[Dapagliflozin, the first SGLT-2 inhibitor in the treatment of type 2 diabetes].
Dapagliflozin is the first novel sodium-glucose co-transporter-2 (SGLT2) inhibitor approved by the European Medicines Agency (EMA) for the treatment of type 2 diabetes. By inhibiting SGLT2, dapagliflozin blocks reabsorption of filtered glucose in the kidney, increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of pancreatic β cell function and modulation of insulin sensitivity. The results of phase III clinical trials showed that dapagliflozin, at a dose of 5 or 10mg/day for 24 weeks as monotherapy in previously untreated patients, or as add-on combination therapy with metformin, glimepiride, pioglitazone or insulin-based therapy, significantly reduced both HbA1c and fasting plasma glucose levels compared with placebo. In addition, dapagliflozin was noninferior to glipizide, in terms of glycemic control after 52 weeks, when used as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. In most clinical trials, dapagliflozin reduced body weight. The combination of both effects (improved glycemic control and weight loss) is achieved to a greater extent in treatments that include dapaglifozin. Longer-term extension studies indicated that the efficacy of dapagliflozin on the glycemic control and weight reducción is maintained for up to 2 and 4 years. Dapagliflozin was well tolerated. Genital infections and urinary tract infections were more frequent in patients who received dapagliflozin than in placebo recipients. Hypoglycemic episodes were scarce with dapagliflozin. In conclusion, dapagliflozin is a novel option for the management of type 2 diabetes, particularly when used as add-on therapy.
Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, España.
Olga González
OG
Albarrán
Unidad de Referencia de Diabetes, Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valencia, Valencia, España. Electronic address: fjab63@gmail.com.
F Javier
FJ
Ampudia-Blasco
D001559:Benzhydryl Compounds; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004198:Disease Susceptibility; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006029:Glycosuria / Q000139:chemically induced; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000209:etiology; D015431:Weight Loss
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005947:Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C089180:SLC5A2 protein, human; C529054:dapagliflozin
Clinical trials; Cotransportadores de sodio-glucosa; Dapagliflozin; Dapagliflozina; Diabetes tipo 2; Efficacy; Eficacia; Estudios clínicos; Glucosúricos; Inhibidores de SGLT2; SGLT2 inhibitors; Safety; Seguridad; Sodium-glucose co-transporters; Tolerability; Tolerancia; Type 2 diabetes