Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes

• Published in: JAMA : the journal of the American Medical Association Vol. 320; no. 1; pp. 53 - 62
• Main Authors: Lipska, Kasia J, Parker, Melissa M, Moffet, Howard H, Huang, Elbert S, Karter, Andrew J
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 03.07.2018
• Subjects: Adult; Aged; Blood Glucose - drug effects; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Emergency medical care; Emergency medical services; Emergency Service, Hospital - statistics & numerical data; Female; Glycemic index; Hospitalization - statistics & numerical data; Humans; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemia - prevention & control; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Insulin Detemir - adverse effects; Insulin Detemir - therapeutic use; Insulin Glargine - adverse effects; Insulin Glargine - therapeutic use; Insulin, Isophane - adverse effects; Insulin, Isophane - therapeutic use; Male; Middle Aged; Online First; Original Investigation; Patients; Protamine; Retrospective Studies; Risk reduction
• DOI: 10.1001/jama.2018.7993
• ISSN: 0098-7484

IMPORTANCE: In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from trial results. OBJECTIVE: To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss of health plan coverage, change in insulin treatment, or study end on September 30, 2015. EXPOSURE: Initiation of basal insulin analogs (glargine or detemir) vs NPH insulin. MAIN OUTCOMES AND MEASURES: The primary outcome was the time to a hypoglycemia-related ED visit or hospital admission and the secondary outcome was the change in hemoglobin A1c level within 1 year of insulin initiation. RESULTS: There were 25 489 patients with type 2 diabetes who initiated basal insulin therapy (mean age, 60.2 [SD, 11.8] years; 51.9% white; 46.8% female). During a mean follow-up of 1.7 years, there were 39 hypoglycemia-related ED visits or hospital admissions among 1928 patients who initiated insulin analogs (11.9 events [95% CI, 8.1 to 15.6] per 1000 person-years) compared with 354 hypoglycemia-related ED visits or hospital admissions among 23 561 patients who initiated NPH insulin (8.8 events [95% CI, 7.9 to 9.8] per 1000 person-years) (between-group difference, 3.1 events [95% CI, −1.5 to 7.7] per 1000 person-years; P = .07). Among 4428 patients matched by propensity score, the adjusted hazard ratio was 1.16 (95% CI, 0.71 to 1.78) for hypoglycemia-related ED visits or hospital admissions associated with insulin analog use. Within 1 year of insulin initiation, hemoglobin A1c level decreased from 9.4% (95% CI, 9.3% to 9.5%) to 8.2% (95% CI, 8.1% to 8.2%) after initiation of insulin analogs and from 9.4% (95% CI, 9.3% to 9.5%) to 7.9% (95% CI, 7.9% to 8.0%) after initiation of NPH insulin (adjusted difference-in-differences for glycemic control, −0.22% [95% CI, −0.09% to −0.37%]). CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes, initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.