Impact of Pharmacological Interventions on Anthropometric Indices in Women With Polycystic Ovary Syndrome

A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Mohammed A. Abdalla; Najeeb Shah; Harshal Deshmukh; Amirhossein Sahebkar; Linda Östlundh; Rami H. Al-Rifai PhD; Stephen L. Atkin; Thozhukat Sathyapalan

Disclosures

Clin Endocrinol. 2022;96(6):758-780.

Abstract and Introduction

Abstract

Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight.

Objective: To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS.

Data Sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021.

Study Selection: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020.

Data Extraction: Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool.

Results: 80 RCTs were included in the meta-analysis. Metformin vs placebo showed significant reduction in the mean body weight (MD: −3.13 kg; 95% confidence interval [CI]: −5.33 to −0.93, I ² = 5%) and the mean body mass index (BMI) (MD: −0.75 kg/m²; 95% CI: −1.15 to −0.36, I ² = 0%). There was a significant reduction in the mean BMI with orlistat versus placebo (MD: −1.33 kg/m²; 95% CI: −2.16 to −0.66, I ² = 0.0%), acarbose versus metformin (MD: −1.26 kg/m²; 95% CI: −2.13 to −0.38, I ² = 0%), and metformin versus pioglitazone (MD: −0.91 kg/m²; 95% CI: −1.62 to −0.19, I ² = 0%). A significant increase in the mean BMI was also observed in pioglitazone versus placebo (MD: + 2.59 kg/m²; 95% CI: 1.78–3.38, I ² = 0%) and in rosiglitazone versus metformin (MD: + 0.80 kg/m²; 95% CI: 0.32–1.27, I ² = 3%). There was a significant reduction in the mean waist circumference (WC) with metformin versus placebo (MD: −1.21 cm; 95% CI: −3.71 to 1.29, I ² = 0%) while a significant increase in the mean WC with pioglitazone versus placebo (MD: + 5.45 cm; 95% CI: 2.18–8.71, I ² = 0%).

Conclusion: Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.

Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex endocrine disorder affecting women of reproductive age, with a prevalence ranging from 8% to 13%.^[1,2] PCOS is characterized by both clinical and biochemical evidence of excess androgen levels (manifested as acne and hirsutism), menstrual irregularities, and sonographic polycystic ovarian morphology.^[3] Metabolic disorders such as insulin resistance (IR) and impaired glucose tolerance are common in women with PCOS, leading to an increased risk of type 2 diabetes mellitus (T2DM).^[4] Moreover, PCOS predisposes to a range of other complications including infertility, increased body weight, increased risk of cardiovascular disease (CVD), and endometrial cancer.^[5–7]

Increased body weight is a prominent feature of PCOS and around 50% of women with PCOS are either overweight or obese.^[8] Obesity exacerbates PCOS features such as excessive hair growth, infertility, and pregnancy complications, aggravating IR, which culminates in an increased metabolic risk associated with PCOS.^[9] Therapeutic approaches including lifestyle modifications through dietary interventions and physical activity are the cornerstone in the management of PCOS.^[10] There are also differing pharmacotherapeutic interventions including insulin sensitizers (metformin and thiazolidinediones) that improve IR and peripheral glucose uptake.^[11,12] However, these therapeutic options are primarily licensed to treat other conditions such as T2DM and their effectiveness in PCOS remains unclear in the literature. There are also significant gaps between the available evidence and the evidence-based treatment options.^[3] This might often lead to the delay in offering satisfactory treatment options and the clinical inertia around treating PCOS.^[3] Therefore, this systematic review and meta-analysis aimed to evaluate and analyze the available evidence on the effectiveness of different therapeutic options used to treat PCOS in improving anthropometric outcomes.

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Next Section

Abstract and Introduction
Methods
Results
Discussion
Conclusion
References

Table 1. The inclusion criteria for the included studies in this systematic review
Inclusion criteria 1. Study design: randomized controlled trials including (randomized open-label trials, double-blind controlled trials, crossover randomized trials, and parallel randomized trials). 2. Population: adult females aged 18 and over with a diagnosis of PCOS based on a robust diagnostic criterion. 3. Comparator: reported pharmacological interventions compared to placebo or other pharmacological agents. 4. Outcomes: reported outcomes such as BMI, body weight, waist circumference, and waist to hip ratio.
Exclusion criteria 1) Study design: case studies, cross-sectional studies, and animal studies. 2) Patient population: adolescents females, postmenopausal women, and women without PCOS. Comparators: Nonpharmacological interventions, pharmacological interventions versus dietary interventions, pharmacological interventions versus physical activities or surgery.

