SitagliptinJanorix
Type 2 diabetes mellitus in combination with insulin, with or without metformin, in patients with inadequate glycaemic control despite insulin treatment with or without other oral antidiabetic agents.
Decisions on record
- Meeting Nov 2015 Not recommended Initial therapy in patients with type 2 diabetes mellitus to improve glycaemic control when diet and exercise do not provide adequate glycaemic control
- Meeting Mar 2009 Recommended Anti-diabetic agent no PSD
Access path
- TGA registered · Janorix
TGA label narrower than the PBS population
- Jul 2015Recommended
vs dapagliflozin
- Jul 2015Not recommended
- Nov 2015Not recommended
uncertain clinical effectiveness (inconsistent insulin dose outcomes across trials), inadequate evidence of…
From the public summary
7.1 The PBAC rejected the minor resubmission to extend the PBS listing for sitagliptin for use in combination with insulin in patients with type 2 diabetes, with or without metformin. The PBAC noted the sponsor’s arguments regarding the differences in trial design between trial P260 and Wilding.PSD · Nov 2015
7.2 The PBAC noted the resubmission’s claim that trial P051 “…is the appropriate key trial to compare with Wilding [and that]… [t]he indirect analysis of P051 to Wilding supports the non-inferiority claims presented in the submission.”PSD · Nov 2015
6.16 In the previous major submission considered by PBAC in July 2015, the submission presented a cost-minimisation analysis against dapagliflozin. The equi-effective doses were sitagliptin 100mg once daily and dapagliflozin 10mg daily. The PBAC noted “…that the increased daily insulin dose accompanying sitagliptin treatment (+19.0IU/day, compared with -1.18IU/day for dapagliflozin) was not factored into the cost-minimisation analysis.PSD · Nov 2015
6.17 The minor re-submission did not alter the economic analysis from July 2015, but updated the analysis with the most current DPMQ prices for both drugs.PSD · Nov 2015
6.14 The clinical claim remained unchanged from the previous major submission considered in July 2015. The previous submission claimed non-inferior comparative effectiveness and similar comparative safety of sitagliptin compared with dapagliflozin.PSD · Nov 2015
6.15 The PBAC considered in July 2015 that the clinical trials presented in the submission did not provide adequate data to support the clinical claim that sitagliptin is non- inferior in terms of comparative effectiveness (as measured by reduction in HbA1c) and similar in terms of reduction in mean daily insulin dose compared to dapagliflozin. 7PSD · Nov 2015
Cost-effectiveness
Cost-minimisation analysis presented; however, PBAC considered the analysis inadequate as it did not factor in the increased insulin costs associated with sitagliptin use (+19.0 IU/day vs −1.18 IU/day for dapagliflozin).
The PBAC noted that the increased daily insulin dose accompanying sitagliptin treatment (+19.0IU/day, compared with -1.18IU/day for dapagliflozin) was not factored into the cost-minimisation analysis. PBAC · 2015
Decision context
PopulationAdults with type 2 diabetes mellitus inadequately controlled on insulin with or without other oral antidiabetic agents, treated in combination with insulin (and optionally metformin).
Why it was knocked back
- uncertain clinical effectiveness (inconsistent insulin dose outcomes across trials), inadequate evidence of non-inferiority in HbA1c reduction and insulin dose reduction compared to dapagliflozin, cost-minimisation analysis did not account for increased insulin costs with sitagliptin, clinical place in therapy not well established (clinicians unlikely to prescribe a drug resulting in increased insulin use), inconsistent safety profile across trials (hypoglycaemia and weight gain benefits not consistent)
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2015 | Not recommended | dapagliflozin | — | RCT · HbA1c reduction |
| Jul 2015 | Recommended | dapagliflozin | — | RCT · HbA1c |
| Jul 2015 | Not recommended | dapagliflozin | — | RCT · OS | PFS | DFS | ORR | QoL | Surrogate | Cost-minimisation | Other | null |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| TECOS | Ph 3 | 14,671 | Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse… | completed |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to type 2 diabetes inadequately controlled on insulin, requiring combination therapy; TGA label does not specify this treatment-failure prerequisite.