Canagliflozin / Metformin (1) – Vokanamet®

• Clinical trials
  • This three-arm, double-blind, multicentre, randomised clinical trial investigated the efficacy and safety of canagliflozin in combination with metformin compared with a combination of metformin and glimepiride over a period of 104 weeks.
  • The DIA3006 study was a four-arm, double-blind, randomised clinical trial with a total duration of 52 weeks.

a) Combination therapy with metformin, where metformin at the maximum tolerated dose, together with diet and exercise, does not adequately control blood glucose

• For the combination of canagliflozin and metformin, where metformin monotherapy, together with diet and exercise, does not adequately control blood glucose, the additional benefit is not proven.
• Having assessed the methodological shortcomings described in the data submitted for this patient group from the DIA3009 study, as well as the failure to take into account the specified appropriate comparator therapy in the DIA3006 study, the G-BA concludes that no additional benefit has been established for canagliflozin in combination with metformin compared with the appropriate comparator therapy of a sulphonylurea (glibenclamide or glimepiride) with metformin.
• Overall assessment
  • The validity of study DIA3009 is limited, amongst other things, by the inability to increase the dose of canagliflozin and by the strict glimepiride titration regimen, which is further constrained by a low target value (fasting plasma glucose: 110 mg/dL; guideline for the treatment target: 100–125 mg/dL), is so limited that no valid conclusions regarding additional benefit can be drawn.

b) Combination therapy with other blood glucose-lowering medicinal products other than insulin, where blood glucose is not adequately controlled with metformin and these medicinal products in conjunction with diet and exercise

• For the combination of canagliflozin/metformin with other blood glucose-lowering medicinal products (other than insulin), where blood glucose is not adequately controlled with metformin and these medicinal products in conjunction with diet and exercise, the additional benefit is not proven.
• No study has been submitted to assess the additional benefit of a treatment consisting of canagliflozin in combination with metformin and other blood glucose-lowering medicinal products (other than insulin), where blood glucose is not adequately controlled with metformin and these medicinal products in combination with diet and exercise, compared with the appropriate comparator therapy (human insulin + metformin or human insulin alone).

c) Combination therapy with insulin, where blood glucose is not adequately controlled with metformin and insulin, together with diet and exercise

• For combination therapy with canagliflozin and metformin plus insulin, where blood glucose is not adequately controlled with metformin and insulin in conjunction with diet and exercise, the additional benefit is not proven.
• No study was submitted to assess the additional benefit of a treatment consisting of canagliflozin in combination with metformin and insulin – where blood glucose is not adequately controlled by metformin and insulin in conjunction with diet and exercise – compared with the appropriate comparator therapy (human insulin + metformin or human insulin alone) would have been suitable.

Courtesy translation only, please refer to the German original.