Why carry out this study?
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The surge in fees of high-cost new antidiabetic drugs will likely pose a challenge for the healthcare system. There are weak supporting evidence and extensive debate regarding the best second-line agent considering long-term efficacy, quality of life, and cost. Therefore, whether new antidiabetic drugs are superior to classic ones remains unclear |
This systematic review summarizes the pharmacoeconomic studies thus far performed in newer antidiabetic drugs as second-line treatment for type 2 diabetes and provides further evidence to guide treatment strategies |
What was learned from the study?
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Newer antidiabetic drugs appear to be generally cost-effective therapy in second-line options with T2D compared to classic antidiabetic drugs |
SGLT2i was superior to GLP-1RA and DPP-4i; DPP-4i has a good safety profile and weight neutrality, making it more cost-effective than other classical antidiabetic drugs, but not as favorable as GLP-1RA and SGLT2 |
With the continued improvement in the accessibility and affordability of newer antidiabetic drugs, SGLT2i can be a preferred option for second-line treatment with a great future |
Introduction
Methods
Search Strategy
Study Selection
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Participants: Adults with T2D.
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Intervention: second-line therapy.
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Outcome: cost, life gain year (LYG), quality-adjusted life year (QALY), incremental cost-effective ratio (ICER), and incremental net monetary benefit (INMB).
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Study design: cost-effectiveness analysis (CEA) and cost-utility analysis (CUA).
Data Extraction and Synthesis Strategy
Quality Assessment Reporting
Results
Search Results
General Characteristics of the Included Studies
Author, year | Region | Perspective | Interventions | Model | Time horizon | Discount rate | Sensitivity analysis | Funding |
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GLP-1RA vs. SGLT2i | ||||||||
Ehlers et al., 2022 [18] | Denmark | Payer | Semaglutide (sc) vs. empagliflozin | CORE | 50Y | 4% | Scenario, DSA and PSA | Industry |
Ehlers et al., 2021 [14] | Denmark | Healthcare | Liraglutide vs. empagliflozin | CORE | 50Y | 4% | Scenario, DSA and PSA | Industry |
Ramos et al., 2020 [16] | UK | Payer | Semaglutide (po) vs. empagliflozin | CORE | 50Y | 3.5% | Scenario and PSA | Industry |
Reifsnider et al., 2022 [19] | USA | Payer | Liraglutide vs. empagliflozin | DICE | Lifetime | 3% | Scenario, DSA and PSA | Industry |
GLP-1RA vs. othersa | ||||||||
Steen Carlsson et al., 2014 [17] | Sweden | Societal | Liraglutide vs. Glimepiride or Sitagliptin | IHECM | 40Y | 3% | Scenario and PSA | Industry |
Davies et al., 2012 [25] | UK | Payer | Liraglutide vs. sitagliptin or glimepiride | CORE | 50Y | 3.5% | DSA and PSA | Industry |
Sinha et al., 2010 [27] | USA | Healthcare | Exenatide (daily) vs. sitagliptin or glyburide | UKPDS | Lifetime | 3% | DSA | Industry |
