| Study . | Participant characteristics . | Study arms . | Study duration . | Primary outcome . | Other outcomes . | Body weight Loss (kg) . | Metabolic changes . | Menstrual pattern/other . | Attrition rate . |
|---|---|---|---|---|---|---|---|---|---|
| Elkind- Hirsch et al (86) | Overweight (BMI >27), insulin-resistant, oligoovulatory women. Age 18-40 years. PCOS diagnosed according to a modification of Rotterdam criteria 2003 | 1) MET:1000 mg bid (n = 14) 2) EXE (10 μg bid) (n = 14) 3) MET 1000 mg bid + EX 10 μg bid (n = 14) | 24 weeks | Menstrual frequency | Ovulation rate Insulin action FAI Inflammatory markers | 1) −1.6 ± 0.2 2) −3.2 ± 0.1 3) −6.0 ± 0.5 | FAI reduced and Insulin sensitivity improved in combination arm | Combination therapy superior to EX or MET (menses and ovulation) | 30% |
| Rasmussen et al (87) | Overweight or obese women, pre-treated with MET for at least 6 months. PCOS diagnosed according to Rotterdam criteria. | Add-on of LIRA 1.2-1.8 mg (n = 84) | Mean of 27.8 weeks | Weight loss | - | −9.0 (95% CI, 7.8- 10.1) | Mean decrease in BMI of 3.2 kg/m2 Weight loss >5% and >10% in 81.7% and 32.9% of patients, respectively | 20.0% | |
| Kahal et al (88) | Obese women (BMI 30-45) Age 18-45 years Healthy controls. PCOS diagnosed according to Rotterdam criteria. | LIRA:1.8 mg (19 obese women with PCOS and 17 controls) | 6 months | CV risk markers | Weight loss | PCOS: -3.0 ± 4.2 Controls: −3.8 ± 3.0 | HOMA-IR, hsCRP, endothelial adhesion markers significantly and equally reduced in both groups No changes in cIMT | 30.6% | |
| Jensterle et al (89) | Obese (BMI ≥30) women Age ≥18 years, premenopause. PCOS diagnosed by ASRM-ESHRE Rotterdam criteria. | 1) MET:1000 mg bid (n = 14) 2) LIRA 1.2 mg (n = 14) 3) ROF 500 mg qd (n = 14) | 12 weeks | Weight loss | Hormonal and metabolic changes | 1) −0.8 ± 1.0 2) −3.1 ± 3.5 3) −2.1 ± 2.0 | FAI reduction in ROF arm; decrease in visceral fat in LIRA arm. HOMA-IR decreased in all treatment arms. LIRA superior to MET in reducing glucose at 120 min of OGTT | Menstrual frequency increased with all treatments. | 8.9% |
| Frøssing et al (90) | Women with BMI >25 and/ or insulin resistance PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg OD s.c. (n = 48) 2) Placebo (n = 24) | 26 weeks | Liver fat VAT Prevalence of NAFLD | Weight change OGTT, SHBG, testosterone | 1) −5.2 ± 0.7 2) +0.2 ± 0.9 | LIRA reduced liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds. With LIRA, SHBG levels increased by 19%, and free testosterone decreased by 19%. | 28% | |
| Jensterle Sever et al (91) | Obese (BMI ≥30), nondiabetic women who had lost ≥5% body weight during pretreatment with MET for at least 6 months. Age >18 years. PCOS diagnosed by the NICHD criteria. | 1) MET: 1000 mg BID (n = 14) 2) LIRA: 1.2 mg OD s.c. (n = 11) 3) MET 1000 mg BID + LIRA 1.2 mg QD s.c.(n = 11) | 12 weeks | Weight loss | Body composition IR | 1) −1.2 ± 1.4 2) −3.8 ± 3.7 3) −6.5 ± 2.8 | No major changes in fasting glucose, insulin, and insulin during OGTT. Glucose value after 120 min during OGTT significantly reduced in the combination arm vs MET. | No significant changes in menstrual pattern. | 10% |
| Jensterle et al (92) | Obese (BMI ≥30) women with newly diagnosed PCOS. Age ≥18 years, premenopause. PCOS diagnosed by the NICHD criteria. | 1) MET:1000 mg bid/ daily (n = 14) 2) LIRA 1.2 mg (n = 14) | 12 weeks | Weight loss | Body composition IR | 1) −2.3 2) −3.0 LIRA superior in severe IR (BMI reduction 2.13 vs 0.62 kg/m2) | Decrease in total testosterone in MET Increase in LH in LIRA | 12.5% | |
