Abstract and Introduction
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.
Introduction
Individuals with diabetes face many disease-related complications, although perhaps the most difficult and feared by patients, caregivers, and providers alike is hypoglycemia. Hypoglycemia limits how aggressively blood glucose (BG) can be treated, and thus restricts our ability to tightly control hyperglycemia and its complications, including both microvascular and macrovascular disease. Hypoglycemia also limits physical activity and affects the sleep and daily activities of those with diabetes, greatly affecting their quality of life and physical and mental health.[1–7] Hypoglycemia also affects the quality of life of those caring for individuals with diabetes.[8] Those with type 1 diabetes (T1D) are at particularly high risk for hypoglycemia, with most individuals reporting having at least 2 episodes of symptomatic hypoglycemia each week.[9] Individuals with type 2 diabetes (T2D) are also affected by hypoglycemia, especially those taking medications known to cause hypoglycemia (including insulin and sulfonylureas), those with impaired kidney or liver function, those with food insecurity, and older individuals.[10] Patients with a history of recurrent hypoglycemia may develop impaired awareness of hypoglycemia and are at high risk for life-threatening severe hypoglycemia (hypoglycemia requiring assistance from another to treat).[11] Hypoglycemia is associated with significant morbidity and mortality as well as high costs and disproportionately affects those with lower socioeconomic status.[12–14] In hospitalized patients with diabetes, the presence of hypoglycemia leads to increased costs and longer length of stays.[15]
In 2009, the Endocrine Society developed a Clinical Practice Guideline titled "Evaluation and Management of Adult Hypoglycemic Disorders," which included patients with and without diabetes mellitus.[16] Since 2009, a significant number of advances in medical therapy, including advances in insulin delivery and especially in glycemic management, have been developed and are more commonplace in the care of individuals with diabetes. Each of these advances has had a significant impact on the development of, monitoring for, and prevention of hypoglycemia. Health care providers face frequent decisions regarding how best to prevent and manage hypoglycemia in caring for patients with diabetes who are at highest risk. In the outpatient setting, there are questions regarding the use of continuous glucose monitoring (CGM) technology compared with self-monitoring of blood glucose (SMBG) in both those with T1D and T2D as well as the use of algorithm-driven insulin pumps (ADIPs) and CGM compared with SMBG in those with T1D. Questions also remain regarding whether long-acting and rapid-acting insulin analogs should be used for people at high risk for hypoglycemia compared with human insulins, and whether structured patient education vs unstructured advice reduces hypoglycemia risk. New formulations of glucagon are available that do not require reconstitution, and questions exist regarding their use compared with older formulations. In the inpatient setting, providers face questions regarding the use of CGM and its role in reducing hypoglycemia and whether inpatient glycemic surveillance and management programs using electronic health records can reduce inpatient hypoglycemia.
The Endocrine Society identified the management of hypoglycemia in individuals with diabetes at high risk as an important topic for developing clinical guidance. The guideline writing panel prioritized multiple clinical questions that health care providers and patients face in daily practice. We conducted a systematic review and meta-analysis to summarize the evidence base relevant to these selected questions.
J Clin Endocrinol Metab. 2023;108(3):592-603. © 2023 Endocrine Society
