SGLT2 inhibitor/DPP-4 inhibitor combination therapy - complementary mechanisms of action for management of type 2 diabetes mellitus.
Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence. Two classes of glucose-lowering agents that meet these criteria are the sodium glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. This article reviews the rationale for combination therapy with these agents, and evidence from clinical trials with empagliflozin and linagliptin or dapagliflozin and saxagliptin in the management of type 2 diabetes mellitus. Both combinations have been approved as single-pill formulations.
a Endocrine & Metabolic Disorders Institute , Tupelo , MS , USA.
Jayant
J
Dey
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004338:Drug Combinations; D005960:Glucosides / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069476:Linagliptin / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D001559:Benzhydryl Compounds; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin; D000069476:Linagliptin; C502994:saxagliptin; C570240:empagliflozin; D000218:Adamantane
Combination therapy; dapagliflozin; empagliflozin; linagliptin; mechanism of action; saxagliptin; type 2 diabetes mellitus