Combination therapy of SGLT2 inhibitors with incretin-based therapies for the treatment of type 2 diabetes mellitus: Effects and mechanisms of action

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide; its pathogenesis is multifactorial and its progressive nature often necessitates a combination therapy with multiple antihyperglycemic agents. Sodium glucose cotransporter 2 (SGLT2) inhibitors and the incretin-based therapies - dipeptidyl peptidase 4(DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists – were introduced for the treatment of T2DM within the last decade. Evidence of the beneficial effects of these antihyperglycemic agents on micro- and macrovascular complications have started to emerge, which will become important in individualizing different combinations of antihyperglycemic agents to different patient populations. We review here the mechanisms of action, glycemic and cardiovascular effects of SGLT2 inhibitors and incretin-based therapies and their combination in the treatment of T2DM.

KEYWORDS:

• Type 2 diabetes mellitus
• sodium glucose cotransporter 2
• glucagon-like peptide 1
• dipeptidyl peptidase-4
• cardiovascular outcomes
• combination therapy
• endogenous glucose production

Financial and competing interests disclosure

M.H. Schernthaner-Reiter served on advisory boards for Boehringer Ingelheim and Novartis. G. Schernthaner served on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, and Takeda. G. Schernthaner has served as a speaker for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novo Nordisk, Sanofi, and Takeda. 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.