This systematic review compared the evidence for premixed insulin analogues (a mixture of rapid-acting and intermediate-acting insulin analogues) with other antidiabetic agents in adults with type 2 diabetes.

Published data from MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched as was unpublished data from the U.S. Food and Drug Administration, European Medicines Agency, and industry.

Since evidence was inconclusive for clinical outcomes, such as mortality, the review focused on intermediate outcomes. The authors noted the following findings:

• Premixed insulin analogues were similar to premixed human insulin in decreasing fasting glucose levels, haemoglobin A1c levels, and the incidence of hypoglycaemia 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 haemoglobin 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 hypoglycaemia.
• 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 haemoglobin A1c levels (mean difference, –0.49% [CI, –0.86% to –0.12%]) but were associated with a higher incidence of hypoglycaemia.

In terms of limitations of the review, the authors noted that the small number of studies for each comparison limited the assessment of between-study heterogeneity. They concluded that “premixed insulin analogues provide glycaemic control similar to that of premixed human insulin and may provide tighter glycaemic control than long-acting insulin analogues and noninsulin antidiabetic agents”.