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.

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.

Liraglutide and cardiovascular outcomes in a real world type 2 diabetes cohort.

In the last years, due to new regulatory guidelines requiring a stringent documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes, cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the knowledge about the safety profile of the new drugs, but they have intrinsic limits that make difficult their transferability to clinical practice. For this reason, real world evidence is considered an important complement to experimental data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the LEADER CVOT demonstrated superiority in reducing the risk of major CV events (MACEs) vs. placebo. We conducted an observational, retrospective, longitudinal study based on 307 patients with T2DM treated with liraglutide under routine clinical practice conditions. Real world impact of liraglutide on metabolic control, CV risk factors, hypoglycemia and CV events was assessed. Improvements during 36 months were found in HbA1c (-1.0%; p < 0.0001), fasting blood glucose (-17.6 mg/dL; p < 0.0001), body weight (-3.2 kg; p < 0.0001), waist circumference (-1.45 cm; p = 0.004), systolic blood pressure (-10.41 mmHg; p < 0.0001), diastolic blood pressure (-3.69 mmHg; p < 0.0001), total cholesterol (-7.96 mg/dL; p =0.008) and triglycerides (-20.60 mg/dl; p = 0.01). No severe hypoglycemia occurred. Incidence of MACEs in this cohort was lower than in the LEADER study (2.59 vs. 3.4 events per 100 person-years), confirming CV safety of liraglutide even in the real world. On the other hand, a higher incidence of CV event in patients with established CV disease was documented (8.1 events per 100 person-years), in spite of the use of liraglutide. In conclusion, 36-month durability and CV safety of liraglutide were documented in a real world cohort of T2DM patients, with sustained benefits on a large array of CV risk factors.