Assessment of the relative effectiveness and tolerability of treatments of type 2 diabetes mellitus: a network meta-analysis.

PURPOSE: The relative effectiveness and tolerability of treatments for type 2 diabetes mellitus (T2DM) is not well understood because few randomized, controlled trials (RCTs) have compared these treatments directly. The purpose of the present study was to evaluate the relative effectiveness and tolerability of treatments of T2DM. METHODS: We performed a network meta-analysis of available RCTs with pharmacologic interventions in T2DM and compared antidiabetic drugs and combination regimens with metformin (the reference drug). Glycemic control (proportion achieving HbA1c goal) and tolerability (risk of hypoglycemia) were the primary outcomes of interest. Direct and indirect relative effects (unadjusted) were expressed as odds ratios and 95% CIs. FINDINGS: Eight treatments (glucagon-like peptide-1 [GLP-1] agonists plus metformin, sulfonylureas plus metformin, dipeptidyl peptidase-4 [DPP-4] inhibitors] plus metformin, colesevelan plus metformin, thiazolidinediones plus metformin, meglitinides plus metformin, α-glucosidase inhibitor plus metformin, and rosiglitazone monotherapy) outperformed metformin (direct effects). Triple combinations of GLP-1, thiazolinedione, insulin, metiglinide, or sulfonylureas added to a metformin backbone improved glycemic control (indirect effects). Higher risk of hypoglycemia was noted for sulfonylureas, α-glycosidases, and metiglinides when added to metformin (direct effects). Across indirect effects, only 17% of comparisons yielded less risk of hypoglycemia (70% were worse and 13% were comparable). IMPLICATIONS: Our results point out the relative superiority of 2- and 3-drug combination regimens over metformin and summarize treatment effects and tolerability in a comprehensive manner, which adds to our knowledge regarding T2DM treatment options.

Randomized trials of dopamine agonists in restless legs syndrome: a systematic review, quality assessment, and meta-analysis.

BACKGROUND: The use of dopamine agonists (DAs) for the treatment of restless legs syndrome (RLS) has been assessed in numerous randomized clinical trials (RCTs). OBJECTIVES: The aims of this study were to assess the reporting quality of published RCTs according to the Consolidated Standards of Reporting Trials (CONSORT) statement and to synthesize the study results in terms of efficacy and tolerability to inform the clinical management of RLS. METHODS: PubMed and Cochrane Controlled Trials Register were searched for English-language RCTs that assessed the effects of DAs in RLS. Quality of reporting was measured using the proportion of 17 CONSORT checklist items included in each study. The 2 primary outcomes were pooled mean change from baseline in International RLS (IRLS) Study Group rating scale score (Deltamu) (95% CI) and relative risk (RR) (95% CI) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score. The pooled proportions of adverse events (PAEs) (95% CI) were also estimated. RESULTS: Eighteen RCTs (N = 2848 patients) were included. Two of the 17 CONSORT checklist items were reported in 7 studies (39%) and 9 of the 17 items were reported in all 18 studies (100%). The differences in the IRLS scores and RR for CGI-I were significantly greater with pramipexole, ropinirole, rotigotine, and cabergoline compared with placebo. Results for heterogeneity were nonsignificant. The difference in Deltamu (95% CI) was significant with pramipexole (-6.63 [-9.15 to -4.10]) versus ropinirole (-3.64 [-4.76 to 2.51]) (P = 0.04). The difference between pramipexole and rotigotine was nonsignificant. The pooled PAEs (95% CI) for pramipexole, ropinirole, and rotigotine were 4.8% (2.0% to 8.7%), 10.2% (2.6% to 22.1%), and 7.6% (1.3% to 18.5%), respectively. In the trial of sumanirole, the PAE value was 2% (0% to 5.4%). CONCLUSION: Based on the findings from the meta-analysis, DAs were significantly more efficacious in the treatment of RLS compared with placebo.