Time to first remission and survival in patients with acromegaly: Evidence from the UK Acromegaly Register Study (UKAR).

OBJECTIVE: This study aimed to understand the effect of time to remission of acromegaly on survival in people living with acromegaly. DESIGN, PATIENTS AND MEASUREMENT: This cross-sectional study used data from the UK Acromegaly Register. We considered remission of acromegaly growth hormone controlled at ≤2 µg/L following the diagnosis of acromegaly. We used the accelerated failure time model to assess the effect of time to remission on survival in acromegaly. RESULTS: The study population comprises 3569 individuals with acromegaly, with a median age of diagnosis of 47.3 (36.5-57.8) years, 48% females and a majority white population (61%). The number of individuals with the first remission of acromegaly was 2472, and the median time to first remission was 1.92 (0.70-6.58) years. In this study, time to first remission in acromegaly was found to have a significant effect on survival (p < .001); for every 1-year increase in time to first remission, there was a median 1% reduction in survival in acromegaly. In an analysis adjusted for covariates, the survival rate was 52% higher (p < .001) in those who underwent surgery as compared to those who did not have surgery, 18% higher (p = .01) in those who received treatment with somatostatin analogues (SMA) as compared to those with dopamine agonists and 21% lower (p < .001) in those who received conventional radiotherapy as compared to those who did not receive radiotherapy. CONCLUSION: In conclusion, this population-based study conducted in patients with acromegaly revealed that faster remission time, surgical intervention and treatment with SMA are linked to improved survival outcomes.

The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. METHODS: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20 mmol/L; 95% CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47 mmol/L; 95% CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95% CI - 1.25-0.00, p = 0.05). CONCLUSION: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO REGISTRATION NO: CRD42020178783.

Clinical features of type 1 diabetes in older adults and the impact of intermittently scanned continuous glucose monitoring: An Association of British Clinical Diabetologists (ABCD) study.

AIMS: To evaluate the clinical features and impact of flash glucose monitoring in older adults with type 1 diabetes (T1D) across age groups defined as young-old, middle-old, and old-old. MATERIALS AND METHODS: Clinicians were invited to submit anonymized intermittently scanned continuous glucose monitoring (isCGM) user data to a secure web-based tool within the National Health Service secure network. We collected baseline data before isCGM initiation, such as demographics, glycated haemoglobin (HbA1c) values from the previous 12 months, Gold scores and Diabetes Distress Scale (DDS2) scores. For analysis, people with diabetes were classified as young-old (65-75 years), middle-old (>75-85 years) and old-old (>85 years). We compared baseline clinical characteristics across the age categories using a t test. All the analyses were performed in R 4.1.2. RESULTS: The study involved 1171 people with diabetes in the young-old group, 374 in the middle-old group, and 47 in the old-old group. There were no significant differences in baseline HbA1c and DDS2 scores among the young-old, middle-old, and old-old age groups. However, Gold score increased with age (3.20 [±1.91] in the young-old vs. 3.46 [±1.94] in the middle-old vs. 4.05 [±2.28] in the old-old group; p < 0.0001). This study showed reduced uptake of insulin pumps (p = 0.005) and structured education (Dose Adjustment For Normal Eating [DAFNE] course; p = 0.007) in the middle-old and old-old populations compared to the young-old population with T1D. With median isCGM use of 7 months, there was a significant improvement in HbA1c in the young-old (p < 0.001) and old-old groups, but not in the middle-old group. Diabetes-related distress score (measured by the DDS2) improved in all three age groups (p < 0.001) and Gold score improved (p < 0.001) in the young-old and old-old populations but not in the middle-old population. There was also a significant improvement in resource utilization across the three age categories following the use of is CGM. CONCLUSION: This study demonstrated significant differences in hypoglycaemia awareness and insulin pump use across the older age groups of adults with T1D. The implementation of isCGM demonstrated significant improvements in HbA1c, diabetes-related distress, hypoglycaemia unawareness, and resource utilization in older adults with T1D.

Effect of intermittently scanned continuous glucose monitoring in people with diabetes with a psychosocial indication for initiation.