| Jensterle et al (94) | Obese (BMI ≥30) women Age ≥18 years, premenopause PCOS diagnosed by ASRM-ESHRE Rotterdam criteria | 1) MET 1000 mg BID + LIRA 1.3 mg OD s.c. (n = 15) 2) LIRA 3 mg OD s.c. (n = 15) | 12 weeks | Weight loss | Metabolic and hormonal changes | 1) −3.6 ± 2.5 2) −6.3 ± 3.7 | Both interventions resulted in a significant decrease of post-OGTT glucose levels. Combination therapy significantly reduced total testosterone | 6.7% | |
| Nylander et al (96). | Overweight (BMI ≥25) women and/ or insulin resistance Age ≥18 years PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg (n = 44) 2) Placebo (n = 21) | 26 weeks | Bleeding pattern | Levels of AMH, sex hormones, and gonadotrophins, ovarian morphology | LIRA vs Placebo: −5.2 (95% CI, 3.0-7.5) | In the LIRA group, SHBG increased and free testosterone decreased. Ovarian volume decreased with LIRA vs placebo. | Bleeding ratio significantly improved with LIRA vs placebo | 9.7% |
| Salamun et al (97) | Infertile, obese women (BMI ≥30) Age ≤38 years, first or second IVF attempt PCOS diagnosed according to revised Rotterdam criteria | 1) MET 1000 mg bid (n = 14) 2) MET 1000 mg bid + LIRA 1.3 mg QD s.c. (n = 14) | 12 weeks | IVF pregnancy rate | Weight change | 1) −7.0 ± 6.0 2) −7.5 ± 3.9 | Pregnancy rate per embryo transfer significantly higher with combined therapy (85.7%) compared with MET (28.6%) | 18% | |
| Liu et al (98). | Overweight or obese women (BMI ≥24) Age 18-40 years PCOS diagnosed according to Rotterdam criteria | 1) MET:1000 mg bid (n = 88) 2) EXE: 10 μg BID (n = 88) | 12 weeks; after 12 weeks all patients treated with MET alone for additional 12 weeks | Weight loss | Fat mass, hormonal levels, insulin resistance, lipid profile, inflammatory marker, menstrual frequency, and rate of pregnancy. | 1) −2.28 ± 0.55 2) −4.29 ± 1.29 | Decrease in android fat mass% and total fat mass% with EXE, but not with MET. Greater decrease in HOMA-IT and insulin levels with EXE than with MET. HsCRP levels decreased significantly in the EXE group only. | Menstrual frequency increased significantly in both groups. Rate of natural pregnancy significantly higher following EXE treatment than following MET treatment | 10.2% |
| Study . | Participant characteristics . | Study arms . | Study duration . | Primary outcome . | Other outcomes . | Body weight Loss (kg) . | Metabolic changes . | Menstrual pattern/other . | Attrition rate . |
|---|---|---|---|---|---|---|---|---|---|
| Elkind- Hirsch et al (86) | Overweight (BMI >27), insulin-resistant, oligoovulatory women. Age 18-40 years. PCOS diagnosed according to a modification of Rotterdam criteria 2003 | 1) MET:1000 mg bid (n = 14) 2) EXE (10 μg bid) (n = 14) 3) MET 1000 mg bid + EX 10 μg bid (n = 14) | 24 weeks | Menstrual frequency | Ovulation rate Insulin action FAI Inflammatory markers | 1) −1.6 ± 0.2 2) −3.2 ± 0.1 3) −6.0 ± 0.5 | FAI reduced and Insulin sensitivity improved in combination arm | Combination therapy superior to EX or MET (menses and ovulation) | 30% |
| Rasmussen et al (87) | Overweight or obese women, pre-treated with MET for at least 6 months. PCOS diagnosed according to Rotterdam criteria. | Add-on of LIRA 1.2-1.8 mg (n = 84) | Mean of 27.8 weeks | Weight loss | - | −9.0 (95% CI, 7.8- 10.1) | Mean decrease in BMI of 3.2 kg/m2 Weight loss >5% and >10% in 81.7% and 32.9% of patients, respectively | 20.0% | |
| Kahal et al (88) | Obese women (BMI 30-45) Age 18-45 years Healthy controls. PCOS diagnosed according to Rotterdam criteria. | LIRA:1.8 mg (19 obese women with PCOS and 17 controls) | 6 months | CV risk markers | Weight loss | PCOS: -3.0 ± 4.2 Controls: −3.8 ± 3.0 | HOMA-IR, hsCRP, endothelial adhesion markers significantly and equally reduced in both groups No changes in cIMT | 30.6% | |
| Jensterle et al (89) | Obese (BMI ≥30) women Age ≥18 years, premenopause. PCOS diagnosed by ASRM-ESHRE Rotterdam criteria. | 1) MET:1000 mg bid (n = 14) 2) LIRA 1.2 mg (n = 14) 3) ROF 500 mg qd (n = 14) | 12 weeks | Weight loss | Hormonal and metabolic changes | 1) −0.8 ± 1.0 2) −3.1 ± 3.5 3) −2.1 ± 2.0 | FAI reduction in ROF arm; decrease in visceral fat in LIRA arm. HOMA-IR decreased in all treatment arms. LIRA superior to MET in reducing glucose at 120 min of OGTT | Menstrual frequency increased with all treatments. | 8.9% |
| Frøssing et al (90) | Women with BMI >25 and/ or insulin resistance PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg OD s.c. (n = 48) 2) Placebo (n = 24) | 26 weeks | Liver fat VAT Prevalence of NAFLD | Weight change OGTT, SHBG, testosterone | 1) −5.2 ± 0.7 2) +0.2 ± 0.9 | LIRA reduced liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds. With LIRA, SHBG levels increased by 19%, and free testosterone decreased by 19%. | 28% | |
| Jensterle Sever et al (91) | Obese (BMI ≥30), nondiabetic women who had lost ≥5% body weight during pretreatment with MET for at least 6 months. Age >18 years. PCOS diagnosed by the NICHD criteria. | 1) MET: 1000 mg BID (n = 14) 2) LIRA: 1.2 mg OD s.c. (n = 11) 3) MET 1000 mg BID + LIRA 1.2 mg QD s.c.(n = 11) | 12 weeks | Weight loss | Body composition IR | 1) −1.2 ± 1.4 2) −3.8 ± 3.7 3) −6.5 ± 2.8 | No major changes in fasting glucose, insulin, and insulin during OGTT. Glucose value after 120 min during OGTT significantly reduced in the combination arm vs MET. | No significant changes in menstrual pattern. | 10% |
| Jensterle et al (92) | Obese (BMI ≥30) women with newly diagnosed PCOS. Age ≥18 years, premenopause. PCOS diagnosed by the NICHD criteria. | 1) MET:1000 mg bid/ daily (n = 14) 2) LIRA 1.2 mg (n = 14) | 12 weeks | Weight loss | Body composition IR | 1) −2.3 2) −3.0 LIRA superior in severe IR (BMI reduction 2.13 vs 0.62 kg/m2) | Decrease in total testosterone in MET Increase in LH in LIRA | 12.5% | |
| Jensterle et al (94) | Obese (BMI ≥30) women Age ≥18 years, premenopause PCOS diagnosed by ASRM-ESHRE Rotterdam criteria | 1) MET 1000 mg BID + LIRA 1.3 mg OD s.c. (n = 15) 2) LIRA 3 mg OD s.c. (n = 15) | 12 weeks | Weight loss | Metabolic and hormonal changes | 1) −3.6 ± 2.5 2) −6.3 ± 3.7 | Both interventions resulted in a significant decrease of post-OGTT glucose levels. Combination therapy significantly reduced total testosterone | 6.7% | |
| Nylander et al (96). | Overweight (BMI ≥25) women and/ or insulin resistance Age ≥18 years PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg (n = 44) 2) Placebo (n = 21) | 26 weeks | Bleeding pattern | Levels of AMH, sex hormones, and gonadotrophins, ovarian morphology | LIRA vs Placebo: −5.2 (95% CI, 3.0-7.5) | In the LIRA group, SHBG increased and free testosterone decreased. Ovarian volume decreased with LIRA vs placebo. | Bleeding ratio significantly improved with LIRA vs placebo | 9.7% |