Kiadaliri et al., 2014 [26] | Sweden | Societal | GLP-1RA vs. DPP-4i or NPH insulin | IHECM | 35Y | 3% | DSA and PSA | Public funding |
SGLT2i vs. othersb | ||||||||
Reifsnider et al., 2021 [23] | USA | Payer | Empagliflozin vs. sitagliptin | DICE | Lifetime | 3% | Scenario, DSA and PSA | Industry |
Charokopou et al., 2015 [22] | UK | Healthcare | Dapagliflozin vs. sitagliptin | Cardiff | 40Y | 3.5% | Scenario, DSA and PSA | Industry |
Bagepally et al., 2021 [20] | India | Payer | Dapagliflozin vs. SU | Markov | Lifetime | 3% | DSA and PSA | Public funding |
Charokopou et al., 2015 [21] | UK | Healthcare | Dapagliflozin vs. SU | Cardiff | 40Y | 3.5% | Scenario, DSA and PSA | Industry |
Tzanetakos et al., 2016 [24] | Greece | Payer | Dapagliflozin vs. DPP-4i or SU | Cardiff | 40Y | 3.5% | Scenario, DSA and PSA | Industry |
DPP-4i vs. othersc | ||||||||
Gu et al., 2015 [33] | China | Payer | Saxagliptin vs. glimepiride | Cardiff | 40Y | 3% | DSA and PSA | Industry |
Elgart et al., 2013 [28] | Argentina | Payer | Saxagliptin vs. SU | Cardiff | 20Y | 3.5% | DSA and PSA | Industry |
Granström et al., 2012 [31] | Sweden | Not specified | Saxagliptin vs. glipizide | Cardiff | 40Y | 3% | DSA and PSA | Not specified |
Erhardt et al., 2012 [29] | Germany | Payer | Saxagliptin vs. glipizide | Cardiff | 40Y | 3% | DSA and PSA | Industry |
Grzeszczak et al., 2012 [32] | Poland | Payer | Saxagliptin vs. NPH insulin | Cardiff | 40Y | 3.5% | Scenario, DSA and PSA | Industry |
Kousoulakou et al., 2017 [35] | Greece | Payer | Vildagliptin vs. glimepiride | UKPDS | Lifetime | 4% | DSA | Industry |
Viriato et al., 2014 [37] | Portugal | Healthcare | Vildagliptin vs. SU | UKPDS | 40Y | 5% | Scenario, DSA and PSA | Industry |
Gordon et al., 2016 [30] | UK | Not specified | Alogliptin vs. glipizide | CORE | 50Y | 3.5% | Scenario, DSA and PSA | Industry |
Schwarz et al., 2008 [36] | Europe | Not specified | Sitagliptin vs. rosiglitazone or SU | JADE | Lifetime | 3%-6% | DSA | Not specified |
Gu et al., 2016 [34] | China | Payer | Saxagliptin vs. acarbose | Cardiff | 40Y | 3% | DSA and PSA | Industry |
Gordon et al., 2017 [15] | UK | Payer | DPP-4i vs. SU or TZD | CORE | 50Y | 3.5% | PSA | Industry |
Multiple antidiabetic drugs | ||||||||
CADTH, 2017 [40] | Canada | Healthcare | SU, DPP-4i, SGLT2i, GLP-1RA, basal insulin or biphasic insulin | UKPDS | 40Y | NA | Scenario, DSA and PSA | Public funding |
Klarenbach et al., 2011 [41] | Canada | Payer | Metformin, SU, Meglitinide, AGI, TZD, DPP-4i, basal insulin or biphasic insulin | UKPDS | 40Y | 5% | DSA | Public funding |
Chien et al., 2020 [39] | Taiwan | Payer | SU, SGLT2i, GLP-1RA, DPP-4i or insulin | Cardiff | 40Y | 3% | Scenario, DSA and PSA | Public funding |
Gu et al., 2020 [38] | China | Healthcare | SU, TZD, AGI, meglitinide or DPP-4i | Cardiff | 40Y | 3% | Scenario, DSA and PSA | No funding |
Quality of the Included Studies
Pharmacoeconomics Evaluation Results
Author | Currency year | Interventions | Comparator | ICERa | INMBb | Cost-effectiveness | ||
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Original | 2022 US dollars | Original | 2022 US dollars | |||||
GLP-1RA vs. SGLT2i | ||||||||
