title: Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm.
abstract: 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.
authors.affiliation: Obesity and Endocrinology Clinical Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K. j.p.h.wilding@liverpool.ac.uk.
authors.forename: John P H
authors.initials: JP
authors.lastname: Wilding
authors.affiliation: Obesity and Endocrinology Clinical Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, U.K.
authors.forename: Surya Panicker
authors.initials: SP
authors.lastname: Rajeev
authors.affiliation: Diabetes Division, The University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D000465:Algorithms; D001559:Benzhydryl Compounds / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination / Q000379:methods; D005960:Glucosides / Q000008:administration & dosage; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D054795:Incretins / Q000008:administration & dosage* / Q000009:adverse effects; D018027:Receptors, Glucagon / Q000819:agonists; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D054795:Incretins; D018027:Receptors, Glucagon; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin