2.1 Population and treatment mix
Two budget impact models were constructed. The first one assessed the budget impact of the use of liraglutide versus other glucose lowering drugs while the second model assessed the budget impact of the use of sitagliptin versus other glucose lowering drugs. The target population of T2DM patients was estimated with the current Egyptian adult population and the prevalence of T2DM in Egypt [2, 5]. The estimated target population was then narrowed to a group of diagnosed and treated patients at risk of cardiovascular events as demonstrated in Fig. 1 [6]. This study focused exclusively on the proportion of this patient group covered by private health insurance companies [7]. The number of targeted patients was estimated to be 120,574. A gradual market introduction of liraglutide or sitagliptin was assumed, and the existing market shares for the other glucose lowering drugs were provided and validated by Expert Panel.
2.2 Clinical Parameters
The event rates for cardiovascular complications were extracted from the LEADER trial [3]. The events considered in this study included mortality, myocardial infarction, stroke, heart failure [HF], coronary revascularization, and microvascular complications (retinopathy, and nephropathy). The event rate difference per complication (liraglutide vs. standard of care) was multiplied by the number of patients on liraglutide to determine the number of cardiovascular events avoided. Similarly, sitagliptin inputs were extracted from the TECOS trial and all clinical parameters were included in the model (Table 1).
Table 1
The Model inputs parameters
Parameter | Base Value | Low Value | High Value | Source |
Population data |
Total Adult Population | 50,364,992 | 40,291,994 | 60,437,990 | [5] |
T2DM prevalence | 13.7% | 10.9% | 16.4% | [2] |
Proportion of patients with Type 2 Diabetes diagnosed & treated (with CV morbidity) | 35% | 28% | 42% | [6] |
Proportion of patients covered by private insurance companies in Egypt | 5% | 4% | 6% | [7] |
GLP-1RA Adoption year 1 | 3% | 2.4% | 3.6% | IMS data |
GLP-1RA Adoption year 2 | 4% | 3.2% | 4.8% | IMS data |
GLP-1RA Adoption year 3 | 5% | 4% | 6% | IMS data |
Clinical parameters from the LEADER Trial. |
MI* | -0.80% | -0.00640 | -0.00960 | [3] |
Ischemic Stroke* | -0.40% | -0.00320 | -0.00480 | [3] |
HF (hospitalization)* | -0.60% | -0.00480 | -0.00720 | [3] |
Coronary Revascularization* | -0.70% | -0.00560 | -0.00840 | [3] |
Retinopathy* | 0.30% | 0.00240 | 0.00360 | [3] |
Nephropathy* | -1.50% | -0.01200 | -0.01800 | [3] |
Unstable Angina Pectoris (hospitalization)* | -0.10% | -0.00080 | -0.00120 | [3] |
All-cause mortality* | -1.40% | -0.01120 | -0.01680 | [3] |
Clinical parameters from the TECOS Trial. |
MI# | -0.10% | -0.00080 | -0.00120 | [4] |
Ischemic Stroke# | -0.20% | -0.00160 | -0.00240 | [4] |
Unstable Angina Pectoris (hospitalization)# | -0.20% | -0.00160 | -0.00240 | [4] |
Severe hypoglycemia# | 0.30% | 0.00240 | 0.00360 | [4] |
CV Death# | 0.30% | 0.00240 | 0.00360 | [4] |
Acute pancreatitis# | 0.10% | 0.00080 | 0.00120 | [4] |
HF (hospitalization) # | 0.10% | 0.00080 | 0.00120 | [4] |
Pancreatic cancer# | -0.10% | -0.00080 | -0.00120 | [4] |
Treatment Costs per unit (Egyptian Pounds) |
Liraglutide | 87.60 | 70.08 | 105.12 | [8] |
Sitagliptin 100 | 11.00 | 8.80 | 13.20 | [8] |
Metformin 1000 | 0.90 | 0.72 | 1.08 | [8] |
Insulin (Glargine) 100 IU | 126.00 | 100.80 | 151.20 | [8] |
SU (Gliclazide 60 mg) | 1.58 | 1.26 | 1.89 | [8] |
TZD (Pioglitazone 15mg) | 5.13 | 4.11 | 6.16 | [8] |
Novonorm 2 mg (Repaglinide) | 1.47 | 1.17 | 1.76 | [8] |
SGLT2i (Empagliflozin) | 16.53 | 13.23 | 19.84 | [8] |
Event Costs excluding medicines (in Egyptian Pounds) |
Non-fatal MI | 76719 | 61375 | 92062 | [8] |
Non-fatal Stroke | 65928 | 52742 | 79113 | [8] |
HF (hospitalization) | 161249 | 128999 | 193498 | [8] |
Coronary Revascularization | 67919 | 54335 | 81502 | [8] |
Retinopathy | 20000 | 16000 | 24000 | [8] |
Nephropathy | 215695 | 172556 | 258834 | [8] |
Unstable Angina Pectoris (hospitalization) | 76719 | 61375 | 92062 | [8] |
Acute Pancreatitis | 55883 | 44706 | 67059 | [8] |
Severe Hypoglycemia | 8059 | 6447 | 9670 | [8] |
Pancreatic cancer | 92136 | 73708 | 110563 | [8] |
Mortality | 750,000 | 600,000 | 900,000 | [8] |
*rate difference with and without liraglutide, #rate difference with and without sitagliptin |
