Bottom-line conclusion: Premixed insulin analogues provide glycemic control similar to that of premixed human insulin and may provide tighter glycemic control than long-acting insulin analogues and noninsulin antidiabetic agents.
Method: The authors searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to February 2008 and sought unpublished data from the U.S. Food and Drug Administration, European Medicines Agency, and industry. Studies with control groups that compared premixed insulin analogues with another antidiabetic medication in adults with type 2 diabetes. Two reviewers using standardized protocols performed serial abstraction.
Results: Evidence from clinical trials was inconclusive for clinical outcomes, such as mortality. Therefore, the review focused on intermediate outcomes. Premixed insulin analogues were similar to premixed human insulin in decreasing fasting glucose levels, hemoglobin A1c levels, and the incidence of hypoglycemia but were more effective in decreasing postprandial glucose levels (mean difference, -1.1 mmol/L; 95% CI, -1.4 to -0.7 mmol/L [-19.2 mg/dL; 95% CI, -25.9 to -12.5 mg/dL]). Compared with long-acting insulin analogues, premixed insulin analogues were superior in decreasing postprandial glucose levels (mean difference, -1.5 mmol/L; CI, -1.9 to -1.2 mmol/L [-27.9 mg/dL; CI, -34.3 to -21.5 mg/dL]) and hemoglobin A1c levels (mean difference, -0.39% [CI, -0.50% to -0.28%]) but were inferior in decreasing fasting glucose levels (mean difference, 0.7 mmol/L; CI, 0.3 to 1.0 mmol/L [12.0 mg/dL; CI, 6.0 to 18.1 mg/dL]) and were associated with a higher incidence of hypoglycemia. Compared with noninsulin antidiabetic agents, premixed insulin analogues were more effective in decreasing fasting glucose levels (mean difference, -1.1 mmol/L; CI, -1.7 to -0.6 mmol/L [-20.5 mg/dL; CI, -29.9 to -11.2 mg/dL]), postprandial glucose levels (mean difference, -2.1 mmol/L; CI, -3.4 to -0.8 mmol/L [-37.4 mg/dL; CI, -61.0 to -13.7 mg/dL]), and hemoglobin A1c levels (mean difference, -0.49% [CI, -0.86% to -0.12%]) but were associated with a higher incidence of hypoglycemia.
Citation: Qayyum, R., Bolen, S., Maruthur, N., Feldman, L., Wilson, L. M., Marinopoulos, S. S., Ranasinghe, P., Amer, M. & Bass, E. B. (2008) Systematic Review: Comparative Effectiveness and Safety of Premixed Insulin Analogues in Type 2 Diabetes. Annals of Internal Medicine, 149, 549-559.
Publication history information: Published in 2008.
Access: Available to the general public.