Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS

Xing, Chuan; Li, Chun‐Zhu; He, Bing

doi:10.1210/clinem/dgaa337

Cited by 48 publications

(50 citation statements)

References 52 publications

(52 reference statements)

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“…The TMA also demonstrated that Met + TZDs was superior to Met monotherapy at reducing FINS and TC level. Our previous NMA in overweight women with PCOS revealed that Met + TZDs was superior to Met in recovering menstrual function, whereas there were no evident differences in TT and FINS [ 44 ]. Different inclusion criteria might explain these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

“…This is the first report on the analysis of efficacy of Met and MI + DCI in women with PCOS; it revealed that among all of the agents investigated here MI + DCI appeared to be the best intervention for restoring regular menses and decreasing HOMA-IR, while the combination was also able to reduce TT better than Met. No side effects have been described in clinical studies examining the effect of inositol [ 26 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

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Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

et al. 2021

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Background Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. Methods We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. Results Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + d-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31–93.58]). Myo-inositol + d-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + d-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: − 0.72 [95% CI (− 1.11)–(− 0.34)] to − 0.89 [95% CI (− 1.460)–(− 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. Conclusions Ours is the first study to report that for women with PCOS, myo-inositol combined with d-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with d-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

et al. 2021

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“…Thiazolidinediones (TZDs) are a well-known family of drugs used to improve levels of lipids and glucose, mainly in T2DM (but they are also applied to nonalcoholic steatohepatitis, psoriasis, autism and other conditions) [ 136 ]. For PCOS treatment, TDZs were successfully used in combination with metformin [ 137 ] and other natural compounds (such as inositol and α-lipoic acid) [ 138 ], improving metabolic and endocrine parameters. However, TDZs had worsening weight gain that is considered a main negative side effect [ 139 ].…”

Section: Pcos Treatments: Classical and Modern Mitochondria–oriented Approachesmentioning

confidence: 99%

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Dabravolski

Nikiforov

Eid

et al. 2021

IJMS

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Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

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“…This is the rst report on the analysis of e cacy of Met and MI + DCI in women with PCOS; it revealed that among all of the agents investigated here MI + DCI appeared to be the best intervention for restoring regular menses and decreasing HOMA-IR, while the combination was also able to reduce TT better than Met. No side effects have been described in clinical studies examining the effect of inositol [26,44]. Berberine (BBR), a natural isoquinoline alkaloid, has been studied in various randomized clinical trials in patients with PCOS and has been shown to be safe and promising for decreasing insulin resistance, lowering blood lipids, and restoring ovulation [52][53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy of Oral Insulin Sensitizers Metformin, Thiazolidinediones, Inositol, and Berberine in Improving Endocrine and Metabolic Profiles in Women With Pcos: A Network Meta-analysis

Zhao

Xing

Zhang

et al. 2021

Preprint

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BackgroundMultiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS.MethodsWe identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed.ResultsTwenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with Myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: -0.72 [95% CI (-1.11)- (-0.34)] to -0.89 [95% CI (-1.460)- (-0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. ConclusionsOurs is the first study to report that for women with PCOS, Myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registrationPROSPERO CRD42020211524

show abstract

Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS

Cited by 48 publications

References 52 publications

Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

Comparative Efficacy of Oral Insulin Sensitizers Metformin, Thiazolidinediones, Inositol, and Berberine in Improving Endocrine and Metabolic Profiles in Women With Pcos: A Network Meta-analysis

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