Table 2. Characteristics of the included RCTs
Author	Study design	Country	PCOS diagnostic Criteria	Participants characteristics (PCOS)	Interventions	Durations	Outcomes
Amiri et al.²⁰	RCT	Iran	Rotterdam	Age: 25.6 ± 4.02	Metf, Flu, Metf+ Flu, Placebo	6 months	BMI, WHR, WC, FBG, LDL, HDL, TG
				BMI: 28.9 ± 5			FAI.
J.Ahmad et al.⁷⁵	RCT	India	NIH	Age: 22.81 ± 4.52	Rosig, Metf	12 months	WHR, BMI
				BMI: 27.66 ± 5.44
Aroda et al.⁶³	RCT	USA	NIH	Age: 27.87 ± 0.87	Piog, Placebo	6 months	Weight, BMI, WHR, WC, FBG, FI
				BMI: 36.29 ± 1.34
Ashraf Ganie et al.⁶⁴	RCT	India	NIH	Age: 22.9 ± 5.3	Spironolactone vs Met	3 months	BMI, FBG, FI, WHR
				BMI: 26.8 ± 4.0
Batista et al.⁷³	RCT	Brazil	AES-2006	Age: 24.5 ± 4.33	Rosig, placebo	12 weeks	FBG.FI, HOMA-IR
				BMI: 27.89 ± 6.10
Brettenthaler et al.²¹	RCT	Switzerland	Rotterdam	Age: 30.2 ± 1.4	Piog, placebo	3 months	BMI, WHR, FBG, FI, HOMA-IR
				BMI: 29.4 ± 1.7
Cataldo et al.⁷⁶	RCT	USA	NICHD	Age: 29.3 ± 1.5	Rosig 2 mg, 4 mg, 8 mg	12 weeks	BMI, WHR, Wt
				BMI: 37.2 ± 2.1
Cheng et al.⁷⁷	RCT	Australia	Rotterdam	Age: 26 ± 4	Metf, placebo	6 months	Wt, BMI, WC, WHR, LDL, HDL,
				BMI: 24.2 ± 5.3			TG, TC, HOMA-IR, HOMA-B
Chou et al.⁷⁸	RCT	Brazil	N/A	Age: 24 ± 5	Metf, placebo	3 months	BMI, WHR, FBG, FI, TG, TC, HDL, LDL
				BMI: 35.6 ± 4.9
Cetinkalp et al.²²	RCT	Turkey	Rotterdam	Age: N/A	Met, Rosigl, ECA	4 months	FBG, FI, Wt, BMI, HOMA-IR, TC,
				BMA: 25.82 ± 6.12			TG, HDL, LDL
Cho et al.²³	RCT	UK	Rotterdam	Age: 26·4 ± 1·5	Metf, Orlistat, Piog	12 weeks	BMI, HOMA-IR
				BMI: 36·0 ± 1·2
Ciotta et al.⁷⁹	RCT	Italy	N/A	Age: 20.5 ± 0.6	Acarbose, Placebo	3 months	BMI, PRL
				BMI: 22.7 ± 0.34
Dereli et al⁸⁰		Turkey	NICHD	Age: 31.4 ± 0.9	Rosig 2 mg, 4 mg	8 months	BMI, WHR
				BMI: 24.2 ± 1.3
Diamanti-Kandarakis et al²⁵ RCT	RCT	Greece	Rotterdam	Age: 27·52 ± 5·77	Orli, placebo	6 months	BMI, WHR, HOMA
				BMI: 35·43 ± 5·3
Devin et al.²⁴	RCT-cross over	USA	Rotterdam	Age: N/A	Sitag, placebo	4 weeks	BMI, WHR, WC, LDL.HDL, TC
				BMI: N/A
Elkind-Hirsch et al.²⁷	RCT	USA	Rotterdam	Age: 28.2 ± 1.1	Exen, Metf, Exen+Metf	24 weeks	Wt, BMI, CRP, TG, TC, HDL, LDL
				BMI: 39.9 ± 1.5
Elkind-Hirsch et al.⁶⁵	RCT	USA	NIH	Age: 29.9 ± 7	Sax, Metf, Sax+Metf	16 weeks	FBG, FI, HDL, TG, LDL, HOMA-IR
				BMA: 42.1 ± 7.3
Eisenhardt et al.²⁶	RCT	Germany	Rotterdam	Age: 27.0	Metf, Placebo	12 weeks	FBG.FI, HOMA-IR
				BMI: 28.9
Ferjan et al.²⁸	RCT	Slovenia	Rotterdam	Age: 34.3 ± 6.8	Metf, Metf+Sitag	12 weeks	Wt, BMI, WC TC, TG, LDL, HDL,
				BMI: 36.3 ± 5.2			HOMA-IR
Ferjan et al.²⁹	RCT	Slovenia	Rotterdam	Age: 35.0 ± 7.2	Sitag, Placebo	12 weeks	HOMA-IR, BMI, HOMA-B, FBG
				BMI: 36.9 ± 5.5
Glintborg et al.⁸¹	RCT	USA	N/A	Age: 32	Piog, Placebo	16 weeks	FI, HOMA-IR
				BMI: N/A
Glintborg et al.⁸²	RCT	USA	N/A	Age: 32	Piog, Plcebo	16 weeks	BMI, WHR, WC, FI
				BMI: 32.2
Glintborg et al.⁸³	RCT	Denmark	N/A	Age: N/A	Piog, placebo	16 weeks	BMI, CRP, LDL
				BMI: 33·1
Gambineri et al.⁸⁴	RCT	Italy	N/A	Age: 27·1 ± 3·6	Plac, metfo, flut, metf + flut	6 months	FBG, FI, Wt, BMI, HOMA-IR
				BMI: 37·6 ± 4·1
Ghandi et al.³⁰	RCT	Iran	Rotterdam	Age: 27 ± 4.92	Orlistat, Metf	3 months	BMI, WC, TC, TG
				BMI: 34.88 ± 4.90
Ganie et al.⁶⁶	RCT	USA	NIH	Age: 22.6 ± 5.0	Spironolactone, Metf	6 months	WHR, BMI, FBG, FI
				BMI: 26.5 ± 5.6
Hanjalic-Beck et al.⁶⁷	RCT	Germany	NIH	Age: N/A	Metf, Acarbose	12 weeks	BMI, FBG, FI
				BMI: N/A
Heidari et al.³¹	RCT	USA	Rotterdam	Age: 32.47.5	Metf, placebo	3 months	BMI, WC, WHR, Weight
				BMI: 37.19.1
Jayagopal et al.⁸⁵	RCT	UK	N/A	Age: 27 ± 0.9	Orlistat, Metf	3 months	FBG, FI, TC, TG, HDL
				BMI: 36.7 ± 3.3
Javanmanesh et al.³²	RCT	Iran	Rotterdam	Age: 29.75 ± 4.90	Metf, NAC	24 weeks	BMI, FBG, FI, LDL, TC, TG, HDL
				BMI: 29.05 ± 2.80			HOMA-IR
Jensterle et al.⁸⁶	RCT	Slovenia	NIH	Age: 27.6 ± 7.2	Metf, Lira	12 weeks	BMI, WC, TC, TG, LDL, HDL
				BMI: 39.5 ± 6.2
Jensterle et al.⁶⁹	RCT	Slovenia	Rotterdam	Age: 30.7 ± 7.9	Metf, Lira, Rofl	12 weeks	Wt, BMI, WC, FI, FBG, HOMA-IR
				BMI: 38.6 ± 6.0
Jensterle et al.³⁴	RCT	Slovenia	Rotterdam	Age: 33.1 ± 6.1	Met+Lira, Lira	12 weeks	BMI, Wt, WC, FBG, FI, HOMA-IR
				BMI: 37.2 ± 4.5
Jensterle et al.³⁵	RCT	Slovenia	Rotterdam	Age: 34.4 ± 6.5	Met+Lira, Lira	12 weeks	Wt, BMI, WC, FI, FBG,
				BMI: 39.0 ± 4.9
Jensterle Sever et al.⁷¹	RCT	Slovenia	NIH	Age: 31.3 ± 7.1	Lira, Metf, Lira+Metf	12 weeks	FBG, BMI, WC, FI, TC, TG, HDL, LDL
				BMI: 37.1 ± 4.6
Jensterle et al.³³	RCT	Slovenia	NIH	Age: 23.5 ± 0.7	Metf, Rosi	6 months	FBG, FI, BMI, HOMA-IR
				BMI: 20.9 ± 0.73			FBG, FI, BMI, HOMA-IR
Jensterle et al.⁷⁰	RCT	Slovenia	NIH	Age: 23.1 ± 3.7	Metf, Rosi	6 months	WC, BMI, FI, FBG, TC, TG,
				BMI: 29.6 ± 6.9			LDL, HDL, HOMA-IR
Kilicdag et al.³⁸	RCT	Turkey	Rotterdam	Age: 24.13 ± 1.42	Metf, Rosi	3 months	BMI, FI, FBG, TC, TG, HOMA-IR
				BMI: 26.17 ± 1.44
Kocak et al.³⁹	RCT	Turkey	Rotterdam	Age: 26.2 ± 3.7	Metf, Placebo	2 months	BMI, FI, FBG, WHR
				BMI: 31.91 ± 5.38
Karimzadeh et al.³⁶	RCT	Iran	Rotterdam	Age: 28.81 ± 3.18	Metf, placebo	3months	BMI, FI, FBG, TC, TG, HDL, LDL
				BMI: 29.49 ± 4.7
Kazerooni et al.³⁷	RCT	Iran	Rotterdam	Age: 25.6 ± 4.32	Metf, simva, placebo	12 weeks	BMI, FI, FBG, TC, TG, HDL, LDL
				BMI: 28.52 ± 1.61
Lam et al.⁴⁰	RCT	China	RoTterdam	Age: N/A	Rosi, placebo	12 months	WC, BMI, FI, FBG, TC, TG,
				BMI: N/A			LDL, HDL, HOMA-IR
