Objectives We aimed to conduct a systemic review and meta-analysis of the relevant studies to further investigate the association between age at menarche and insulin resistance. Methods PubMed, EMBASE and Web of Science (SCI) databases were systemically searched until December, 2017. Observational studies comparing the incidences of insulin resistance in patients with early, average and late menarchal ages were identified. Weighted mean difference (WMD) for HOMA-IR scores and fasting serum insulin levels in early vs late, early vs average and average vs late comparisons were calculated with a random or fixed effects model. Results A total of 8 articles involving 5504 subjects were finally included. In the analysis of HOMA-IR, the pooled WMD in 5 studies were 0.45 (95% CI 0.31-0.60, P<0.001), 0.40 (95% CI 0.28-0.52, P<0.001) and -0.01 (95% CI -0.09-0.07, P=0.854) for early vs late, early vs average and average vs late comparisons, respectively. The fasting serum insulin levels in 8 studies were analyzed and it was significantly higher in subjects with earlier age at menarche (WMD 1.28, 95%CI 0.92-1.63, P<0.001 for early vs late comparison, WMD 1.28, 95%CI 1.13-1.43, P<0.001 for early vs average comparison) with mild and acceptable heterogeneity (I²=42.5% and 7.4%, respectively). Publication bias was not detected via funnel plots and Egger’s tests. Conclusions Our study revealed that earlier age at menarche was significantly associated with insulin resistance. Trial Registration Number: CRD42018083874 Keywords: Age at menarche, Insulin resistance, HOMA-IR, Meta-analysis.

Aim of the review: To assess the risk of hypovolemia for sodium–glucose cotransporter-2 (SGLT2) inhibitors treatment.Method: A systematic literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus from inception up to 4 October 2022, Data for study characteristics and outcomes of interest were extracted from each eligible study. Risk ratios (RRs) with a 95% confidence interval (CI) for hypovolemia were calculated using a random-effect model.Results: A total of 57 studies (n = 68,622) were included in our meta-analysis, with a result of 1,972 hypovolemia incidents (1,142 in the SGLT2 inhibitors group and 830 in the control group). The pooled RR was 1.12 (95% CI: 1.02–1.22). It is evident that receiving SGLT2 inhibitors increased the risk of hypovolemia. When stratified by category of SGLT2 inhibitors the result was consistent; when the subgroup was analyzed by age, the pooled RR was 1.07 (95% CI: 0.94–1.23) in patients aged ≥65 years and 1.14 (95% CI: 1.02–1.28) in those aged <65 years. When comparing the baseline estimated glomerular filtration rate (eGFR) of less than or equal to 60 mL/min/1.73 m² with a baseline eGFR greater than 60 mL/min/1.73 m², the pooled RR was 1.21, (95% CI: 1.00–1.46) and 1.08, (95%CI: 0.98–1.20), respectively.Conclusion: Our meta-analysis has demonstrated that SGLT2 inhibitors increased the risk of hypovolemia in patients with Type 2 Diabetes Mellitus (T2DM). It is necessary to pay attention to the risk of hypovolemia associated with SGLT2 inhibitors, especially in older individuals and those with moderate renal impairment.Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020156254].