Rosiglitazone 2mg / Metformin 500mg tablets

Background: Diabetes is a risk factor for dementia, but we do not know whether specific diabetes medications ameliorate this risk. Objective: To systematically review and meta-analyze such medication's effect on the risk of developing dementia, mild cognitive impairment (MCI), or cognitive decline. Methods: We searched three databases until 21 November 2023. We included randomized controlled trials (RCT), cohort, and case-control studies assessing association between antidiabetic medication and future dementia, MCI, or cognitive decline. We meta-analyzed studies separately for individual drug classes and their comparators (no medication, placebo, or another drug). We appraised study quality using the Newcastle-Ottawa Scale and Physiotherapy Evidence Database Scale. Results: 42 studies fulfilled inclusion criteria. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) versus placebo reduced dementia risk by 53% in three RCTs (n = 15,820, RR = 0.47[0.25, 0.86]) and 27% in three case-control studies (n = 312,856, RR = 0.73[0.54, 0.99], I2 = 96%). Repaglinide was superior to glibenclamide by 0.8 points on the Mini-Mental State Examination scale in another RCT. Meta-analysis of seven longitudinal studies showed glitazones (n = 1,081,519, RR = 0.78[0.76, 0.81], I2 = 0%) were associated with reduced dementia risk. Metformin (n = 999,349, RR = 0.94[0.79, 1.13], I2 = 98.4%), sulfonylureas (RR = 0.98[0.78, 1.22], I2 = 83.3%), dipeptidyl peptidase-IV inhibitors (DPP-1V) (n = 192,802, RR = 0.86[0.65, 1.15], I2 = 92.9%) and insulin (n = 571,274, RR = 1.09[0.95, 1.25], I2 = 94.8%) were not. Most studies were observational and limited by confounding by indication. Conclusions: In people with diabetes, RCTs consistently showed GLP-RAs reduce future dementia risk. Glitazones consistently showed protective effects, without heterogeneity, suggesting potential generalizability of these results. Metformin, sulfonylureas, insulin, and DPP-1V studies had inconsistent findings. If information is available future studies should consider dosage, severity, and duration.

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Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [-0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: -0.23, 95% CI [-0.39, -0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies' number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

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IntroductionPioglitazone, a thiazolidinedione, effectively reduces stroke and cardiovascular events in individuals with type 2 diabetes, insulin resistance, and/or stroke. However, its potential to increase fracture risk, particularly among women and those with pre-existing skeletal conditions, has not yet been completely understood. This meta-analysis aims to clarify fracture risk associated with pioglitazone, thereby focusing on individuals with a history of stroke.MethodsA systematic review was performed for clinical trials conducted up to March 2024, focusing on trials comparing pioglitazone to placebo or other antihyperglycemic drugs that reported fracture outcomes.ResultsFrom 860 trials identified, 78 satisfied the inclusion criteria: 34 with a high risk of bias, 8 with unclear risk, and 36 with low risk. The meta-analysis revealed an association between pioglitazone and a significant increase in fracture risk (risk ratio [RR] 1.21; 95% CI 1.01-1.45; P = 0.04), including non-serious (RR 1.25; 95% CI 1.03-1.51; P = 0.02) and serious fractures (RR 1.48; 95% CI 1.10-1.98; P = 0.01). Notably, the risk was exacerbated for low-energy fractures, particularly resulting from falls (RR 1.49; 95% CI 1.20-1.87; P = 0.0004), in insulin resistance individuals (RR 0.87; 95% CI 0.43-1.76; P = 0.69), and stroke survivors (RR 1.41; 95% CI 1.09-1.83; P = 0.008). Fractures were most frequently observed in lower extremities (RR 1.85; 95% CI 1.33-2.56; P = 0.0002), with women at a greater risk (RR 1.56; 95% CI 1.20-2.02; P = 0.0008). When compared with other antihyperglycemic drugs, no significant difference in fracture risk was noted (RR 1.08; 95% CI 0.73-1.59; P = 0.70), except rosiglitazone, which showed higher fracture risk (RR 1.42; 95% CI 1.23-1.64; P DiscussionThough pioglitazone offers several cardiovascular benefits, its association with increased fracture risk, especially among women and non-diabetic individuals post-stroke, warrants careful consideration. Individualized treatment interventions balancing cardiovascular and skeletal outcomes are essential, and further research is needed to optimize therapeutic strategies in this population.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016038242, identifier CRD42016038242.

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IntroductionPolycystic 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.MethodsWe 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.ResultsOut 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 2; 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).ConclusionBoth 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 noCRD42020178783.

