Tirzepatid (1) – Mounjaro®
Diabetes mellitus type 2
Characteristics
| Start date | 15.11.2023 – Marketing authorisation: 15.09.2022 |
|---|---|
| Resolution | 02.05.2024 |
| INN | Tirzepatid |
| Brand name | Mounjaro® |
| Pharm. company | Lilly Deutschland GmbH |
| G-BA Procedure ID | D-987 |
| ATC code | A10BX16 Other blood glucose lowering drugs, excl. insulins (A10BX) |
| 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, E13.01Other specified diabetes mellitus with hyperosmolarity with coma, E13.11Other specified diabetes mellitus with ketoacidosis with coma, E13.20, E13.21Other specified diabetes mellitus with intercapillary glomerulosclerosis, E13.30, E13.31Other specified diabetes mellitus with unspecified diabetic retinopathy with macular edema, E13.40Other specified diabetes mellitus with diabetic neuropathy, unspecified, E13.41Other specified diabetes mellitus with diabetic mononeuropathy, E13.50, E13.51Other specified diabetes mellitus with diabetic peripheral angiopathy without gangrene, E13.60, E13.61Other specified diabetes mellitus with diabetic neuropathic arthropathy, E13.72, E13.73, E13.74, E13.75, E13.80, E13.81, E13.90, E13.91, E14.01, E14.11, E14.20, E14.21, E14.30, E14.31, E14.40, E14.41, E14.50, E14.51, E14.60, E14.61, E14.72, E14.73, E14.74, E14.75, E14.80, E14.81, E14.90, E14.91 Show more >> |
| Alpha-ID codes (AIS) | I110911Diabetic foot syndrome, I110976Diabetes mellitus with eye complications, I110978Diabetes mellitus with neurological complications, I111029Diabetes mellitus with complication, I111031Diabetes mellitus with vascular complication, I111458Secondary diabetes mellitus, I111462Diabetic derailment, 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), I127364Insulin resistance syndrome, type A, I127626Wolfram syndrome, I2202Diabetes mellitus without complications, I25564Diabetes mellitus with coma, I31391Diabetes mellitus with multiple complications, I97452Diabetes mellitus with hypoglycemia, I98004Diabetes mellitus with ketoacidosis, I98511Hypoglycemic coma in diabetes mellitus, 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 |
| Therapeutic area | Metabolic diseases Diabetes mellitus (DM type 1-2) |
| Reason for procedure | Initial assessment |
| Specialty | ACT change Combination therapy confidential reimbursement price |
| Therapeutic indication of the resolution |
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Mounjaro is indicated for the treatment of adults with inadequately controlled type 2 diabetes mellitus as an adjunct to diet and exercise – as monotherapy if the use of metformin is not indicated due to intolerances or contraindications, – in addition to other medicines for the treatment of diabetes mellitus. |
| Subpopulation | Indication | Comparator |
|---|---|---|
| a1) | Insulin-naive adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous 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-naive adults with type 2 diabetes mellitus with manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous drug therapy consisting of a blood glucose-lowering drug in addition to diet and exercise | - Metformin + empagliflozin, or – metformin + liraglutide, or – metformin + dapagliflozin |
| b1) | Insulin-naive adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous 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 + sitagliptin, or – metformin + empagliflozin + liraglutide |
| b2) | Insulin-naive adults with type 2 diabetes mellitus with manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous drug therapy consisting of two blood glucose-lowering drugs in addition to diet and exercise, and for whom there is no indication for insulin therapyb | - Metformin + empagliflozin + liraglutide, or – metformin + dapagliflozin + liraglutide |
| c1) | Insulin-naive adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous 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 type 2 diabetes mellitus with manifest cardiovascular disease with manifest cardiovascular disease, who have been treated with their previous drug therapy consisting of at least two blood glucose-lowering drugs in addition to diet and exercise have not achieved adequate blood glucose control and for whom there is an indication for insulin therapy is indicated | - Human insulin + metformin + empagliflozin, or – human insulin + metformin + dapagliflozin, or – human insulin + metformin + liraglutide |
| d1) | Insulin-experienced adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate glycemic control with their current insulin regimen in addition to diet and exercise | Escalation of insulin therapy (conventional therapy (CT) possibly + metformin or dulaglutide or intensified insulin therapy (ICT)) |
| d2) | Insulin-experienced adults with type 2 diabetes mellitus with manifest cardiovascular disease who have not achieved adequate glycemic control with their current insulin regimen in addition to diet and exercise | Escalation of insulin therapy: conventional therapy (CT) or intensified insulin therapy (ICT), in each case in combination with metformin and empagliflozin or dapagliflozin or liraglutide |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (Surpass 6) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
no |
| Reason for dividing into subpopulations (G-BA) | Previous treatment, Disease stage |
| ACT change | 25.01.2022 – Neue Therapiestandards |
- Clinical trials
- SURPASS-4 is an open-label, randomised, active-controlled trial with four parallel treatment arms. The trial compared the administration of tirzepatide (3 arms, 5 mg, 10 mg and 15 mg per week respectively) versus insulin glargine (1 arm, U100), in each case in addition to the patient’s existing oral antidiabetic therapy.
