Table 1.

Study characteristics

Study ID	Country/Center	Criteria for prediabetes diagnosis	Definition of new-onset diabetes	Prediabetic sample size/Total sample size	Follow-up duration	Intervention group	Control group	Comedications status
Ariel et al. 2014	USA (Single-center)	FPG ≥ 100 and < 126 mg/dL and/or a plasma glucose concentration ≥ 140 and < 190 mg/dL 2-h after a 75-g oral glucose challenge	NA	68/68	14 weeks	Liraglutide, 1.8 mg/day, SC, starting at 0.6 mg daily, increased by 0.6 mg weekly to 1.8 mg/day + calorie-restricted diet	Placebo + calorie-restricted diet	Patients were excluded if they were taking any medications that affect lipoprotein or carbohydrate metabolism or promote weight loss
Rosenstock et al. 2010	USA	IGT (fasting glucose < 7 mmol/L and 2-h postprandial glucose ≥ 7.8 and < 11.1 mmol/L), IFG (fasting glucose 6.1– 6.9 mmol/l and 2-h postprandial glucose < 7.8 mmol/l)	NA	33/152	24 weeks	Exenatide, 10 µg, twice/day + a structured program of diet and physical activity	Placebo + a structured program of diet and physical activity	Patients with previous use of glucose-lowering medications for more than 3 months were excluded
Mashayekhi et al. 2022	USA (Single-center)	FPG between 100–125 mg/dL or IGT after a 75-g glucose challenge of 140–199 mg/dL or HbA1c = 5.7 to 6.4%	NA	88/88	14 weeks	Liraglutide, 1.8 mg/day, SC, starting at 0.6 mg daily, increased by 0.6 mg weekly to 1.8 mg/day	Sitagliptin 100 mg/day or a hypocaloric diet	NA
Pratley et al. 2021	Five countries (Multicenter)	HbA1c = 5.7% to 6.4% or FPG = 100 to 125 mg/dL	NA	140/140	20 weeks	Efpeglenatide, 4 mg QW, 6 mg QW, 6 mg Q2W, or 8 mg Q2W, SC + reducing calorie intake by approximately 500 kcal each day and increasing physical activity	Placebo + reducing calorie intake by approximately 500 kcal each day and increasing physical activity	NA
Kim et al. 2013	USA (Single-center)	FPG = 5.6 to 6.9 mmol/L or elevated 2-h glucose (7.8–11.0 mmol/L) concentration after a 75 g OGTT	NA	68/68	14 weeks	Liraglutide, 1.8 mg/day, SC, starting at 0.6 mg daily, increased by 0.6 mg weekly to 1.8 mg/day + decreasing total caloric intake by 500 kcal/day, and keeping baseline physical activity	Placebo + decreasing total caloric intake by 500 kcal/day and keeping baseline physical activity	Patients using medications that affect carbohydrate metabolism or promote weight loss were excluded
Lundkvist et al. 2017	Sweden (Single-center)	Prediabetes was defined as any IFG or IGT. IFG (FPG ≥ 5.6 mmol/L measured just before the OGTT), IGT ≥ 7.8 mmol/L measured 120 min after the start of the OGTT)	FPG > 7.0 mmol/L, 2-h OGTT > 11.1 mmol/L, and/or HbA1c > 48 mmol/mol	33/49	24 weeks	Dapagliflozin 10 mg, once/day, oral + Exenatide 2 mg QW, SC + balanced diet and moderate exercise. However, diet and exercise modifications were not mandated or documented	Placebo + balanced diet and moderate exercise. However, diet and exercise modification were not mandated or documented	Remained on the same medication without alternations
Zhou et al. 2017	China (Single-center)	IFG: FPG (5.6–6.9 mmol/L), while 2 h OGTT < 7.8 mmol/L, IGT: OGTT 2 h blood glucose (7.8–11.0) while FPG < 5.6	FPG ≥ 7.0 or OGTT 2 h blood glucose > 11.1	42/42	12 weeks	Liraglutide, 1.2 mg/day, SC, starting at 0.6 mg daily, increased to 1.2 mg/day after one week + a unified diet and exercise prescription with regular telephone conversations and outpatient follow-up	A unified diet and exercise prescription with regular telephone conversations and outpatient follow-up	NA
Astrup et al. 2009	19 clinical research sites in eight European countries	Either IFG (5·6–6·9 mmol/L) or IGT (7·8–11·0 mmol/L) during OGTT	Fasting plasma glucose ≥ 7·0 mmol/L or ≥ 11·1 mmol/L during OGTT	187/564	20 weeks	Liraglutide, 1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg, once/day, SC + decreasing total caloric intake by 500 kcal/day, and increasing physical activity	Placebo or orlistat + decreasing total caloric intake by 500 kcal/day, and increasing physical activity	Patients were excluded weight-lowering pharmacotherapy or participation in a clinical weight control study