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Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age. Treatment or management of this syndrome includes several pharmacological and non-pharmacological treatment approaches for different manifestations of the disease that vary with the patient's age, symptoms, requirements, and geographical location. Objective: This systematic review aims to conduct a comprehensive and evidence-based analysis of the various available treatment options and identify knowledge gaps in PCOS management in India. Methods: A comprehensive search was conducted in PubMed, Scopus, and Embase databases from January 2010 till February 2024. We included randomized control trials (RCTs) using any pharmacological drugs (e.g., insulin sensitizers, anti-androgens, anti-obesity drugs, oral contraceptive pills, ovulation induction drugs, etc.) or non-pharmacological intervention (e.g., yoga, diet, herbal supplements, etc.) with Indian PCOS patients for improving common manifestations of PCOS and written in the English language. Studies were screened by two authors independently in a two-level process. Data extraction was also performed by two authors. Risk of bias was performed using the RoB 2 Tool. Subgroup analysis and meta-analysis were performed using the RevMan tool. Results: Thirty RCTs on pharmacological and eight on non-pharmacological interventions were included in the study. However, all the RCTs were so heterogeneous in terms of intervention used, subject recruited, and outcomes measured that meta-analysis was possible for only three subgroups (metformin vs. inositol, metformin vs. metformin+ inositol, and letrozole vs. clomiphene citrate), with only two or three studies per analysis. Most studies were single-centric and small-sized and had a high risk of bias, limiting their generalizability. Conclusions: This systematic review synthesized existing research and evaluated the effectiveness and safety of existing treatments. Limitations and gaps in the current research were identified, which may inform future research for better understanding and management of PCOS in the Indian context.

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AimThis study compared the effects of hypoglycaemic drugs on beta-cell function among type 2 diabetes mellitus (T2DM) patients through a network meta-analysis of randomized controlled trials (RCTs).MethodsWe searched the PubMed, EMBASE, and Cochrane Library databases for RCTs of different hypoglycaemic drugs as T2DM treatment from database inception to December 1, 2024. The primary outcome was homeostasis model assessment-β (HOMA-β), and the secondary outcome was glycated haemoglobin (HbA1c). Direct and indirect evidence types were combined to calculate weighted mean difference (WMD) and 95% confidence interval (CI) values for the change in (△) HOMA-β and △HbA1c, and to determine surface under the cumulative ranking curve (SUCRA) values.ResultsA total of 58 RCTs involving 16,345 T2DM patients were incorporated into this network meta-analysis. The mean patient age was 66.70 years, and 54.14% were male. For improving HOMA-β, the top treatments were glimepiride + rosiglitazone (WMD = 81.83, 95% CI 45.85-117.82) and glibenclamide + rosiglitazone (WMD = 79.51, 95% CI 40.66-118.36). Acarbose (WMD = 60.90, 95% CI 27.56-94.25) ranked third as monotherapy. For reducing HbA1c, glibenclamide + rosiglitazone was the most efficacious treatment (WMD = - 2.48, 95% CI - 3.67 to - 1.29), followed by metformin + exenatide (WMD = - 1.77, 95% CI - 2.25 to - 1.29) and liraglutide (WMD = - 1.77, 95% CI - 2.33 to - 1.21). The treatment with the highest SUCRA value for HOMA-β improvement was glimepiride + rosiglitazone (95.1%), followed by glibenclamide + rosiglitazone (94.9%). For HbA1c improvement, glibenclamide + rosiglitazone had the highest SUCRA value (97.6%).ConclusionsThe combination of glimepiride/glibenclamide and rosiglitazone was the most effective hypoglycaemic regimen for protecting beta-cell function and improving glycaemic control in T2DM treatment, possibly due to control of HbA1c and glycotoxicity.

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IntroductionAtherosclerotic cardiovascular disease (ASCVD) is a global concern, with diabetes being a key risk factor. Preventive measures increasingly rely on surrogate markers, such as carotid artery intima-media thickness (CIMT), a marker linked to ASCVD. Given the connection between dysglycaemia and ASCVD, the impact of oral hypoglycaemic agents (OHA) on CIMT is of interest. Despite the cardiovascular benefits of several OHAs, their effect on CIMT remains uncertain. This review aims to clarify the influence of OHAs on CIMT in patients with ASCVD and/or diabetes.ObjectivesThis systematic review aims to assess the effect of OHAs on CIMT in patients with ASCVD and/or diabetes mellitus (Type 1 or Type 2). We aim to provide evidence on the role of OHAs in reducing cardiovascular events in these high-risk patients.MethodologyA systematic search of databases, including Cochrane, Embase, CINAHL, Scopus and PubMed, was conducted to identify relevant randomised controlled trials (RCTs). We analysed the efficacy and adverse effects of OHAs on CIMT in adults with diabetes and/or cardiovascular disease.ResultsThe initial search identified 629 studies, with 13 selected, involving 3849 participants. Pioglitazone showed effectiveness in slowing CIMT progression in two out of three studies. Repaglinide was effective in reducing CIMT and inflammation, while Rosiglitazone showed no significant effect. Metformin, Sitagliptin and Alogliptin studies yielded mixed results, with some showing reduced CIMT progression but increased gastrointestinal and hypoglycaemia risks. SGLT-2 inhibitors Tofogliflozin and Ipragliflozin showed no significant CIMT reduction.ConclusionThe study suggests that prolonged use of Pioglitazone, Repaglinide and Alogliptin may significantly slow CIMT progression, improving cardiovascular risk management in patients with diabetes and/or cardiovascular disease. Further research is needed to understand the benefits and optimise oral hypoglycaemic treatment strategies for these patients.

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