Linagliptin (1) – Trajenta®

a) Monotherapy in patients with type 2 diabetes mellitus

• The G-BA notes that, in the dossier submitted by the pharmaceutical manufacturer for the benefit assessment of linagliptin, the manufacturer did not set out and demonstrate, in a manner compliant with statutory and subordinate legal requirements, that linagliptin offers additional benefit compared with the appropriate comparator therapy determined by the G-BA and communicated to the manufacturer during the consultation.
• The dossier must therefore be regarded as incomplete in this respect.
• Pursuant to Section 35a(1), fifth sentence, of SGB V, this means that the additional benefit of linagliptin over the appropriate comparator therapy is deemed not proven.
• Appropriate comparator therapy: sulphonylureas (glibenclamide, glimepiride).
• Sulfonylureas have marketing authorisation for monotherapy in type 2 diabetes mellitus.
• Given the proof of benefits in terms of their effect on patient-relevant endpoints such as microvascular and macrovascular complications, sulphonylureas and metformin are, according to the generally accepted state of medical knowledge, considered appropriate therapies for the therapeutic indication.
• To date, there are no studies available on the gliptins that could be considered as comparator therapies, providing results on patient-relevant endpoints such as cardiovascular mortality and diabetes-related complications.
• As the use of metformin is unsuitable in monotherapy in accordance with the intended therapeutic indication for linagliptin, metformin is excluded as an appropriate comparator therapy in this treatment situation.

b) Dual combination therapy with linagliptin and metformin in patients with type 2 diabetes mellitus

• The G-BA notes that, in the dossier submitted by the pharmaceutical manufacturer for the benefit assessment of linagliptin, the manufacturer has not demonstrated or substantiated, in a manner compliant with statutory and subordinate legal requirements, that linagliptin offers additional benefit compared with the appropriate comparator therapy determined by the G-BA and communicated to the manufacturer during the consultation.
• The dossier must therefore be regarded as incomplete in this respect.
• Pursuant to Section 35a(1), fifth sentence, of SGB V, this means that the additional benefit of linagliptin compared with the appropriate comparator therapy is deemed not proven.
• Appropriate comparator therapy: sulphonylurea (glibenclamide, glimepiride) + metformin.
• Sulfonylureas and metformin have marketing authorisation for combination therapy.
• Given the proof of benefits in terms of their effect on patient-relevant endpoints such as microvascular and macrovascular complications, metformin and sulphonylureas are, according to the generally accepted state of medical knowledge, considered appropriate therapies within the therapeutic indication.
• There are as yet no studies on patient-relevant endpoints such as cardiovascular mortality and diabetes-related complications for the gliptins that are under consideration as comparator therapies.

c) Triple combination therapy with linagliptin + sulphonylurea + metformin in patients with type 2 diabetes mellitus

• The G-BA notes that, in the dossier submitted by the pharmaceutical manufacturer for the benefit assessment of linagliptin, the manufacturer has not demonstrated or substantiated, in a manner compliant with statutory and subordinate legal requirements, that linagliptin offers additional benefit compared with the appropriate comparator therapy determined by the G-BA and communicated to the manufacturer during the consultation.
• The dossier must therefore be regarded as incomplete in this respect.
• Pursuant to Section 35a(1), fifth sentence, of SGB V, this means that the additional benefit of linagliptin over the appropriate comparator therapy is deemed not proven.
• Appropriate comparator therapy: metformin + human insulin.
• Given the proof of benefits in terms of their impact on patient-relevant endpoints such as microvascular and macrovascular complications, metformin is, according to the generally accepted state of medical knowledge, the first-line treatment, and human insulin forms part of the appropriate therapy for the therapeutic indication.
• To date, there have been no studies on patient-relevant endpoints such as cardiovascular mortality and diabetes-related complications for the gliptins under consideration as comparator therapies.
• For the triple combination, metformin plus human insulin is the appropriate comparator therapy.
• A combination of three blood glucose-lowering active ingredients (INNs) is classified by the G-BA as inappropriate; consequently, in this therapeutic situation, insulin therapy in combination with metformin is indicated.

Courtesy translation only, please refer to the German original.