The safety of DPP-4 inhibitor and SGLT2 inhibitor combination therapies

ABSTRACT

Introduction: Type 2 diabetes (T2D), a multifactorial and chronic disease, requires in an elevated percentage of patients the association of several antidiabetic drugs to achieve optimal glycemic control. Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium–glucose cotransporter inhibitors (SGLT2i) are new classes of oral antidiabetic drugs developed over the last years.

Areas covered: This paper summarizes the safety of DPP-4i and SGLT2i combination therapies. Relevant studies were identified through searches in PubMed.

Expert opinion: DPP4i and SGLT2i are antidiabetic drugs that lower blood glucose without causing hypoglycaemia or weight increase. More importantly, cardiovascular trials have clearly demonstrated the cardiovascular safety of DPP4i and a reduction in cardiovascular events with SGLT2i (empagliflozin and canagliflozin). Therefore, the association of both therapeutic groups could be an attractive option to achieve optimal blood glucose control in T2D because of their complementary mechanism of action. Clinical trials evaluating the combination of SGLT2i and DPP4i show that the co-administration of these drugs in fixed-dose combinations in comparison to separate tablets does not carry additional safety concerns that each individual drug, but increases therapeutic effects. Therefore, this antidiabetic combination is a safe and effective therapy for patients with T2D.

KEYWORDS:

• SGLT-2 inhibitor
• DPP-4 inhibitor
• combination
• safety

Article highlights

• T2D, a prevalent chronic disease, frequently requires the combination of different antidiabetic drugs to achieve an adequate glycemic control.

• Both DPP-4i and SGLT2i are new classes of oral antidiabetic drug that have demonstrated clinical efficacy with an acceptable safety profile.

• The concomitant use of both therapeutic agents is a potential therapeutic option to treat T2D, as SGLT2i and DPP4i exert additive effects on hyperglycemia, and do not produce hypoglycaemia or weight increase.

• All studies to date have shown that the combination of SGLT2i and DPP4i has a similar safety profile than each individual drug separately.

• The combination of SGLT-2 and DPP4i is an attractive antidiabetic therapy for patients with T2D, potentially increasing adherence and exerting beneficial effects on glycemic control and other cardiovascular risk factors, altogether with an adequate safety profile.

Declaration of interest

M Molina-Vega has received speaker fees from AstraZeneca, and has received research grant support from Sanofi. A Muñoz-Garach has received speaker fees from AstraZeneca, Novo Nordisk, Sanofi, Eli Lilly, and Boehringer Ingelheim, and has received research grant support from Novo Nordisk. JC Fernández-García has received speaker fees from AstraZeneca, Novo Nordisk, Sanofi, Eli Lilly, and Boehringer Ingelheim, and has received research grant support from Menarini and Novo Nordisk. FJT declares research support from AstraZeneca and Menarini and advisory board membership and receipt of consulting honoraria from AstraZeneca, Novo Nordisk, Sanofi, Eli Lilly, Janssen, Angem, Mylan, Regeneron, Orexigen, Rovi, and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

José C. Fernández-García was supported by a research contract from Servicio Andaluz de Salud (SAS) grant x B-0033-2014