Astrup et al. 2012	19 clinical research sites in eight European countries	Either IFG (5·6–6·9 mmol/L) or IGT (7·8–11·0 mmol/L) during OGTT	Fasting plasma glucose ≥ 7·0 mmol/L or ≥ 11·1 mmol/L during OGTT	187/564	52 weeks	Liraglutide, 1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg, once/day, SC + decreasing total caloric intake by 500 kcal/day, and increasing physical activity	Placebo or orlistat + decreasing total caloric intake by 500 kcal/day, and increasing physical activity	Patients were excluded if they used weight-lowering pharmacotherapy or participation in a weight-control stud
Le Roux et al. 2017	191 clinical research sites in 27 countries	One of the three American Diabetes Association (ADA) 2010 criteria: HbA1c = 5·7 − 6·4%, or FPG = 5·6 mmol/L to 6·9 mmol/L, or 2-h OGTT = 7·8 mmol/L to 11·0 mmol/L	Two consecutive measurements of HbA1c ≥ 6.5%, or FPG ≥ 126 mg/dl (7.0 mmol/liter), or 2-h OGTT ≥ 200 mg/dl (11.1 mmol/liter)	2254/2254	160 weeks	Liraglutide, 3.0 mg, once/day, SC, starting at 0.6 mg with weekly 0.6-mg increments to 3.0 mg + reduced-calorie diet, and increased physical activity	Placebo + reduced-calorie diet, and increased physical activity	Patients were excluded medications causing significant weight gain or loss
Perreault et al. 2022a	16 countries (multicenter)	American Diabetes Association criteria. Prediabetes was defined as FPG 5.6–6.9 mmol/L or HbA1c 5.7–6.4% (39–47 mmol/mol)	HbA1c = 48 mmol/L (6.5%) or greater	856/1961	68 weeks	Semaglutide, 2.4 mg, QW, SC, starting with 0.25 mg weekly for the first 4 weeks, increased every 4 weeks to reach 2.4 mg weekly + decreasing total caloric intake by 500 kcal/day, and increasing physical activity by 150 min/week of physical activity. Both diet and activity were recorded daily	Placebo + decreasing total caloric intake by 500 kcal/day, and increasing physical activity. Both diet and activity were recorded daily	The individual has not had any prior surgical obesity treatment or use of antiobesity medication within 90 days prior to enrollment
Perreault et al. 2022b	USA (multicenter)	American Diabetes Association criteria. Prediabetes was defined as FPG 5.6–6.9 mmol/L or HbA1c 5.7–6.4% (39–47 mmol/mol)	HbA1c = 48 mmol/L (6.5%) or greater	304/611	68 weeks	Semaglutide, 2.4 mg, QW, SC, starting with 0.25 mg weekly for the first 4 weeks, increased every 4 weeks to reach 2.4 mg weekly + intensive behavioral intervention (low-calorie diet (1000–1200 kcal/d) in the initial 8 weeks + hypocaloric diet (1200–1800 kcal/d) for the rest of the 68 weeks) + 100 min of physical activity per week, which increased by 25 min every 4 weeks to reach 200 min/week	Placebo + intensive behavioral intervention (low-calorie diet (1000–1200 kcal/d) in the initial 8 weeks + hypocaloric diet (1200–1800 kcal/d) for the rest of 68 weeks) + 100 min of physical activity per week, which increased by 25 min every 4 weeks, to reach 200 min/week	NA
Perreault et al. 2022c	10 countries (multicenter)	American Diabetes Association criteria. Prediabetes was defined as FPG 5.6–6.9 mmol/L or HbA1c 5.7–6.4% (39–47 mmol/mol)	HbA1c = 48 mmol/L (6.5%) or greater	376/803	48 weeks	Semaglutide, 2.4 mg, QW, SC, starting with 0.25 mg weekly for the first 4 weeks, increased every 4 weeks to reach 2.4 mg weekly + decreasing total caloric intake by 500 kcal/day, and increasing physical activity by 150 min/week of physical activity. Both diet and activity were recorded daily	Placebo + decreasing total caloric intake by 500 kcal/day, and increasing physical activity. Both diet and activity were recorded daily	NA

IGT: impaired glucose tolerance; IFG: impaired fasting plasma glucose; FPG: fasting plasma glucose; OGTT: oral glucose tolerance test; SC: subcutaneous; QW: once weekly; Q2W: once every 2 weeks