Ertugliflozin (1) – Steglatro®

Diabetes mellitus (DM) type 2

Characteristics

Start date 01.12.2021 – Marketing authorisation: 22.10.2021
Resolution 19.05.2022
INN Ertugliflozin
Brand name Steglatro®
Pharm. company MSD Sharp & Dohme GmbH
G-BA Procedure ID D-756
ATC code A10BK04 SGLT2 inhibitors (A10BK)
ICD-10 codes (AIS) E11.01Type 2 diabetes mellitus with hyperosmolarity with coma, E11.11Type 2 diabetes mellitus with ketoacidosis with coma, E11.20, E11.21Type 2 diabetes mellitus with intercapillary glomerulosclerosis, E11.30, E11.31Type 2 diabetes mellitus with unspecified diabetic retinopathy with macular edema, E11.40Type 2 diabetes mellitus with diabetic neuropathy, unspecified, E11.41Type 2 diabetes mellitus with diabetic mononeuropathy, E11.50, E11.51Type 2 diabetes mellitus with diabetic peripheral angiopathy without gangrene, E11.60, E11.61Type 2 diabetes mellitus with diabetic neuropathic arthropathy, E11.72, E11.73, E11.74, E11.75, E11.80, E11.81, E11.90, E11.91, E12.01, E12.11, E12.20, E12.21, E12.30, E12.31, E12.40, E12.41, E12.50, E12.51, E12.60, E12.61, E12.72, E12.73, E12.74, E12.75, E12.80, E12.81, E12.90, E12.91 Show more >>
Alpha-ID codes (AIS) I111702Diabetes mellitus type 2b with nephropathy, I111707Diabetes mellitus type 2b with complications, I115660Type 2 diabetes mellitus with diabetic foot syndrome, I119462Type 2 diabetes mellitus in conjunction with malnutrition (malnutrition), I99009Type 2 diabetes mellitus with coma, I99030Type 2 diabetes mellitus with peripheral vascular complication, I99034Type 2 diabetes mellitus with multiple complications, I99037Diet-treated type 2 diabetes mellitus without complications, I99064Hypoglycemic coma in type 2 diabetes mellitus, I99192Type 2 diabetes mellitus with ketoacidosis, I99238Diabetes mellitus type 2 with hypoglycemia
DDD 10 mg O
Therapeutic area Metabolic diseases Diabetes mellitus (DM type 1-2)
Reason for procedure Initial assessment
Specialty Combination therapy

Therapeutic indication of the resolution

Steglatro is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise:

– as monotherapy when metformin is considered inappropriate due to intolerance or contraindications.

– in addition to other medicinal products for the treatment of diabetes
Subpopulation Indication Comparator
a1) Insulin-naive adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate glycaemic control with their current drug therapy consisting of a blood glucose-lowering drug in addition to diet and exercise Patient-specific therapy taking into account the patient-specific therapy goal depending on comorbidities, duration of diabetes, possible risks of hypoglycaemia, with selection of: – Metformin + sulphonylurea (glibenclamide or glimepiride), – Metformin + sitagliptin, – metformin + empagliflozin, – metformin + liraglutide
a2) Insulin-naïve adults with diabetes mellitus type 2 with manifest cardiovascular disease who have not achieved adequate glycaemic control with their current drug therapy consisting of a blood glucose-lowering drug in addition to diet and exercise. have achieved adequate glycaemic control - Metformin + empagliflozin, or – metformin + liraglutide, or – metformin + dapagliflozin
b1) Insulin-naïve adults with diabetes mellitus type 2 without manifest cardiovascular disease, who have not been adequately treated with their previous drug therapy consisting of two medication in addition to diet and exercise, and for whom there are no indication for insulin therapy - Metformin + empagliflozin + sitagliptin, or – metformin + empagliflozin + liraglutide
b2) Insulin-naïve adults with diabetes mellitus type 2 with manifest cardiovascular disease who have not achieved adequate glycaemic control with their current drug therapy consisting of two blood glucose-lowering drugs in addition to diet and exercise, and for whom there is no indication for insulin therapy - Metformin + empagliflozin + liraglutide, or – metformin + dapagliflozin + liraglutide
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 drugs in addition to diet and exercise, and for whom there is an indication for insulin therapy - Human insulin + metformin
c2) Insulin-naïve adults with diabetes mellitus type 2 with manifest cardiovascular disease who have not achieved adequate glycaemic control with their current drug therapy consisting of at least two blood glucose-lowering drugs in addition to diet and exercise have achieved adequate glycaemic control and for whom insulin therapy is indicated - Human insulin + metformin + empagliflozin, or – human insulin + metformin + dapagliflozin, or – human insulin + metformin + liraglutide
d1) Insulin-pretreated adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate glycaemic control with their previous insulin regime in addition to diet and exercise Escalation of insulin therapy (conventional therapy (CT) if necessary + metformin or dulaglutide or intensified insulin therapy (ICT))
d2) Insulin-pretreated adults with type 2 diabetes mellitus with manifest cardiovascular disease who have not achieved adequate glycaemic control with their previous insulin regime in addition to diet and exercise Escalation of insulin therapy (conventional therapy (CT) if necessary + metformin or empagliflozin or liraglutide or dapagliflozin or intensified insulin therapy (ICT))

Studies and Results

No. of studies
(best subpopulation) 		1 (VERTIS SU)
Study design
(best subpopulation) 		H2H vs. ACT (off-label)
Meta analysis
(best subpopulation) 		no
Reason for dividing into subpopulations (G-BA) Previous treatment, Disease stage

  • 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.

Associated procedures

Ertugliflozin (1) Steglatro® MSD Sharp & Dohme GmbH Metabolic diseases Diabetes mellitus (DM) type 2 1,451,000–2,021,000 100% additional benefit not proven


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