1 Recommendations

1.1 The committee was minded not to recommend dapagliflozin with insulin as an option for treating type 1 diabetes in adults with a BMI of at least 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy.

1.2 The committee recommends that NICE requests clarification and analyses from the company for the second appraisal committee meeting, including:

  • a clear presentation of the risk equations in the model and their sources (see section 3.11)

  • scenario analyses in which the source of risk equations for macrovascular complications is varied (see section 3.13)

  • a clear presentation of the relationship assumed between the degree and duration of improvement in HbA1c seen in the DEPICT trials, and the reduction in long-term complications based on the data from the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) study (see sections 3.13 and 3.14)

  • scenario analyses in which the benefit associated with the degree and duration of improvement in HbA1c seen in the DEPICT trials is not proportional to that resulting from the larger, sustained reduction in HbA1c seen in DCCT/EDIC (see section 3.14)

  • scenario analyses in which the risk of developing diabetes-related complications does not change immediately when HbA1c changes (see section 3.14)

  • analyses that include the baseline characteristics that reflect people in England with type 1 diabetes likely to have dapagliflozin (see sections 3.8 and 3.15), and excludes people with a 'low insulin need' defined as 0.5 units/kg of body weight (see sections 3.3 and 3.15)

  • analyses that include a progressive increase in HbA1c and weight over time in the model (see section 3.16)

  • scenario analyses that include a waning over time of the treatment effect for dapagliflozin (see section 3.17)

  • scenario analyses that include criteria defining when to stop treatment (see section 3.18)

  • analyses that include a stopping rate for dapagliflozin based on the probability of stopping for any reason from the DEPICT trials in year 1, and decreased rates in subsequent years (see section 3.19)

  • analyses that include a stopping rate for the standard of care arm of 0 (see section 3.19)

  • analyses that include the disutility and risk of death from Fournier's gangrene, severe hypoglycaemia and diabetic ketoacidosis (see section 3.20)

  • analyses using disutilities with face validity for minor and major amputations (see section 3.22)

  • analyses that include additional ketone monitoring, increased blood glucose testing and additional visits to diabetes specialist teams for people having dapagliflozin (see section 3.23)

  • the results of probabilistic sensitivity analyses (see section 3.24)

  • both the additive and multiplicative approach to disutilities (see section 3.21)

  • scenario analyses including EQ‑5D data from DEPICT (see section 3.22)

  • a clear presentation of the different utility values available from the literature and sensitivity analyses exploring the effect of using values from different sources (see section 3.22).

    Where appropriate, these analyses should be combined to give cumulative results.

Why the committee made these recommendations

Evidence from the 1‑year clinical trials shows small improvements in blood glucose (HbA1c levels) and weight loss, and very small improvements in quality of life, when dapagliflozin and insulin is compared with placebo and insulin in adults with type 1 diabetes and inadequate blood sugar control despite optimised insulin therapy. The company extrapolates the effects of the small improvement in HbA1c levels seen at 1 year in the trials to a lower risk of long-term complications over a patient's lifetime with dapagliflozin.

There is no clinical evidence to show that dapagliflozin increases how long people live, but this assumption is included in the economic model. The model and other assumptions, such as how treatment effects are likely to change after 1 year, lack credibility. Therefore, the committee is minded not to recommend dapagliflozin as an option for type 1 diabetes in the NHS.