Lixisenatid (1) – Lyxumia®

• Clinical trials
  • The GetGoal-X trial was a randomised, actively controlled, open-label Phase III trial with a primary study duration of 24 weeks, followed by a variable open-label extension phase of up to 52 weeks.
  • In this trial, treatment with lixisenatide in combination with metformin was compared with treatment with exenatide in combination with metformin.
  • The EFC10780 study is a randomised, actively controlled, double-blind Phase III study with a study duration of 24 weeks.
  • This study compared treatment with lixisenatide in combination with metformin to treatment with sitagliptin in combination with metformin.

a) Add-on combination therapy with metformin, if metformin, together with diet and exercise, does not sufficiently lower blood glucose levels

• Additional benefit from lixisenatide in combination with metformin compared with the appropriate comparator therapy, a sulphonylurea (glibenclamide or glimepiride) in combination with metformin, is not proven.
• In its summary assessment of the methodological shortcomings described in the data submitted for the combination of lixisenatide plus metformin, the G-BA concludes that no additional benefit of lixisenatide has been established compared with the appropriate comparator therapy - metformin in combination with sulphonylureas (glibenclamide or glimepiride) - has been established.

b) Add-on dual combination with an oral antidiabetic (other than metformin), where this, together with diet and exercise, does not sufficiently lower blood glucose

• For patients in whom treatment with an oral antidiabetic agent (other than metformin), together with diet and exercise, is insufficient on its own to control blood glucose levels, the additional benefit is not proven.
• No study has been submitted that would have been suitable for assessing the additional benefit of a treatment consisting of an oral antidiabetic (other than metformin) in combination with lixisenatide compared with the appropriate comparator therapy.

c) Add-on triple combination therapy with oral antidiabetic agents, where these, together with diet and exercise, do not sufficiently lower blood glucose

• For patients in whom combination therapy with two oral antidiabetics, together with diet and exercise, is insufficient to control blood glucose levels, the additional benefit is deemed not proven.
• In summary, the pharmaceutical manufacturer’s argument regarding the choice of appropriate comparator therapy is not accepted. As there is therefore no evidence to support the benefit assessment of lixisenatide in a triple combination with oral antidiabetic agents (metformin and sulphonylureas) compared with the appropriate comparator therapy of human insulin plus metformin, or, where applicable, human insulin alone, the additional benefit of lixisenatide is deemed not proven.

d) Add-on combination with a basal insulin, with or without metformin, where basal insulin (with or without metformin), together with diet and exercise, does not sufficiently lower blood glucose

• For patients in whom treatment with a basal insulin (with or without metformin), together with diet and exercise, does not sufficiently lower blood glucose, the additional benefit compared with the appropriate comparator therapy (human insulin in combination with metformin, or human insulin alone where appropriate) does not provide proof.
• Overall, therefore, there is no additional benefit from lixisenatide in combination with a basal insulin (with or without metformin) compared with the appropriate comparator therapy (metformin + human insulin, or human insulin alone where appropriate).

Courtesy translation only, please refer to the German original.