Dapagliflozin in the treatment of patients with type 2 diabetes presenting with high baseline A1C

ABSTRACT

Objectives: To evaluate the efficacy and safety of dapagliflozin 5 and 10 mg/d versus placebo in patients with type 2 diabetes and high baseline A1C defined as A1C ≥ 9% or ≥ 10%.

Methods: A post-hoc analysis was conducted of pooled data from 9, 24-week, placebo-controlled clinical studies investigating dapagliflozin as monotherapy, add-on therapy to other oral antidiabetes drugs or insulin, or initial combination therapy with metformin.

Results: At week 24, dapagliflozin 5 and 10 mg/d decreased A1C (≥ 9%: –1.37% and –1.39%, respectively, vs. –0.65% with placebo, both P < 0.0001 and ≥ 10%: –2.13% [P < 0.0001] and –1.59% [P = 0.0003], respectively, vs. –0.82% with placebo), reduced fasting plasma glucose as early as week 1 (P < 0.001 for each dose at all time points for both treatments), and decreased body weight (≥ 9%: P < 0.0001 vs. placebo for both doses; ≥ 10%: P = 0.0065 vs. placebo, 10 mg/d only). Among patients with baseline A1C ≥ 9% who received dapagliflozin 5 or 10 mg/d, 15.7% and 18.9%, respectively, achieved a ≥ 5% decrease in body weight (both P < 0.0001 vs. 3.6% with placebo). Dapagliflozin 10 mg/d decreased systolic and diastolic blood pressure (P < 0.0001 and P = 0.0074 vs. placebo). Adverse events were generally similar across treatment groups, with the exception of a greater frequency of genital infections and hypoglycemia (mostly minor episodes not requiring third-party assistance) in patients receiving dapagliflozin.

Conclusion: In patients with poorly controlled type 2 diabetes defined as A1C ≥ 9% or ≥ 10%, dapagliflozin provided clinically meaningful improvements in glycemic parameters, body weight, and blood pressure, and was generally well tolerated, making it a good therapeutic option for patients with high A1C.

KEYWORDS:

• A1C
• dapagliflozin
• post-hoc analysis
• sodium-glucose cotransporter-2 inhibitor
• type 2 diabetes

Financial & competing interests disclosure

Medical writing support was provided by Scarlett Geunes-Boyer, PhD, and Janet E. Matsuura, PhD, from Complete Healthcare Communications, LLC, and was funded by AstraZeneca. N Skolnik has served on advisory boards for AstraZeneca, Sanofi, Eli Lilly, and Teva. H Bonnes has no financial or commercial interest to disclose. H Yeh is an employee of AstraZeneca. A Katz was an employee of AstraZeneca at the time this research was conducted. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.