AIM: To understand the effect of intermittently scanned continuous glucose monitoring (isCGM) in people with diabetes with a 'psychosocial' indication for access. METHODS: The study utilized baseline and follow-up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes in the UK. Diabetes-related distress (DRD) was assessed using the two-item diabetes-related distress scale (DDS). Participants were categorized into two groups: high DRD (DDS score ≥ 3) and lower DRD (DDS score < 3). The t-test was used to assess the difference in the pre- and post-isCGM continuous variables. RESULTS: The study consisted of 17 036 people with diabetes, with 1314 (7%) using isCGM for 'psychosocial' reasons. Follow-up data were available for 327 participants, 322 (99%) of whom had type 1 diabetes with a median diabetes duration of 15 years; 75% (n = 241) had high levels of DRD. With the initiation of isCGM, after a mean follow-up period of 6.9 months, there was a significant reduction in DDS score; 4 at baseline versus 2.5 at follow-up (P < .001). The prevalence of high DRD reduced from 76% to 38% at follow-up (50% reduction in DRD, P < .001). There was also a significant reduction in HbA1c (78.5 mmol/mol [9.3%] at baseline vs. 66.5 mmol/mol [8.2%] at follow-up; P < .001). This group also experienced an 87% reduction in hospital admissions because of hyperglycaemia/diabetic ketoacidosis (P < .001). CONCLUSION: People with diabetes who had isCGM initiated for a psychosocial indication had high levels of DRD and HbA1c, which improved with the use of isCGM.

Intermittently scanned continuous glucose monitoring and hypoglycaemia awareness in drivers with diabetes: Insights from the Association of British Clinical Diabetologists Nationwide audit.

AIM: Frequent hypoglycaemia results in disruption to usual hypoglycaemic autonomic responses leading to impaired awareness of hypoglycaemia, which is associated with an increased risk of severe hypoglycaemia requiring third-party assistance (SH). The UK Driving and Vehicle Licensing Agency (DVLA) does not permit car driving if they have either a complete loss of hypoglycaemia awareness or more than one SH event a year. METHODS: The FreeStyle Libre (FSL) Association of British Clinical Diabetologists (ABCD) Nationwide Audit consists of data collected by clinicians during routine clinical work, submitted into a secure web-based tool held within the National Health Service (NHS) N3 network. Analysis of paired baseline and follow-up data for people with type 1 diabetes who also held a driving licence was undertaken. RESULTS: The study consisted of 6304 people who had data recorded about driving status from 102 UK specialist diabetes centres, of which 4218 held a driving licence: 4178 a group 1, standard licence, 33 a group 2, large lorries and buses, seven a taxi licence; 1819 did not drive. Paired baseline and follow-up data were available for a sub-cohort of 1606/4218. At a mean follow-up of 6.9 months [95% CI (6.8, 7.1)], the Gold score had improved (2.3 ± 1.5 vs. 2.0 ± 1.3 p < .001), and the number of people who experienced an SH episode was also significantly lower (12.1% vs. 2.7%, p < .001). CONCLUSION: This study suggests that intermittently scanned continuous glucose monitoring may improve impaired awareness of hypoglycaemia and reduce the number of people with type 1 diabetes with a driving licence experiencing a severe hypoglycaemic episode.

The Effect of a Very-Low-Calorie Diet (VLCD) vs. a Moderate Energy Deficit Diet in Obese Women with Polycystic Ovary Syndrome (PCOS)-A Randomised Controlled Trial.

We performed an open-label, randomised controlled trial to compare the effects of a very-low-calorie diet (VLCD) vs. moderate energy deficit approach on body weight, body composition, free androgen index (FAI), and metabolic markers in obese women with polycystic ovary syndrome (PCOS). Forty eligible patients were randomly assigned to a VLCD (n = 21) or a conventional energy deficit approach (n = 19) over the same period. After eight weeks, both groups experienced significant weight loss; however, this was greater in the VLCD arm (-10.9% vs. -3.9%, p < 0.0001). There was also a trend towards a reduction in FAI in the VLCD group compared to the energy deficit group (-32.3% vs. -7.7%, p = 0.07). In the VLCD arm, two women (18%) had a biochemical remission of PCOS (FAI < 4); this was not the case for any of the participants in the energy deficit arm. There was a significant within-group increase in the sex-hormone-binding globulin (p = 0.002) and reductions in fasting blood glucose (p = 0.010) and waist to hip ratio (p = 0.04) in the VLCD arm, but not in the energy deficit arm. The VLCD resulted in significantly greater weight reduction and was accompanied by more pronounced improvements in hyperandrogenaemia, body composition, and several metabolic parameters in obese women with PCOS as compared to the energy deficit approach.

Metabolic and Endocrine Complications of Long-COVID-19: A Review.

Over the past two years, the outbreak of coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has centralized the interest of the health care systems and the scientific world. The majority of COVID-19-infected individuals recover fully. However, about 12-50% of patients experience various mid- and long-term effects after recovering from the initial illness. These mid- and long-term effects are collectively known as post-COVID-19 condition or 'long-COVID'. In the coming months, the long-term consequences of COVID-19 on the metabolic and endocrine systems may expect to rise and pose a global healthcare challenge. This review article discusses the possible metabolic and endocrine complications of long-COVID and the relevant research findings.