Li et al.⁴¹	RCT	China	Rotterdam	Age: 25.95 ± 4.36	Rosi, metformin	6 months	WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
				BMI: 27.54 ± 2.21
Lingaiah et al.⁴²	RCT	Finland	Rotterdam	Age: 27.6 ± 4.0	Metf, placebo	3 months	BMI, FI, FBG, WC, WHR
				BMI: 26.5 ± 6.0
Liu et al.⁴³	RCT	China	Rotterdam	Age: 27.69 ± 3.80	Metf, Exena	24 weeks	WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
				BMI: 28.29 ± 1.86			HOMA-IR
Lord et al.⁸⁷	RCT	UK	N/A	Age: 27.76 ± 4.89	Metf, placebo	3 months	WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
				BMI: 33.74 ± 6.74			HOMA-IR
Legro et al.⁸⁸	RCT	USA	N/A	Age: 28.0 ± 4.0	Metf, Rosi	3 months	WC, BMI, FI, FBG, WHR
				BMI: 40.0 ± 10.1
Morin-Papunen et al.⁴⁶	RCT	Finland	Rotterdam	Age: 28.4 ± 3.9	Metf, placebo	3months	Wt, WC, BMI, WHR
Morin-Papunen et al.⁴⁶				BMI: 27.1 ± 6.3
Morteza Taghavi et al.⁴⁷	RCT	Iran	Rotterdam	Age: N/A	Metf, placebo	6 months	BMI
Morteza Taghavi et al.⁴⁷				BMI: N/A
Mohiyiddeen et al.⁴⁴	RCT	UK	Rotterdam	Age: 29.0 ± 1.0	Metf, Rosig	3 months	WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
				BMI: 29.7 ± 1.0			WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
Moini et al.⁴⁵	RCT	Iran	Rotterdam	Age: 27.42 ± 3.31	Orlistat, placebo	3 months	BMI, FI, FBG, TC, TG, Wt, LDL, HDL
				BMI: 29.01 ± 2.09			BMI, FI, FBG, TC, TG, Wt, LDL, HDL
Muneyyirci-Delale et al.⁴⁸	RCT	USA	Rotterdam	Age: N/A	Metf, spironolactone	12 weeks	BMI, TC, TG,
Muneyyirci-Delale et al.⁴⁸				BMI: NA	Metf, spironolactone
Mehrabian et al.⁶⁸	RCT	Iran	NIH	Age: 29.18 ± 8.28	Metf, flut, simva	6 months	WC, CRP, BMI, FBG, TG, HDL
				BMI: 29.83 ± 4.1			WC, CRP, BMI, FBG, TG, HDL
Navali et al.⁸⁹	RCT	Iran	N/A	Age: 26.43 ± 4.67	Metf, Simva	3 months	BMI, FI, FBG, TC, TG, WHR, LDL, HDL
				BMI: 27.71 ± 0.73			BMI, FI, FBG, TC, TG, WHR, LDL, HDL
Nemati et al.⁴⁹	RCT	Iran	Rotterdam	Age: N/A	Metf, NAC	12 weeks	BMI, FBG, FI
				BMI: 36.3 ± 8.4
Ng et al.⁹⁰	RCT	China	N/A	Age: 30.5	Metf, placebo	3 months	BMI, FBG, FI, TC, TG
				BMI: N/A
Naka et al⁹¹	RCT	Greece	N/A	Age: 23.3 ± 4.9	Metf, Piogl	6 months	WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
				BMI: 28.7 ± 5.5			WC, BMI, FI, FBG, TC, TG, WHR, LDL, HDL
Ortega-González et al.⁹²	RCT	Mexico	N/A	Age: 28.8 ± 0.9	Metf, Piogl	6 months	Wt, BMI, WHR
Ortega-González et al.⁹²				BMI: 32.2 ± 1.0
Palomba et al.⁹³	RCT	Italy	N/A	Age: 24.3 ± 3.1	Metf, Placebo	24 months	BMI, LDL
				BMI: 22.2 ± 2.0
Paredes Palma et al.⁹⁴	RCT	Mixeco	N/A	Age: N/A	Metf, Sitag	N/A	BMI, HOMA-IR
Paredes Palma et al.⁹⁴				BMI: N/A
Penna et al.⁹⁵	RCT	Brazil	N/A	Age: 26.69 ± 1.46	Acarbose, Placebo	6 months	BMI
				BMI: 35.8 ± 2.60
Puurunen et al.⁹⁶	RCT	Finland	N/A	Age: 40.5 ± 5.9	Atorva, placebo	6 months	BMI, WHR, LDL, HDL
