Effects of Dapagliflozin Compared with Sitagliptin and Metformin in Drug-Naïve Japanese Patients with Type 2 Diabetes: A 12-Week, Open-Label, Randomized, Active-Controlled Trial.

INTRODUCTION: To compare the efficacy and tolerability of dapagliflozin with those of sitagliptin and metformin in patients with type 2 diabetes who have never received glucose-lowering agents. METHODS: In this randomized, 12-week, open-label, active-controlled trial, 32 patients were randomly assigned to receive dapagliflozin 5 mg, sitagliptin 50 mg, or metformin 1000 mg per day for 12 weeks. At baseline and at week 12, the patients underwent a meal tolerance test (MTT). RESULTS: After 12 weeks of treatment, the changes in fasting and postprandial plasma glucose and plasma glucose area under the curve (AUC)0-120 min levels during the MTT from baseline were significantly improved in the three study groups, and there were no significant differences among the three study groups (P < 0.05). The mean changes in glycated hemoglobin (HbA1c) from baseline to week 12 were - 0.96%, - 1.24%, and - 1.40% in the dapagliflozin, sitagliptin, and metformin groups, respectively. Although there was no significant difference among the three study groups, the lowering effect of HbA1c tended to be greater in the metformin group than in the dapagliflozin group. In contrast, the insulin AUC0-120 min levels at week 12 significantly decreased only in the dapagliflozin group (P = 0.049). Similarly, body weight was significantly reduced only in the dapagliflozin group (- 2.1 kg [- 2.7%], P = 0.047). Moreover, dapagliflozin significantly improved serum adiponectin levels (P = 0.003). However, there were no significant differences in the changes in these glycemic and metabolic parameters among the three study groups. No serious adverse events were documented in any group. CONCLUSIONS: Dapagliflozin exerted beneficial effects similar to sitagliptin and metformin on glycemic parameters. In addition, dapagliflozin significantly reduced body weight and insulin AUC levels and improved serum adiponectin levels. Therefore, we suggest that these three hypoglycemic agents could be viable first-line medications for drug-naïve Japanese patients with type 2 diabetes. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000024427).

Long-Term Effects of Ipragliflozin on Diabetic Nephropathy and Blood Pressure in Patients With Type 2 Diabetes: 104-Week Follow-up of an Open-Label Study.

BACKGROUND: In our previous study, we investigated the efficacy of ipragliflozin, a sodium-glucose cotransporter (SGLT) 2 inhibitor on diabetic nephropathy in patients with type 2 diabetes and demonstrated that ipragliflozin significantly improved diabetic nephropathy in addition to reducing HbA1c and body weight. Herein, we conducted post-trial monitoring to determine whether these lowering effects on blood glucose and body weight or the beneficial effects on diabetic nephropathy were maintained long-term (104 weeks) after starting ipragliflozin treatment. METHODS: Initially, during a 24-week interventional trial period, a 50 mg dose of ipragliflozin was administered to 50 patients with type 2 diabetes without changing other treatments. During the post-trial monitoring period, these patients returned to hospital-based diabetes care according to their clinical needs. We continued monitoring their clinical data for 104 weeks in each hospital and analyzed the results on an intention-to-treat basis. RESULTS: The improvements in glycemic control and body weight reduction provided by 24-week ipragliflozin administration were maintained for 104 weeks. Despite a transient decrease during the intervention period, the estimated glomerular filtration rate (eGFR) was restored to near the baseline level at 104 weeks. Notably, in patients with diabetic nephropathy, the median urinary albumin-to-creatinine ratio (UACR) was significantly decreased from 119.2 (98.9 - 201.8) at baseline to 36.9 (19.7 - 204.7) mg/gCr at 104 weeks. In addition, eGFR was stable for 104 weeks, showing no decrease. In contrast, a significant positive correlation between UACR and blood pressure observed at 24 weeks disappeared after discontinuation of the intervention therapy. CONCLUSIONS: The well-controlled HbA1c and body weight reductions were maintained for 104 weeks of post-trial follow-up. Moreover, ipragliflozin significantly reduced urinary albumin excretion in patients with diabetic nephropathy without decreasing eGFR.