Ehlers et al. [18] | 2019 | Semaglutide 1 mg/week | Empagliflozin 25 mg/day | DKK 745,561 | USD 108,332 | DKK -50,500 | USD -7338 | SGLT-2i |
Ehlers et al. [14] | 2019 | Liraglutide 1.8 mg/day | Empagliflozin 25 mg/day | Dominated | DKK -88,420 | USD -12,848 | SGLT-2i | |
Ramos et al. [16] | NA | Semaglutide 14 mg/day | Empagliflozin 25 mg/day | Dominated | GBP -6648 | USD -9940 | SGLT-2i | |
Reifsnider et al. [19] | 2019 | Liraglutide 1.8 mg/day | Empagliflozin 25 mg/day | Dominated | USD -27,244 | USD -28,978 | SGLT-2i | |
GLP-1RA vs. othersc | ||||||||
Steen Carlsson et al. [17] | 2013 | Liraglutide 1.2 mg/day | Glimepiride 4 mg/day | SEK 226,047 to 255,121f | USD 30,563 to 34,494f | SEK 77,765 to 99,642f SEK 113,102 to 133,377f | USD 10,514 to 13,472 f USD 15,292 to 18,034 f | GLP-1RA |
Liraglutide 1.2 mg/day | Sitagliptin 100 mg/day | SEK 148,766 to 160,827 f | USD 20,114 to 21,745 f | |||||
Davies et al. [25] | 2008 | Liraglutide 1.2/1.8 mg/day | Glimepiride 4 mg/day | GBP 9449/16,501 | USD 17,337/30,275 | GBP 3397/1,112 | USD 12,104/7,361 | GLP-1RA |
Liraglutide 1.2/1.8 mg/day | Sitagliptin 100 mg/day | GBP 9851/10,465 | USD 18,074/19,201 | GBP 1758/2776 | USD 6528/10,598 | |||
Sinha et al. [27] | 2008 | Exenatide 20 μg/d | Glyburide 7.5 mg/d | USD 278,935 | USD 353,523 | USD -14,253 | USD -18,064 | SU |
Sitagliptin 100 mg/day | Glyburide 7.5 mg/day | USD 169,572 | USD 214,916 | USD -19,574 | USD -24,808 | |||
Exenatide 20 μg/d | Sitagliptin 100 mg/d | Dominated | USD -5321 | USD -6744 | ||||
Kiadaliri et al. [26] | 2013 | GLP-1RA | DPP-4i | SEK 353,172 | USD 47,752 | SEK 15,135 | USD 2046 | GLP-1RA |
GLP-1RA | NPH insulin 40 IU/day | SEK 160,618 | USD 21,717 | SEK 84,198 | USD 11,384 | |||
DPP-4i | NPH insulin 40 IU/day | SEK 36,050 | USD 4874 | SEK 69,063 | USD 9338 | |||
SGLT2i vs. othersd | ||||||||
Reifsnider et al. [23] | 2018 | Empagliflozin 10–25 mg/day | Sitagliptin 50–100 mg/day | USD 6967 | USD 7542 | USD 8182 | USD 8858 | SGLT-2i |
Charokopou et al. [22] | 2011 | Dapagliflozin 10 mg/day | Sitagliptin 100 mg/day | GBP 6761 | USD 11,797 | GBP 424 | USD 740 | SGLT-2i |
Bagepally et al. [20] | 2017 | Dapagliflozin 10 mg/day | SU | INR 106,133 | USD 6596 | USD 87,061 | USD 5410 | SGLT-2i |
Charokopou et al. [21] | 2011 | Dapagliflozin 10 mg/day | SU | GBP 1246 | GBP 2671 | GBP 7954 | USD 13,878 | SGLT-2i |
Tzanetakos et al. [24] | 2015 | Dapagliflozin 10 mg/day | DPP-4i | EUR 17,695 | USD 32,665 | EUR 944 | USD 1743 | SGLT-2i |
SU | EUR 10,623 | USD 19,610 | EUR 11,518 | USD 21,262 | ||||
DPP-4i vs. otherse | ||||||||
Gu et al. [33] | 2014 | Saxagliptin 5 mg/day | Glimepiride 2.8 mg/day | Dominate | CNY 88,136 | USD 28,697 | DPP-4i | |
Elgart et al. [28] | 2009 | Saxagliptin | SU | USD 7374 | USD 11,666 | USD 45 | USD 2 | DPP-4i |
Granström et al. [31] | 2008 | Saxagliptin 5 mg/day | Glipizide 14.7 mg/day | SEK 91,260 | USD 13,184 | SEK 40,516 | USD 5853 | DPP-4i |
Erhardt et al. [29] | 2009 | Saxagliptin | Glipizide | EUR 13,931 | USD 22,199 | NA | NA | DPP-4i |
Grzeszczak et al. [32] | 2009 | Saxagliptin 5 mg/day | NPH insulin 25 IU/day | PLN 27,454 | USD 19,245 | PLN 9336 | USD 6544 | DPP-4i |
Kousoulakou et al. [35] | 2014 | Vildagliptin | Glimepiride | Dominate | EUR 1561 | USD 2872 | DPP-4i | |