				BMI: 30.4 ± 8.6
Rautio et al⁹⁷	RCT	Finland	N/A	Age: 29.1 ± 1.2	Rosig, placebo	4 months	BMI, WHR, Wt
				BMI: 33.1 ± 1.7
Romualdi et al.⁵⁰	RCT	Italy	Rotterdam	Age: 24.7 ± 4.4	Metf, placebo	6 months	BMI, WHR, LDL, HDL, TC
				BMI: 22.2 ± 2.2			BMI, WHR, LDL, HDL, TC
Rezai et al.⁵¹	RCT	Iran	Rotterdam	Age: 26.3 ± 4	Metf, Acarbose	3 months	BMI, FBG, HDL, TG, TC.LDL
				BMI: 26.9 ± 1.8			BMI, FBG, HDL, TG, TC.LDL
Steiner et al⁹⁸	RCT	Germany	NIH	Age: 22.9 ± 4.5	Metf, Rosig	6months	BMI, HOMA-IR, FBG, FI
				BMI: 27.4 ± 6.0
Sova et al.⁵⁴	RCT	Finland	Rotterdam	Age: 27.7 ± 4.0	Metf, placebo	3 months	Wt, WC, WHR, BMI, FBG, FI
				BMI: 27.5 ± 6.2			Wt, WC, WHR, BMI, FBG, FI
Shahebrahimi et al.⁵³	RCT	Iran	Rotterdam	Age: 27.5 ± 3.68	Metf, piog	3 months	Wt, BMI, WC, FBG, LDL, HDL, TG
				BMI: 27.71 ± 4.36			Wt, BMI, WC, FBG, LDL, HDL, TG
Sohrevardi et al.⁹⁹	RCT	Iran	Rotterdam	Age: N/A	Metf, piog, Metf+Piog	3 months	Wt, BMI, WHR, HOMA-IR, FBG, FI
				BMI: 27.5 ± 3.6	Metf, piog, Metf+Piog		Wt, BMI, WHR, HOMA-IR, FBG, FI
Sathyapalan et al.⁵²	RCT	UK	Rotterdam	Age: 27.7 ± 1.4	Atorvas, placebo	12 weeks	Wt, BMI, WC, WHR, HOMA-IR, FBG, FI
				BMI: 33.20 ± 1.4			LDL, TC, TG, HDL
Sönmez et al.⁷²	RCT	Turkey	NIH	Age: 26.13 ± 5.08	Metf, Acarbose	3 months	BMI, Wt, FBG, FI
				BMI: 27 ± 2.2
Tao et al.⁵⁵	RCT	China	Rotterdam	Age: 30 ± 5	Saxag, Metf	24 weeks	Wt, BMI, WC, WHR, LDL, HDL, TG, HOMA-IR
				BMI: 27.2			Wt, BMI, WC, WHR, LDL, HDL, TG, HOMA-IR
Trolle et al.¹⁰⁰	RCT	Denmark	N/A	Age: 31	Metf, placebo	6 months	Wt, WHR, FBG, FI, HOMA-IR, LDL, HDL
				BMI: 32			Wt, WHR, FBG, FI, HOMA-IR, LDL, HDL
Underdal et al.⁵⁶	RCT	Denmark	Rotterdam	Age: 29.5 ± 3.9	Metf, placebo	NA	Wt, BMI, WC, WHR
				BMI: 28.7 ± 6.9
Vanky et al.⁵⁷	RCT	Norway	Rotterdam	Age: 28.9 ± 4.8	Metf, placebo	36 weeks	BMI, DHEAS
				BMI: 30.6 ± 7.3
Vandermolen et al.¹⁰¹	RCT	USA	N/A	Age: 29 6 ± 1.2	Metf, Placebo	7 weeks	Wt, BMI, FBG, FI
				BMI: 37.6 ± 4.3
Yarali et al.¹⁰²	RCT	Turkey	N/A	Age: 29.7 ± 5.6	Metf, placebo	6 weeks	WHR, BMI, FBG, FI
				BMI: 28.6 ± 4
Yilmaz et al.⁵⁸	RCT	Turkey	Rotterdam	Age: 24.67 + 4.60	Metf, Rosig	24 weeks	FBG, FI, BMI, WHR
				BMI: 27.12 + 6.18
Zahra et al.⁵⁹	RCT	Pakistan	Rotterdam	Age: 25.8 ± 6.1	Metf, placebo	3 months	Wt, BMI, FBG, FI, HOMA-IR
				BMI: 26.7 ± 6.5			Wt, BMI, FBG, FI, HOMA-IR
Zheng et al.⁶⁰	RCT	China	Rotterdam	Age: 27.70 ± 3.41	Exena, Metf	12 weeks	Wt, BMI, WHR, FBG, FI, HDL, LDL, TG, TC
				BMI: 28.27 ± 4.85			Wt, BMI, WHR, FBG, FI, HDL, LDL, TG, TC
Ziaee et al.⁶¹	RCT	Iran	Rotterdam	Age: 25.28 ± 4.38	Metf, piog	12 weeks	BMI, HOMA-IR, HDL, LDL, TG, TC
				BMI: 26.13 ± 3.03			BMI, HOMA-IR, HDL, LDL, TG, TC