| Salamun et al (97) | Infertile, obese women (BMI ≥30) Age ≤38 years, first or second IVF attempt PCOS diagnosed according to revised Rotterdam criteria | 1) MET 1000 mg bid (n = 14) 2) MET 1000 mg bid + LIRA 1.3 mg QD s.c. (n = 14) | 12 weeks | IVF pregnancy rate | Weight change | 1) −7.0 ± 6.0 2) −7.5 ± 3.9 | Pregnancy rate per embryo transfer significantly higher with combined therapy (85.7%) compared with MET (28.6%) | 18% | |
| Liu et al (98). | Overweight or obese women (BMI ≥24) Age 18-40 years PCOS diagnosed according to Rotterdam criteria | 1) MET:1000 mg bid (n = 88) 2) EXE: 10 μg BID (n = 88) | 12 weeks; after 12 weeks all patients treated with MET alone for additional 12 weeks | Weight loss | Fat mass, hormonal levels, insulin resistance, lipid profile, inflammatory marker, menstrual frequency, and rate of pregnancy. | 1) −2.28 ± 0.55 2) −4.29 ± 1.29 | Decrease in android fat mass% and total fat mass% with EXE, but not with MET. Greater decrease in HOMA-IT and insulin levels with EXE than with MET. HsCRP levels decreased significantly in the EXE group only. | Menstrual frequency increased significantly in both groups. Rate of natural pregnancy significantly higher following EXE treatment than following MET treatment | 10.2% |
AMH, anti-Müllerian hormone; cIMT, carotid-intima media thickness; EXE, exenatide; FAI, free androgen index; HOMA-IR, homeostasis model assessment-IR; hsCRP, high-sensitivity C-reactive protein; IR, insulin resistance; IVF, in vitro fertilization; LIRA, liraglutide; MET, metformin; NAFLD, nonalcoholic fatty liver disease; NICHD, National Institute of Child Health and Human Development; OGTT, oral glucose tolerance test; PIIINP, Procollagen Type III N-Terminal Peptide; SHBG, sex hormone binding globulin; VAT, visceral adipose tissue.
| Study . | Participant characteristics . | Study arms . | Study duration . | Primary outcome . | Other outcomes . | Body weight Loss (kg) . | Metabolic changes . | Menstrual pattern/other . | Attrition rate . |
|---|---|---|---|---|---|---|---|---|---|
| Elkind- Hirsch et al (86) | Overweight (BMI >27), insulin-resistant, oligoovulatory women. Age 18-40 years. PCOS diagnosed according to a modification of Rotterdam criteria 2003 | 1) MET:1000 mg bid (n = 14) 2) EXE (10 μg bid) (n = 14) 3) MET 1000 mg bid + EX 10 μg bid (n = 14) | 24 weeks | Menstrual frequency | Ovulation rate Insulin action FAI Inflammatory markers | 1) −1.6 ± 0.2 2) −3.2 ± 0.1 3) −6.0 ± 0.5 | FAI reduced and Insulin sensitivity improved in combination arm | Combination therapy superior to EX or MET (menses and ovulation) | 30% |
| Rasmussen et al (87) | Overweight or obese women, pre-treated with MET for at least 6 months. PCOS diagnosed according to Rotterdam criteria. | Add-on of LIRA 1.2-1.8 mg (n = 84) | Mean of 27.8 weeks | Weight loss | - | −9.0 (95% CI, 7.8- 10.1) | Mean decrease in BMI of 3.2 kg/m2 Weight loss >5% and >10% in 81.7% and 32.9% of patients, respectively | 20.0% | |
| Kahal et al (88) | Obese women (BMI 30-45) Age 18-45 years Healthy controls. PCOS diagnosed according to Rotterdam criteria. | LIRA:1.8 mg (19 obese women with PCOS and 17 controls) | 6 months | CV risk markers | Weight loss | PCOS: -3.0 ± 4.2 Controls: −3.8 ± 3.0 | HOMA-IR, hsCRP, endothelial adhesion markers significantly and equally reduced in both groups No changes in cIMT | 30.6% | |
