Phase 3 Study of Dapagliflozin in Combination with Sitagliptin for Type 2 Diabetes
Bristol-Myers Squibb and AstraZeneca announced results from a Phase 3 clinical study that showed the investigational compound dapagliflozin demonstrated significant reductions in HbA1C compared with placebo at 24 weeks when added to sitagliptin (Januvia; Merck & Co), with or without metformin (Glucophage; Bristol-Myers Squibb), in adult patients with type 2 diabetes. The study also demonstrated significant reductions in total body weight and fasting plasma glucose (FPG).
This was a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study with a 24-week blinded extension. The primary efficacy endpoint at 24 weeks was mean change in HbA1c from baseline. The 24-week extension was designed to assess the maintenance of efficacy with the dapagliflozin treatment group, as well as safety and tolerability over 48 weeks. The study included 447 adults with type 2 diabetes (aged ≥18 years) with inadequate glycemic control (HbA1c≥7% and ≤10%). Patients (n=223) receiving dapagliflozin demonstrated significantly greater improvements in glycemic control at the end of 24 weeks compared to patients (n=224) taking placebo added to sitagliptin with or without metformin, with a change in baseline in HbA1c of -0.48% (P-value<0.0001, Last Observation Carried Forward [LOCF]).
Additional results of the key primary and secondary endpoints included the following:
- Dapagliflozin added to sitagliptin (stratum 1) resulted in a greater reduction in HbA1c compared to placebo added to sitagliptin, with a change in HbA1c of -0.56% (P-value<0.0001, LOCF).
- Dapagliflozin added to sitagliptin and metformin (stratum 2) resulted in a greater reduction in HbA1c compared to placebo added to sitagliptin plus metformin, with a change in HbA1c of -0.4% (P-value<0.0001, LOCF).
- Reductions in HbA1c were notable at four weeks (the first recorded time point) and maintained to 48 weeks.
- Patients with a higher baseline HbA1c (≥ 8%) receiving treatment with dapagliflozin achieved greater reductions in HbA1c.
- Significant reductions in body weight were observed with dapagliflozin compared to placebo in the entire treatment cohort (-1.89kg, LOCF), stratum 1 (-1.85kg, LOCF) and stratum 2 (-1.87kg, LOCF), and were sustained out to 48 weeks.
- Significant differences were also observed in adjusted mean FPG in patients who received dapagliflozin.
Dapagliflozin is an inhibitor of SGLT2, a sodium-glucose cotransporter in the kidney. It is being evaluated for use as a monotherapy and in combination with other anti-diabetic agents in adults with type 2 diabetes as an adjunct to diet and exercise.