Ertugliflozin (1) – Steglatro®

• Clinical trials
  • The VERTIS CV trial is a three-arm, placebo-controlled, double-blind, randomised, parallel-group trial.

a1) Insulin-naïve adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their current medication regimen consisting of a blood glucose-lowering medicinal product in addition to diet and exercise

• An additional benefit is not proven.
• For the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous therapy consisting of a blood glucose-lowering medicinal product, the VERTIS SU study was submitted.
• Glimepiride was administered according to a fixed titration schedule, in which the dose was to be increased to a maximum of 6 mg or 8 mg, respectively, for blood glucose levels ≥ 110 mg/dl.
• This approach is consistent neither with the marketing authorisation for glimepiride nor with the guidelines’ recommendations for an individualised treatment target.
• Furthermore, it was not demonstrated that the single-comparator design, with the choice of glimepiride and metformin for all included patients, represents the most appropriate therapeutic option for the appropriate comparator therapy.
• The study is therefore unsuitable and no additional benefit is proven.

a2) Insulin-naïve adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous drug therapy consisting of a blood glucose-lowering medicinal product in addition to diet and exercise

• The additional benefit is not proven.
• For the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their current therapy consisting of a blood glucose-lowering medicinal product, the VERTIS CV study was submitted.
• Due to the varying prior antidiabetic therapies and treatment stages within the study population, the patients examined cannot be assigned to the corresponding patient groups and respective options for appropriate comparator therapy.
• It is noted that almost no SGLT-2 inhibitors were used in the comparator arm and that GLP-1-RAs were administered in only approximately 5% of cases.
• Consequently, the active ingredients specified in the appropriate comparator therapy for the subpopulations with manifest cardiovascular disease were not taken into account.
• The guideline recommendations for the treatment of this patient group were disregarded.
• The study is therefore unsuitable and no additional benefit is proven.

b1) Insulin-naïve adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their current medication regimen consisting of two blood glucose-lowering medicinal products in addition to diet and exercise, and for whom there is no indication for insulin therapy

• The additional benefit is not proven.
• No data were provided for the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their current therapy consisting of two blood glucose-lowering medicinal products – excluding insulin – have not achieved adequate blood glucose control, no data were submitted.
• An additional benefit is therefore not proven.

b2) Insulin-naïve adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their current drug therapy consisting of two blood glucose-lowering medicinal products in addition to diet and exercise, and for whom there is no indication for insulin therapy

• The additional benefit is not proven.
• For the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus and manifest cardiovascular disease who, with their previous therapy consisting of two blood glucose-lowering medicinal products – excluding insulin – have not achieved adequate blood glucose control, the VERTIS CV study was submitted.
• Due to the varying prior antidiabetic therapies and treatment stages within the study population, the patients examined cannot be assigned to the corresponding patient groups or the respective options for appropriate comparator therapy.
• It is noted that SGLT-2 inhibitors were used in almost no patients in the comparator arm, and GLP-1-RA was administered in only approximately 5%.
• Consequently, the active ingredients specified in the appropriate comparator therapy for the subpopulations with manifest cardiovascular disease were not taken into account.
• The guideline recommendations for the treatment of this patient group were disregarded.
• The study is therefore unsuitable and no additional benefit is proven.

c1) Insulin-naïve adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate glycaemic control with their current drug therapy consisting of at least two blood-glucose-lowering medicinal products in addition to diet and exercise, and for whom there is an indication for insulin therapy

• The additional benefit is not proven.
• No data were provided for the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their current therapy consisting of at least two blood glucose-lowering medicinal products, and for whom there is an indication for insulin therapy for the first time, no data were submitted.
• An additional benefit is therefore not proven.

c2) Insulin-naïve adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their current drug therapy consisting of at least two blood glucose-lowering medicinal products in addition to diet and exercise, and for whom there is an indication for insulin therapy

• An additional benefit is not proven.
• For the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous therapy consisting of at least two blood glucose-lowering medicinal products, and for whom there is an indication for insulin therapy for the first time, the VERTIS CV study was submitted.
• Due to the varying prior antidiabetic treatments and treatment stages within the study population, the patients studied cannot be assigned to the corresponding patient groups and respective options for appropriate comparator therapy.
• It is noted that almost no SGLT-2 inhibitors were used in the comparator arm and that GLP-1 RAs were administered in only approximately 5% of cases.
• Consequently, the active ingredients specified in the appropriate comparator therapy for the subpopulations with manifest cardiovascular disease were not taken into account.
• The guideline recommendations for the treatment of this patient cohort were disregarded.
• The study is therefore unsuitable and an additional benefit is not proven.

d1) Insulin-experienced adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their current insulin regimen in addition to diet and exercise

• The additional benefit is not proven.
• No data were submitted for the assessment of the additional benefit of ertugliflozin for the treatment of adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their current insulin regimen.
• The additional benefit is not proven.

d2) Insulin-experienced adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their current insulin regimen, in addition to diet and exercise

• The additional benefit is not proven.
• The VERTIS CV study was submitted for the assessment of the additional benefit of ertugliflozin in the treatment of adults with type 2 diabetes mellitus and manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous insulin regimen.
• Due to the varying prior antidiabetic treatments and treatment stages within the study population, the patients studied cannot be assigned to the corresponding patient groups and respective options for appropriate comparator therapy.
• It is noted that SGLT-2 inhibitors were used in virtually no patients in the comparator arm, and GLP-1 RAs were administered in only approximately 5 per cent of cases.
• Consequently, the active ingredients specified in the appropriate comparator therapy for the subpopulations with manifest cardiovascular disease were not taken into account.
• The guideline recommendations for the treatment of this patient cohort were disregarded.
• The study is therefore unsuitable and an additional benefit is not proven.

Courtesy translation only, please refer to the German original.