| Jensterle et al (89) | Obese (BMI ≥30) women Age ≥18 years, premenopause. PCOS diagnosed by ASRM-ESHRE Rotterdam criteria. | 1) MET:1000 mg bid (n = 14) 2) LIRA 1.2 mg (n = 14) 3) ROF 500 mg qd (n = 14) | 12 weeks | Weight loss | Hormonal and metabolic changes | 1) −0.8 ± 1.0 2) −3.1 ± 3.5 3) −2.1 ± 2.0 | FAI reduction in ROF arm; decrease in visceral fat in LIRA arm. HOMA-IR decreased in all treatment arms. LIRA superior to MET in reducing glucose at 120 min of OGTT | Menstrual frequency increased with all treatments. | 8.9% |
| Frøssing et al (90) | Women with BMI >25 and/ or insulin resistance PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg OD s.c. (n = 48) 2) Placebo (n = 24) | 26 weeks | Liver fat VAT Prevalence of NAFLD | Weight change OGTT, SHBG, testosterone | 1) −5.2 ± 0.7 2) +0.2 ± 0.9 | LIRA reduced liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds. With LIRA, SHBG levels increased by 19%, and free testosterone decreased by 19%. | 28% | |
| Jensterle Sever et al (91) | Obese (BMI ≥30), nondiabetic women who had lost ≥5% body weight during pretreatment with MET for at least 6 months. Age >18 years. PCOS diagnosed by the NICHD criteria. | 1) MET: 1000 mg BID (n = 14) 2) LIRA: 1.2 mg OD s.c. (n = 11) 3) MET 1000 mg BID + LIRA 1.2 mg QD s.c.(n = 11) | 12 weeks | Weight loss | Body composition IR | 1) −1.2 ± 1.4 2) −3.8 ± 3.7 3) −6.5 ± 2.8 | No major changes in fasting glucose, insulin, and insulin during OGTT. Glucose value after 120 min during OGTT significantly reduced in the combination arm vs MET. | No significant changes in menstrual pattern. | 10% |
| Jensterle et al (92) | Obese (BMI ≥30) women with newly diagnosed PCOS. Age ≥18 years, premenopause. PCOS diagnosed by the NICHD criteria. | 1) MET:1000 mg bid/ daily (n = 14) 2) LIRA 1.2 mg (n = 14) | 12 weeks | Weight loss | Body composition IR | 1) −2.3 2) −3.0 LIRA superior in severe IR (BMI reduction 2.13 vs 0.62 kg/m2) | Decrease in total testosterone in MET Increase in LH in LIRA | 12.5% | |
| Jensterle et al (94) | Obese (BMI ≥30) women Age ≥18 years, premenopause PCOS diagnosed by ASRM-ESHRE Rotterdam criteria | 1) MET 1000 mg BID + LIRA 1.3 mg OD s.c. (n = 15) 2) LIRA 3 mg OD s.c. (n = 15) | 12 weeks | Weight loss | Metabolic and hormonal changes | 1) −3.6 ± 2.5 2) −6.3 ± 3.7 | Both interventions resulted in a significant decrease of post-OGTT glucose levels. Combination therapy significantly reduced total testosterone | 6.7% | |
| Nylander et al (96). | Overweight (BMI ≥25) women and/ or insulin resistance Age ≥18 years PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg (n = 44) 2) Placebo (n = 21) | 26 weeks | Bleeding pattern | Levels of AMH, sex hormones, and gonadotrophins, ovarian morphology | LIRA vs Placebo: −5.2 (95% CI, 3.0-7.5) | In the LIRA group, SHBG increased and free testosterone decreased. Ovarian volume decreased with LIRA vs placebo. | Bleeding ratio significantly improved with LIRA vs placebo | 9.7% |
| Salamun et al (97) | Infertile, obese women (BMI ≥30) Age ≤38 years, first or second IVF attempt PCOS diagnosed according to revised Rotterdam criteria | 1) MET 1000 mg bid (n = 14) 2) MET 1000 mg bid + LIRA 1.3 mg QD s.c. (n = 14) | 12 weeks | IVF pregnancy rate | Weight change | 1) −7.0 ± 6.0 2) −7.5 ± 3.9 | Pregnancy rate per embryo transfer significantly higher with combined therapy (85.7%) compared with MET (28.6%) | 18% | |
