Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

[Anti-diabetics and chronic kidney disease]

Diabetes mellitus (DM) is the most important non-communicable disease after hypertension. Prevalence of type 2 DM has progressively increased over the last decades. In Italy, 11.8% of the general adult population can be identified as diabetic. The major complication of DM is diabetic nephropathy (DM-CKD), which develops in approximately one-third of diabetics. Achieving optimal glycemic control is the first therapeutic goal in the management of DM-CKD. In recent years, new antidiabetic drugs have been marketed (GLP1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors) to ameliorate glycemia in patients nave or treated by means of traditional agents, such as sulfonylureas, metformin, glinides, insulin. However, use of these drugs in DM-CKD should be evaluated carefully, mainly because of the higher risk of hypoglycemia that requires dosing adjustments. Metformin still represents an adequate choice if proper dose adjustments are made on the basis of renal function. Sulfonylureas with limited renal clearance, i.e., gliquidone, glipizide and gliclazide are an alternative to metformin and more effective than repaglinide on glycemic control. Other antidiabetic agents with potential nephroprotective effects, namely DPP-4 inhibitors, incretin analogues and SGLT-2 inhibitors, may allow nephroprotective effects independent of glycemic control. Insulin remains the cornerstone of therapy when oral therapy is no longer effective

Premature aging in Werner's syndrome spares the central nervous system

Werner's Syndrome is a rare genetic disease, characterized by premature aging of many tissues and organs. We studied the brain morphology and function in two patients with Werner's syndrome to assess the possible involvement of the central nervous system in this premature aging process. The two patients (brother and sister, respectively) were studied by magnetic resonance imaging (MRI) and angiography (MRA), single photon emission computed tomography (SPECT) with (99mTc)-d,l-hexamethyl propilene amine oxime (HMPAO), positron emission tomography (PET) with 2(18F)-Fluoro-2-deoxyglucose (FDG), electroencephalography (EEG), and electromyography (EMG). Some of these investigations were also repeated after 1 year. The results of all these studies were normal. The premature aging process in patients with Werner's syndrome, while affecting most tissues, seems to spare the central nervous syste

Nephroprotection with saxagliptin

The nephroprotective effect of the new anti-diabetic drugs acting on incretin system is suggested by preclinical studies. However, no study evaluating kidney effects of these drugs as primary outcome on the long term has been conducted in patients followed in diabetes centers. We designed a pilot observational study involving two diabetes clinics to evaluate the effect of prolonged treatment with saxagliptin on renal function in type 2 diabetics. Patients were enrolled if treated for at least 12 months with saxagliptin without concurrent changes to anti-hypertensive and lipid-lowering therapy. Primary outcome was to evaluate the effect of saxagliptin on albuminuria and estimated glomerular filtration rate (eGFR). Secondary outcomes were the effects of treatment on common clinical and laboratory parameters. Sixty-three patients were enrolled. After 12 months of treatment with saxagliptin, albuminuria declined from a mean (95%CI) of 39 (25-52) to 22 (14-30) mg/l (P<0.001), and the prevalence of increased albuminuria (>20 mg/L) diminished by 27% versus baseline. The anti-albuminuric effect was independent of glycemic and blood pressure control. The eGFR remained unchanged after treatment in the presence of decreased glycated hemoglobin (from 7.1 to 6.7%). Therefore, this pilot study suggests that saxagliptin treatment in diabetic patients at high renal risk is associated with a reduction in albuminuria and GFR stability. Prospective trials are required to confirm the potential nephroprotective effects of saxagliptin