Table 1 Characteristics of the included RCTs

Mojca Jensterle [37] (2015)

NICHD (Slovenia)

12wk

LIRA 1.2 mg QD (n = 17)

vs

MET 1000 mg BID (n = 15)

Not actively promoted

29.5 ± 7.7(y);

40.8 ± 6.1 kg/m²

25.3 ± 5.2(y);

38.2 ± 7 kg/m²

MF, weight, metabolic, endocrine changes, TBF

Karen Elkind-Hirsch [25] (2008)

Rotterdam (Louisiana)

24wk

COMBI (EXE 10 μg BID + MET 1000 mg BID) (n = 20)

vs

EXE 10 μg BID (n = 20)

vs

MET 1000 mg BID (n = 20)

On unrestricted diet

COMBI:

32.1 ± 0.7(y);

41.2 ± 1.7 kg/m²

EXE:28.2 ± 1.1(y);

39.9 ± 1.5 kg/m²

27.7 ± 1.3(y);

41.3 ± 1.8 kg/m²

MF, ovulation rate, insulin action, anthropometric measures, androgen levels, inflammatory markers

Renyuan Li [26] (2022)

Rotterdam (China)

12wk

EXE 5–10 μg BID (n = 80)*12wk + MET 1000 mg BID*52wk

vs

MET 1000 mg BID (n = 80)*12wk + MET 1000 mg BID*52wk

Actively promoted

28.19 ± 3.96(y);

29.07 ± 3.92 kg/m²

27.83 ± 3.52(y);

29.15 ± 4.11 kg/m²

Spontaneous and total PR, pregnancy outcomes, metabolic parameters

Juan Wang [27] (2017)

Rotterdam (China)

3 month

EXE 10 μg BID (n = 45)

vs

MET 500–2000 mg daily (n = 33)

NM

25.92 ± 6.75(y);

26.26 ± 5.71 kg/m²

25.67 ± 7.33(y);

25.74 ± 6.37 kg/m²

PR, sex hormone, ovulation rate, glucose metabolic index, AngII/Ang(1–7)

Malin Nylander [28] (2017)

Rotterdam (Denmark)

26wk

LIRA 1.8 mg QD (n = 48)

vs

Placebo 1.8 mg QD (n = 24)

NM

31.4(24.6–35.6)(y);

33.3 ± 5.1 kg/m²

26.2(24.8–31.5)(y);

33.3 ± 4.6 kg/m²

MF, ovarian and stromal volume, antral follicle count, sex hormone

Xin Liu [38] (2017)

Rotterdam (China)

12wk

EXE 10 μg BID*12wk + MET*12wk (n = 88)

vs

MET 1000 mg BID*12wk + MET*12wk (n = 88)

Promoted

27.93 ± 2.70(y);

29.16 ± 3.11 kg/m²

27.69 ± 3.80(y);

28.29 ± 1.86 kg/m²

Natural PR, MF, weight, BMI, TBF, metabolic and endocrine changes, inflammatory markers

Karen E. Elkind-Hirsch [39] (2022)

NIH (Louisiana)

32wk

LIRA 3 mg QD (n = 55)

vs

Placebo 3 mg QD (n = 27)

Promoted

31 ± 0.8(y);

41.6 ± 0.9 kg/m²

32 ± 1.1(y);

43.9 ± 1.5 kg/m²

MF, weight and FAI, waist circumference, BMI, sex hormone, OGTT result, insulin action, lipids profile, BP, TBF

Vesna Salamun [40] (2018)

Rotterdam (Slovenija)

12wk

COMBI (LIRA 1.2 mg QD + MET 1000 mg BID) (n = 14)

vs

MET 1000 mg BID (n = 14)

Actively promoted

30.1 ± 3.6(y);

37.8 ± 3.0 kg/m²

31.1 ± 4.7(y);

35.5 ± 4.9 kg/m²

Cumulative PR(IVF and spontaneous); oocyte and embryo quality, weight, metabolic and endocrine parameters, TBF

Siyuan Zheng [41] (2017)

Rotterdam (China)

12wk

EXE 10 μg BID (n = 41)

vs

MET 1000 mg BID (n = 41)

Promoted

27.7 ± 3.41(y);

29.18 ± 4.15 kg/m²

28.16 ± 3.92(y);

29 ± 4.1 kg/m²

MF, weight, hirsutism, metabolic and endocrine change, inflammatory marker levels

Mojca Jensterle [42] (2014)

NICHD (Slovenia)

12wk

LIRA 1.2 mg QD (n = 15)

vs

MET 1000 mg BID (n = 15)

Promoted

30.7 ± 7.9(y)^a;

36.7 ± 5.6 kg/m²

30.7 ± 7.9(y)^a;

39.4 ± 6.9 kg/m²

MF, weight, metabolic and endocrine change

Mojca Jensterle Sever [35] (2014)

NICHD (Slovenia)

12wk

COMBI (LIRA 1.2 mg QD + MET 1000 mg BID) (n = 13)

vs

LIRA 1.2 mg QD (n = 13)

vs

MET 1000 mg BID (n = 14)

Not actively promoted

COMBI:31.1 ± 5.1(y);

37.6 ± 5.1 kg/m²

LIRA:31.5 ± 6.4(y);

39.3 ± 4.2 kg/m²

31.3 ± 9.4(y);

36.6 ± 3.5 kg/m²

MF, weight, metabolic and endocrine change, TBF