Tolerability and Efficacy of Ipragliflozin in The Management of Inadequately Controlled Type 2 Diabetes mellitus: A Systematic Review and Meta-analysis.

AIM: Ipragliflozin is a new antidiabetic agent that works through enhancing renal glucose excretion. We aim to synthesize evidence from published randomized controlled trials (RCTs) on the safety and efficacy of ipragliflozin in the management of type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central register of clinical trials using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup and sensitivity analyses were conducted. RESULTS: We included 13 RCTs (N=2535 patients) in the final analysis. The overall effect estimates favoured ipragliflozin 50mg monotherapy group over placebo in terms of: HbA1c (Standardized mean difference (SMD)=-1.20%, 95% Confidence interval (95% CI)=[-1.47, -0.93]; p<0.001), fasting plasma glucose (SMD=-1.30 mg/dL, 95% CI [-1.93, -0.67]; p<0.001), fasting serum insulin (SMD=-1.64 µU/mL, 95% CI [-2.70, -0.59]; p=0.002), and body weight (SMD=-0.85 kg, 95% CI [-1.19, -0.51]; p<0.001). Similarly, better glycemic control and significant body weight reduction compared to placebo were attained in ipragliflozin 50 mg combination with metformin, insulin with/without dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone. Ipragliflozin, either alone or in combination, exhibits acceptable safety profile. CONCLUSION: The presented meta-analysis provides class one evidence that ipragliflozin is safe and effective in the management of T2DM either as monotherapy or an add-on.

Efficacy and safety of tramadol in pain relief during diagnostic outpatient hysteroscopy: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the evidence about the safety and efficacy of tramadol in pain relief during diagnostic outpatient hysteroscopy (OH). DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: Not applicable. PATIENT(S): Patients undergoing diagnostic OH received tramadol versus those who were administered placebo. INTERVENTION(S): Electronic databases were searched using the following MeSH terms (tramadol OR opioids OR opioid OR narcotic OR narcotics) AND (hysteroscopy OR hysteroscopic). MAIN OUTCOME MEASURE(S): Pain assessed by visual analogue scale (VAS) during OH, immediately and 30 minutes after the procedure. RESULT(S): One hundred thirteen studies were identified of which four randomized clinical trials were deemed eligible for this review (tramadol: n = 209; placebo: n = 209). The pooled estimate showed that tramadol significantly reduced VAS during procedure than placebo (weighted mean difference [WMD] = -1.33; 95% confidence interval [CI] -1.78 to -0.88, I2 = 3%, P = .36). In addition, tramadol significantly reduced VAS immediately after the procedure (WMD = -1.05; 95% CI -1.49 to -0.61, I2= 0, P = .84) and 30 minutes after (WMD = -0.98; 95% CI -1.30 to -0.65, I2 = 0, P = .88). CONCLUSION(S): This meta-analysis suggests that tramadol is safe, effective, and gives favorable results in reducing pain during diagnostic OH.

Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension.

PURPOSE: Droxidopa has been approved for the treatment of neurogenic orthostatic hypotension (NOH) under the US Food and Drug Administration accelerated approval program, which warrants confirmatory evidence on long-term efficacy of droxidopa. Hereby, we synthesize evidence from published randomized controlled trials (RCTs) about the safety and efficacy of droxidopa for patients with neurogenic orthostatic hypotension. METHODS: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 5.3 for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate long-term durability of droxidopa against placebo. RESULTS: Four RCTs with a total of 485 patients (droxidopa, n = 246; placebo, n = 239) were eligible for the final analysis. The mean difference (MD) of change in the main outcomes from baseline to endpoint favored droxidopa than placebo [Orthostatic Hypotension Questionnaire (OHQ) MD -0.61, P = 0.004; dizziness/lightheadedness score MD -0.83, P = 0.008; and standing systolic blood pressure (SBP) MD 4.09, P = 0.03]. The efficacy of droxidopa decreased gradually after 2 weeks, and its statistical significance was lost after 8 weeks (OHQ score MD -0.18, P = 0.61; dizziness/lightheadedness score MD -0.71, P = 0.11; and standing SBP MD 2.96, P = 0.29). None of the adverse events were significantly higher in the case of droxidopa compared to placebo. CONCLUSION: Droxidopa is a safe and effective drug for the short-term management of NOH symptoms. However, current evidence is insufficient to confirm the efficacy of droxidopa for long-term use. Therefore, further studies with increased sample size are needed.