Abbreviations: Atrova: atorvastatin; BMI, body mass index; CRP, C-reactive protein; FBG, fasting blood glucose; FI, fasting insulin, HDL, high-density liporotein; HOMA-IR, homeostatic model of insulin resistance; LDL, low-density lipoprotein; Lira, liraglutide; Metf, metformin; N/A, not available; NICHD, National Institute of Child Health and Development; NIH, National Institute for Health; Piog, pioglitazone; RCT, randomized clinical trial; Rosig, rosiglitazone; Saxa, saxagliptin; Simva, simvastatin; TC, total cholesterol; TG, triglycerides; WHO, World Health Organisation; WHR, waist-hip ratio; Wt, weight; UK, United Kingdom; USA: United State of America.

Table 3. Summary pooled effect estimates of various medications on body weight, BMI, WC, and WHR in women with PCOS
Intervention
Outcome: mean body weight in kilograms (kg)	Comparison	No of women in the intervention arm	No of women in the control arm	No of RCTs	Pooled effect estimates	95% CI	I ² (%)	I ² (p value)	Overall effect (p- value*)
Rosiglitazone vs. metformin
Rosiglitazone 4 mg QD	Metformin 850 mg BID for 3 months	15	15	1	0.35	−2.58 to 3.28	–	–	–
Rosiglitazone 4 mg QD	Metformin 1500 mg QD for 6 months	67	68	1	3.19	0.65–5.73	–	–	–
Rosiglitazone 4 mg QD	Metformin 2000 mg QD for 4 months	14	33	1	1.83	−6.62 to 10.28	–	–	–
Overall: Rosiglitazone versus Metformin		96	116	3	1.95	0.03–3.87	3.0	0.36	0.05
Metformin vs. pioglitazone
Metformin 850 mg BID for 6 months	Pioglitazone 45 mg QD	33	31	2	−1.66	−3.19 to 0.59	0.0	0.56
Metformin 1500 mg QD for 3 months	Pioglitazone 45 mg QD	50	51	2	−1.45	−6.40 to 3.51	0.0	0.90
Overall: Metformin versus Pioglitazone		83	82	4	−1.62	−3.67 to 0.43	0.0	0.95	0.12
Liraglutide vs. metformin
Liraglutide 1.2 mg QD for 12 weeks	Metformin 1000 mg QD for 12 weeks	42	27	2	2.17	−10.66 to 14.99	51	0.15	0.74
Liraglutide 1.2 mg QD for 12 weeks	Liraglutide 1.2 mg QD with Metformin 1000 mg QD for 12 weeks	46	47	3	3.30	−2.95 to 9.54	0.0	0.59	0.30
Metformin vs. orlistat
Metformin 1500 mg QD for 3 months	Orlistat 120 mg tds	60	61	3	−3.28	−7.29 to 0.74	58	0.09	0.11
Exenatide vs. metformin
Exenatide 10 μg BID	Metformin 1000 mg BID for 12 weeks	109	112	2	0.22	−2.01 to 2.44	0.0	0.51	0.85
Outcome: mean BMI in kg/m²
Metformin vs. pioglitazone
Metformin 850 mg BID for 6 months	Pioglitazone	33	31	2	−1.07	−2.02 to 0.12	0.0	0.80	–
Metformin 1500 mg QD for 3 months	Pioglitazone	86	86	4	−0.69	−1.78 to 0.41	0.0	0.55	–
Overall: Metformin versus Pioglitazone		119	117	6	−0.91	−1.62 to 0.19	0.0	0.78	0.01
Rosiglitazone vs. metformin
Rosiglitazone 4 mg QD	Metformin 850 mg BID	154	133	6	0.22	−1.33 to 1.77	0.0	0.73	–
Rosiglitazone 4 mg QD	Metformin 1000 mg QD	18	17	1	1.38	0.76–2.0	–	–	–
Rosiglitazone 4 mg QD	Metformin 1500 mg QD	67	69	1	0.33	−0.37 to 1.03	–	–	–
Rosiglitazone 4 mg QD	Metformin 2000 mg QD	23	39	2	-0.32	−2.78 to 2.14	0.0	0.82	–
