This systematic review aimed to compare the e cacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) in adults with type 2 diabetes mellitus (T2DM). PubMed, the Cochrane Library and ClinicalTrials.gov, from database inception to 15 October 2020, and other sources were searched for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis were performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes (glycemic and serum lipid control and anthropometrics) and risk ratio (RR) for dichotomous outcomes (gastrointestinal and serious adverse events). Statistical analysis involving 9 published RCTs with 2609 subjects revealed that MIR was associated with better HbA1c lowering (MD 0.09% [95% con dence interval, 0.02%, 0.017%]) and serum lipid control except LDL-C lowering, while MXR reduced only the cumulative incidence of dyspepsia (RR 0.58 [0.34, 0.98]). MXR and MIR were similar in all other considered outcomes. The use of MXR over MIR among adults with T2DM was associated with statistically worse but likely clinically insigni cant HbA1c lowering, similar plasma glucose lowering, and minimal improvement of metformin intolerance. This information may guide patient-physician discussions in choosing between the two formulations.

Saliva has been demonstrated as feasible alternative to naso-oropharyngeal swab (NOS) for SARS-CoV-2 detection through reverse transcription quantitative/real-time polymerase chain reaction (RT-qPCR). This study compared the diagnostic agreement of conventional NOS, saliva with RNA extraction (SE) and saliva without RNA extraction (SalivaDirect) processing for RT-qPCR in identifying SARS-CoV-2. All techniques were also compared, as separate index tests, to a composite reference standard (CRS) where positive and negative results were defined as SARS-CoV-2 detection in either one or no sample, respectively. Of 517 paired samples, SARS-CoV-2 was detected in 150 (29.01%) NOS and 151 (29.21%) saliva specimens. The saliva-based tests were noted to have a sensitivity, specificity and accuracy (95% confidence interval) of 92.67% (87.26%, 96.28%), 97.55% (95.40%, 98.87%) and 96.13% (94.09%, 97.62%), respectively, for SE RT-qPCR and 91.33% (85.64%, 95.30%), 98.91% (97.23%, 99.70%) and 96.71% (94.79%, 98.07%), respectively, for SalivaDirect RT-qPCR compared to NOS RT-qPCR. Compared to CRS, all platforms demonstrated statistically similar diagnostic performance. These findings suggest that both conventional and streamlined saliva RT-qPCR are at least non-inferior to conventional NOS RT-qPCR in detecting SARS-CoV-2.

Background: Saliva has been demonstrated as a feasible alternative specimen to nasopharyngeal swab for the detection of SARS-CoV-2 using real-time or quantitative reverse transcription polymerase chain reaction (qRT-PCR) method that bypasses the need for explicit viral ribonucleic acid (RNA) extraction. Aim: To assess the diagnostic validity of direct saliva-to-qRT-PCR in the detection of SARS-CoV-2 compared to conventional nasopharyngeal swab qRT-PCR. Methodology: Self-collected saliva samples were processed by heating at 95oC for 30 minutes followed by addition of buffer and detergent while viral RNA from nasopharyngeal swabs were extracted using the Sansure Biotech sample release reagent.  Paired samples were used as templates for qRT-PCR using the Sansure Novel Coronavirus (COVID-19) Nucleic Acid Diagnostic Kit and Sansure Biotech MA6000 Real-Time Quantitative PCR System. Direct saliva-to-qRT-PCR was compared to nasopharyngeal swab qRT-PCR in terms of diagnostic validity and agreement parameters, and both platforms were compared separately in terms of similar parameters with a composite reference standard (CRS) wherein the criteria for a positive result is SARS-CoV-2 detection in at least either nasopharyngeal swab or saliva. Results:  Of the 238 nasopharyngeal swab-saliva pairs tested, 20 (8.4%) nasopharyngeal swab and 24 (10.1%) saliva specimens tested positive. We documented a sensitivity of 85.0% (95% CI: 62.1%, 96.8%), specificity of 96.8% (95% CI: 93.5%, 98.7%), accuracy of 95.8% (95% CI: 92.4%, 98.0%) and Cohen Kappa of 0.75 (95% CI: 0.60, 0.90) when direct saliva-to-qRT-PCR was compared to the conventional platform. When the two platforms were individually compared to the CRS, numerically higher but not statistically significant sensitivity and accuracy were noted for direct saliva-to-qRT-PCR than for nasopharyngeal swab qRT-PCR. Conclusion: Direct saliva-to-qRT-PCR is non-inferior to nasopharyngeal swab qRT-PCR for detecting SARS-CoV-2 using the Sansure Novel Coronavirus Nucleic Acid Diagnostic Kit.

This systematic review aimed to compare the efficacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) in adults with type 2 diabetes mellitus (T2DM). PubMed, the Cochrane Library and ClinicalTrials.gov, from database inception to 15 October 2020, and other sources were searched for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis was performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes (glycemic and serum lipid control and anthropometrics) and risk ratio (RR) for dichotomous outcomes (gastrointestinal and serious adverse events). Statistical analysis involving 9 published RCTs with 2609 subjects revealed that MIR was associated with better HbA1c lowering (MD 0.09% [95% confidence interval, 0.02%, 0.17%]) and serum lipid control except LDL-C lowering, while MXR reduced only the cumulative incidence of dyspepsia (RR 0.58 [0.34, 0.98]). MXR and MIR were similar in all other considered outcomes. The use of MXR over MIR among adults with T2DM was associated with statistically worse but likely clinically insignificant HbA1c lowering, similar plasma glucose lowering, and minimal improvement of metformin intolerance. This information may guide patient-physician discussions in choosing between the two formulations.