A Systematic Review Supporting the Endocrine Society Guidelines: Management of Diabetes and High Risk of Hypoglycemia

Abstract

Context Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. Objective To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. Methods We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. Results We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. Conclusion This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

Management of Outpatients With Diabetes at High Risk of Hypoglycemia

“…In a meta-analysis of 6 RCTs (1454 patients with type 1 and 737 with type 2 diabetes), use of long-acting insulin analogues such as glargine was associated with 5.7% less level 1 to 2 hypoglycemia (95% CI, 1%-10.2%) vs intermediate-acting insulin. In a meta-analysis of 22 RCTs (7355 patients with type 1 and 1255 with type 2 diabetes), long-acting insulin analogues were associated with 2.7% less level 3 hypoglycemia vs intermediate-acting insulin (95% CI, 1.4%-3.8%) . In a meta-analysis of 15 RCTs (2470 patients with type 1 diabetes), rapid-acting insulin analogues such as lispro and aspart were associated with fewer severe hypoglycemia events vs short-acting insulin (both used in basal-bolus regimens) (IRR, 0.74; 95% CI, 0.65-0.86).…”

A Consensus Statement for Continuous Glucose Monitoring Metrics for Inpatient Clinical Trials

“…The rapid introduction of CGM into the inpatient care area has provided more detailed information as to the frequency and timing of hyperglycemic events and hypoglycemia. 13,84,85 Studies examining traditional POC BG to either real-time CGM or blinded CGM have demonstrate general reliability and an increase in the detection of nocturnal hypoglycemia. 11,13,84,85 Glucose values in hospitalized patients vary by time of day.…”

“…13,84,85 Studies examining traditional POC BG to either real-time CGM or blinded CGM have demonstrate general reliability and an increase in the detection of nocturnal hypoglycemia. 11,13,84,85 Glucose values in hospitalized patients vary by time of day. The overnight period is associated with the highest rate of hypoglycemia and the least amount of BG tests.…”

“…This metric is generally easy to obtain and follow for evaluation of inpatient hyperglycemia glycemic management but likely misses many important clinical events. 21,84 While nocturnal hypoglycemia is a frequent and often clinically missed event—no specific recommendations exist for glucose targets based on time of day for inpatients. The rapid introduction of CGM into the inpatient care area has provided more detailed information as to the frequency and timing of hyperglycemic events and hypoglycemia.…”

“…The rapid introduction of CGM into the inpatient care area has provided more detailed information as to the frequency and timing of hyperglycemic events and hypoglycemia. 13,84,85…”