Viriato et al. [37] | 2013 | Vildagliptin | SU | EUR 9072 | USD 17,291 | EUR 2679 | USD 5106 | DPP-4i |
Gordon et al. [30] | 2015 | Alogliptin 12.5/25 mg/day | Glipizide 5 mg/day | GBP 10,959/7217 | USD 18,092/11,915 | GBP 1989/3218 | USD 3284/5313 | DPP-4i |
Schwarz et al. [36] | 2007 | Sitagliptin | Rosiglitazone | Dominate to EUR 4766 | Dominate to USD 6918 | NA | NA | DPP-4i |
Sitagliptin g | SU g | EUR 5949 to 20,350 | USD 11,923 to 31,880 | NA | NA | |||
Sitagliptinh | SUh | EUR 6029 to 13,655 | USD 12,084 to 21,392 | NA | NA | |||
Gu et al. [34] | 2014 | Saxagliptin 5 mg/day | Acarbose 150 mg/day | Dominate | CNY 41,304 | USD 12,927 | DPP-4i | |
Gordon et al. [28] | 2015 | DPP-4i | SU | GBP 18,680 | USD 30,839 | GBP 531 | USD 877 | DPP-4i |
TZD | GBP 15,343 | USD 25,480 | GBP 1431 | USD 2362 |
Author | Currency year | Second line | QALYs | Total costs | Rank of cost-effectiveness | |
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Original | 2022 US dollar | |||||
CADTH [40] | 2016 | SU | 8.8784 | CAD 39,251 | USD 35,219 | 1 |
Metformin | 8.8369 | CAD 37,648 | USD 33,780 | 2 | ||
SGLT2i | 8.9530 | CAD 49,308 | USD 44,242 | 3 | ||
DPP-4i | 8.8998 | CAD 48,859 | USD 45,674 | 4 | ||
Basal insulin | 8.8998 | CAD 54,852 | USD 51,276 | 5 | ||
GLP-1RA | 8.9894 | CAD 55,946 | USD 52,299 | 6 | ||
Biphasic insulin | 8.9340 | CAD 63,719 | USD 59,565 | 7 | ||
Klarenbach et al. [41] | 2009 | SU | 8.72 | CAD 40,669 | USD 42,318 | 1 |
AGI | 8.77 | CAD 42,797 | USD 44,532 | 2 | ||
Meglitinide | 8.78 | CAD 42,269 | USD 43,983 | 3 | ||
Metformin | 8.72 | CAD 39,924 | USD 41,543 | 4 | ||
TZD | 8.78 | CAD 46,202 | USD 48,075 | 5 | ||
DPP-4i | 8.78 | CAD 47,191 | USD 49,104 | 6 | ||
Basal insulin | 8.78 | CAD 47,348 | USD 49,268 | 7 | ||
Biphasic insulin | 8.77 | CAD 52,367 | USD 54,490 | 8 | ||
Chien et al. [39] | 2019 | SGLT2i (SU as third line) | 12.483 | NTD 283,709 | USD 7593 | 1 |
SGLT2i (DPP-4i as third line) | 12.548 | NTD 287,891 | USD 7705 | 2 | ||
SU (SGLT2i as third line) | 11.943 | NTD 249,626 | USD 6681 | 3 | ||
DPP-4i (SGLT2i as third line) | 12.345 | NTD 282,722 | USD 7566 | 4 | ||
DPP-4i (SU as third line) | 11.931 | NTD 270,820 | USD 7248 | 5 | ||
GLP-1RA (SU as third line) | 12.453 | NTD 452,043 | USD 12,098 | 6 | ||
SU (DPP-4i as third line) | 11.469 | NTD 246,858 | USD 6607 | 7 | ||
Insulin (SU as third line) | 11.064 | NTD 278,502 | USD 7453 | 8 | ||
Gu et al. [38] | 2019 | Meglitinide (Insulin as third line) | 14.085 | CNY 55,729 | USD 16,872 | 1 |
AGI (Insulin as third line) | 14.019 | CNY 60,741 | USD 18,390 | 2 | ||
DPP-4i (insulin as third line) | 14.051 | CNY 69,467 | USD 21,031 | 3 | ||
Meglitinide (GLP-1RA as third line) | 14.117 | CNY 85,142 | USD 25,777 | 4 | ||
SU (insulin as third line) | 13.965 | CNY 52,923 | USD 16,023 | 5 | ||
TZD (INS as third line) | 13.978 | CNY 56,374 | USD 17,067 | 6 | ||
AGI (GLP-1RA as third line) | 14.053 | CNY 89,690 | USD 27,154 | 7 | ||
DPP-4i (GLP-1RA as third line) | 14.084 | CNY 98,597 | USD 29,850 | 8 | ||
SU (GLP-1RA as third line) | 13.997 | CNY 81,569 | USD 24,695 | 9 | ||
TZD (GLP-1RA as third line) | 14.011 | CNY 85,095 | USD 25,763 | 10 |