Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes

By J. List, V. Woo, E. Morales, Wei-hua Tang, F. Fiedorek. Diabetes Care, 2008

690 citations recorded by the source corpus.

OBJECTIVE Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Type 2 diabetic patients were randomly assigned to one of five dapagliflozin doses, metformin XR, or placebo for 12 weeks. The primary objective was to compare mean change from baseline in A1C. Other objectives included comparison of changes in fasting plasma glucose (FPG), weight, adverse events, and laboratory measurements. RESULTS After 12 weeks, dapagliflozin induced moderate glucosuria (52–85 g urinary glucose/day) and demonstrated significant glycemic improvements versus placebo (ΔA1C −0.55 to −0.90% and ΔFPG −16 to −31 mg/dl). Weight loss change versus placebo was −1.3 to −2.0 kg. There was no change in renal function. Serum uric acid decreased, serum magnesium increased, serum phosphate increased at higher doses, and dose-related 24-h urine volume and hematocrit increased, all of small magnitude. Treatment-emergent adverse events were similar across all groups. CONCLUSIONS Dapagliflozin improved hyperglycemia and facilitates weight loss in type 2 diabetic patients by inducing controlled glucosuria with urinary loss of ∼200–300 kcal/day. Dapagliflozin treatment demonstrated no persistent, clinically significant osmolarity, volume, or renal status changes.

Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/6d5e854be5ee63a961b777df460a1f526f988727

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Citations in the corpus

Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus (2014, background): “This is further reflected by mild but significant increases in hematocrit and plasma urea within the normal range.(18) Our study is the first to demonstrate that similar to familial renal glucosuria, pharmacological SGlT2 inhibition-induced effective circulating volume contraction is accompanied by ”
Update on the treatment of type 2 diabetes mellitus. (2016, background): “Also the effects on blood pressure were not dose-dependent and were not accompanied by any notable changes in heart rate or increases in hypotension and/ or syncope [158,159] .”
SGLT2 inhibition — a novel strategy for diabetes treatment (2010, methodology): “Subsequent to this initial 2-week study, List and colleagues performed a 12-week, double-blind, randomized, parallel-group, placebo-controlled Phase II trial in 389 treatment-naive subjects with T2D”
Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes (2013, result): “Previous studies have shown greater reductions of office SBP with dapagliflozin treatment than placebo treatment [7,8].”