Ertugliflozin as monotherapy or with metformin for treating type 2 diabetes

3.1 Ertugliflozin is a sodium-glucose cotransporter 2 (SGLT‑2) inhibitor. NICE has already produced technology appraisal guidance on 3 other SGLT‑2 inhibitors for treating type 2 diabetes (canagliflozin, dapagliflozin and empagliflozin). These treatments are recommended:

3.2 The company presented the results of the VERTIS‑MONO trial. This compared ertugliflozin monotherapy at the licensed dosages (5 mg and 15 mg) against placebo in 461 people aged 18 years or older with inadequate glycaemic control (defined as HbA1c 7.0% to 10.5% [53 to 91 mmol/mol]) despite diet and exercise. The primary outcome was change in HbA1c (measured as change in least-squared means from baseline to week 26). Both doses of ertugliflozin showed a statistically significant improvement compared with placebo in the full analysis set, which included all randomised patients who took at least 1 dose of study medication and had at least 1 measurement of the outcome variable (at baseline or after baseline). The results for secondary outcomes (percentage of patients with HbA1c less than 7% [less than 53 mmol/mol] at week 26, and changes in body weight and systolic and diastolic blood pressure from baseline to week 26) were favourable for both doses, although not all findings were statistically significant. The committee concluded that ertugliflozin monotherapy is a clinically effective treatment compared with placebo.

3.3 The company presented the results of 2 clinical trials that provided evidence on the efficacy of ertugliflozin as dual therapy with metformin:

3.4 The company presented 2 network meta-analyses (NMAs) comparing the clinical effectiveness of ertugliflozin as monotherapy and dual therapy against canagliflozin, dapagliflozin and empagliflozin (all outcomes were assessed at 24 to 26 weeks). The NMAs included the pivotal trials for ertugliflozin (VERTIS‑MONO, VERTIS‑MET and VERTIS‑FACTORIAL). The results showed that ertugliflozin, canagliflozin, dapagliflozin and empagliflozin had similar efficacy and safety. The trials included in the NMAs were generally the same as the trials that were assessed for the previous NICE technology appraisals of canagliflozin, dapagliflozin and empagliflozin. The ERG commented that differences between the studies included in the company's NMAs and the NMAs in the previous appraisals were either well-justified by the company or had little impact on the overall results of the analyses. However, the ERG also took the view that it was unnecessary, under the fast track appraisal cost-comparison process, for the company to have conducted the NMAs at all because they only needed to show that ertugliflozin has similar health benefits compared with 1 previously recommended product. In its own analysis, the ERG compared the results from each of the placebo-controlled trials for ertugliflozin against the results of another well-matched study; VERTIS‑MONO was compared with the CANTATA‑M trial of canagliflozin by Stenlof et al. 2013 and VERTIS‑MET was compared with a dapagliflozin trial by Bailey et al. 2010. The ERG did not do any statistical analysis but presented the results of the selected trials alongside the results of the VERTIS studies for the committee to compare visually. The ERG's interpretation of its additional analysis aligned with the company's conclusion that ertugliflozin and its comparators have similar efficacy and safety. The committee concluded that the clinical effectiveness of ertugliflozin, both as monotherapy and in dual therapy, is likely to be similar to that of the comparator treatments.

3.5 The company's NMAs showed no statistically significant differences in adverse-event rates between ertugliflozin and its comparators (canagliflozin, dapagliflozin and empagliflozin). The committee noted that women taking ertugliflozin monotherapy (5 mg and 15 mg) in VERTIS‑MONO had a statistically significantly higher rate of genital mycotic infections than women in the placebo group. Similarly, women taking the 15‑mg dose in VERTIS‑MET had a statistically significantly higher rate of genital mycotic infections than women in the placebo group. However, the committee noted the ERG's comment that the event rate observed in VERTIS‑MONO seemed high compared with the rates observed in other ertugliflozin trials, and it considered this to be reassuring. The committee concluded that the adverse events associated with ertugliflozin are likely to be similar to those for canagliflozin, dapagliflozin or empagliflozin.

3.6 The company assumed that, apart from direct drug acquisition costs, resource use and costs would be identical for ertugliflozin and its comparators. These costs included starting and administering treatment, treatment monitoring, managing adverse events and long-term disease management. The committee agreed with this assumption.

3.7 The company presented the results of a cost-comparison analysis for 1 year of treatment. It showed that, at list price, the acquisition cost of ertugliflozin is lower than that of canagliflozin, dapagliflozin and empagliflozin. The committee concluded that ertugliflozin, both as monotherapy and in dual therapy, meets the criteria for recommendation on the basis of a cost comparison, because: