Insufficient evidence of benefit for colesevelam in glycemic control in type 2 diabetes

Another drug for type 2

Colesevelam is a bile acid sequestrant drug that was originally approved in the US for the treatment of hyperlipidaemia.  It was subsequently found to help improve glycaemic control in type 2 diabetes.  This dual benefit offers significant potential in reducing the risk of complications in T2.  This Cochrane systematic review set out to summarise all of the evidence from randomised trials looking that impact of colesevalam on glyceamic control.

Bottom line:

This is a good quality systematic review of a question that is relevant to clinical practice.  It is unlikely that important evidence was missed and the reviewers took all appropriate steps to review the evidence in an unbiased way.  Although the results show that colesevelam reduced HbA1c, the results should be interpreted with caution due to the small sample size, heterogeneity and risk of bias in the individual studies.

Clinical question:

  • Patients:  adults with type 2 diabetes
  • Interventions:  colesevelam alone vs placebo, or colesevelam plus other antihyperlipidaemic and/or antiglycaemic agents vs placebo plus other antihyperlipiaemic and/or antiglycaemic agents
  • Outcomes: glycaemic control (HbA1c, FPG and PPG), morbidity and adverse effects

Methods

A comprehensive literature search was carried out, including key databases and hand searching of journals and theses.  Non-English papers were included and appropraite search methods were employed.

Study selection, study assessment and data extraction were carried out by two blind, independent reviewers.  Individual studies were assessed for their risk of bias according to Cochrane protocols.

The reviewers assessed both clinical and statistical heterogeneity of the individual studies.  Sensitivity analyses were planned to investigate different patient subgroups and the potential impact of bias in individual studies.

Results

Six trials were found, comprising 1,450 particiants.  One trial compared colesevelam with placebo and the other five comparing colesevelam in combination with other agents. All of the studies were assessed as having unclear risk of bias.

Across all studies, colesevelam was associated with a reduction in HbA1c of -0.48% [95% CI -0.61% to -0.36%].

There were no significant differences in adverse events, including hypoglycemia, or morbidity.  Due to lack of data, the planned subgroup analyses could not be performed.

Conclusion

Although there was a statistically significant impact on HbA1c, the reviewers comment that each trial investigated a different treatment regimen.  The reviewers comment:

Caution is needed when interpreting these findings. The effect estimates were small. The relatively small sample size in each of the colesevelam or colesevelam combination trials contributed to the low power of the studies. Further, there were no data published on mortality, diabetic complications, functional outcomes, costs of treatment and health-related quality of life.

Comments

  • It wasn’t clear from the review whether all patients also had hypercholesterolemia in addition to type 2.
  • All of the trials failed to report adequate allocation concealment.  There is some risk of bias in the individual studies.
  • There was insufficient data in these trials to rule in or rule out other benefits or adverse effects.

Reference

Ooi CP, Loke SC. Colesevelam for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD009361. DOI: 10.1002/14651858.CD009361.pub2.

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Badenoch

Badenoch
I am an information scientist with an interest in making knowledge from systematic research more accessible to people who need it. This means you. I've been attempting this in the area of Evidence-Based Health Care since 1995. So far the results have been mixed. For some reason we expected busy clinicians to search databases and appraise papers instead of seeing patients. We also expected publishers to make the research freely available to the people who paid for it.. Ha! Hence The National Elf service.

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