| Liu et al (98). | Overweight or obese women (BMI ≥24) Age 18-40 years PCOS diagnosed according to Rotterdam criteria | 1) MET:1000 mg bid (n = 88) 2) EXE: 10 μg BID (n = 88) | 12 weeks; after 12 weeks all patients treated with MET alone for additional 12 weeks | Weight loss | Fat mass, hormonal levels, insulin resistance, lipid profile, inflammatory marker, menstrual frequency, and rate of pregnancy. | 1) −2.28 ± 0.55 2) −4.29 ± 1.29 | Decrease in android fat mass% and total fat mass% with EXE, but not with MET. Greater decrease in HOMA-IT and insulin levels with EXE than with MET. HsCRP levels decreased significantly in the EXE group only. | Menstrual frequency increased significantly in both groups. Rate of natural pregnancy significantly higher following EXE treatment than following MET treatment | 10.2% |
| Study . | Participant characteristics . | Study arms . | Study duration . | Primary outcome . | Other outcomes . | Body weight Loss (kg) . | Metabolic changes . | Menstrual pattern/other . | Attrition rate . |
|---|---|---|---|---|---|---|---|---|---|
| Elkind- Hirsch et al (86) | Overweight (BMI >27), insulin-resistant, oligoovulatory women. Age 18-40 years. PCOS diagnosed according to a modification of Rotterdam criteria 2003 | 1) MET:1000 mg bid (n = 14) 2) EXE (10 μg bid) (n = 14) 3) MET 1000 mg bid + EX 10 μg bid (n = 14) | 24 weeks | Menstrual frequency | Ovulation rate Insulin action FAI Inflammatory markers | 1) −1.6 ± 0.2 2) −3.2 ± 0.1 3) −6.0 ± 0.5 | FAI reduced and Insulin sensitivity improved in combination arm | Combination therapy superior to EX or MET (menses and ovulation) | 30% |
| Rasmussen et al (87) | Overweight or obese women, pre-treated with MET for at least 6 months. PCOS diagnosed according to Rotterdam criteria. | Add-on of LIRA 1.2-1.8 mg (n = 84) | Mean of 27.8 weeks | Weight loss | - | −9.0 (95% CI, 7.8- 10.1) | Mean decrease in BMI of 3.2 kg/m2 Weight loss >5% and >10% in 81.7% and 32.9% of patients, respectively | 20.0% | |
| Kahal et al (88) | Obese women (BMI 30-45) Age 18-45 years Healthy controls. PCOS diagnosed according to Rotterdam criteria. | LIRA:1.8 mg (19 obese women with PCOS and 17 controls) | 6 months | CV risk markers | Weight loss | PCOS: -3.0 ± 4.2 Controls: −3.8 ± 3.0 | HOMA-IR, hsCRP, endothelial adhesion markers significantly and equally reduced in both groups No changes in cIMT | 30.6% | |
| Jensterle et al (89) | Obese (BMI ≥30) women Age ≥18 years, premenopause. PCOS diagnosed by ASRM-ESHRE Rotterdam criteria. | 1) MET:1000 mg bid (n = 14) 2) LIRA 1.2 mg (n = 14) 3) ROF 500 mg qd (n = 14) | 12 weeks | Weight loss | Hormonal and metabolic changes | 1) −0.8 ± 1.0 2) −3.1 ± 3.5 3) −2.1 ± 2.0 | FAI reduction in ROF arm; decrease in visceral fat in LIRA arm. HOMA-IR decreased in all treatment arms. LIRA superior to MET in reducing glucose at 120 min of OGTT | Menstrual frequency increased with all treatments. | 8.9% |
| Frøssing et al (90) | Women with BMI >25 and/ or insulin resistance PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg OD s.c. (n = 48) 2) Placebo (n = 24) | 26 weeks | Liver fat VAT Prevalence of NAFLD | Weight change OGTT, SHBG, testosterone | 1) −5.2 ± 0.7 2) +0.2 ± 0.9 | LIRA reduced liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds. With LIRA, SHBG levels increased by 19%, and free testosterone decreased by 19%. | 28% | |
| Jensterle Sever et al (91) | Obese (BMI ≥30), nondiabetic women who had lost ≥5% body weight during pretreatment with MET for at least 6 months. Age >18 years. PCOS diagnosed by the NICHD criteria. | 1) MET: 1000 mg BID (n = 14) 2) LIRA: 1.2 mg OD s.c. (n = 11) 3) MET 1000 mg BID + LIRA 1.2 mg QD s.c.(n = 11) | 12 weeks | Weight loss | Body composition IR | 1) −1.2 ± 1.4 2) −3.8 ± 3.7 3) −6.5 ± 2.8 | No major changes in fasting glucose, insulin, and insulin during OGTT. Glucose value after 120 min during OGTT significantly reduced in the combination arm vs MET. | No significant changes in menstrual pattern. | 10% |