Overall: Rosiglitazone versus Metformin		262	358	10	0.80	0.32–1.27	3.0	0.41	0.001
Sitagliptin + metformin vs. metformin
Sitagliptin 100 mg QD with Metformin 850 mg BID	Metformin 850 mg BID	5	5	1	−2.00	−10.87 to 6.87	–	–	–
Sitagliptin 100 mg QD with Metformin 1000 mg BID	Metformin 1000 mg BID	12	12	1	−4.40	−8.69 to 0.11	–	–	–
Overall: Sitagliptin plus Metformin versus Metformin		17	17	2	−3.94	−7.81 to 0.08	0.0	0.63	0.05
Exenatide vs. metformin
Exenatide 10 μg BID	Metformin 1000 mg BID for 12 weeks	31	32	1	−1.15	−3.47 to 1.17	–	–	–
Exenatide 10 μg BID	Metformin 1000 mg BID for 24 weeks	92	94	2	−0.68	−1.88 to 0.52	51	0.15	–
Overall: Exenatide versus Metformin		123	126	3	−0.85	−1.61 to 0.08	6	0.35	0.03
Acarbose vs. metformin
Acarbose 100 mg QD for 3 months	Metformin	30	30	1	−1.30	−2.40 to 0.20	–	–	–
Acarbose 300 mg QD for 3 months	Metformin	44	42	2	−1.18	−2.63 to 0.27	0.0	0.56	–
Overall: Acarbose versus Metformin		74	72	3	−1.26	−2.13 to 0.38	0.0	0.84	0.005
Liraglutide vs. metformin
Liraglutide 1.2 mg QD	Metformin 1000 mg BID for 12 weeks	42	21	2	3.09	−1.11 to 7.29	4.0	0.31	0.23
Liraglutide 1.2 mg QD for 12 weeks	Liraglutide 1.2 mg QD with Metformin 1000 mg QD for 12 weeks	46	47	3	0.74	−1.27 to 2.74	0.0	0.53	0.47
Orlistat vs. metformin
Orlistat 120 mg tds	Metformin 1500 mg QD for 3 months	55	55	2	0.04	−4.18 to 4.26	93	0.0002	0.87
Spironolactone vs. metformin
Spironolactone 50 mg QD	Metformin 1500 mg QD for 12 weeks	12	24	1	0.47	−1.02 to 1.97	–	–	–
Spironolactone 50 mg QD	Metformin 1000 mg QD for 6 months	85	153	2	0.04	−0.88 to 0.96	0.0	0.89	–
Overall: Spironolactone versus Metformin		97	177	3	0.16	−0.62 to 0.94	0.0	0.88	0.69
Saxagliptin vs. metformin
Saxagliptin 5 mg QD	Metformin 2000 mg QD for 24 weeks	21	21	1	1.36	−1.39 to 4.11	–	–	–
Saxagliptin 5 mg QD	Metformin 2000 mg QD for 16 weeks	11	12	1	0.00	−7.44 to 7.44	–	–	–
Overall: Saxagliptin versus Metformin		32	33	2	1.20	−1.38 to 3.78	0.0	0.74	0.36
Metformin vs. simvastatin
Metformin 1000 mg QD	Simvastatin 20 mg QD for 6 months	34	34	1	−0.21	−2.15 to 1.73	–	–	–
Metformin 1500 mg QD	Simvastatin 20 mg QD for 3 months	100	100	1	−0.08	−1.46 to 1.30	–	–	–
Overall: Metformin versus Simvastatin		134	134	2	−0.12	−1.25 to 1.00	0.0	0.91	0.83
Metformin vs. NAC
Metformin 1500 mg QD	NAC 1800 mg QD for 12 weeks	54	54	1	−4.10	−6.63 to 1.57	–	–	–
Metformin 1500 mg QD	NAC 600 mg tds for 24 weeks	48	46	1	1.25	0.04–2.46	–	–	–
Overall: Metformin versus NAC		102	100	2	−1.30	−6.54 to 3.93	93	0.0002	0.63
Outcome: mean waist circumference in cm
Metformin vs. pioglitazone
Metformin 1500 mg QD	Pioglitazone 30 mg QD for 3 months	28	28	1	−0.45	−5.42 to 4.52	–	–	–
Metformin 850 mg BID	Pioglitazone 30 mg QD for 6 months	15	14	1	0.30	−8.94 to 9.54	–	–	–
Overall: Metformin versus Pioglitazone		43	42	2	−0.28	−4.66 to 4.10	0.0	0.98	0.90
