FORXIGA® (dapagliflozin)

FORXIGA® (dapagliflozin) is a highly selective SGLT2 inhibitor for type 2 diabetes mellitus, with 4-year safety and efficacy data, that removes glucose and its associated calories via the kidney.1

FORXIGA®(dapagliflozin) in secondary care

Start change earlier for your patients

Consider FORXIGA® (dapagliflozin) ahead of a GLP-1 for:

  • A numerically similar reduction in HbA1c to once-weekly exenatide, a GLP-1 (in an RCT)10
  • The secondary benefit of weight loss, proportional to patient BMI1,4
  • Simple dosing1

RCT randomised controlled trial.

What could FORXIGA® (dapagliflozin) do for your patients ahead of a GLP-1 and across the treatment pathway?

FORXIGA®  (dapagliflozin) can be used in combination with insulin, with data available up to 104 weeks32

Reduction in HbA1c from baseline at over 104 weeks (FORXIGA® + insulin vs placebo + insulin)
Reduction in HbA1c from baseline at over 104 weeks (FORXIGA® + insulin vs placebo + insulin)

Adapted from Wilding JP et al. 2014

At 24 weeks (primary endpoint), mean HbA1c was reduced by 0.96% with FORXIGA® (dapagliflozin) compared with 0.39% with placebo (p<0.001, mean difference 0.57% [CI 0.42%, 0.72%]).36

In a Phase 3 trial, FORXIGA® (dapagliflozin) showed:

  • A numerically similar reduction in HbA1c to once-weekly exenatide (a GLP-1)10
  • A 2% reduction in HbA1c at 28 weeks when given in combination with once-weekly exenatide (as a dual add on)10
  • No new, or unexpected, safety findings for Bydureon or Forxiga were noted during the DURATION-8 trial, consistent with the PI, over 52 weeks10

Reduction from baseline in HbA1c at week 28 with FORXIGA® (dapagliflozin), exenatide and FORXIGA® (dapagliflozin) + exenatide10

Reduction in HbA1c from baseline at week 28 with FORXIGA®, exenatide and FORXIGA® + exenatide
Reduction in HbA1c from baseline at week 28 with FORXIGA®, exenatide and FORXIGA® + exenatide

Adapted from Frías JP et al. 2016.

Statistical significance for the between-group difference was not tested.10
GLP-1, glucagon-like peptide 1; LS, least-squares; CI, confidence interval.

In a Phase 3 trial, FORXIGA®(dapagliflozin), once weekly exenatide (a GLP-1) and a combination of FORXIGA® (dapagliflozin) + exenatide all showed reductions in weight at 28 weeks10

Reduction from baseline in weight at week 28 with FORXIGA®(dapagliflozin) , exenatide and FORXIGA® (dapagliflozin) + exenatide10

Reduction in weight from baseline at week 28 with FORXIGA®, exenatide and FORXIGA® + exenatide
Reduction in weight from baseline at week 28 with FORXIGA®, exenatide and FORXIGA® + exenatide

Adapted from Frias JP et al. 2016

*Neither FORXIGA® (dapagliflozin) or exenatide are indicated for weight loss. Weight change was a secondary endpoint in clinical trials.1

Statistical significance for the between-group difference was not tested.10

GLP-1, glucagon-like peptide 1; LS, least-squares; CI, confidence interval.

FORXIGA®(dapagliflozin) can be used in combination with insulin, with data available up to 104 weeks32

Significant reductions in weight from baseline over 104 weeks with FORXIGA® (dapagliflozin) 10 mg plus insulin32

Reduction in weight from baseline over 104 weeks with FORXIGA® plus insulin
Reduction in weight from baseline over 104 weeks with FORXIGA® plus insulin

Adapted from Wilding JP et al. 2014

*Neither FORXIGA® (dapagliflozin) or exenatide are indicated for weight loss. Weight change was a secondary endpoint in clinical trials.1
CI, confidence interval; ST, shorter therapy; LT, longer therapy.

DURATION-8 was a 28 week, multicentre, double-blind, randomised, active-controlled phase 3 trial at 109 sites in six countries, and a subsequent ongoing 52-week extension. Adults (aged ≥18 years) with type 2 diabetes and inadequate glycaemic control (HbA1c 8–12% [64–108 mmol/mol]) despite stable metformin monotherapy (≥1500 mg/day) were randomly assigned 1:1:1.  695 patients were randomly assigned to receive once-weekly exenatide 2 mg by subcutaneous injection plus once-daily FORXIGA® (dapagliflozin) 10 mg oral tablets (n=231), exenatide with FORXIGA® (dapagliflozin)-matched oral placebo (n=231; n=1 untreated), or FORXIGA® (dapagliflozin) with exenatide matched placebo injections (n=233). Randomisation was stratified by baseline HbA1c (<9.0% vs ≥9.0% [<75 mmol/mol vs ≥75 mmol/mol]). The intention-to-treat population comprised 685 participants (mean HbA1c 9.3% [SD 1.1]; 78 mmol/mol), of whom 611 (88%) completed the study.

The primary endpoint was change in HbA1c from baseline to week 28. Secondary endpoints were the change from baseline in fasting plasma glucose at week 2 and week 28, and 2 h postprandial glucose at week 28; the proportion of patients with an HbA1c less than 7.0% (<53 mmol/mol) at week 28; change in weight at week 28; the proportion of patients with weight loss of 5% or more at week 28; and change in systolic blood pressure at week 28. Analyses were by intention-to-treat.

Safety assessments included adverse events, laboratory abnormalities, vital signs, and hypoglycaemic events. Outcomes for the 52-week extension now published.14

 

This was a 24-week, randomised, placebo-controlled, double-blinded, multicentre trial followed by two site and patient-blinded extension periods of 24 and 56 weeks, respectively. The study aimed to evaluate the efficacy and safety of FORXIGA® (dapagliflozin) 10 mg + insulin after a total of 104 weeks.

A total of 808 patients were recruited from 126 centres, whose T2DM was  inadequately controlled on insulin ≥30 IU/day (HbA1c 7.5-10.5%) for at least 8 weeks with or without up to two oral antidiabetic drugs. Patients were initially randomized on a 1:1:1:1 basis to placebo or FORXIGA® (dapagliflozin) 2.5, 5 or 10 mg once daily, in addition to open-label therapy with their usual daily insulin dose and existing oral antidiabetic drugs. Following completion of 48 weeks of treatment, patients receiving FORXIGA® (dapagliflozin) 5 mg were switched to the 10 mg dose for the remainder of the study. Throughout the study, insulin dose was held within 10% of the baseline level unless insulin up-titration was clinically indicated.

The primary efficacy variable was change in HbA1c from baseline to week 24. Key secondary efficacy variables at 24 weeks included change in total body weight from baseline, change in calculated mean daily insulin dose, proportion of patients with calculated mean daily insulin dose reduction ≥10% from baseline and change in fasting plasma glucose from baseline. At 104 weeks, it was assessed whether the effects on HbA1c, fasting plasma glucose, insulin dose, body weight and urinary glucose excretion were maintained.

Safety evaluations over the 104-week period included adverse events, laboratoryvariables, and vital signs.