Title:
Sliding scale insulin for non-critically ill hospitalised adults with diabetes mellitus.

Abstract:
Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, function, or both. Hyperglycaemia in non-critically ill hospitalised people is associated with poor clinical outcomes (infections, prolonged hospital stay, poor wound healing, higher morbidity and mortality). In the hospital setting people diagnosed with diabetes receive insulin therapy as part of their treatment in order to achieve metabolic control. However, insulin therapy can be provided by different strategies (sliding scale insulin (SSI), basal-bolus insulin, and other modalities). Sliding scale insulin is currently the most commonly used method, however there is uncertainty about which strategy provides the best patient outcomes.
To assess the effects of SSI for non-critically ill hospitalised adults with diabetes mellitus.
We identified eligible trials by searching MEDLINE, Embase, LILACS, and the Cochrane Library. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov trial registers. The date of the last search for all databases was December 2017. We also examined reference lists of identified randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors.
We included RCTs comparing SSI with other strategies for glycaemic control in non-critically ill hospitalised adult participants of any sex with diabetes mellitus.
Two review authors independently extracted data, assessed trials for risk of bias, and evaluated the overall certainty of evidence utilising the GRADE instrument. We synthesised data using a random-effects model meta-analysis with 95% prediction intervals, if possible, or descriptive analysis, as appropriate.
Of 720 records screened, we included eight trials that randomised 1048 participants with type 2 diabetes (387 SSI participants and 615 participants in comparator groups were available for final analysis). We included non-critically ill medical and surgical adults with the diagnosis of diabetes mellitus. The mean follow-up time was measured by the mean length of hospital stay and ranged between five and 24 days. The mean age of participants was 44.5 years to 71 years.Overall, we judged the risk of bias on the trial level as unclear for selection bias, high for outcome-related performance and detection bias with regard to hypoglycaemic episodes, other adverse events, and mean glucose levels, and low for all-cause mortality and length of hospital stay. Attrition bias was low for all outcome measures.Six trials compared SSI with a basal-bolus insulin scheme, three of which investigating 64% of all participants in this category also applying an SSI approach in the bolus comparator part. One trial had a basal insulin-only comparator arm, and the remaining trial used continuous insulin infusion as the comparator. For our main comparison of SSI versus basal-bolus insulin, the results were as follows. Four trials reported mortality data. One out of 268 participants in the SSI group (0.3%) compared with two out of 334 participants in the basal-bolus group (0.6%) died (low-certainty evidence). Severe hypoglycaemic episodes, defined as blood glucose levels below 40 mg/dL (2.2 mmol/L), showed a risk ratio (RR) of 0.22, 95% confidence interval (CI) 0.05 to 1.00; P = 0.05; 5 trials; 667 participants; very low-certainty evidence. The 95% prediction interval ranged between 0.02 and 2.57. All nine severe hypoglycaemic episodes were observed among the 369 participants on basal-bolus insulin (2.4%). The mean length of hospital stay was 0.5 days longer for the SSI group, 95% CI -0.5 to 1.4; P = 0.32; 6 trials; 717 participants; very low-certainty evidence. The 95% prediction interval ranged between -1.7 days and 2.7 days. Adverse events other than hypoglycaemic episodes, such as postoperative infections, showed a RR of 1.16, 95% CI 0.25 to 5.37; P = 0.85; 3 trials; 481 participants; very low-certainty evidence. The mean blood glucose levels ranged across basal-bolus groups from 156 mg/dL (8.7 mmol/L) to 221 mg/dL (12.3 mmol/L). The mean blood glucose level in the SSI groups was 14.8 mg/dL (0.8 mmol/L) higher (95% CI 7.8 (0.4) to 21.8 (1.2); P < 0.001; 6 trials; 717 participants; low-certainty evidence). The 95% prediction interval ranged between -3.6 mg/dL (-0.2 mmol/L) and 33.2 mg/dL (1.8 mmol/L). No trial reported on diabetes-related mortality or socioeconomic effects.
We are uncertain which insulin strategy (SSI or basal-bolus insulin) is best for non-critically hospitalised adults with diabetes mellitus. A basal-bolus insulin strategy in these patients might result in better short-term glycaemic control but could increase the risk for severe hypoglycaemic episodes. The certainty of the body of evidence comparing SSI with basal-bolus insulin was low to very low and needs to be improved by adequately performed, well-powered RCTs in different hospital environments with well-educated medical staff using identical short-acting insulins in both intervention and comparator arms to compare the rigid SSI approach with flexible insulin application strategies.