patients facing the new challenge of maintaining sustainable diabetes care costs in light of an increase in urban population and of the new life-style. The COVID-19 pandemic will modify the management of diabetic and obese patients permanently, via the implementation of approaches that entail telemedicine technology. The pilot study conducted during the lock-down period indicates an improvement of glucose control utilizing a remote glucose control system in the Milano Metropolitan Area, suggesting a wider utilization of similar methodologies during the present "second wave" lock-down.

Switching Patients with Type 1 Diabetes to Insulin Degludec from Other Basal Insulins: Real-World Data of Effectiveness and Safety.

INTRODUCTION: Real-world evidence on the effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. We have therefore evaluated the effectiveness and safety of IDeg, including impact on metabolic control, glycemic variability, weight gain and hypoglycemia, in patients with type 1 diabetes under routine clinical practice conditions. METHODS: This was an observational longitudinal multicenter study. A retrospective chart review of all patients with type 1 diabetes who were switched from basal insulin to IDeg was performed, and temporal trends in clinical outcomes were assessed. RESULTS: Data obtained from 195 patients, with a median age of 42.8 [interquartile range (IQR) 24.6-56.4] years and a median diabetes duration of 16 (IQR 10.0-28) years, were analyzed. Median follow-up was 9.5 (IQR 7.7-11.3) months. Improvements were found in glycated hemoglobin (- 0.34%; p < 0.0001), fasting blood glucose (- 24.82 mg/dL; p < 0.0001), post-prandial glucose (- 17.23 mg/dL; p = 0.0009), glycemic variability as indicated by standard deviation of blood glucose (- 5.67 mg/dL; p < 0.0001) and high blood glucose index (- 3.77; p < 0.0001). Body weight and body mass index remained substantially stable during the follow-up (- 0.18 kg; p = 0.56 and - 0.12; p = 0.42, respectively). Risk of nocturnal hypoglycemia decreased by 52% [incidence rate ratio 0.48; 95% confidence interval (CI) 0.29-0.77] and risk of total hypoglycemic episodes by 41% (incidence ratio 0.59; 95% CI 0.45-0.83). Basal and short-acting insulin doses decreased by - 1.4 and - 3.1 IU, respectively. CONCLUSION: Switching patients with type 1 diabetes to IDeg from other basal insulins was associated with relevant improvements in metabolic control and glycemic variability without weight gain; the risk of hypoglycemic episodes also significantly declined. FUNDING: Novo Nordisk S.p.A. unconditional grant.

Hypoglycemia and hyperglycemia are risk factors for falls in the hospital population.

OBJECTIVE: To determine the role of hypoglycemia, hyperglycemia or the combination of both as independent risk factors for falls in a hospital population. Secondary objectives included evaluation of other risk factors for falling and their relationships with glucose levels. RESEARCH DESIGN AND METHODS: Retrospective cohort study over 2 years on hospitalized subjects (N = 57411) analyzing in-hospital-falls and capillary glucose values. Bivariate analysis (χ2 test) and multivariate analysis (logistic regression) were performed to test for correlation of glucose values, age, sex, Charlson index, service of care, diagnosis at discharge and diabetes treatment with risk of in-hospital-falls. RESULTS: The comparison of patients who experienced a fall (fall population) with the non-fall population suggested that: glucose determinations were significantly more frequent in the fall population (OR 3.45; CI 2.98-3.99; p < 0.0001); values of glucose below 70 mg/dl and over 200 mg/dl were significantly associated to falls during hospitalization (OR 1.76; CI 1.42-2.19; p < 0.001) as compared to glycemic values between 70 and 200 mg/dl; diabetes treatment was significantly correlated to risk of fall (OR 2.97; CI 2.54-3.49; p < 0.001); the frequency of glycemia measurements below 70 mg/dl and over 200 mg/dl in the same subject was significantly associated to falls during hospitalization (OR 1.01; CI 1.01-1.02; p < 0.001). CONCLUSION: Hypoglycemia and hyperglycemia during hospital stays are correlated with an increased risk for falls in the hospitalized population. Presence of diabetes, use of insulin or glucose variability could potentially constitute risk factors for falls inside the hospital as well.

Multiple target tissue effects of GLP-1 analogues on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Accumulating experimental and clinical evidences over the last decade indicate that GLP-1 analogues have a series of central nervous system and peripheral target tissues actions which are able to significantly influence the liver metabolism. GLP-1 analogues pleiotropic effects proved to be efficacious in T2DM subjects not only reducing liver steatosis and ameliorating NAFLD and NASH, but also in lowering plasma glucose and liver inflammation, improving cardiac function and protecting from kidney dysfunction. While the experimental and clinical data are robust, the precise mechanisms of action potentially involved in these protective multi-target effects need further investigation. Here we present a systematic review of the most recent literature data on the multi-target effects of GLP-1 analogues on the liver, on adipose and muscular tissue and on the nervous system, all capable of influencing significant aspects of the fatty liver disease physiopathology. From this analysis, we can conclude that the multi-target beneficial action of the GLP-1 analogues could explain the positive effects observed in animal and human models on progression of NAFLD to NASH.

Impact of Insulin Degludec in Type 2 Diabetes: Real-World Data on Effectiveness and Safety.

INTRODUCTION: Real-world evidence on effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. The aim of the study was to evaluate patterns of use and the long-term effectiveness and safety of IDeg in routine clinical practice. METHODS: This was an observational longitudinal study. A retrospective chart review of all patients with type 2 diabetes treated with IDeg was performed and temporal trends in clinical outcomes were assessed. All data was stratified by treatment modality: the switch group consisted of patients already treated with another basal insulin before initiating IDeg; the add-on group consisted of basal insulin-naïve patients. RESULTS: Overall, 247 patients were analyzed (55 in the add-on group and 192 in the switch group), mean age 67.0 ± 10.9 years ,and diabetes duration 16.3 ± 8.9 years. Median (interquartile range) follow-up was 9.7 (8.0-11.9) months. In the add-on group, improvements were found in glycated hemoglobin (HbA1c) (- 1.68%; p < 0.0001), fasting blood glucose (FBG) (- 64.7 mg/dL; p < 0.0001), post-prandial glucose (PPG) (- 81.1 mg/dl; p < 0.0001), and glycemic variability (i.e., standard deviation of blood glucose) (- 11.6 mg/dl; p = 0.04). Even in the switch group, improvements were found in HbA1c (- 0.57%; p < 0.0001), FBG (- 28.1 mg/dL; p < 0.0001), and PPG (- 22.6 mg/dl; p = 0.001). Body weight increase during the follow-up was not statistically significant vs. baseline in both groups. Benefits on overall, nocturnal, and severe hypoglycemia were found in the switch group. CONCLUSION: These real-world data documented that initiating IDeg or switching to IDeg from other basal insulins in type 2 diabetes was associated with significant improvement in metabolic control without significant weight gain; a decrease in the risk of hypoglycemia was observed when switching to IDeg from another basal insulin.