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ABSTRACT
Introduction: Combining a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter type 2 inhibitor is an attractive option to treat hyperglycaemia in type 2 diabetes.
Areas covered: The saxagliptin plus dapagliflozin combination is carefully analysed, focusing on: 1) pharmacokinetic properties, 2) pharmacodynamics data, and 3) results of randomised controlled trials (dual combination versus either monotherapy, sequential therapy saxagliptin added to dapagliflozin or dapagliflozin added to saxagliptin).
Expert opinion: Pharmacokinetic findings demonstrate the absence of drug-drug interaction and the bioequivalence of the FDC compared with separated tablets. Pharmacodynamic observations confirm a complementary mode of action of the two agents. Dual saxagliptin-dapagliflozin therapy is more potent than either monotherapy. It may be used as an initial combination, although this approach remains debatable and should probably be reserved in case of high glycated hemoglobin, or a stepwise strategy, according to a personalized approach. The developed saxagliptin-dapagliflozin FDC may simplify anti-hyperglycemic therapy and improve drug compliance.
Article highlights
The combination of a dipeptidyl peptidase-4 inhibitor (DPP-4i, gliptin) and a sodium-glucose cotransporter type 2 inhibitor (SGLT2i, gliflozin) is an attractive approach for the management of T2D because the two pharmacological approaches have different and potentially complementary targets.
From a pharmacokinetic point of view, saxagliptin and dapagliflozin did not show clinically relevant drug-drug interactions and demonstrated bioequivalence of fixed-dose combination (FDC) compared to separate tablets.
From a pharmacodynamic point of view, saxagliptin, an agent that increases insulin and reduces glucagon, both in a glucose-dependent manner, and dapagliflozin, an agent that promotes glucosuria, reduces glucose toxicity, but increases glucagon, have complementary mechanisms of action.
From a clinical point of view, saxagliptin plus dapagliflozin combined therapy added to metformin is more efficacious to control blood glucose than either saxagliptin or dapagliflozin monotherapy, without worsening of the safety/tolerance profile.
After metformin failure, DPP-4i – SGLT2i combination may be added as initial therapy or one compound may the added to the other, although the most appropriate sequence remains controversial and should probably be individualized according to patient’s characteristics.
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Declaration of interest
A.J. Scheen has received lecture/advisor fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, NovoNordisk, and Sanofi. The author has 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.