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. 2020 Dec 3;18:378. doi: 10.1186/s12916-020-01837-x

Table 1.

Model inputs: patient profiles, treatment effects, costs, and utility changes

Patient profiles of the initial cohort Value Source
 Patient characteristics Mean SE
  Age, year 55.7 0.17 [21, 22]
  Female proportion, % 45.8 0.70
  Duration of diabetes, year 0.50 –
  Height, metera 1.65 0.02
  Smokers proportion, % 22 0.50
 Modifiable risk factors Mean SE
  HbA1c, % 8.40 0.03 [21, 22]
  TC, mg/dlb 193.05 0.66
  HDL-C, mg/dlb 46.33 0.20
  LDL-C, mg/dlb 111.97 0.51
  SBP, mmHg 129 0.18
  Weight, kgc 68.20 2.42
Treatment effects of first therapyd Metformin Source
Mean SE
 HbA1c change, % − 1.57 0.22 Meta-analysis and indirect treatment comparison
 TC change, mg/dlb − 30.50 6.30
 HDL-C change, mg/dlb 10.04 2.36
 SBP change, mmHg − 0.36 2.26
 Weight change, kge − 7.51 1.09
 Symptomatic hypoglycemia, %f 1.81 1.04
 Severe hypoglycemia, %f 0.04 0.02
 Gastrointestinal reactions, % 2.15 1.06
Treatment effects of second therapyd Metformin + sulfonylurea Metformin + thiazolidinedione Metformin + α-glucosidase inhibitor Metformin + glinide Metformin + DPP-4 inhibitor Source
Mean SE Mean SE Mean SE Mean SE Mean SE
 HbA1c change, % − 2.61 0.18 − 2.40 0.22 − 2.41 0.28 − 2.64 0.25 − 2.52 0.22 Meta-analysis and indirect treatment comparison
 TC change, mg/dlb − 6.56 2.36 − 8.88 4.81 − 31.66 12.06 − 2.70 5.10 − 24.32 5.46
 HDL-C change, mg/dlb − 1.16 3.25 5.41 5.73 11.58 5.52 − 4.63 6.50 2.70 4.24
 SBP change, mmHg − 3.80 1.17 − 4.64 3.06 − 3.68 3.02 – – − 6.22 2.52
 Weight change, kge − 0.95 1.21 − 1.42 1.69 − 2.70 1.60 − 8.06 1.43 − 4.14 1.36
 Symptomatic hypoglycemia, %f 4.46 0.57 1.52 0.98 0 1.37 0 1.19 0.54 1.06
 Severe hypoglycemia, %f 0.09 0.01 0.03 0.02 0 0.03 0 0.02 0.01 0.02
 Gastrointestinal reactions, % 4.62 0.59 7.62 1.41 9.62 1.55 7.62 1.74 6.62 1.27
Treatment effects of third therapyd Metformin + insulin Metformin + GLP-1 receptor agonist Source
Mean SE Mean SE
 HbA1c change, % − 2.51 0.29 − 2.89 0.20 Meta-analysis and indirect treatment comparison
 TC change, mg/dlb − 69.50 12.15 − 55.60 7.88
 HDL-C change, mg/dlb – – 0 5.71
 SBP change, mmHg – – − 7.38 1.62
 Weight change, kge − 4.22 2.69 − 7.54 0.92
 Symptomatic hypoglycemia, %f 3.47 0.58 3.47 0.58
 Severe hypoglycemia, %f 0.07 0.01 0.07 0.01
 Gastrointestinal reactions, % 11.78 2.22 6.78 0.98
Costs of glucose-lowering treatments Cost, ¥ ($)g,i Individual drug Cost, ¥ ($)g,h Source
 Metformin 679.05 (98.30) Metformin 679.05 (98.30) [23]
 Sulfonylurea 632.74 (91.60) Glyburide 2.70 (0.39)
Glimepiride 1210.95 (175.30)
Gliclazide 414.59 (60.02)
Glipizide 902.72 (130.68)
 Thiazolidinedione 1148.06 (166.19) Rosiglitazone 938.83 (135.90)
Pioglitazone 1357.28 (196.48)
 α-Glucosidase inhibitor 1815.60 (262.83) Acarbose 1830.98 (265.05)
Voglibose 1356.07 (196.30)
Miglitol 2259.77 (327.12)
 Glinide 1124.13 (162.73) Repaglinide 1259.80 (182.37)
Nateglinide 988.46 (143.09)
 DPP-4 inhibitor 3069.95 (444.41) Sitagliptin 2814.34 (407.40)
Saxagliptin 3017.02 (436.74)
Vildagliptin 3192.47 (462.14)
Linagliptin 3137.21 (454.14)
Alogliptin 3188.72 (461.60)
 GLP-1 receptor agonist 14,578.94 (2110.44) Exenatide 18,990.33 (2749.03)
Liraglutide 10,167.55 (1471.85)
 Insulin cost per kg weight per day 0.137 (0.020) – –
Costs and utility changes associated with diabetes-related events Fatal costs, ¥ ($)g Non-fatal costs, ¥ ($)g Maintenance costs, ¥ ($)g Source Utility change Source
Mean SE Mean SE Mean SE Mean SE
 Ischemic heart disease 21,574.18 (3123.07) 6359.88 (920.65) 23,860.32 (3454.01) 1576.61 (228.23) 3293.02 (476.70) 435.07 (62.98) Claims data − 0.028 0.005 [24]
 Myocardial infarction 39,463.58 (5712.74) 8360.32 (1210.24) 53,131.50 (7691.30) 3774.74 (546.43) 6543.01 (947.16) – − 0.028 0.005
 Congestive heart failure 35,521.34 (5142.06) 13,196.13 (1910.27) 32,469.77 (4700.31) 6315.33 (914.21) 3113.24 (450.67) 1797.6 (260.22) − 0.028 0.005
 Stroke 69,427.06 (10,050.24) 18,792.10 (2720.34) 25,465.96 (3686.44) 2418.01 (350.03) 4274.23 (618.74) 735.06 (106.41) − 0.101 0.006
 Amputation – – 22,281.86 (3225.52) – 3542.36 (512.79) – − 0.118 0.009
 Blindness – – 15,846.21 (2293.89) 617.89 (89.45) 5227.01 (756.66) 484.87 (70.19) − 0.022 0.005
 End-stage renal disease 15,531.40 (2248.32) 3715.52 (537.86) 16,002.73 (2316.55) 554.07 (80.21) 5595.21 (809.96) 543.32 (78.65) − 0.058 0.006
 Symptomatic hypoglycemia – 0 – Assumed − 0.007 0.002
 Severe hypoglycemia – 4116.10 (595.85) – [25] − 0.008 0.004
 Gastrointestinal reactions – 0 – Assumed − 0.034 0 [26]
 BMI per unit increase – – – − 0.0061 0.001 [27]
 BMI per unit decrease – – – + 0.0061 0.001
BMI-related costs Costs, ¥ ($)g BMI Costs, ¥ ($)g BMI Costs, ¥ ($)g Source
 ≤ 23 0 29 14,230.2 (2059.96) 35 29,252.9 (4234.64) [28]
 24 1711.3 (247.73) 30 16,734.0 (2422.41) 36 31,756.7 (4597.09)
 25 4215.1 (610.18) 31 19,237.8 (2784.86) 37 34,260.5 (4959.54)
 26 6718.9 (972.63) 32 21,741.6 (3147.31) 38 36,764.3 (5321.99)
 27 9222.7 (1335.08) 33 24,245.4 (3509.76) 39 39,268.0 (5684.42)
 28 11,726.4 (1697.51) 34 26,749.1 (3872.19) ≥ 40 41,771.8 (6046.87)

