RESUMO
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.
RESUMO
Objective It is difficult to compare directly the practical effects of lifestyle modifications and antihypertensive medications on reducing cardiovascular disease (CVD). The purpose of this study was to compare the hypothetical potential of lifestyle modifications with that of antihypertensive medications in reducing CVD in an aging society using a success rate-oriented simulation. Methods We constructed a simulation model for virtual Japanese subpopulations according to sex and age at 10-year intervals from 40 years of age as an example of an aging society. The fractional incidence rate of CVD was calculated as the product of the incidence rate at each systolic blood pressure (SBP) level and the proportion of the SBP frequency distribution in the fractional subpopulations of each SBP. The total incidence rate was calculated by the definite integral of the fractional incidence rate at each SBP level in the sex- and age-specific subpopulations. Results If we consider the effects of lifestyle modifications on metabolic factors and transfer them onto SBP, the reductions in the total incidence rate of CVD were competitive between lifestyle modifications and antihypertensive medications in realistic scenarios. In middle-aged women, the preventive effects of both approaches were limited due to a low incidence rate. In middle-aged men and extremely elderly subjects whose adherence to antihypertensive medications is predicted to be low, lifestyle modifications could be an alternative choice. Conclusion The success rate-oriented simulation suggests that the effectiveness of lifestyle modifications or antihypertensive medications in preventing cardiovascular events largely depends on the baseline incidence rate and sex- and age-specific behavioral factors.
