Abbreviations: (CGM) continuous glucose monitoring, (CI) confidence interval, (HbA1c) hemoglobin A1c, (RCT) randomized controlled trial, (RR) relative risk, (SMBG) Abstract Objective:We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG). Methods:We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model. Results:Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30) and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-realtime devices (WMD -0.22%, 95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews.

Hyperglycemia in the critically ill is a well-known phenomenon, even in those without known diabetes. The stress response is due to a complex interplay between counter-regulatory hormones, cytokines, and changes in insulin sensitivity. Illness/infection, overfeeding, medications (e.g., corticosteroids), insufficient insulin, and/or volume depletion can be additional contributors. Acute hyperglycemia can adversely affect fluid balance (through glycosuria and dehydration), immune and endothelial function, inflammation, and outcome. While there are several insulin infusion protocols that are able to safely and effectively treat hyperglycemia, the bulk of accumulated evidence does not support a causal relationship between acute hyperglycemia and adverse outcomes in the medical intensive care unit. Meta-analysis of randomized controlled trials suggests there is no benefit to tightening glucose control to normal levels compared to a reasonable and achievable goal of 140 to 180 mg/dl. There is a significantly increased risk of hypoglycemia. Although there is some evidence that patients without known diabetes have worse outcomes than those with known diabetes, more recent evidence is conflicting. Glycemic control in critically ill patients should not be neglected, as studies have not tested tight versus no/poor control, but tight versus good control. A moderate approach to managing critical illness hyperglycemia seems most prudent at this juncture. Future research should ascertain whether there are certain subgroups of patients that would benefit from tighter glycemic goals. It also remains to be seen if tight glucose control is beneficial once hypoglycemia is minimized with technological advances such as continuous glucose monitoring systems.

Incretins such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis. While incretin mimetics and enhancers are approved for treatment of outpatients with diabetes, evidence is only starting to accumulate regarding the therapeutic potential of incretins in hospitalized patients. Small exploratory studies suggest that GLP-1 safely reduces hyperglycemia without causing hypoglycemia, a key advantage over insulin if efficacy is established in larger studies. Potential limitations include the need for a continuous infusion for delivery, attenuation but not normalization of glucose levels, increased deceleration of gastric emptying and nausea. The exact mechanism of action, dosing, adverse effects, patient subgroups that would be most suitable and safety of combination treatment with insulin remain to be studied. While promising, additional research is required studying effects on hard clinical endpoints.