- SURPASS-6 is an open-label, randomised, active-controlled trial with four parallel treatment arms. The study investigates the comparison of tirzepatide (3 arms, 5 mg, 10 mg and 15 mg per week respectively), each in combination with insulin glargine and, where applicable, (±) metformin, against a combination of insulin glargine and insulin lispro ± metformin.
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
- The additional benefit is not 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 antidiabetic medicinal product in addition to diet and exercise
- The additional benefit is not proven.
b1) Insulin-naïve adults with type 2 diabetes mellitus without manifest cardiovascular disease who have not achieved adequate blood glucose control with their previous 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.
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.
c1) Insulin-naïve adults with type 2 diabetes mellitus without 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
- The additional benefit is 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
- No conclusions regarding additional benefit can therefore be drawn from the SURPASS-4 study.
- Additional benefit is therefore 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
- Overall, for tirzepatide in patient group d1, there is a hint of a minor additional benefit compared with the appropriate comparator therapy.
- Overall, the certainty of the evidence is therefore classified as ‘hint’.
- mortality
- There are no statistically significant differences in overall mortality between the treatment arms.
- Morbidity – Diabetic retinopathy
- For the endpoint ‘diabetic retinopathy’, there is no statistically significant difference between the treatment arms.
- Morbidity – Health status (EQ-5D VAS)
- For an improvement of ≥ 15 points at week 52, there was a statistically significant difference between the treatment arms in favour of tirzepatide.
- Morbidity – Myocardial infarction
- For the endpoint ‘myocardial infarction’, 4 events occurred in the comparator arm. It is not possible to estimate the effect.
- Morbidity – Hospitalisation due to angina pectoris or heart failure
- For the endpoints ‘hospitalisation due to angina pectoris or heart failure’, one event occurred in each of the comparator arms. It is not possible to estimate the effect.
- Morbidity – Cerebrovascular morbidity
- For the endpoint ‘cerebrovascular morbidity’, no statistically significant differences were observed between the treatment arms.
- Quality of life – Short Form-36 Health Survey Version 2 (mental health summary score)
- For the mental health summary score (MCS) of the SF-36v2, a statistically significant difference was observed in favour of tirzepatide compared with the control arm.
- Quality of life – Short Form-36 Health Survey Version 2 (mental health summary score)
- No statistically significant difference was observed between the treatment arms for the physical composite score (PCS) of the SF-36v2.
- Side effects – Serious adverse events (SAE)
- For the SAE endpoint, there is a statistically significant advantage in favour of tirzepatide compared with the comparator arm.
- Side effects – Discontinuation due to adverse events (AE)
- For the endpoint ‘discontinuation due to AEs’, tirzepatid showed a disadvantage compared with the comparator arm.
- Side effects – Non-severe symptomatic, confirmed hypoglycaemia
- For both operationalisations, there is a statistically significant advantage of tirzepatide over the comparator arm.
- Side effects – Severe hypoglycaemia
- For this endpoint, there is a statistically significant advantage of tirzepatide over the comparator arm.
- Side effects – Gastrointestinal disorders (nausea, vomiting, diarrhoea)
- For the endpoint ‘gastrointestinal disorders’ (SOC) – specifically nausea, vomiting and diarrhoea – tirzepatide showed a statistically significant disadvantage compared with the comparator arm in each case.
- Overall assessment
- Data are available for the evaluation of patient population d1 from a patient population of the SURPASS-6 study comprising adults with type 2 diabetes mellitus without manifest cardiovascular disease.
- For tirzepatide, statistically significant advantages over the comparator arm were observed in morbidity in terms of health status (EQ-5D VAS), in quality of life as measured by the SF-36 mental health summary score, and in side effects as measured by the overall rate of SAE, as well as in the prevention of severe hypoglycaemia and non-severe symptomatic, confirmed hypoglycaemia. At the same time, tirzepatide showed statistically significant disadvantages compared with the comparator arm in terms of side effects, the endpoint of discontinuation due to side effects, and gastrointestinal disorders (nausea, vomiting, diarrhoea).
- Overall, tirzepatide shows minor positive effects compared with the appropriate comparator therapy. The extent of the additional benefit is therefore classified as minor.
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.
Courtesy translation only, please refer to the German original.
Associated procedures
| Tirzepatid (2) | Mounjaro® | Lilly Deutschland GmbH | Type 2 diabetes mellitus, aged ≥ 10 to ≤ 17 years | n.d. | active procedure | |
| Tirzepatid (1) | Mounjaro® | Lilly Deutschland GmbH | Diabetes mellitus type 2 | 1,461,000–2,021,000 | 23% Hint for minor additional benefit |
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