Table 1.
Summary of model inputs: baseline characteristics and treatment effects
| Baseline characteristic | Baseline value | |||
|---|---|---|---|---|
| Age (years) | 57.51 | |||
| Proportion female (%) | 47.00 | |||
| Duration of diabetes (years) | 6.01 | |||
| Height (m) | 1.69 | |||
| Proportion Afro-Caribbean (%) | 6.20b | |||
| Proportion smokers | 36.90 | |||
| HbA1ca (%) | 8.05 | |||
| Weight (kg) | 87.84 | |||
| SBP (mmHg) | 133.30 | |||
| TC (mg/dL) | 199.57 | |||
| HDL-C (mg/dL) | 44.09 | |||
| Treatment effect | DAPA + MET | DPP-4i + MET | Insulin + METg | Intensified insulinc |
| ∆HbA1cc (%) | −0.69 | −0.61 | −1.10 | −1.11 |
| ∆Weightc (kg) | −3.36 | −0.61 | +1.08 | +1.90h |
| ∆SBPc (mmHG) | 0d | 0d | 0d | 0d |
| ∆TCc (mg/dL) | 0d | 0d | 0d | 0d |
| ∆HDL-Cc (mg/dL) | 0d | 0d | 0d | 0d |
| Probability of Discontinuatione | 0.081 | 0.043 | 0d | 0d |
| Probability. of hypoglycaemic events (symptomatic)f | 0.031 | 0.046 | 0.011 | 0.616 |
| Probability of hypoglycaemia (severe)f | 0.0004 | 0.001 | 0.037 | 0.022 |
| Probability of urinary tract infectionf | 0.074 | 0.054 | 0d | 0d |
| Probability of genital infectionf | 0.123 | 0d | 0d | 0d |
| Event | Utility decrement | Source | ||
| Diabetes-related complications | ||||
| Ischaemic heart disease | 0.090 | Clarke, 2003 [23] | ||
| Myocardial infarction | 0.550 | Clarke, 2003 [23] | ||
| Congestive heart failure | 0.108 | Clarke, 2003 [23] | ||
| Stroke | 0.164 | Clarke, 2003 [23] | ||
| Amputation | 0.280 | Clarke, 2003 [23] | ||
| Blindness | 0.074 | Clarke, 2003 [23] | ||
| End-stage renal disease | 0.263 | Currie, 2005 [24] | ||
| Hypoglycaemia | ||||
| Symptomatic | 0.042 | Currie, 2006 [39] | ||
| Nocturnal | 0.008 | Currie, 2006 [39] | ||
| Severe | 0.047 | Currie, 2006 [39] | ||
| Adverse events | ||||
| Urinary tract infection (UTI) | 0.00283 | Barry, 1997 [25] | ||
| Genital infection | 0.00283 | Assumed to be the same as UTI | ||
| BMI changes | ||||
| Per unit increase | 0.0472 | Lane, 2012 [26] | ||
| Per unit decrease | +0.0171 | Lane, 2012 [26] | ||
| Drug acquisition cost | Price per tableti | Dose per tablet/pen | Daily dose | Annual cost (£) |
| Dapagliflozin | £1.31 | 10 mg | 10 mg | £476.92 |
| DPP-4i (sitagliptinj) | £1.19 | 100 mg | 100 mg | £433.57 |
| Metformin | £0.02 | 500 mg | 2000 mg | £23.46 |
| Insulink (Insuman® Basal) | £0.47/day | 300 IU | 40 IU | £170.23 |
| Intensified insulin | £0.70/day | 300 IU | 60 IU | £256.96 |
| Diabetes-related complication costl | Fatal | Non-Fatal | Maintenance | Source |
| Ischaemic heart disease | - | £3,479 | £1,149 | Clarke, 2003 [21] |
| Myocardial infarction | £2,244 | £6,709 | £1,105 | Clarke, 2003 [21] |
| Congestive heart failure | £3,880 | £3,880 | £1,360 | Clarke, 2003 [21] |
| Stroke | £5,658 | £4,103 | £776 | Clarke, 2003 [21] |
| Amputation | £13,359 | £13,359 | £771 | Clarke, 2003 [21] |
| Blindness | - | £1,752 | £742 | Clarke, 2003 [21] |
| End-stage renal disease | - | £34,806 | £34,806 | Baboolal, 2008 [40] |
| Adverse event, renal monitoring and discontinuation costs | Cost input | Source | ||
| Severe hypoglycaemic event | £390 | Hammer, 2009 [41] | ||
| Renal monitoring | £38.67 | Assumed to incur one GP visit cost and a 24-hour creatine clearance determination [42, 43] | ||
| Urinary tract infection, genital infection | £36 | Assumed to incur one GP visit cost [42] | ||
| Discontinuation | £36 | Assumed to incur one GP visit cost [42] | ||
aValue was applied as the HbA1c switching threshold; it was considered to be a representative threshold value in real-world UK clinical practice as it was the average baseline HbA1c value of patients entering the phase 3 clinical trials that were included in the indirect comparison before switching to dual oral therapy
bValue sourced from randomised controlled trial by Nauck et al., 2010 [19]
∆ Mean change from baseline
c Effects apply to the first year after treatment initiation
d No estimate available and/or zero value assumed
eProbability of discontinuation was applied during the first model cycle
fProbabilities of adverse events were applied during every model cycle
gMonami, 2008 [44]
‡‡NICE HTA report Chapter 4 [45]
hWeight change from Montanana, 2008 [46]. Chosen as most recent study reporting weight effect included in the NICE HTA report
iThe daily costs are based on pack costs and have been rounded. The source of the unit costs are England and Wales Drug Tariff costs, February 2012. These costs are in general consistent with BNF63 drug prices
jSitagliptin is the most frequently prescribed DPP-4i in the UK (80 % of DPP-4i market as of December 2011, data on file)
kThe cost of insulin was based on a patient baseline weight of 88 kg, which if it remained stable would equate to an annual cost of £170.23 (and £256.96 for intensified insulin). However, in the model, weight changed over time, hence the actual annual cost of insulin (with dosage according to weight) in the economic analysis varies according to the simulated change in weight. Insulin daily cost per kg = £0.0053, insulin intensified daily cost per kg = £0.008
lPrices were indexed to 2011 using the Hospital and Community Health Services Pay & Prices index
Abbreviations: HbA1c, Glycated haemoglobin; SBP, systolic blood pressure; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; ∆, absolute change from baseline; GP, general practitioner