Hypoglycaemia has been linked to an increased risk of cardiac arrhythmias by causing autonomic and metabolic alterations, which may be associated with detrimental outcomes in individuals with diabetes(IWD), such as cardiovascular diseases (CVDs) and mortality, especially in multimorbid or frail people. However, such relationships in this population have not been thoroughly investigated. For this reason, we conducted a systematic review and meta-analysis.2 statistic, pooled relative risks (RRs) and 95% confidence intervals (CI) were obtained using random-effects models.Relevant papers published on PubMed, Embase, Cochrane, Web of Knowledge, Scopus, and CINHAL complete from inception to December 22, 2022 were routinely searched without regard for language. All of the selected articles included odds ratio, hazard ratio, or relative risk statistics, as well as data for estimating the connection of hypoglycaemia with cardiac arrhythmia, CVD-induced death, or total death in IWD. Regardless of the heterogeneity assessed by the IAfter deleting duplicates and closely evaluating all screened citations, we chose 60 studies with totally 5,960,224 participants for this analysis. Fourteen studies were included in the arrhythmia risk analysis, and 50 in the analysis of all-cause mortality. Hypoglycaemic patients had significantly higher risks of arrhythmia occurrence , CVD-induced death , and all-cause mortality  compared to euglycaemic patients with significant heterogeneity.Hypoglycaemic individuals are more susceptible to develop cardiac arrhythmias and die, but evidence of potential causal linkages beyond statistical associations must await proof by additional specifically well planned research that controls for all potential remaining confounding factors. Diabetes, a non-communicable disease, is a serious public health concern worldwide. More than half a billion people (536.6 million) aged 20-79 were predicted to develop diabetes mellitus (DM) in 2021, with roughly 90% having type 2 DM (T2DM) (Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality in this populace . NumerouFor these reasons, our aim was to assess if hypoglycaemia affects the risk of arrhythmia or mortality in IWD.Two separate reviewers searched PubMed, EMBASE, Wiley Cochrane Central Register of Controlled Trials(CENTRAL), Web of knowledge, Scopus and CINAHL complete up to December 22, 2022 as per applicable recommendations . Any dispost-hoc analysis or sub-analysis of randomised controlled trials (p-h/sa of RCTs); (ii) focusing on the relationship of any hypoglycaemia with arrhythmias or CVD-induced death or overall death in IWD, and reporting risk or prevalence or incidence of arrhythmias  for IWD with hypoglycaemia as compared with euglycaemia, and (iii) standardized mortality or incidence ratio (SMR or SIR), or incidence rate ratio (IRR), or odds ratios (OR), or hazard ratio (HR), or relative risk (RR), as well as pertinent relevant raw data for recalculation are all used to report effect estimates. Exclusion criteria were as follows: (I) emphasizing the connection of hypoglycaemia with adverse outcomes such as arrhythmias- or CVD-caused death or all-cause mortality in non-diabetic people; (II) case report, quasiexperiment (in which subjects are not assigned at random), editorial, remark, review, letter or unpublished study; (III) only published as abstract or conference proceeding. Diabetes studies that did not provide such estimations were also omitted. When a site-specific dataset was published multiple times, the study with the newest t publication or the largest sample size was generally picked.The inclusion criteria were: (i) observational studies (OSs) , Data were collected about the research , participants (mean age and the gender), analysis strategy , effect size , as well as pertinent raw data for recalculation.Two researchers independently assessed the quality of each p-h/sa of RCT and enrolled study based on cohort or case-control design utilizing the 9-star Newcastle-Ottawa Scale (NOS) . A ratin2 statistic was used to determine the fraction of variability between studies because of heterogeneity between studies, and with I2 values greater than 50%, 25-50%, and less than 25%, was classified as high, medium, and low respectively  whereas the analysis period, respectively. OR, or RR with 95% confidence interval (CI) was used to summarize dichotomous outcomes. ORs are comparable to RRs since the absolute risk of arrhythmias or death is minimal in these populations and the two indices provide equivalent RR estimates . The I2 ectively . The iteively , diurnal differences , severity of hypoglycaemia , clarity of diabetes , and type of arrhythmia . For all-cause mortality analysis, subgroup analyses were conducted with sample size, country/region , study population , hypoglycaemia episode , clarity of diabetes, study design , severity of hypoglycaemia, follow-up duration , and methods for effect estimate extraction . Any quantifiable source of heterogeneity was identified through sensitivity analysis by excluding each study individually.Publication bias was examined using Begg’s and Egger’s tests when at least five studies were available for analysis, as well as by visually inspecting the asymmetry of funnel plots of estimated effects against standard errors . Any pubFrom the 51,794 articles discovered through a systematic search, 137 were selected for further analysis Figure 1Apart from 10 studies on multinational origins, other origins were mentioned developed countries or regions in 46 articles, and developing countries in 4 articles. More than 50% studies (34/60) reported severe hypoglycaemia. Sixteen articles reported IWD with comorbidities or at high risk of CVD. Definitions of hypoglycaemia varied widely and were mostly based on blood