The long-term impact of glucose monitoring with the FreeStyle Libre on glycaemic control and hypoglycaemia awareness in people with type 1 diabetes: Insights from the Association of British Clinical Diabetologists national audit.

AIMS: To investigate the change in glycated haemoglobin (HbA1c), hypoglycaemia awareness and diabetes-related distress in people with type 1 diabetes (T1D) using FreeStyle Libre (FSL) over a 2-year follow-up period. METHODS: FSL user data from U.K wide hospitals collected during routine clinical care were analysed. People living with T1D were categorised into four groups based on the duration of follow-up. Group I (< 1 year, n = 6940), group II (1 to 1.5 years, n = 662), group III (1.5 to 2 years, n = 385), and group IV (> 2 years, n = 642). The t-test was used to compare the baseline and follow-up HbA1c, GOLD score (a measure of hypoglycaemia awareness) and diabetes-related distress scale (DDS score) (quality of life measure). RESULTS: The study consisted of 16,834 people, with follow-up data available for 8,629 participants. The change in HbA1c, GOLD and DDS score from baseline within the follow-up sub-groups (group I vs group II vs group III vs group IV) was HbA1c (-6 vs -6 vs -4 vs -4 mmol/mol; p < 0.001) (-0.55 vs -0.55 vs -0.37 vs -0.37 %), GOLD score (-0.31 vs -0.45 vs -0.26 vs -0.42; p < 0.0001 group I, II, IV and p 0.07 group III), and DDS score(-0.59 vs -0.58 vs -0.63 vs -0.50; p < 0.001), respectively. CONCLUSIONS: In people with T1D, FSL use resulted in a sustained improvement in HbA1c, hypoglycaemia awareness and diabetes-related distress for over two years.

Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. AIM: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. DATA SOURCE: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. DATA SYNTHESIS: Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI  - 0.49 to  - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI  - 1.34 to  - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD:  - 0.47; 95% CI  - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD:  - 0.37 µg/dL; 95% CI  - 0.05 to  - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD:  - 1.67; 95% CI  - 2.27 to  - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. CONCLUSION: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. PROSPERO REGISTRATION NO: CRD42020178783.

Assessing the androgenic and metabolic heterogeneity in polycystic ovary syndrome using cluster analysis.

INTRODUCTION: Some but not all women with polycystic ovary syndrome (PCOS) develop the metabolic syndrome (MS). The objective of this study was to determine if a subset of women with PCOS had higher androgen levels predisposing them to MS and whether routinely measured hormonal parameters impacted the metabolic syndrome score (siMS). METHODS: We included data from a discovery (PCOS clinic data) and a replication cohort (Hull PCOS Biobank) and utilized eight routinely measured hormonal parameters in our clinics (free androgen index [FAI], sex hormone-binding globulin, dehydroepiandrosterone sulphate (DHEAS), androstenedione, luteinizing hormone [LH], follicular stimulating hormone, anti-Müllerian hormone and 17 hydroxyprogesterone [17-OHP]) to perform a K-means clustering (an unsupervised machine learning algorithm). We used NbClust Package in R to determine the best number of clusters. We estimated the siMS in each cluster and used regression analysis to evaluate the effect of hormonal parameters on SiMS. RESULTS: The study consisted of 310 women with PCOS (discovery cohort: n = 199, replication cohort: n = 111). The cluster analysis identified two clusters in both the discovery and replication cohorts. The discovery cohort identified a larger cluster (n = 137) and a smaller cluster (n = 62), with 31% of the study participants. Similarly, the replication cohort identified a larger cluster (n = 74) and a smaller cluster (n = 37) with 33% of the study participants. The smaller cluster in the discovery cohort had significantly higher levels of LH (7.26 vs. 16.1 IU/L, p < .001), FAI (5.21 vs. 9.22, p < .001), androstenedione (3.93 vs. 7.56 nmol/L, p < .001) and 17-OHP (1.59 vs. 3.12 nmol/L, p < .001). These findings were replicated in the replication cohort. The mean (±SD) siMS score was higher in the smaller cluster, 3.1 (±1.1) versus 2.8 (±0.8); however, this was not statistically significant (p = .20). In the regression analysis, higher FAI (ß = .05, p = .003) and androstenedione (ß = .03, p = .02) were independently associated with a higher risk of SiMS score, while higher DHEAS levels were associated with a lower siMS score (ß = -.07, p = .03) CONCLUSION: We identified a subset of women in our PCOS cohort with significantly higher LH, FAI, and androstenedione levels. We show that higher levels of androstenedione and FAI are associated with a higher siMS, while higher DHEAS levels were associated with lower siMS.

