Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of
type 2 diabetes and became available after the introduction of
incretin-based
therapies,
dipeptidyl peptidase 4 inhibitors and
glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their
weight loss-promoting effect, low risk of
hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with
empagliflozin). Apart from these clinically important outcomes, they may also correct core defects present in
type 2 diabetes (i.e., improvement in β-cell function and
insulin sensitivity). They do, however, have some adverse effects, notably,
nausea with
GLP-1 RAs and
genital tract infections and potential for volume depletion with SGLT2i. Whether
incretin-based
therapies are associated with an increased risk of
pancreatitis is unclear. Most recently,
diabetic ketoacidosis has been reported with SGLT2i. Therefore, a key clinical question in relation to guidelines is whether these clinical advantages, in the context of the adverse effect profile, outweigh the additional cost compared with older, more established
therapies. This article reviews the therapeutic rationale for the use of these newer drugs for diabetes treatment, considers their place in current guidelines, and discusses how this may change as new data emerge about their long-term efficacy and safety from ongoing outcome trials.