Sulfonylurea includes glyburide, glimepiride, gliclazide, and glipizide. Thiazolidinedione includes rosiglitazone and pioglitazone. α-Glucosidase inhibitor includes acarbose, voglibose, and miglitol. Glinide includes repaglinide and nateglinide. DPP-4 inhibitor includes sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin. Insulin includes various kinds of insulin and insulin analogs. GLP-1 receptor agonist includes exenatide and liraglutide

BMI body mass index, DPP-4 dipeptidyl peptidase 4, GLP-1 glucagon-like peptide 1, HbA1c glycosylated hemoglobin Alc, HDL-C high-density lipoprotein-cholesterol, LDL-C low-density lipoprotein-cholesterol, RCT randomized controlled trial, SBP systolic blood pressure, SE standard error, TC total cholesterol

aAs only BMI and weight of the patients were reported, height was calculated by: sqrt (weight/BMI)

bThe unit of cholesterol in the included 324 RCTs was mmol/l, while the Cardiff model requires mg/dl, which was converted by: 1 mg/dl = 0.0259 mmol/l [29]

cThe “criteria of weight for adults” published by the National Health Commission of China defines weight categories as underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24 kg/m2), overweight (24 ≤ BMI < 28 kg/m2), and obese (BMI ≥ 28 kg/m2) [30]. As the BMI of patients in our initial cohort was 25 kg/m2, they were overweight

dThe treatment effect of each glucose-lowering treatment was with or without a background of lifestyle interventions

eOnly BMI change was reported in the 324 RCTs, while the Cardiff model requires weight change; thus, it was calculated by: weight = BMI × height2

fHypoglycemia is differentiated as symptomatic and severe ones in the Cardiff model, but most of the 324 RCTs did not clearly differentiate between symptomatic and severe episodes; thus, we estimated that a rate of 2% represented the proportion of severe cases out of all hypoglycemia events [25]

gFor the costs, data are 2019 Chinese yuan, ¥ (2019 US dollar, $). One US dollar was equal to ¥6.908 in 2019 [31]

hAnnual pharmacy cost of a drug was calculated as its retail price times its annual dose. The retail price was sourced from government medicine purchase platform, and the drug dose was obtained from the 324 RCTs. One year was counted as 365 days. For individual drugs, only the drugs reported in the 324 RCTs were included

iAnnual pharmacy costs of each drug class were calculated based on a simple arithmetic average of the costs of individual drugs