Impact of metformin on the clinical and metabolic parameters of women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

Context: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition. Aim: To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS. Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022. Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m² (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo. Conclusion: In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.

Time in range following flash glucose monitoring: Relationship with glycaemic control, diabetes-related distress and resource utilisation in the Association of British Clinical Diabetologists national audit.

AIMS: The aim of this study was to understand the relationship between time in range (TIR) achieved using the isCGM with changes in glycaemic control, diabetes-related distress (DRD) and resource utilisation in people living with diabetes. METHODS: Clinicians from 106 National Health System (NHS) UK hospitals submitted isCGM user baseline and follow-up data in a web-based tool held within the UK NHS network. Linear regression analysis was used to identify the relationship between follow-up glucose TIR (3.9-10 mmol/L) categories (TIR% 50-70 and TIR% >70) with change in haemoglobin A1c (HbA1c), DRD and Gold score (measure of hypoglycaemia unawareness, where a score ≥4 suggests impaired awareness of hypoglycaemia). RESULTS: Of 16,427 participants, 1241 had TIR follow-up data available. In this cohort, the mean TIR was 44.8% (±22.5). With the use of isCGM, at 7.9 months mean follow-up, improvements were observed in HbA1c (-6.9 [13.5] mmol/mol, p < 0.001), Gold score (-0.35 [1.5], p < 0.001) and Diabetes Distress Screening (-0.73 [1.23], p < 0.001). In the regression analysis restricted to people living with type 1 diabetes, TIR% 50-70 was associated with a -8.9 mmol/mol (±0.6, p < 0.001) reduction in HbA1c; TIR% >70 with a -14 mmol/mol (±0.8, p < 0.001) reduction in HbA1c. Incremental improvement in TIR% was also associated with significant improvements in Gold score and DRD. TIR% >70 was associated with no hospital admissions due to hypoglycaemia, hyperglycaemia/diabetic ketoacidosis, and a 60% reduction in the paramedic callouts and 77% reduction in the incidence of severe hypoglycaemia. CONCLUSION: In a large cohort of UK isCGM users, we demonstrate a significant association of higher TIR% with improvement in HbA1c, hypoglycaemia awareness, DRD and resource utilisation.

FreeStyle Libre Flash Glucose Monitoring system for people with type 1 diabetes in the UK: a budget impact analysis.

INTRODUCTION: This study aims to estimate the budget impact of increased uptake of the FreeStyle Libre Flash Glucose Monitoring system in people with type 1 diabetes mellitus (T1DM) in the UK. RESEARCH DESIGN AND METHODS: A budget impact model was developed, applying real-world data collected in the Association of British Clinical Diabetologists (ABCD) FreeStyle Libre Nationwide Audit. Costs of diabetes glucose monitoring in a T1DM population (n=1790) using self-monitoring of blood glucose (SMBG) or the FreeStyle Libre system were compared with a scenario with increased use of the FreeStyle Libre system. RESULTS: The ABCD audit demonstrates FreeStyle Libre system use reduces diabetes-related resource utilization. The cost analysis found that higher acquisition costs are offset by healthcare costs avoided (difference £168 per patient per year (PPPY)). Total costs were £1116 PPPY with FreeStyle Libre system compared with £948 PPPY with SMBG. In an average-sized UK local health economy, increasing FreeStyle Libre system uptake from 30% to 50% increased costs by 3.4% (£1 787 345-£1 847 618) and when increased to 70% increased by a further 3.3%. CONCLUSION: Increased uptake of the FreeStyle Libre system in the T1DM population marginally increases the cost to UK health economies and offers many system benefits.

Unilateral adrenal infarction in pregnancy with associated acute hypoadrenalism and subsequent spontaneous biochemical and radiological resolution.

Adrenal infarction is a rare cause of abdominal pain during pregnancy, and if missed, it can result in devastating clinical consequences for the mother and the child. The authors report a case of a young female who presented with severe abdominal pain and nausea. The biochemistry showed raised inflammatory markers and significant lactic acidosis. As the cause of the symptoms was not clear and the patient continued to deteriorate, a contrast-enhanced CT abdomen and pelvis was done which was suggestive of an acute left adrenal infarction. Subsequently, the patient was confirmed to have biochemical hypoadrenalism and required replacement doses of hydrocortisone until recovery of the adrenal glucocorticoid reserve and anticoagulation for the duration of pregnancy. We discuss the workup including diagnostic imaging, follow-up, and considerations for future pregnancies in this case.

Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. DESIGN: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I² = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I² = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I² = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I² = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. CONCLUSIONS: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

Effect of pharmacological interventions on lipid profiles and C-reactive protein in polycystic ovary syndrome: A systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.