. 2021 Oct 22;11:20938. doi: 10.1038/s41598-021-00418-z

Table 2.

Study characteristics of the 11 selected RCTs with population, intervention, comparison, outcomes, and study design.

Trial	Study design	Study size and population	Study duration	Gemigliptin dose	Primary outcome	Secondary outcome	Drop out
Trial	Study design	Study size and population	Study duration	Comparator dose	Primary outcome	Secondary outcome	Drop out
Rhee 2010	RCT, Double blind, Placebo controlled, Optimal dose evaluation, Parallel, Multicenter	145 patients, Hb A1c: 7–11% Age: 18–75 years	12 w	GEM 50 mg	Change in HbA1c at 12 w	HbA1c responder rate at 12 w, Change in FPG, serum insulin, proinsulin and serum C-peptide, HOMA-β, HOMA-IR at 12 w	160 eligible participants, 145 randomized subjects, 4 excluded from efficacy analysis
				GEM 100 mg
				GEM 200 mg
				PBO
Yang 2013	RCT, Double blind, Placebo controlled, Parallel, Multicenter, Multinational	182 patients, HbA1c: 7–11% Age: 18–75 years	24 w	GEM 50 mg	Change in HbA1c at 24 w	HbA1c responder rate at 24 w	GEM 50 mg = 7 Placebo = 8
Yang 2013		182 patients, HbA1c: 7–11% Age: 18–75 years	24 w	PBO	Change in HbA1c at 24 w	HbA1c responder rate at 24 w	GEM 50 mg = 7 Placebo = 8
Yoon 2017 (GUARD study)	RCT, Double blind, Placebo controlled, Parallel, 40-w extension, Multicenter	132 patients with renal impairment, HbA1c: 7–11% Age: 19–75 years	12 w	GEM 50 mg	Change in HbA1c at 12 w	HbA1c responder rate at 6 w, Change in body weight at 6 w, 12 w, Change in eGFR, UACR, FPG, glycated albumin, fructosamine, fasting serum C-peptide, HOMA- β, HOMA-IR, fasting lipid at 12 w	GEM 50 mg = 11 Placebo = 11
Yoon 2017 (GUARD study)			12 w	PBO	Change in HbA1c at 12 w		GEM 50 mg = 11 Placebo = 11
Lim 2017 (INICOM study)	RCT, Double blind, Placebo controlled, Parallel, Multicenter, Multinational	132 patients, HbA1c: 7.5–11% and FPG < 270 mg/dL Age: 19–75 years	24 w	GEM 50 mg + MET	Change in HbA1c at 24 w	HbA1c responder rate, Change FPG, fasting insulin, fasting C-peptide, HOMA-β, HOMA-IR at 24 w	GEM 50 mg + MET = 16 Placebo + MET = 17 Placebo + GEM 50 mg = 11
				PBO + MET
				PBO + GEM 50 mg
Ahn 2017 (TROICA study)	RCT, Double blind, Placebo controlled, Parallel, Multicenter	219 patients, HbA1c: 7–11% with glimepiride (> = 4 mg/d) and metformin (> = 1000 mg) at a stable dose Age: over 19 years	24 w	GEM 50 mg + MET + GLM	Change in HbA1c at 24 w	HbA1c responder rate, Change FPG, fasting serum insulin, fasting proinsulin and fasting C-peptide, proinsulin to insulin ratio, HOMA-IR, HOMA-β, fasting lipid variables at 24 w	GEM 50 mg + MET + GLM = 11 Placebo + MET + GLM = 5
Ahn 2017 (TROICA study)			24 w	PBO + MET + GLM	Change in HbA1c at 24 w		GEM 50 mg + MET + GLM = 11 Placebo + MET + GLM = 5
Cho 2020 (ZEUS II study)	RCT, Double blind, Placebo controlled, Parallel, Multicenter, Multinational	290 patients, HbA1c: 7–11% with a stable dose of insulin Age: over 19 years	24 w	GEM 50 mg + MET + INS	Change in HbA1c at 24 w	HbA1c responder rate, Change FPG, fasting C-peptide at 24 w	GEM 50 mg + MET + INS = 5 Placebo + MET + INS = 4