Liraglutide vs. metformin
Liraglutide 1.2 mg QD for 12 weeks	Metformin 1000 mg BID for 12 weeks	28	27	2	−3.66	−14.84 to 7.52	49	0.16	0.52
Liraglutide 1.2 mg QD for 12 weeks	Liraglutide 1.2 mg QD with Metformin 1000 mg QD for 12 weeks	46	47	3	3.34	−2.61 to 9.29	0.0	0.94	0.27
Rosiglitazone vs. metformin
Rosiglitazone 4 mg QD	Metformin 1500 mg QD	67	67	1	-0.04	−2.43 to 2.35	–	–	–
Rosiglitazone 4 mg QD	Metformin 850 mg BID	58	56	1	-0.68	−6.07 to 4.70	–	–	–
Rosiglitazone 4 mg QD	Metformin 2000 mg QD	6	99	1	0.80	−6.30 to 7.90	–	–	–
Overall: Rosiglitazone versus Metformin		131	222	3	-0.06	−2.15 to 2.03	0.0	0.98	0.95
Saxagliptin vs. metformin
Saxagliptin 5 mg QD	Metformin 2000 mg QD for 12 weeks	21	21	1	2.80	−0.29 to 5.89	–	–	–
Saxagliptin 5 mg QD	Metformin 2000 mg QD for 16 weeks	11	12	1	−3.00	−14.98 to 8.98	–	–	–
Overall: Saxagliptin versus Metformin		32	33	2	2.44	−0.55 to 5.43	0.0	0.36	0.11
Outcome: mean WHR
Exenatide vs. metformin
Exenatide 10 μg BID	Metformin 1000 mg BID for 24 weeks	78	80	1	−0.02	−0.04 to 0.00	–	–	–
Exenatide 10 μg BID	Metformin 1000 mg BID for 12 weeks	31	32	1	−0.01	−0.05 to 0.03	–	–	–
Overall: Exenatide versus Metformin		109	112	2	−0.02	−0.04 to 0.00	0.0	0.67	0.56
Spironolactone vs. metformin
Spironolactone 50 mg QD	Metformin 1000 mg QD for 6 months	85	153	2	0.03	0.01–0.05	0.0	0.33	0.96
Metformin vs. pioglitazone
Metformin 1500 mg QD for 3 months	Pioglitazone 30 mg for 3 months	22	23	1	0.02	−0.01 to 0.05	–	–	–
Metformin 850 mg BID for 6 months	Pioglitazone 30 mg for 3 months	33	31	2	0.01	−0.03 to 0.05	0.0	0.96	–
Overall: Metformin versus Pioglitazone		55	54	3	0.02	−0.00 to 0.04	0.0	0.93	0.12
Rosiglitazone vs. metformin
Rosiglitazone 4 mg QD	Metformin 1500 mg QD	67	68	1	0.01	−0.01 to 0.03	–	–	–
Rosiglitazone 4 mg QD	Metformin 850 mg BID	45	43	1	0.00	−0.03 to 0.03	–	–	–
Overall: Rosiglitazone versus Metformin		112	111	2	0.01	−0.01 to 0.02	0.0	0.59	0.38
Saxagliptin vs. metformin
Saxagliptin 5 mg QD	Metformin 2000 mg QD for 16 weeks	11	11	1	−0.06	−0.48 to 0.36	–	–	–
Saxagliptin 5 mg QD	Metformin 2000 mg QD for 24 weeks	21	21	1	0.03	−0.01 to 0.07	–	–	–
Overall: Saxagliptin versus Metformin		32	32	2	0.03	−0.01 to 0.07	0.0	0.67	0.15
Saxagliptin vs. saxagliptin + metformin
Saxagliptin 5 mg QD	Saxagliptin 5 mg QD with Metformin 2000 mg QD for 24 weeks	21	21	1	0.03	−0.01 to 0.07	–	–	–
Saxagliptin 5 mg QD	Saxagliptin 5 mg QD with Metformin 2000 mg QD for 16 weeks	12	11	1	−0.01	−0.07 to 0.05	–	–	–
Overall: Saxagliptin versus Saxagliptin with Metformin		33	32	2	0.02	−0.02 to 0.05	9	0.30	0.34

Abbreviations: BID, twice a day; BMI, body mass index; CI, confidence interval; I ², heterogeneity; QD, once a day; RCT, randomized control trials; WC, waist circumference; WHR, waist to hip ratio.
*The overall effect was significant at < 0.05.