Combined metformin and dapagliflozin therapy in diabetes: an evidence based review

Abstract

Objectives: To compare the effect of the combination of metformin and dapagliflozin compared with metformin and other oral anti-diabetics as an add-on therapy in patients inadequately controlled with metformin alone. Data sources: MEDLINE and other evidence-based medicine databases Review methods: A review was made of meta-analyses, systematic reviews, randomized controlled clinical trials and clinical guidelines, published between January 2007 and March 2017, in Portuguese, English and Spanish, using the MeSH terms ‘dapagliflozin’, ‘diabetes mellitus type 2’, and ‘metformin’. The American Family Physician Strength of Recommendation Taxonomy (SORT) was used to establish the quality of the studies and to define the strength of recommendations. Results: There were 59 articles found. Eight met the inclusion criteria. These included one meta-analysis, one systematic review, five randomized controlled clinical trials, and one clinical guideline. There is evidence that dual therapy with metformin and dapagliflozin is effective in reducing glycosylated haemoglobin and body weight, when compared to other oral anti-diabetics, without increasing the risk of hypoglycemic episodes. The most frequent adverse effects related to this drug were urinary tract and genital infections, especially in women (SORT C). Dapagliflozin seems to be neutral regarding cardiovascular risk and its association with cancer is yet to be clarified. Conclusions: There was not enough evidence to support the claim that dapagliflozin combined with metformin is more effective or better for the patient when compared to other oral anti-diabetics (SORT C). Given these limitations, we conclude that more controlled studies are required to determine the effects of dapagliflozin in terms of efficacy, safety, morbidity and mortality, as well as the maintenance of the results with this combination of drugs.