Dapagliflozin when added to existing glimepiride (sulphonylurea) therapy significantly reduced HbA1C (glycosylated hemoglobin) in adults with Type 2 Diabetes, compared to patients taking glimepiride plus a placebo, a 24-week Phase 3 Study revealed. In a joint announcement, Astra Zeneca PLC. and Bristol-Myers Squibb Company said the trial met the study goals.

Study researchers reported that dapagliflozin plus glimepiride successfully achieved reductions in secondary efficacy endpoints of change in total body weight, OGTT (oral glucose tolerance test), as well as FPG (fasting plasma glucose) levels from baseline at 24 weeks, compared to glimepiride with a placebo (just glimepiride).

A significantly larger number of study participants were able to achieve a target HbA1c of under 7% compared to those on just glimepiride.

The study findings were presented at the EASD (European Association for the Study of Diabetes) Annual Meeting, Stockholm, Sweden.

Treatment groups had similar overall frequency of drug-related adverse events (undesirable side effects), the researchers informed. Those being treated with dapagliflozin had a higher incidence of signs and symptoms suggestive of genital tract infections (not urinary tract infections).

Dapagliflozin is an SGLT2 (sodium-glucose cotransporter-2); according to AstraZeneca and Bristol-Myers Squibb, a first-in-class. It is currently undergoing Phase 3 Trials as a once-daily oral therapy for adults with Type 2 Diabetes. SGLT2 inhibitors act independently of insulin mechanisms. They facilitate the excretion of glucose and associated calories in urine, resulting in lower levels of glucose in the blood.

Krzysztof Strojek, Professor, Department of Internal Diseases Diabetology & Nephrology Silesian Medical University, Zabrze (Poland), study leader, said:

With type 2 diabetes, we often see a progressive deterioration of glycemic control in patients, which may require treatment intensification with additional drug therapy. This study, which adds to the Phase 3 data available for this investigational compound, demonstrated that dapagliflozin improved glycemic control, as measured by HbA1c, FPG and PPG, in adult patients with type 2 diabetes when added to the commonly used oral diabetic agent – glimepiride.

It was a 24-week, multicenter, international, randomized, parallel-group, double-blind, placebo-controlled Phase 3 study.

The aim was to determine the efficacy of dapagliflozin (2.5 mg, 5 mg or 10 mg per day) as adjunct therapy to glimepiride (4 mg/day) in improving levels of sugar in the blood (glycemic control) in Type 2 Diabetes adult patients, as determined by the change in HbA1c levels from baseline at week 24, and includes a 24-week double-blind extension.

There were 592 patient participants; all aged at least 18 years. They all had HbA1c of at least 7% and less than 10% at baseline on at least half the maximum recommended dose of glimepiride alone.

The patients were randomly selected into one of four treatment groups:

  • dapagliflozin 2.5 mg + glimepiride
  • dapagliflozin 5 mg + glimepiride
  • dapagliflozin 10 mg + glimepiride
  • placebo + glimepiride

The study’s primary endpoint was to assess the change from HbA1 baseline at 24 weeks. Key secondary endpoints included the change from baseline in body weight, change in oral glucose tolerance test (OGTT), proportion of patients achieving an HbA1c of less than 7% and reduction in fasting plasma glucose (FPG) levels at week 24.

Those on dapagliflozin + glimepiride achieved considerable dose-dependent reductions from baseline in HbA1C of:

  • -0.58% for dapagliflozin 2.5 mg
  • -0.63% for dapagliflozin 5 mg
  • -0.82% for dapagliflozin 10 mg
  • Compared to -0.13% for placebo plus glimepiride (p-value of less than 0.0001 for all three treatment arms)

Compared to those on a placebo plus glimepiride, participants in the dapagliflozin plus glimepiride group achieved greater weight loss.

Patients receiving dapagliflozin plus glimepiride attained considerably reductions from baseline in the OGTT of -32.0 mg/dL and -34.9 mg/dL for dapagliflozin 5 mg and 10 mg, respectively compared to -6.0 mg/dL for placebo plus glimepiride (p-value less than 0.01 and less than 0.0001 for dapagliflozin 5 mg and 10 mg, respectively). Dapagliflozin 2.5 mg reduced OGTT by 37.5 mg/dL.

More patients on dapagliflozin plus glimepiride also achieved an HBA1c level of under 7% than those on glimepiride plus placebo at week 24:

  • 30.3% for dapagliflozin 5 mg
  • 31.7% for dapagliflozin 10 mg
  • compared to 13.0% for glimepiride plus placebo (p-value less than 0.01 and less than 0.0001 for dapagliflozin 5 mg and 10 mg, respectively)
  • 26.8% of those on dapagliflozin 2.5 mg achieved HbA1c of less than 7%

Those in the dapagliflozin 5 mg and 10 mg plus glimepiride group had better FPG from baseline results at week 24, than individuals in the placebo plus glimepiride group:

  • dapagliflozin 5 mg and plus glimepiride, -21.2 mg/dL
  • dapagliflozin 10 mg plus glimepiride, -28.5 mg/dL
  • Compared to -2.0 mg/dL for placebo plus glimepiride (p-value less than 0.0001 for both treatment arms)
  • dapagliflozin 2.5 mg and plus glimepiride, -16.8 mg/dL

The percentage of people experiencing side effects after 24 weeks was:

  • 51.9% for those on for dapagliflozin 2.5 mg
  • 48.3% for those on for dapagliflozin 5 mg
  • 50.3% for those on for dapagliflozin 10 mg
  • compared to 47.3% for glimepiride plus placebo

Source: Astra Zeneca

Written by Christian Nordqvist