Real-world use of oral versus subcutaneous semaglutide in a cohort of type 2 diabetic patients: which option to which patient?

PURPOSE: To evaluate the variables influencing the therapeutic choice toward oral versus subcutaneous semaglutide in a cohort of diabetic subjects. METHODS: We retrospectively collected data of 292 patients followed at the Diabetes Unit of the University Hospital of Siena and the Hospital of Grosseto, who were prescribed oral (n = 115) or subcutaneous (n = 177) semaglutide between October 2021 and October 2022. RESULTS: Oral semaglutide was preferentially prescribed in older subjects with longer disease duration in replacement of other antidiabetic drugs, while subcutaneous semaglutide was preferentially prescribed in add-on to metformin in subjects with higher body weight and BMI. After 6 months, both formulations significantly improved glycemic control and body weight, however injectable semaglutide showed a greater efficacy on A1c levels, weight loss, BMI and waist circumference reduction. No differences were found in terms of adverse events. CONCLUSION: In our experience, injectable semaglutide is preferred in patients with excess weight and shorter disease duration, while the oral formulation was used later and especially after therapeutic failure of previous therapies. Follow-up data indicate similar tolerability and efficacy of both formulations, despite subcutaneous semaglutide demonstrated greater efficacy.

Dapagliflozin modulates glucagon secretion in an SGLT2-independent manner in murine alpha cells.

AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin. Data were validated in murine and human pancreatic islets. RESULTS: SLC5A2 (the SGLT2-encoding gene) was nearly undetectable in αTC1 cells, not even by a digital PCR technique using different probes. In contrast, SLC5A1 (the SGLT1-encoding gene) was constitutively abundant in αTC1 cells and in islets, and increased with Dapa. This was associated with greater glucagon release, preceded by increased expression of preproglucagon and HNF4α. Looking at the candidate intracellular signalling pathway, reduced PASK and increased AMPK-α2 expression were also detected. GLUT1 and GLUT2, as well as regulators of glucagon release and alpha-cell phenotype (chromogranin A, paired box 6, proprotein convertase 1/2, synaptophysin), were unaffected by Dapa, as were GLP-1 receptor expression and GLP-1 release. Low glucose did not influence the stimulatory effect of Dapa on glucagon release, but was instead almost fully reverted by SLC5A1 silencing. When the effect of Dapa on AMPK and PASK, emerging regulators of lipid and glucose metabolism, was tested, upregulated AMPK-α2 appeared to be involved in molecular signalling. CONCLUSION: Our study has shown that, in αTC1 cells, Dapa acutely upregulates SGLT1 expression and increases glucagon release through an SGLT1-dependent mechanism, with SGLT2 expression virtually undetectable. These results suggest the involvement of SGLT1 in modulating glucagon increases following SGLT2 inhibition.

Circulating microRNAs and diabetes mellitus: a novel tool for disease prediction, diagnosis, and staging?

Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility. Recently, a new class of endogenous non-coding small RNAs, namely microRNAs, have been indicated as putative biomarkers, being released by cells and tissues and found in a cell-free circulating form in many biological fluids, including serum and/or plasma. MicroRNAs have been initially identified as promising biomarkers in cancer, and nowadays their application has been extended to other diseases, including diabetes. Although an increasing number of studies focused on the evaluation of circulating microRNAs in diabetes, few reproducibly identified microRNAs as biomarkers for disease prediction or follow-up. Technological problems as well as the need to obtain highly standardized operating procedures and methods are still an issue in such research field. In this review, we comprehensively resume the main and most recent findings on circulating microRNAs, and their possible use as biomarkers to predict and follow-up diabetes and its complications, as well as the methodological challenges to standardize accurate operating procedures for their analysis.

Grade 2 urethroprostatic papillary urothelial carcinoma with positive urinary cytology.

A rare case of papillary urothelial grade 2 carcinoma of the prostate and urethra in a patient with a previous papillary neoplasm of the bladder is reported. The tumor caused hematuria and prostatic enlargement suspicious for cancer. Urinary cytology was diagnostic.