glucose concentration or the presence of symptoms necessitating the assistance of another individual or medical help. Ten, 46, and 15 articles presented data on arrhythmia risk only, all-cause mortality only, and CVD death only, respectively, and four studies reported data on both arrhythmia and all-cause mortality risk.For cardiac arrhythmia analysis, quality analysis showed about 7 of 11 cohort studies and one case-control study were of high methodological quality, with ≥7 NOS scores  , but there was evident heterogeneity between studies (Ip<0.001) Figure 2The pooled RRs were essentially uniform regardless of the sample size , severity of hypoglycaemia , noctural hypoglycaemia (P=0.012), type of arrhythmia , T2DM (P =0.001), or total diabetes (P<0.001) Figure 32 = 97.1%; P<0.001; Fifty studies reported a link between hypoglycemia and overall death in IWD. In a random-effects model, the pooled RR was 1.68  with severe heterogeneity  nor visual inspection revealed significant publication bias  from 15 relevant studies found that hypoglycemic versus euglycaemic IWD had a 59% significantly higher risk  in susceptibility to CVD-caused death. A random-effects model exhibiting substantial heterogeneity , carries a greater proarrhythmic risk than euglycemia or hyperglycemia, as also observed in this study. The proarrhythmic mechanisms of hypoglycaemia, especially SH, may be various . Low gluEven though the overall pooled RR suggests a 42% substantially higher likelihood of cardiac arrhythmia in hypoglycemic patients over euglycaemia patients, around 57% (8/14) recruited studies report no significant link between hypoglycemia and cardiac arrhythmia. There can be several reasons for this null result. First, the antagonistic autonomic nerve responses are a fundamental mechanism underlying the harmful effect of SH, but can be diminished in patients with long-standing diabetes, long follow-up, or established cardiovascular risks –97. ConsAs for the mortality analysis, we did not aim to prove causality, but did highlight the associations between hypoglycemia and death. Due to pre-existing comorbidities, CVD-induced death usually accounted for the majority of deaths in the diabetes group. The relationship between hypoglycaemia and cardiovascular events is bidirectional in accordance with previous studies , 86. FirSecondly, hypoglycaemia or SH is a plausible indicator instead of a direct cause of an elevated risk of unfavorable clinical outcomes, which reflects the influence of concomitant illnesses in addition to unmeasured or incompletely defined confounding variables  that indThe mechanisms that relate SH to non-cardiovascular fatalities remain unknown , 54. SH Subgroup analyses were performed so as to clarify whether the incidence of cardiac arrhythmia or all-cause death differed among relevant characteristics. In the trials with T2DM patients, preliminary subgroup analysis revealed a substantial increase in overall death risk among hypoglycemic versus euglycaemic individuals. Because T1DM patients are frequently younger than T2DM patients, they have less risk factors for death. Despite this, SH is more likely to attack T1DM patients, raising the risk of arrhythmia. SH is more likely to assault T1DM patients, increasing the risk of arrhythmia. This is not the case, and the underlying reason is unknown . In termNo review or meta-analysis can avoid heterogeneity of OS due to the lack of standardisation of method for clarifying cases, study design and time, classification of endpoints, and the amount of inter-study confounding that has been adjusted. For example, definitions of hypoglycaemia differ greatly. In spite of the sensitivity testing, we were unable to account for the greatest between-study heterogeneity in the outcome of cardiac arrhythmia and death. Therefore, these results need confirmation from more research. Furthermore, the statistical methodologies used in p-h/sa of RCTs and OSs did not adequately address the influence of unmeasured confounding components regarding overall effect estimation. The origins of variability were attributed to differences in study populations and exposure, according to sensitivity analyses.Some of the significant strengths of this meta-analysis include the detailed retrieval plan with Cochrane procedures, the broad search approach, the relatively large sample size, and the capacity to investigate the link between hypoglycemia and cardiac arrhythmia or death. Nevertheless, this study has some limitations. First, the avoidance of unreported reports can have influenced our findings. Second, there is also a wide range of exposure, including severe hypoglycemia and any hypoglycemia. Third, the analyses employed for arrhythmia source research have drawbacks as well. Some studies have presented incident rate ratios for arrhythmias, implying that an increased risk applies to the whole research group whereas, in fact, only a few individuals who are extremely vulnerable may be impacted . Fourth,In summary, hypoglycemia, as opposed to euglycaemia, is associated with a higher risk of cardiac arrhythmia and mortality. Nevertheless, evidence of potential causal linkages beyond statistical associations must await proof by additional specifically well planned research that controls for all potential remaining confounding factors, including a unified definition of hypoglycemia  as recomThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.XW and GL conceived the conception and design of the study, the search of the relevant literature, the extraction and analysis of data, and the drafting and revision of the final manuscript. SZ and FZ interpreted the analysed data, reviewed the manuscript critically, and contributed to its drafting. The final manuscript was read and approved by all authors.