Addition of dapagliflozin may benefit patients whose blood glucose is uncontrolled with both metformin and sulfonylurea…
Dapagliflozin is a selective and reversible sodium-glucose co-transporter 2 (SGLT2) inhibitor, which lowers plasma glucose level by increasing urinary excretion of glucose. Addition of dapagliflozin may benefit patients whose blood glucose is uncontrolled with both metformin and sulfonylurea; however, the effectiveness and safety of this combination is unknown.
This study was a 24-week, international, multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase IIIb study, designed to evaluate the efficacy and safety of dapagliflozin compared to placebo in uncontrolled type 2 diabetic patients with metformin and sulfonylurea combination therapy. The study population included 219 patients more than 18 years of age and inadequate glycemic control (HbA1C ≥ 7.0% and ≤ 10.5%). They were randomly assigned to either dapagliflozin 10 mg group or a placebo group, along with metformin and a sulfonylurea. HbA1C levels were measured at baseline and after 24 weeks of treatment. The primary end point was change of HbA1C levels from baseline to week 24. Key secondary end points included change from baseline to week 24 in FPG, total body weight, proportion of patients having HbA1C < 7%, and change from baseline to week 8 in SBP. Statistical tests included ANCOVA and last observation carried forward (LOCF) approach.
At the end of the study, patients treated with dapagliflozin demonstrated significant improvements in glycemic control compared to patients with placebo. HbA1c levels were significantly lower in dapagliflozin group compared to placebo group, with a decrease of 0.86% and 0.17% from baseline levels, respectively (p-value < 0.0001). In patients with higher baseline HbA1C levels, the decreases were even higher. Patients with baseline HbA1C levels over 9% and less than 8% had a decrease of 0.82% and 0.36%, respectively. After 24 weeks, 31.8% of patients in dapagliflozin group achieved HbA1C levels less than 7%, compared to 11.1% of patients in placebo group (p-value < 0.0001). In addition, dapagliflozin showed significant reductions compared to placebo in adjusted mean fasting plasma glucose (-34.23 and -0.78 mg/dL, respectively) and body weight (-2.65 and -0.58 kg, respectively) at 24 weeks (p-value < 0.0001), and SBP (-4.04 mmHg and -0.27 mmHg) at 8 weeks (p-value = 0.025). Both groups experienced similar mild to moderate intensity adverse events, with 48.6% in dapagliflozin group, and 51.4% in placebo group. Those adverse events included hypoglycemia, genital infection, renal events, and urinary tract infection. One event of pyelonephritis was seen in the dapagliflozin group. Higher incidence of hypoglycemia in dapagliflozin group (12.8%) was seen compared to placebo group (3.7%).
This study showed that dapagliflozin is safe and effective in lowering plasma glucose level in uncontrolled diabetic type 2 patients on metformin and sulfonylurea. It is also important to note the adverse effects of dapagliflozin, which include hypoglycemia and genital infections or urinary tract infections. Further studies are needed to analyze the long-term effects of dapagliflozin.
- Dapagliflozin is well tolerated and effective monotherapy or in combination with other antihyperglycemic medications.
- When prescribing or dispensing dapagliflozin, it is important to advise the patients to watch for signs and symptoms of genital or urinary tract infections.
- In patients who already exposed to sulfonylurea, after adding dapagliflozin, it is recommended to discontinue or titrate down sulfonylurea.
Stephan Matthaei, Keith Bowering, KatjaRohwedder, AnkeGrohl, and Shamik Parikh. “Dapagliflozin Improves Glycemic Control and Reduces Body Weight as Add-on Therapy to Metformin Plus Sulfonylurea: A 24-Week Randomized, Double-Blind Clinical Trial”. Diabetes Care. 2015;38:365–372.