Effects of Ipragliflozin on Diabetic Nephropathy and Blood Pressure in Patients With Type 2 Diabetes: An Open-Label Study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel agents used to treat type 2 diabetic patients. We investigated the efficacy of the SGLT2 inhibitor ipragliflozin on diabetic nephropathy in Japanese patients with type 2 diabetes. METHODS: A 50 mg dose of ipragliflozin was administered for 24 weeks to 50 patients with type 2 diabetes who were concomitantly managed with diet and exercise therapy alone or antidiabetic medications other than SGLT2 inhibitors. RESULTS: At the end of the 24-week ipragliflozin treatment, significant decreases in mean glycated hemoglobin (HbA1c) (1.0±1.2%) and body weight (2.7 ± 2.5 kg) were observed; in addition, median urinary albumin-to-creatinine ratio (UACR) significantly decreased from 15.5 (8.0 - 85.7) to 12.9 (7.4 - 36.3) mg/gCr. Sub-analysis by renal function at baseline revealed that median UACR in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 decreased significantly from 12.3 (7.5 - 89.6) to 10.6 (5.8 - 27.3) mg/gCr. Furthermore, mean eGFR decreased significantly from 102.4 ± 8.6 to 93.6 ± 10.5 mL/min/1.73 m2 in these patients. In contrast, UACR and eGFR did not change significantly in patients with eGFR < 90. In addition, analysis of the relationship between the amount of change in UACR and blood pressure at 24 weeks revealed a significant positive correlation between UACR and SBP values, independently of the presence of diabetic nephropathy. CONCLUSIONS: Our results indicate that ipragliflozin may facilitate HbA1c control and body weight reduction. Furthermore, our results also raise the possibility that ipragliflozin significantly reduces urinary albumin levels and improves glomerular hyperfiltration in a subset of patients with type 2 diabetes.

The efficacy of vildagliptin concomitant with insulin therapy in type 2 diabetic subjects.

BACKGROUND: In Japan, dipeptidyl peptidase 4 (DPP4) inhibitors have become standard therapeutic agents for type 2 diabetes, and numbers of patients receiving insulin therapy combined with DPP4 inhibitors, which is a highly effective regimen, are increasing. METHODS: In this study, we evaluated the efficacy of vildagliptin administered at the dose of 100 mg twice daily in 57 patients with type 2 diabetes already receiving insulin treatment. RESULTS: The 36 patients who simply received add-on vildagliptin showed a 0.6% decrease in HbA1c levels, despite a marked insulin dose reduction, mainly bolus insulin, of approximately 8.3 units. In addition, body mass index exhibited a significant negative correlation with the efficacy of vildagliptin, i.e., ΔHbA1c. On the other hand, the 21 patients switched from 50 mg of sitagliptin to vildagliptin showed HbA1c decreases approaching 0.7%. CONCLUSION: Taking into consideration that twice-daily oral vildagliptin has already been reported to be advantageous in reducing postprandial hyperglycemia, this drug was suggested to be more effective in reducing HbA1c than sitagliptin under conditions in which it is used as a supplement to basal insulin, as in this study.

Avaliação epidemiológica e operacional do programa de controle da hanseníase na região de São Carlos - SP.: No período de 1983/1988

Descreve-se e avalia-se, neste estudo, a situação da hansenfase na Região de São Carlos no período de 1983 a 1988. Discute-se os indicadores epidemiológicos e operacionais usuais do Programa de Controle da Hansenfase. Analisando-se o coeficiente de prevalência encontrado no período (1,24 a 1,26) verifica-se que a região apresenta uma alta endèmicidade e um médio coeficiente de detecção de casos (5,40 a 9,90) que encontra-se em gradativo declínio. Assim, observa-se que a hanseníase não está sobre controle na região.

Considering data collected between 1983 - 1988, this paper describes and evaluates leprosy situation at São Carlos region. The epidemiologicals and operationals indicators of the Leprosy Control Program are discussed. By analysis of prevalence of leprosy (1,24 to 1,26) canbe verified that region presents an endemicity high and a mean case detection rate (5,40 to 9,90). This coefficient is gradually decay. So, the leprosy is not on control at region studied.

Casos novos de hanseníase na regiäo de Säo Carlos, SP, de 1983 a 1988 / New cases of leprosy in region of Säo Carlos, Sp, of 1983-1988

O presente estudo analisa a situaçäo da hanseníase nos municípios da regiäo de Säo Carlos entre 1983 e 1988. Apresenta uma caracterizaçäo geral dos 121 casos novos registrados pelas unidades de saúde no período em questäo, a partir de dados contidos nas fichas de Investigaçäo Epidemiológica de hanseníase arquivadas no SUDS - Regiäo de Säo carlos. Pode-se observar que a doença incidiu em maior proporçäo nos casados, brancos, em faixas etárias superiores a 20 anos, com nível de escolaridade baixa a residentes na zona urbana. Observou-se ainda a ineficiência dos serviços de saúde na busca ativa de casos e um desconhecimento da populaçäo em relaçäo à doença, visto que é longo o período entre o aparecimento de sinais e sintomas e o diagnóstico

Avaliaçäo epidemiológica e operacional do programa de controle de hanseníase na regiäo de Säo Carlos-SP, no período de 1983/1988 / Evaluates leprosy situation at Säo Carlos region between 1983-1988

Descreve-se e avalia-se, neste estudo, a situaçäo da hanseníase na Regiäo de Säo Carlos no período de 1983 a 1988. Discute-se os indicadores epidemiológicos e operacionais usuais do Programa de Controle da Hanseníase. Analisando-se o coeficiente de prevalência encontrado no período (1,24 a 1,26) verifica-se que a regiäo apresenta uma alta endemidade e um médio coeficiente de detecçäo de casos (5,40 a 9,90) que encontra-se em gradativo declínio. Assim, observa-se que a hanseníase näo está sobre controle na regiäo.