Prescribing Advice for GPs

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Meta Analysis of DPP-4 Inhibitors

The British Medical Journal has published the results of a meta analysis of trials of dipeptidyl peptidase-4 (DPP-4) inhibitors for treatment of type 2 diabetes mellitus.

This review included data from 19 studies involving 7,136 patients randomised to treatment with a DPP-4 inhibitor and 6,745 patients randomised to another active treatment. The analysis reviewed several outcome measures including reduction in HbA1c, proportion of participants reaching a target HbA1c of 7%, change in body weight, adverse events and mortality.

In 8 studies where DPP-4 inhibitors were compared to metformin, DPP-4 inhibitors were inferior in terms of reduction in HbA1c, proportion reaching target and weight loss.

When compared to second line agents including sulphonylureas, glitazones and glucagon-like peptide-1 (GLP-1) agonists the results were more variable.

DPP-4 inhibitors had similar effects on HbA1c and a similar proportion of patients reached the HbA1c target when compared to sulphonylureas and pioglitazone. DPP-4 inhibitors were superior to these two drug classes in terms of weight. When compared to GLP-1 agonists, DPP-4 inhibitors were inferior in all three of these measures.

The authors conclude that, "DPP-4 inhibitors can lower HbA1c, in a similar way to sulphonylureas or pioglitazone, with neutral effect on body weight" but that higher cost and "uncertainty about their long term safety, should also be considered".

There are limitations in this study. Data were not analysed individually for each DPP-4 inhibitor and the comparative data against GLP-1 agonists and pioglitazone are not very robust due to the limited research data currently available. There was also no correction for baseline characteristics and none of the studies included any cardiovascular end points so no hard outcome endpoints could be analysed.

NICE currently recommend a sulphonylurea as second line with alternatives considered where there is a significant risk of hypoglycaemia and its consequences or there is intolerance or contraindications to such medication.

Action: Clinicians who see and treat patients with diabetes will find this analysis useful. This analysis confirms that DPP-4 inhibitors offer similar benefits in terms of HbA1c to other oral therapies with some advantages in weight but at a higher acquisition cost.

Thanks to Kevin Ashworth for spotting this article

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