Glucose Control, Sulfonylureas, and Insulin Treatment in Elderly People With Type 2 Diabetes and Risk of Severe Hypoglycemia and Death: An Observational Study

Abstract

OBJECTIVE To estimate the relative and absolute risk of severe hypoglycemia and mortality associated with glucose control, sulfonylureas, and insulin treatment in elderly people with type 2 diabetes. RESEARCH DESIGN AND METHODS We identified elderly subjects (≥70 years old) with type 2 diabetes between 2000 and 2017 in the U.K. Clinical Practice Research Datalink primary care database with linkage to hospitalization and death data. Subjects with three consecutive HbA1c values <7% (53 mmol/mol) while on insulin and/or sulfonylureas within 60 days prior to the third HbA1c value (exposed) were matched with subjects not exposed. Hazard ratios (HRs) and absolute risks were estimated for hospitalizations for severe hypoglycemia and cardiovascular and noncardiovascular-related mortality. RESULTS Among 22,857 included subjects (6,288 [27.5%] exposed, of whom 5,659 [90.0%] were on a sulfonylurea), 10,878 (47.6%) deaths and 1,392 (6.1%) severe hypoglycemic episodes occurred during the follow-up. In comparison with nonexposed subjects, the adjusted HR in exposed subjects was 2.52 (95% CI 2.23, 2.84) for severe hypoglycemia, 0.98 (0.91, 1.06) for cardiovascular mortality, and 1.05 (0.99, 1.11) for noncardiovascular mortality. In a 70-, 75-, 80-, and 85-year-old subject, the 10-year risk of severe hypoglycemia was 7.7%, 8.1%, 8.6%, and 8.4% higher than in nonexposed subjects, while differences for noncardiovascular mortality ranged from 1.2% (95% CI −0.1, 2.5) in a 70-year-old to 1.6% (−0.2, 3.4) in an 85-year-old subject. Sulfonylurea and insulin use were more relevant predictors of severe hypoglycemia and death than were glucose levels. CONCLUSIONS Elderly subjects with type 2 diabetes and low HbA1c on sulfonylurea or insulin treatment experienced a substantially higher risk of hospitalization for severe hypoglycemia but had no clear evidence of increased risks of mortality.