Cho 2020 (ZEUS II study)			24 w	PBO + MET + INS	Change in HbA1c at 24 w	HbA1c responder rate, Change FPG, fasting C-peptide at 24 w	GEM 50 mg + MET + INS = 5 Placebo + MET + INS = 4
Rhee 2010	RCT, Double blind, Active- controlled, Parallel, Multicenter, Multinational	425 patients, Age: 18–75 years	24 w	GEM 25 mg bid	Change in HbA1c at 24 w	HbA1c responder rate, Change FPG, fasting insulin, proinsulin, HOMA-β, HOMA-IR at 24 w	GEM 25 mg BID = 5 GEM 50 mg = 7 SIT 100 mg = 9
				GEM 50 mg
				SIT 100 mg
Park 2017 (STABLE study)	RCT, Active controlled, Open label exploratory, Multicenter	69 patients, HbA1c: > 7.5% Age: 20–70 years	12 w	GEM 50 mg	Change in MAGE at 12 w	Change SD, MMT, CRP, nitrotyrosine, glycated albumin, fructosamine, HbA1c, FPG, fasting serum insulin, HOMA- β, HOMA-IR, LDL, HDL	GEM 50 mg = 0, SIT 100 mg = 2, GLIM 2 mg = 1
				SIT 100 mg
				GLIM 2 mg
Han 2018	RCT, Double blind, Placebo controlled, 40-week extension, Multicenter	132 patients with renal impairment HbA1c: 7–11% Age: 19–75 years	52 w	GEM 50 mg	Change in HbA1c at 52 w	HbA1c responder rate, change in eGFR, UACR, FPG, glycated albumin, fructosamine, fasting serum C-peptide, HOMA- β, HOMA-IR at 52 w	GEM 50 mg = 27, LIN 5 mg = 26
Han 2018			52 w	LIN 5 mg	Change in HbA1c at 52 w		GEM 50 mg = 27, LIN 5 mg = 26
Jung 2018	RCT, Double blind, Active controlled, Multicenter, Multinational	425 patients HbA1c: 7–11% with metformin (> = 1000 mg) at a stable dose	52 w	GEM 25 mg bid	Change in HbA1c at 52 w	HbA1c responder rate, change in FPG, serum insulin, proinsulin, serum C-peptide, HOMA-β, HOMA-IR at 52 w	GEM 25 mg = 14, GEM 50 mg = 18, SIT 100 mg = 2
				GEM 50 mg
				SIT 100 mg
Kwak 2020 (Stable II study)	RCT, Open blind end point, multicenter	71 patients HbA1c: 7–11% Age: 20–70 years	12 w	GEM 50 mg	Change in MAGE at 12 w	Change in MBG, SD, CV, HOMA- β, HOMA-IR, LDL, HDL	GEM 50 mg = 1, DAPA 10 mg = 3
Kwak 2020 (Stable II study)	RCT, Open blind end point, multicenter	71 patients HbA1c: 7–11% Age: 20–70 years	12 w	DAPA 10 mg	Change in MAGE at 12 w	Change in MBG, SD, CV, HOMA- β, HOMA-IR, LDL, HDL	GEM 50 mg = 1, DAPA 10 mg = 3

RCT randomized controlled trial, GEM gemigliptin, SIT sitagliptin, LINA linagliptin, MET metformin, GLIM glimepiride, DAPA dapagliflozin, INS insulin, bid twice a day, FPG fasting plasma glucose, GA glycated albumin, HOMA- β homeostatic model assessment for beta cells, HOMA-IR homeostatic model assessment for insulin resistance, CGM continuous glucose monitoring, UACR urine albumin-to-creatinine ratio, LDL low-density lipoprotein, HDL high-density lipoprotein, CV coefficient of variation, SD standard deviation, MMT mixed-meal test, CRP C-reactive protein, w weeks, eGFR estimated glomerular filtration rate, BMI body mass index, MAGE mean amplitude of glycemic excursion.