LiraglutideARX-Liraglutide
Not recommended EndocrinologyAuthority RequiredNot applicable line 💬 consumer voice
Type 2 diabetes mellitus, specifically for dual combination therapy with metformin or a sulfonylurea, and triple combination therapy with metformin and a sulfonylurea (the current submission additionally sought advice on whether liraglutide 1.2 mg meets Special Pricing Arrangement criteria based on claimed cardiovascular benefits).
5
Submissions
4 resub
2010–18
On the record
$15k–75k
ICER range
2 sourced ICERs · 2010–2011
Cost-min
Cost basis
Decisions on record
- Meeting Mar 2018 Not recommended Liraglutide is indicated as an adjunct to diet and exercise for treatment of adults with type 2 diabetes mellitus to achieve glycaemic control: • as monotherapy when metformin is contraindicated or is not tolerated • in combination with other glucose lowering medicines. In patients where Liraglutide
- Meeting Jul 2017 Not recommended Liraglutide is indicated as an adjunct to diet and exercise for treatment of adults with type 2 diabetes mellitus to achieve glycaemic control: • in dual combination, added to metformin or a sulfonylurea, in patients with insufficient glycaemic control despite the use of maximally tolerated or clini
- Meeting Nov 2011 Not recommended An adjunct to diet and exercise for treatment of adults with type 2 diabetes mellitus to achieve glycaemic control: - in dual combination, added to metformin or a sulphonylurea, in patients with insufficient glycaemic control despite the use of maximally tolerated or clinically adequate doses of met
- Meeting Jul 2011 Not recommended Liraglutide is indicated as an adjunct to diet and exercise for treatment of adults with type 2 diabetes mellitus to achieve glycaemic control: in dual combination, added to metformin or a sulphonylurea, in patients with insufficient glycaemic control despite the use of maximally tolerated or clinic no PSD
- Meeting Nov 2010 Not recommended Type 2 diabetes
Access path
- TGA registered · ARX-Liraglutide
TGA label narrower than the PBS population
- Nov 2010Not recommended
vs exenatide
- Nov 2011Not recommended
uncertain clinical benefit of 0.33% HbA1c difference (translation to clinical outcomes uncertain), questionable…
- ↻ resubmittedMar 2013Recommended · restricted
Evidence: RCT → Meta-analysis
- Jul 2017Not recommended
Comparator changed: exenatide → exenatide 10 µg twice daily or 2 mg once weekly
- Mar 2018Not recommended
Insufficient evidence that liraglutide 1.2 mg (the listed dose) provides cardiovascular benefits; LEADER trial used 1.8…
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
7.1 The PBAC did not recommend the listing of liraglutide 1.8 mg daily for treatment of patients with Type 2 diabetes mellitus and high cardiovascular risk on the basis of inadequate comparative clinical data and uncertain cost effectiveness.PSD · Jul 2017
7.2 The PBAC reaffirmed its March 2013 recommendation to list liraglutide 1.2 mg once daily on a cost minimisation basis with exenatide 10 µg twice daily for dual combination therapy with metformin or a sulfonylurea, and as triple combination therapy with metformin and a sulfonylurea. The PBAC noted this recommendation did not include combination use with insulin.PSD · Jul 2017
Economic analysis
6.35 The submission presented a modelled cost utility analysis comparing the cardiovascular benefits of liraglutide with exenatide 10 µg twice daily.PSD · Jul 2017
6.36 Given the base case, which included the costs but not benefits of exenatide, is not informative and is biased in favour of liraglutide, the evaluation presented the results of the placebo comparison as the base case of the modelled economic evaluation. The ESC considered the base case modelled economic evaluation versus exenatide is only relevant if it is accepted that exenatide has no impact on CV events.PSD · Jul 2017
Clinical claim
6.30 The submission noted that liraglutide was considered to be non-inferior to exenatide 10 µg twice daily in terms of glycaemic control and safety by the PBAC at the March 2013 meeting.PSD · Jul 2017
6.31 The submission described liraglutide as superior in terms of comparative effectiveness over exenatide, providing a statistically significant reduction in cardiovascular risk in patients with Type 2 diabetes and high cardiovascular risk. This claim was not adequately supported given the following: 20PSD · Jul 2017
Consumer comments
6.2 The PBAC noted and welcomed the input from health care professionals (1) and organisations (2) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with liraglutide most notably the reduced risk of cardiovascular mortality and lower risk of hypoglycaemia.PSD · Jul 2017
Financial management – risk sharing
6.47 The sponsor proposed a risk share arrangement to offset uncertainty in the economic model, based on a revenue/utilisation cap.PSD · Jul 2017
Cost-effectiveness
Cost-minimisation analysis; no ICER calculated. This was a minor submission on cost-minimisation basis with exenatide.
The PBAC considered an indirect comparison of liraglutide and exenatide including full evaluation of the EXSCEL trial patient characteristics and trial results was required to quantify how the CV benefits of liraglutide compare to exenatide. PBAC · 2018
ICER uncertainEconomic model disputed ×3Surrogate endpointNo head-to-head trialIndirect comparison
Decision context
PopulationAdults with type 2 diabetes mellitus for dual combination therapy with metformin or a sulfonylurea, or triple combination therapy with metformin and a sulfonylurea; the submission also addressed patients at high cardiovascular risk.
Why it was knocked back
- Insufficient evidence that liraglutide 1.2 mg (the listed dose) provides cardiovascular benefits; LEADER trial used 1.8 mg with 84.8% of patients exposed to 1.8 mg, but no evidence that CV benefits extend to 1.2 mg dose; reliance on unsupported assumption that exenatide provides no cardiovascular risk reduction; failure to provide indirect comparison of liraglutide and exenatide with full EXSCEL trial evaluation; does not meet Special Pricing Arrangement criteria (no unique characteristics compared to exenatide b.d., which lacks an SPA)
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2018 | Not recommended | exenatide 10 µg twice daily | — | Cost-minimisation · Cost-minimisation |
| Jul 2017 | Not recommended | exenatide 10 µg twice daily or 2 mg once weekly | — | RCT · Surrogate |
| Mar 2013 | Recommended · restricted | exenatide | — | Meta-analysis · HbA1c change from baseline |
| Nov 2011 | Not recommended | exenatide | $15k–45k | RCT · HbA1c |
| Nov 2010 | Not recommended | exenatide | $45k–75k | RCT, Single-arm, Registry · HbA1c reduction |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| LEADER (NCT01179048) | Ph 3 | 9,341 | Time From Randomisation to First Occurrence of Cardiovascular Death, Non-fatal Myocardial … | completed |
Consumer voice
No consumer comments were received for this item.
The PBAC noted that no consumer comments were received for this item. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricted to specific dual/triple combination regimens with metformin or sulfonylurea; TGA label broader, covering any adjunct therapy in high cardiovascular risk patients.