| Jensterle et al (92) | Obese (BMI ≥30) women with newly diagnosed PCOS. Age ≥18 years, premenopause. PCOS diagnosed by the NICHD criteria. | 1) MET:1000 mg bid/ daily (n = 14) 2) LIRA 1.2 mg (n = 14) | 12 weeks | Weight loss | Body composition IR | 1) −2.3 2) −3.0 LIRA superior in severe IR (BMI reduction 2.13 vs 0.62 kg/m2) | Decrease in total testosterone in MET Increase in LH in LIRA | 12.5% | |
| Jensterle et al (94) | Obese (BMI ≥30) women Age ≥18 years, premenopause PCOS diagnosed by ASRM-ESHRE Rotterdam criteria | 1) MET 1000 mg BID + LIRA 1.3 mg OD s.c. (n = 15) 2) LIRA 3 mg OD s.c. (n = 15) | 12 weeks | Weight loss | Metabolic and hormonal changes | 1) −3.6 ± 2.5 2) −6.3 ± 3.7 | Both interventions resulted in a significant decrease of post-OGTT glucose levels. Combination therapy significantly reduced total testosterone | 6.7% | |
| Nylander et al (96). | Overweight (BMI ≥25) women and/ or insulin resistance Age ≥18 years PCOS diagnosed according to Rotterdam criteria | 1) LIRA 1.8 mg (n = 44) 2) Placebo (n = 21) | 26 weeks | Bleeding pattern | Levels of AMH, sex hormones, and gonadotrophins, ovarian morphology | LIRA vs Placebo: −5.2 (95% CI, 3.0-7.5) | In the LIRA group, SHBG increased and free testosterone decreased. Ovarian volume decreased with LIRA vs placebo. | Bleeding ratio significantly improved with LIRA vs placebo | 9.7% |
| Salamun et al (97) | Infertile, obese women (BMI ≥30) Age ≤38 years, first or second IVF attempt PCOS diagnosed according to revised Rotterdam criteria | 1) MET 1000 mg bid (n = 14) 2) MET 1000 mg bid + LIRA 1.3 mg QD s.c. (n = 14) | 12 weeks | IVF pregnancy rate | Weight change | 1) −7.0 ± 6.0 2) −7.5 ± 3.9 | Pregnancy rate per embryo transfer significantly higher with combined therapy (85.7%) compared with MET (28.6%) | 18% | |
| Liu et al (98). | Overweight or obese women (BMI ≥24) Age 18-40 years PCOS diagnosed according to Rotterdam criteria | 1) MET:1000 mg bid (n = 88) 2) EXE: 10 μg BID (n = 88) | 12 weeks; after 12 weeks all patients treated with MET alone for additional 12 weeks | Weight loss | Fat mass, hormonal levels, insulin resistance, lipid profile, inflammatory marker, menstrual frequency, and rate of pregnancy. | 1) −2.28 ± 0.55 2) −4.29 ± 1.29 | Decrease in android fat mass% and total fat mass% with EXE, but not with MET. Greater decrease in HOMA-IT and insulin levels with EXE than with MET. HsCRP levels decreased significantly in the EXE group only. | Menstrual frequency increased significantly in both groups. Rate of natural pregnancy significantly higher following EXE treatment than following MET treatment | 10.2% |
AMH, anti-Müllerian hormone; cIMT, carotid-intima media thickness; EXE, exenatide; FAI, free androgen index; HOMA-IR, homeostasis model assessment-IR; hsCRP, high-sensitivity C-reactive protein; IR, insulin resistance; IVF, in vitro fertilization; LIRA, liraglutide; MET, metformin; NAFLD, nonalcoholic fatty liver disease; NICHD, National Institute of Child Health and Human Development; OGTT, oral glucose tolerance test; PIIINP, Procollagen Type III N-Terminal Peptide; SHBG, sex hormone binding globulin; VAT, visceral adipose tissue.
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