Search

Selective inhibitors of sodium glucose co-transporter-2 (SGLT2) suppress renal glucose reabsorption and promote urinary glucose excretion, thereby lowering blood glucose. SGLT2 inhibitors have been reported to reduce body weight. However, the mechanism underlying the reduction in the body weight induced by SGLT2 inhibitor treatment remains to be elucidated. In this study, we investigated the effects of SGLT2 inhibitors on the intestinal bacterial flora. A total of 36 Japanese patients with type 2 diabetes mellitus received a SGLT2 inhibitor (luseogliflozin or dapagliflozin) for 3 months, and the prevalences of balance-regulating bacteria and balance-disturbing bacteria in the feces of the patients before and after SGLT2 inhibitor treatment were determined. SGLT2 inhibitor treatment was associated with a significant increase of the overall prevalence of the 12 types of balance-regulating bacteria. In addition, significant increases in the prevalences of the short-chain fatty acid (SCFAs)-producing bacteria among the balance-regulating bacteria were also observed. Individual analyses of the balance-regulating bacteria revealed that the SGLT2 inhibitor treatment was associated with a significant increase in the prevalence of Ruminococci, which are balance-regulating bacteria classified as SCFAs-producing bacteria. However, SGLT2 inhibitor had no effect on the balance-disturbing bacteria. These results suggested that SGLT2 inhibitor treatment was associated with an overall increase in the prevalence of balance-regulating bacteria. Among the balance-regulating bacteria, the prevalences of SCFAs-producing bacteria increased. SCFAs have been reported to prevent obesity. The results of the present study suggest that SGLT2 inhibitors might induce body weight reduction via their actions on the intestinal bacterial flora.

Background: Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm due to breast cancer treatment. Lymphedema is diagnosed and staged on the basis of limb circumference measuremen...

Background Obese patients with type 2 diabetes mellitus often develop obstructive sleep apnea syndrome (OSAS). In this study, continuous positive airway pressure (CPAP) was initiated in Japanese patients with type 2 diabetes mellitus who developed OSAS during treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the effect of the SGLT2 inhibitor therapy on the patients was investigated. Methods The study was conducted in outpatients with type 2 diabetes mellitus with serum hemoglobin A1c (HbA1c) values of ≥ 6.5% who developed OSAS. The patients were divided into two groups according to whether they were receiving treatment with an SGLT2 inhibitor or with other oral hypoglycemic agents: the SGLT2 inhibitor group (n = 9) and non-SGLT2 inhibitor group (n = 7). The patients in the former group were under treatment with one of the following three SGLT2 inhibitors: luseogliflozin (2.5 mg/day), dapagliflozin (5 mg/day) and empagliflozin (10 mg/day). The patients took the drugs once daily, before or after breakfast. The patients were initiated on CPAP therapy for OSAS, and their weight, body mass index (BMI), serum HbA1c level, lipid profile, liver function parameters, serum uric acid, and apnea-hypopnea index (AHI) measured before the initiation of CPAP therapy (baseline) were compared with the values measured 3 months after the start of CPAP therapy. Results The AHI decreased significantly after 3 months of CPAP therapy, as compared to that at the baseline, in both the SGLT2 inhibitor and non-SGLT2 inhibitor groups. There was no significant change in the serum HbA1c value after 3 months of CPAP therapy as compared to that at the baseline in either group. The body weight and BMI increased significantly after 3 months of CPAP therapy in the SGLT2 inhibitor group, but not in the non-SGLT2 inhibitor group. Conclusion The body weight and BMI increased significantly after 3 months of CPAP therapy initiated for OSAS in the type 2 diabetic patients who were receiving SGLT2 inhibitor therapy. Thus, when CPAP therapy is adopted for an obese diabetic patient with OSAS, it should be borne in mind that the body weight may increase if the patient is receiving SGLT2 inhibitor treatment.

Background: Manual lymph drainage (MLD) is one of the common treatments for breast cancer-related lymphedema (BCRL). Although the primary goal of MLD is to drain the excessive fluid accumulated in the affected upper limb and trunk to an area of the body that drains usually, the use of MLD is decided based on swelling and subjective symptoms, without assessing whether there is fluid accumulated in the affected region. The purpose of this study was to examine truncal fluid distribution in a sample of BCRL patients and investigate any correlation between such fluid distribution and swelling or subjective symptoms. Methods and Results: An observational study was conducted with 13 women who had unilateral, upper extremity BCRL. Fluid distribution was evaluated by using two magnetic resonance imaging (MRI) sequences: half-Fourier acquisition single-shot turbo spin echo and three-dimensional double-echo steady-state. The presence of swelling was determined by lymphedema therapists, and subjective symptoms were measured by using a visual analog scale. On MRI, no participants had any free water signals in the trunk. However, seven had swelling and all 13 had some kind of subjective symptoms on the affected side of their trunk. Conclusions: These results suggest that swelling and subjective symptoms do not correlate with the presence of truncal fluid. For such cases, a different approach than MLD may be needed to address truncal swelling and related subjective symptoms. Checking for the presence of fluid in the truncal region may help MLD be used more appropriately.

