Comparison of conventional and sustained-release formulation of metformin in type 2 diabetics

Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

“…MXR rst received regulatory approval for use as a therapeutic agent for adult-onset T2DM in 2005, with accumulated evidence purporting similar glycemic control and improved GI tolerability compared to the conventional MIR formulation [6]. While subsequent RCTs comparing MXR and MIR in equal daily doses individually reported general glycemic control equivalence [20][21][22][23][24][25][26], a portion of these studies that reported cumulative incidence of AEs demonstrated similarity in GI tolerability pro le as well [21,[23][24][25].…”

“…Six trials were explicitly double-blinded involving patients and caregivers [18][19][20][21][22][23] while 2 were open-label [24,25]; it was not apparent in one study whether blinding at any level was performed [26]. Six studies had formal run-in period [18,19,[22][23][24][25], 3 of which having a passive washout period (2 [22], 4 [23] and 6 [18] weeks, respectively).…”

“…In terms of glycemic control parameters, MIR was associated with better mean HbA1c lowering from baseline (0.09% [95% CI, 0.02%, 0.17%]), with neither signi cant nor substantial heterogeneity (χ 2 p = 0.39, I 2 = 6%), than MXR (Table 3 and Figure S7.1). Conditions eliminating [18], with imputed SDs being used, in the sensitivity analyses abolished this nding (Table S8. [18,19,21,[23][24][25]). Heterogeneity was neither signi cant nor substantial (χ 2 p > 0.1, I 2 < 50%) in all dichotomous outcomes reported by more than one study ( Figures S7.5 to S7.8).…”

Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

“…Four studies [18,19,24,26] only reported separate baseline and endpoint means + SDs; thus, Equation 1 was applied to generate MD + SD change from baseline values. Equation 2 was used to generate SDs for one study [18] that reported values that were unanimously considered by the authors as too wide (resulting to a relative weight in the analyses that was too small compared to the contributed sample size, see Supplement 4) and for another [21] where the SDs for mean change from baseline HbA1c could not be obtained.…”

“…Sensitivity analyses show that the statistical signi cance of these ndings were not robust when (1) studies with unclear or high risk for performance and/or reporting bias were removed, (2) at least one of the studies, except the smallest [21], were eliminated and (3) elimination of studies with unclear or high risk for performance, detection, attrition or reporting bias was performed, respectively (Tables S8.9 to S8.11). Mean lowering of LDL-C (-0.03 mmol/L [95% CI, -0.12 mmol/L, 0.06 mmol/L], 5 studies [18,19,21,23,24]) was not signi cantly different between the two arms ( Figure S7.14), with neither signi cant nor substantial heterogeneity (χ 2 p = 0.41, I 2 = 0%). The nding was robust on sensitivity analysis (Table S8. Figures S7.15 and S7.16), with neither signi cant nor substantial heterogeneity (χ 2 p > 0.75, I 2 = 0%).…”