Optimizing glycemic control: clinical utility of exenatide prolonged release injection

Giuseppe Derosa, Pamela MaffioliDepartment of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S Matteo, Pavia, ItalyAbstract: Despite the large variety of antidiabetic drugs currently available, reaching an adequate glycemic control is still difficult. Recently, a new exenatide long acting release (LAR) formulation, which can be administered once a week, has been released. We conducted a review analyzing the clinical utility of this new formulation and its place in antidiabetic therapy, and included the most important studies about exenatide LAR in the latest 10 years. A systematic search strategy was developed to identify randomized controlled trials in both MEDLINE and the Cochrane Register of Controlled Trials. The terms "exenatide," "exenatide long active release," "GLP-1 agonists," "incretins," and "glycemic control" were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. We concluded that exenatide LAR can be a valid option for the treatment of type 2 diabetes mellitus because it showed to be effective in reducing HbA1c, and because of its pleiotropic effects, such as the reduction of blood pressure, the improvement of the patient's lipid profile, and the positive effects on body weight and β-cell function. Moreover, exenatide LAR has demonstrated a favorable cost/effectiveness ratio, and its once weekly administration may help to increase patient compliance.Keywords: β-cell, body weight, exenatide long acting release, glycemic contro

Optimizing glycemic control: clinical utility of exenatide prolonged release injection

Giuseppe Derosa, Pamela MaffioliDepartment of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S Matteo, Pavia, ItalyAbstract: Despite the large variety of antidiabetic drugs currently available, reaching an adequate glycemic control is still difficult. Recently, a new exenatide long acting release (LAR) formulation, which can be administered once a week, has been released. We conducted a review analyzing the clinical utility of this new formulation and its place in antidiabetic therapy, and included the most important studies about exenatide LAR in the latest 10 years. A systematic search strategy was developed to identify randomized controlled trials in both MEDLINE and the Cochrane Register of Controlled Trials. The terms “exenatide,” “exenatide long active release,” “GLP-1 agonists,” “incretins,” and “glycemic control” were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. We concluded that exenatide LAR can be a valid option for the treatment of type 2 diabetes mellitus because it showed to be effective in reducing HbA1c, and because of its pleiotropic effects, such as the reduction of blood pressure, the improvement of the patient's lipid profile, and the positive effects on body weight and β-cell function. Moreover, exenatide LAR has demonstrated a favorable cost/effectiveness ratio, and its once weekly administration may help to increase patient compliance.Keywords: β-cell, body weight, exenatide long acting release, glycemic contro

COVID-19 and surgical training in Italy: Residents and young consultants perspectives from the battlefield

COVID-19 is seriously affecting Italy, putting the health system under extreme pressure. Training of medical students and residents is also suffering from this with the suspension of lectures and clinical rotations. What solutions have been taken to deal with the issue

Proteomic Analysis Reveals a Mitochondrial Remodeling of βTC3 Cells in Response to Nanotopography

Recently, using cluster-assembled zirconia substrates with tailored roughness produced by supersonic cluster beam deposition, we demonstrated that \u3b2 cells can sense nanoscale features of the substrate and can translate these stimuli into a mechanotransductive pathway capable of preserveing \u3b2-cell differentiation and function in vitro in long-term cultures of human islets. Using the same proteomic approach, we now focused on the mitochondrial fraction of \u3b2TC3 cells grown on the same zirconia substrates and characterized the morphological and proteomic modifications induced by the nanostructure. The results suggest that, in \u3b2TC3 cells, mitochondria are perturbed by the nanotopography and activate a program involving metabolism modification and modulation of their interplay with other organelles. Data were confirmed in INS1E, a different \u3b2-cell model. The change induced by the nanostructure can be pro-survival and prime mitochondria for a metabolic switch to match the new cell needs

Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low-, intermediate-1-, intermediate-2-, and high-risk myelofibrosis in JUMP, a Phase 3b, expanded-access study

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, has demonstrated durable improvements in patients with myelofibrosis. In this analysis of the Phase 3b JUMP study, which included patients aged =18 years with a diagnosis of primary or secondary myelofibrosis, we assessed the safety and efficacy of ruxolitinib in patients stratified by Dynamic International Prognostic Scoring System (DIPSS) risk categories. Baseline characteristic data were available to assess DIPSS status for 1844 of the 2233 enrolled patients; 60, 835, 755, and 194 in the low-, intermediate (Int)-1-, Int-2-, and high-risk groups, respectively. Ruxolitinib was generally well tolerated across all risk groups, with an adverse-event (AE) profile consistent with previous reports. The most common hematologic AEs were thrombocytopenia and anemia, with highest rates of Grade =3 events in high-risk patients. Approximately, 73% of patients experienced =50% reductions in palpable spleen length at any point in the =24-month treatment period, with highest rates in lower-risk categories (low, 82.1%; Int-1, 79.3%; Int-2, 67.1%; high risk, 61.6%). Median time to spleen length reduction was 5.1 weeks and was shortest in lower-risk patients. Across measures, 40%–57% of patients showed clinically meaningful symptom improvements, which were observed from 4 weeks after treatment initiation and maintained throughout the study. Overall survival (OS) was 92% at Week 72 and 75% at Week 240 (4.6 years). Median OS was longer for Int-2-risk than high-risk patients (253.6 vs. 147.3 weeks), but not evaluable in low-/Int-1-risk patients. By Week 240, progression-free survival (PFS) and leukemia-free survival (LFS) rates were higher in lower-risk patients (PFS: low, 90%; Int-1, 82%; Int-2, 46%; high risk, 15%; LFS: low, 92%; Int-1, 86%; Int-2, 58%; high risk, 19%). Clinical benefit was seen across risk groups, with more rapid improvements in lower risk patients. Overall, this analysis indicates that ruxolitinib benefits lower-risk DIPSS patients in addition to higher risk

Quercetin as a possible complementary agent for early-stage COVID-19: concluding results of a randomized clinical trial

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host’s hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04861298

effects of one year treatment of sibutramine on insulin resistance parameters in type 2 diabetic patients

Purpose. Comparison of the effects of one year treatment with sibutramine compared to placebo on body weight, glycemic control, lipid profile, and insulin resistance parameters in type 2 diabetic patients. Methods. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP). Results. We observed a faster improvement of HbA1c, FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups. Conclusions. Sibutramine gave a faster improvement of glycemic control, and of insulin resistance parameters compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight

Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus

Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women