SGLT2 inhibitors (SGLT2is) prevent disease progression in diabetic patients with atherosclerotic disease. On the other hand, a similar beneficial effect on disease progression has not been reported for DPP-4 inhibitors (DPP-4is) , which are, however, widely used. To clarify the differences in effects between these two classes of drugs in diabetic patients, we focused on the production of advanced glycation end products (AGEs) and studied the effects of pretreatment with DPP-4i on the production of AGEs in patients who subsequently received SGLT2i. In the present study, Japanese patients with type 2 diabetes mellitus with unchanged glycemia control status for at least 6 months were administered SGLT2i (n = 11) for 3 months and then divided into a group that had already been receiving DPP-4i (n = 11) at the start of administration of the SGLT2i and the SGLT2i monotherapy group. We measured the blood levels of methylglyoxal-derived hydroimidazolone-1 (MG-H1) , which is an AGE, and also diabetes-related parameters before the start and after 3 months’ treatment with the SGLT2i. As a result, significant decreases of both HbA1c (from 8.6 ± 1.4 to 7.2 ± 1.4, P < 0.01) and circulating MG-H1 levels (from 0.48 ± 0.to 0.44 ± 0.07, P < 0.05) were observed in the SGLT2i monotherapy group. On the other hand, in the group that received SGLT2i in addition to a DPP-4i, the HbA1c value decreased significantly (from 7.2 ± 0.4 to 6.8 ± 0.5, P < 0.01) , whereas no significant change of the MG-H1 level was observed after the SGLT2i therapy. In conclusion, SGLT2i monotherapy decreased both the HbA1c and blood MG-H1 levels. However, no significant effect on the blood level of MG-H1 was observed in the combined DPP4i plus subsequent SGLT2i therapy group, suggesting that DPP4i possibly suppress the effect of the SGLT2i in reducing the production of MG-H1. Disclosure M.Kusunoki: Other Relationship; Taisho Pharmaceutical Holdings Co., Ltd. N.Wakazono: None. F.Hisano: None. T.Miyata: None.

Background: Selective sodium-glucose cotransporter 2 inhibitors, known to lower the blood glucose levels by promoting the urinary glucose excretion, can predispose to genitourinary infections. This prospective study investigated the influence of selective sodium-glucose cotransporter 2 inhibitors luseogliflozin on the vaginal flora of the pre- and postmenopausal women with type 2 diabetes mellitus. Methods: Twelve premenopausal and 24 postmenopausal female Japanese patients with type 2 diabetes mellitus took luseogliflozin 2.5 mg once daily for 6 months. The intravaginal fungal and bacterial populations, together with the body weight and serum parameters of diabetes mellitus and lipid metabolism were measured before and after the treatment. Results: After luseogliflozin treatment, the body weight, body mass index and hemoglobin A1c decreased, and the serum levels of high-density lipoprotein cholesterol increased significantly. Luseogliflozin treatment revealed to increase vaginal colony concentrations of Enterococcus faecalis (P = 0.0077) and E. coli (P = 0.0201) in premenopausal patients, and Enterococcus faecalis (P = 0.0051) and Candida albicans (P = 0.0355) in postmenopausal patients. In both pre- and postmenopausal patients, colony concentrations of Staphylococcus spp . had decreased (P = 0.0261 and P = 0.0161). Conclusions: Treatment with selective sodium-glucose cotransporter 2 inhibitors luseogliflozin was associated with changes of the vaginal flora. These findings provide basic data on the increased susceptibility to genital infections during luseogliflozin treatment. J Clin Med Res. 2021;13(5):309-316 doi: https://doi.org/10.14740/jocmr4504

Poor control of blood glucose could result in increase in advanced glycation end products (AGEs). AGEs cause various adverse vascular events such as atherosclerosis. Therefore, production of AGEs should be suppressed to prevent diabetic complications. In the present study, we evaluated effects of SGLT2 inhibitor (SGLT2i) and DPP-4 inhibitor (DPP-4i) on AGEs in patients with type 2 diabetes. The Japanese patients having poorly controlled blood glucose for 6 months were orally received SGLT2i (n=13; 2.5 mg/day luseogliflozin, 10 mg/day dapagliflozin, or 25 mg/day empagliflozin) or DPP-4i (n=11; 100 mg/day sitagliptin, 100 mg/day vildagliptin, or 25 mg/day alogliptin) for 3 months. Before and after the drug treatment, we measured HbA1c level and serum levels of lipids and hepatic function parameters. Besides, circulating methylglyoxal-derived hydroimidazolone-1 (MG-H1), one of AGEs, was determined optically. As shown in Table, SGLT2i significantly lowered HbA1c (P Disclosure M. Kusunoki: Other Relationship; Self; Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd. N. Wakazono: None. F. Hisano: None. T. Miyata: None.