Systematic Review: Comparative Effectiveness and Safety of Premixed Insulin Analogues in Type 2 Diabetes

21 October 2008 | Volume 149 Issue 8 | Pages 549-559

Background: Evidence comparing premixed insulin analogues (a mixture of rapid-acting and intermediate-acting insulin analogues) with other antidiabetic agents is urgently required to guide appropriate therapy.

Purpose: To summarize the English-language literature on the effectiveness and safety of premixed insulin analogues compared with other antidiabetic agents in adults with type 2 diabetes.

Data Sources: 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EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to February 2008 and sought unpublished data from the U.S. Food and Drug Administration, European Medicines Agency, and industry.

Study Selection: Studies with control groups that compared premixed insulin analogues with another antidiabetic medication in adults with type 2 diabetes.

Data Extraction: 2 reviewers using standardized protocols performed serial abstraction.

Data Synthesis: 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 A_1c 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 A_1c 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 A_1c levels (mean difference, –0.49% [CI, –0.86% to –0.12%]) but were associated with a higher incidence of hypoglycemia.

Limitations: The literature search was restricted to studies published in English. Data on clinical outcomes were limited. The small number of studies for each comparison limited assessment of between-study heterogeneity.

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.

Editors' Notes Context The relative effects of premixed insulin analogues, other insulin regimens, and noninsulin antidiabetic agents for adults with type 2 diabetes are unclear. Contribution This systematic review of comparative trials in adults with type 2 diabetes found that premixed insulin analogues and premixed human insulin provided similar glycemic control. Premixed analogues provided tighter glycemic control and caused more hypoglycemia than long-acting insulin analogues and noninsulin antidiabetic agents. Caution Evidence for effects on clinical outcomes was scant and inconclusive. Implication We need large, long-term trials that compare premixed insulin analogues with other agents to see whether improvements in glucose control lead to improved clinical outcomes. —The Editors

 

Author and Article Information

From Evidence-based Practice Center, Johns Hopkins University, Baltimore, Maryland.

Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Grant Support: This article is based on research conducted by the Johns Hopkins Evidence-based Practice Center under contract number 290-02-0018 with the Agency for Healthcare Research and Quality, Rockville, Maryland.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Rehan Qayyum, MD, Johns Hopkins Hospital, Hospitalist Program, 600 North Wolfe Street, Park 307-A, Baltimore, MD 21287; e-mail, rqayyum{at}jhmi.edu.

Current Author Addresses: Dr. Qayyum: Johns Hopkins Hospital, Hospitalist Program, 600 North Wolfe Street, Park 307-A, Baltimore, MD 21287.

Dr. Bolen: 2024 East Monument Street, Suite 2-600, Baltimore, MD 21205.

Dr. Maruthur: 2024 East Monument Street, Suite 2-500, Baltimore, MD 21205.

Drs. Feldman, Ranasinghe, and Amer: Johns Hopkins Hospital, Hospitalist Program, 600 North Wolfe Street, Park 307, Baltimore, MD 21287.

Ms. Wilson: Johns Hopkins Evidence-based Practice Center, 1830 East Monument Street, Room 8064, Baltimore, MD 21287.

Dr. Marinopoulos: Johns Hopkins Outpatient Center Practice, 601 North Caroline Street, Suite 7143, Baltimore, MD 21287.

Dr. Bass: Johns Hopkins Evidence-based Practice Center, 1830 East Monument Street, Room 8068, Baltimore, MD 21287.

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