We report on a critical appraisal by the Centre for Reviews and Dissemination (CRD) of a systematic review of insulin regimens in type 2 diabetes.
In type 2 diabetes inadequately controlled with oral agents, does biphasic insulin, compared with basal insulin, lead to better glycaemic control?
The review defined the proportion of patients reaching HbA1c target (7%) as its measure of glycaemic control.
The systematic review found 16 RCTs, with 7,759 patients. When they combined the data, they found that patients treated with biphasic insulin were more likely to reach their target HbA1c (7%) than those treated with basal or basal-bolus regimens. The odds ratios for these comparisons were:
- Biphasic versus basal (10 studies, mostly on insulin-naive patients): OR 1.88; 95% CI 1.38–2.55.
- Biphasic versus basal-bolus (3 studies, all on patients who were already using insulin): OR 1.75, 95% CI 1.11–2.77.
The following comparisons showed no significant difference in the number of people achieving target:
- Biphasic versus prandial (3 studies),
- Prandial versus basal (4 studies).
The CRD concluded:
The small number of trials for some comparisons and high heterogeneity make generalisability unclear. These limitations of the evidence-base were exacerbated by moderate-to-low trial quality which introduced potential for bias.
Users of this research should consider:
- Was the review clearly focused enough? There may have been important clinical differences between the patient populations of the individual trials. For example, some patients were starting insulin whilst others were already on insulin.
- Very different insulin regimens were involved: basal, biphasic, prandial or basal-bolus. Consider carefully how transferable these findings would be to your circumstances.
- What is the sensitivity of these results to potential bias in individual studies?
- Given the wide confidence intervals, it seems that more research is needed to reduce the uncertainty around the benefits of biphasic insulin.
- The search was done in January 2010; it’s likely that new research has been published since.
Giugliano D, Maiorino MI, Bellastella G, Chiodini P, Ceriello A, Esposito K. Efficacy of insulin analogs in achieving the hemoglobin A1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Care 2011; 34(2): 510-517.