Efficacy and safety of luseogliflozin in improving glycaemic and non-glycaemic outcomes in type-2 diabetes: A meta-analysis.

BACKGROUND & AIMS: No meta-analysis is available analysing the role of luseogliflozin in type-2 diabetes. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving diabetes patients receiving luseogliflozin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, blood pressure, weight, lipids, and adverse events. RESULTS: From initially screened 151 articles, data from 10 RCTs involving 1304 patients was analysed. Individuals receiving luseogliflozin 2.5 mg/d had a significantly lower HbA1c [MD -0.76% (95% CI: 1.01 to -0.51); P < 0.01; I2 = 83%], fasting glucose [MD -26.69 mg/dl (95% CI: 35.41 to -17.96); P < 0.01; I2 = 80%], systolic blood pressure [MD -4.19 mm Hg (95% CI: 6.31 to -2.07); P < 0.01; I2 = 0%], body-weight [MD -1.61 kg (95% CI: 3.14 to -0.08); P = 0.04; I2 = 0%], triglycerides PCG [MD -12.60 mg/dl (95% CI: 24.25 to -0.95); P = 0.03; I2 = 0%], uric acid [MD -0.48 mg/dl (95% CI: 0.73 to -0.23); P < 0.01; I2 = 49%] and alanine aminotransferase [MD -4.11 IU/L (95% CI: 6.12 to -2.10); P < 0.01; I2 = 0%] compared to placebo. Occurrence of treatment-emergent adverse-events [RR 0.93 (95% CI: 0.72-1.20); P = 0.58; I2 = 0%], severe adverse-events [RR 1.19 (95% CI: 0.40-3.55); P = 0.76; I2 = 0%], hypoglycaemia [RR 1.56 (95% CI: 0.85-2.85); P = 0.15; I2 = 0%] and genital infections [RR 1.42 (95% CI: 0.48-4.18); P = 0.53; I2 = 0%] were not increased with luseogliflozin. Cardiovascular outcome trials are lacking and are urgently required. CONCLUSION: Luseogliflozin has good glycaemic and non-glycaemic benefits similar to other SGLT2 inhibitors and is well tolerated.

Efficacy and Safety of Novel Thiazolidinedione Rivoglitazone in Type-2 Diabetes a Meta-Analysis.

No meta-analysis has analyzed the safety and efficacy of rivoglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for RCTs involving T2DM patients receiving rivoglitazone in the intervention arm, and placebo/active comparator in the control arm. The primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids, and adverse events. From initially screened 24 articles, data from 3 RCTs (3591 patients) that fulfilled all criteria was analzsed. HbA1c was significantly lower with standard-dose (1 mg/d) [MD-0.86% (95%CI:-1.11--0.61); P < 0.01; I2 = 87%] and high-dose (1.5-2 mg/d) [MD-0.97%(95%CI:-1.03--0.90); P < 0.01; I2 = 19%] rivoglitazone compared to placebo. When compared to pioglitazone (30-45 mg/d), HbA1c lowering was comparable with standard-dose [MD 0.05%(95%CI:-0.01 - 0.11); P = 0.08; I2 = 11%], but superior with high-dose [MD -0.11%(95%CI:-0.18- -0.04); P < 0.01; I2 = 0%] rivoglitazone. Triglycerides were significantly lower with standard-dose [MD-17.95 mg/dl (95%CI:-34.23--1.66); P = 0.03; I2 = 0%] and high-dose [MD-40.41 mg/dl (95%CI:-72.90- -7.93);P = 0.01;I2 = 71%] rivoglitazone compared to placebo. Adiponectin significantly improved with standard-dose [MD 7.94 ng/ml (95%CI: 5.48-10.39); P < 0.01;I2 = 98%] and high-dose [MD 13.82 ng/ml (95%CI: 8.16-19.48); P < 0.01; I2 = 100%] rivoglitazone compared to placebo. hsCRP was significantly lower with standard-dose [MD -1.00 mg/L (95% CI: -1.20 - -0.80); P < 0.01; I2 = 6%] and high-dose [MD -1.50 mg/L (95%CI:-1.59- -1.40); P < 0.01; I2 = 0%] rivoglitazone compared to placebo. Treatment-emergent adverse events with standard-dose [Risk ratio (RR) 1.16 (95%CI: 0.84 -1.60); P = 0.38; I2 = 0%] and high-dose [RR1.34 (95%CI: 0.99-1.83); P = 0.06; I2 = 0%] rivoglitazone was comparable to placebo. Severe adverse events with standard-dose [RR1.88 (95%CI: 0.69-5.12);P = 0.22;I2 = 0%] and high-dose [RR 1.27 (95% CI: 0.45 - 3.59); P = 0.68; I2 = 0%] rivoglitazone was comparable to placebo. This meta-analysis highlights the good glycaemic efficacy and safety of both standard and high-dose rivoglitazone, and appears to be better than lobeglitazone in T2DM.