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Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e1369 (Published 12 March 2012) Cite this as: BMJ 2012;344:e1369

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Re: Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis

We read with great interest the systematic review and meta-analysis recently published in BMJ by Karagiannis and collaborators. Although the study has methodological strengths worth citing, we disagree with some points related to the authors’ conclusions.
Considering the evaluation of the pre-specified primary endpoint (difference in HbA1c, figure 2), the results show that the DPP-4 inhibitors performance is far below that presented by the antidiabetics used as active comparators (metformin, sulfonylureas, pioglitazone and GLP-1 agonists). Even when the secondary endpoint was evaluated (risk ratio for achieving HbA1c < 7%, figure 3), the DPP-4 inhibitors showed at best similar efficacy to sulfonylureas, but remained less effective than metformin, pioglitazone and GLP-1 agonists. Therefore, we considered it inappropriate to say that the glycaemic efficacy of DPP-4 inhibitors is similar to that of sulfonylureas or pioglitazone.
We think that “What this study adds” is, literally: “As monotherapy or combined therapy, metformin, sulfonylureas, pioglitazone and GLP-1 agonists are superior to DPP-4 inhibitors in reducing HbA1c. Body weight benefits can be expected with DPP-4 inhibitors when these drugs are compared with sulfonylureas and pioglitazone, but not with metformin and GLP-1 agonists. Less hypoglycemia episodes can be expected with DPP-4 inhibitors when these drugs are compared with sulfonylureas, but not with metformin, pioglitazone and GLP-1 agonists.”
The main concern regarding this type of interpretation bias is that authors stress in the abstract and abstract box the findings of secondary endpoints and consider the DPP-4 inhibitors similar to sulfonylureas regarding glycaemic control. This misinterpretation could lead to overprescribing this class of drugs, which are more expensive and have limited data concerning long term safety.

Competing interests: No competing interests

23 March 2012
Rafael S. Scheffel
Endocrinologist. Post Graduate Student.
Beatriz D. Schaan
Hospital de Clínicas de Porto Alegre
Ramiro Barcelos, 2350. Serviço de Medicina Interna. Porto Alegre, RS. Brazil.