Dapagliflozin / Metformin (2) – Xigduo®

a) Dual combination therapy with dapagliflozin and metformin in patients whose blood glucose is not adequately controlled with the maximum tolerated dose of metformin alone

• For patients treated with the dual combination of dapagliflozin and metformin, whose blood glucose levels are not adequately controlled with the maximum tolerated dose of metformin alone, the additional benefit is not proven.
• Conclusion
  • Overall, the G-BA concludes that the studies DapaZu and D1690C00004 submitted for the benefit assessment are not suitable for establishing additional benefit for the dual combination of dapagliflozin andmetformin compared with the appropriate comparator therapy.
  • In the DapaZu study, the glimepiride titration regimen used in the control arm does not correspond to an adequate, patient-specific titration in accordance with the recommendations of the guidelines and the information provided in the summary of product characteristics (SmPC).
  • According to the SmPC, titration above 4 mg/day of glimepiride is not routine but should be considered as a titration step in individual cases; however, in the study, titration above 4 mg/day was carried out in the majority of patients.
  • The results for the endpoint of hypoglycaemia cannot be interpreted with sufficient certainty due to the inadequate titration regimen for glimepiride and the unequal HbA1c levels of patients in the dapagliflozin and control arms.
  • Nor can the results of study D1690C00004 be interpreted due to methodological shortcomings.
  • Taken together, the results of the two studies are highly biased due to the study design, and a valid interpretation of the endpoints is not possible.
  • For this reason, the G-BA concludes that, for patients treated with the dual combination of dapagliflozin and metformin, in whom blood glucose is not adequately controlled with the maximum tolerated dose of metformin alone, no additional benefit is proven compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.