SODIUM GLUCOSE COTRANSPORTER 2 AND DIPEPTIDYL PEPTIDASE-4 INHIBITION: PROMISE OF A DYNAMIC DUO.
OBJECTIVE
This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM).


METHODS
We conducted a nonsystematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States.


RESULTS
SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiologic abnormalities present in T2DM without overlapping toxicities. The combination of these 2 agents has several advantages including a low risk of hypoglycemia, the potential for weight loss, the ability to coformulate into a pill with once-daily administration, and the possibility to use with other classes of glucose-lowering agents. Cardiovascular outcomes trials reported to date support the safety of the DPP-4 class and suggest possible cardioprotective effects for SGLT2 inhibitors - at least based on the first reported study that used empagliflozin. Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy.


CONCLUSIONS
The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.


BACKGROUND
BP = blood pressure; CI = confidence interval; CVOT = cardiovascular outcomes; DKA = diabetic ketoacidosis; DPP-4 = dipeptidyl peptidase-4; EXAMINE = EXamination of cArdiovascular outcoMes with alogliptiN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome; FDA = Food and Drug Administration; HbA1c = glycated hemoglobin; HR = hazard ratio; MACE = major adverse cardiovascular events; SAVOR-TIMI 53 = Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Type 2 Diabetes Mellitus; SBP = systolic blood pressure; SGLT2 = sodium glucose cotransporter 2; TECOS = Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin; T2DM = type 2 diabetes mellitus; XR = extended release.
Ildiko
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Lingvay
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D000068896:Canagliflozin / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069476:Linagliptin / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D010880:Piperidines; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; C529054:dapagliflozin; D000069476:Linagliptin; D014498:Uracil; D008687:Metformin; C502994:saxagliptin; C570240:empagliflozin; C520853:alogliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate