Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

ABSTRACT Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis.

OBJECTIVES: To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. MATERIALS AND METHODS: We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. RESULTS: Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. CONCLUSIONS: Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

Curcumin combining with si-MALAT1 inhibits the invasion and migration of colon cancer SW480 cells

To study the effect of small interfering RNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) combining with curcumin on the invasion and migration abilities of human colon cancer SW480 cells, and to explore the involved molecular mechanism. The recombinant lentiviral vector expressing si-MALAT1 was constructed, and its titer was determined by gradient dilution method. The colon cancer SW480 cells with stable expression of si-MALAT1 was established, followed by treatment with curcumin at different concentrations. The effect of curcumin or si-MALAT1 alone and the combination of the two on the cell activity was detected by MTT assay. The cell invasion and migration abilities were detected by transwell and scratch-wound assay. The relative expression level of MALAT1 was detected by RT-qPCR. The protein expression was determined by Western blot analysis. The IC50 of curcumin alone was 77.69 mmol/L, which was 51.17 mol/L when combined with curcumin and random sequence. The IC50 of curcumin was 30.02 mmol/L when combined with si-MALAT1. The increased susceptibility multiples was 2.58. The wound healing rates were 30.9% and 67.5% after treatment with si-MALAT1 combined with curcumin for 24 hrs and 48 hrs, respectively. The numbers of invasion cells were 200±12, 162±13, 66±8, 53±4 and 16±3 after treatment with si-MALAT1 combined with curcumin for 48 hrs. The relative expression level of lncRNA-MALAT1 in the curcumin group was 68%, and the relative expression level of lncRNA-MALAT1 in si-MALAT1group was 56%, and that for the combination treatment group was about 21%. The protein expression levels of β- catenin, c-myc and cyclinD1 were significantly down-regulated upon treatment with certain concentration of si-MALAT1 alone or combined with curcumin.si-MALAT1 could significantly inhibit the invasion and migration of SW480 cells by enhancing the sensitivity of SW480 cells to curcumin. The mechanism involved mignt be related to the down-regulation of β-catenin, c-myc and cyclinD1 proteins.