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.

A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma.

Pheochromocytoma (Pheo) is a chromaffin tumor arising from the adrenal medulla. The recent discovery of new germline mutations in RET, SDHA, SDHB, SDHC, SDHD, VHL, NF1, TMEM127, MAX genes, increased the rate of genetic disease from 10% to 28% in patients with apparently sporadic tumor. RET germline mutations cause multiple endocrine neoplasia type 2 syndrome (MEN 2A) characterized by complete penetrance of medullary thyroid cancer (MTC), and lower prevalence of Pheo and hyperparathyroidism. We describe the genetic etiology of an apparently sporadic case of monolateral Pheo in a 42-year-old male patient. A new (not previously reported) MEN 2A-associated germline RET mutation located in exon 11 (Glu632Gly, caused by an A>G point mutation at position 1895 of the RET cDNA) was found in the patient but not in his living first-degree relatives. This observation increases the number of possible germline RET mutations. Genotype-phenotype correlation of this new genetic alteration is unknown, but this rare mutation is probably associated with a low risk for MTC (usually the first tumor diagnosed in MEN 2A syndrome) and with the development of Pheo before the onset of MTC. Since we expect MTC to occur in our patient, strict follow-up is mandatory. Our findings emphasize the relevance of genetic testing in patients with Pheo, especially when the clinical presentation (family history, young age at diagnosis, multiple locations, malignant lesions, and bilateralism) is suggestive.

Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease.

CONTEXT: We previously reported that differentiated thyroid cancer (DTC) has higher aggressiveness and poorer prognosis in patients with Graves' disease (GD) than DTC in euthyroid control patients. Subsequent studies on this issue reached controversial conclusions. Genetic and environmental factors, as well as the lack of appropriate control subjects and/or inadequate patient follow-up, may account for these discrepancies. OBJECTIVE: The aim of this study was to investigate the long-term disease-specific mortality of nonoccult DTCs occurring in patients with GD compared with DTCs in matched euthyroid control patients. PATIENTS AND DESIGN: The previously described cohorts of nonoccult DTCs occurring in either patients with GD (DTC-GD, n = 21) or matched euthyroid DTC control patients (n = 70) were compared again after a longer follow-up (50-363.6 months; median, 165.6 months) to compare the major clinical endpoints of persistent/recurrent disease and overall survival. Both cohorts were recruited in 1982-1994 at a single institution. All patients had undergone total thyroidectomy and were followed up according to a standardized protocol. RESULTS: Persistent/recurrent disease was more frequent in DTC-GD patients than in control patients (P = .0119). Disease-specific mortality was also significantly higher in DTC-GD patients (6 of 21, 28.6%) than in euthyroid control patients (2 of 70, 2.9%) (P = .0001). At the last visit, the percentage of disease-free patients was 57.1% (12 of 21) in the DTC-GD group vs 87.1% (61 of 70) in the control group (P = .0025). CONCLUSIONS: Nonoccult DTCs occurring in patients with GD cause increased disease-specific mortality compared with DTCs in matched euthyroid control patients. These findings emphasize the need for early diagnosis and aggressive treatment of nonoccult DTCs in patients with GD.