T2DM: type 2 diabetes mellitus, CV: cardiovascular, GLP1-RA; Glucagon like peptide 1 receptor agonist, HF: heart failure, MI: myocardial infarction, SU: sulphonyl urea, TZD: thiazolidinediones, SGLT2i: Sodium/glucose cotransporter-2 inhibitors |
2.3 Costs
Direct medical costs were estimated for drug acquisition, drug administration, complication management, follow up and adverse events costs. All unit costs of medications were extracted from the private health insurance payer’s lists, as fixed reimbursement amount, and multiplied by the drug utilization to obtain monthly and annual costs for liraglutide, sitagliptin, metformin, thiazolidinediones, sulfonylureas, insulin, meglitinides and SGLT2i. The drug utilization proportions were extracted from the LEADER and TECOS trials [3, 4].
The average management cost for a MI and unstable angina included cost of diagnostic tests (CT scan and ECG test), either percutaneous coronary intervention (PCI) or Coronary artery bypass graft (CABG) intervention, and a 7-day hospital stay including appropriate treatment. The management cost for stroke included a brain magnetic resonance imaging (MRI), 6 days in the ICU and 6 days in general ward including appropriate treatment. The heart failure management costs composed of diagnostic tests (echo doppler and ECG tests), 4 days in the ICU and 10 days in general ward costs including appropriate treatment. The costs of retinopathy included corrective surgery and measures for better glycaemic control, and the costs of nephropathy included measures to control blood pressure, haemodialysis to counteract the kidney damage, and glomerular filtration rate (GFR) test every three months.
The drug related adverse events included were acute pancreatitis, pancreatic cancer, and severe hypoglycaemia [3, 4]. Pancreatitis management costs composed of the cost of 7 days in the intensive care unit (ICU), 3 days of hospitalization in a ward, pain killers and antibiotic. As for the average management cost of pancreatic cancer it was assumed to be limited to the annual price of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for the management of pancreatic cancer, which is given daily via oral route. The cost of severe hypoglycaemia management was calculated as the summation of 4 days of hospitalization, admission to the emergency room, glucose intravenous administration, and laboratory tests (creatinine test, GFR tests, liver function tests, and glucose tests). All unit costs were extracted from the private insurance hospitals [8].
The mortality costs were also considered in our analysis. Even though indirect costs are not typically included in budget impact analysis, according to the ISPOR task force for good research practices for budget impact analysis, we considered the mortality as the private insurance companies have to pay compensation to the patients’ family in case of death based on the contracted life insurance policies [9]. To measure the cost of mortality, each patient life was estimated to have the stated value mentioned in the life insurance policy agreements.
The total event cost for each complication was multiplied by the event rate in each treatment arm (from the LEADER and TECOS trials) to determine the total cost per event. The medication costs were included with event costs, and the total cost difference of liraglutide vs without liraglutide was calculated as the budget impact of adopting liraglutide in T2DM patients with cardiovascular risks from the private health insurance perspective in Egypt. Similarly, the budget impact of sitagliptin vs without sitagliptin was calculated in T2DM patients with cardiovascular risks from the private health insurance perspective. Both liraglutide and sitagliptin were compared to placebo/standard of care. No direct comparison was made between the two interventions. All unit costs in this study were calculated in Egyptian Pounds (EGP) set in 2020 and were exchanged to USD using purchasing power parity rate. The time horizon for the study was 3 years.
2.4 Sensitivity Analyses
To investigate the robustness of our study, several sensitivity analyses were conducted. Clinical and cost parameters were varied from 10–20% more or less from their original value to investigate the impact they would have on the results and to confirm which parameter has the highest impact on our conclusion.