Pioglitazone 15mg / Metformin 850mg tablets

BackgroundType 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR-γ. Evidence on its efficacy and safety as an add-on to metformin and SGLT2 inhibitors in inadequately controlled T2DM is limited. This systematic review and meta-analysis evaluates pioglitazone's role as a third-line therapy for improving glycaemic control in addition to metformin and Dapagliflozin.MethodologyWe conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus and EMBASE until December 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis is registered with PROSPERO ID: CRD42024612005.ResultsWe included three RCTs with 885 patients. Pioglitazone add-on therapy significantly reduced HbA1c levels (MD: -0.41; 95% CI: -0.54 to -0.27, p = 2 = 0%), fasting blood glucose (MD: -11.91; 95% CI: -16.34 to -7.48, p = 2 = 0%), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (MD: -0.65; 95% CI: -1.05 to -0.25, p = 0.001, I2 = 4.89%), increased the rate of achieving HbA1c 2 = 0%), and HbA1c 2 = 0%). However, there was no difference regarding Homeostasis model assessment of β-cell function (HOMA-β) between the two groups (MD: 2.73; 95% CI: -5.24 to 10.70, p = 0.5, I2 = 27.53%).ConclusionPioglitazone add-on therapy significantly improved glycaemic control by reducing HbA1c, fasting blood glucose and HOMA-IR while increasing the likelihood of achieving HbA1c targets. However, no significant difference was observed in HOMA-β between groups. These findings suggest the potential benefit of pioglitazone in enhancing glycaemic outcomes in diabetes management.

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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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Background/Objectives: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, impaired insulin secretion, and chronic hyperglycemia. Recent studies have identified microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level, as modulators of pathways involved in T2DM pathophysiology. Dysregulated miRNA expression has been detected in various samples collected from patients with T2DM, implicating these molecules in disease onset and progression. Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available records to 18 August 2025 using the following Boolean search terms: "miRNA AND gliclazide", "miRNA AND glibenclamide", "miRNA AND gliquidone", "miRNA AND glimepiride", "mirRNA AND metformin", "miRNA AND pioglitazone", "miRNA AND rosiglitazone", "miRNA AND sitagliptin", "miRNA AND vildagliptin", "miRNA AND alogliptin", "miRNA and saxagliptin", "miRNA AND linagliptin", "miRNA AND liraglutide", "miRNA and dulaglutide", "miRNA AND semaglutide", "miRNA AND tirzepatide", "miRNA AND lixisenatide", "miRNA AND empagliflozin", "miRNA AND dapagliflozin", miRNA AND insulin glargine", "miRNA AND insulin detemir", "miRNA AND insulin degludec", "miRNA AND insulin aspart", "miRNA AND insulin glulisine", and "miRNA AND insulin lispro". Additionally, gray literature was searched in ClinicalTrials.gov, the EU Clinical Trials Register (EudraCT), and the ISRCTN Registry to identify unpublished studies. Studies were eligible for inclusion if they were clinical interventional studies assessing the impact of currently available antidiabetic treatments on miRNA expression. Only articles published in English were considered. The risk of bias was evaluated using the RoB2 (Risk of Bias 2) and ROBINS-I (Risk Of Bias In Non-randomized Studies-of Interventions) tools. Study characteristics and major findings were tabulated. Results: A total of 1263 manuscripts was identified initially. After removing duplicates, 726 articles remained for further screening. Ultimately, 17 manuscripts reporting interventional clinical trials on the effects of antidiabetic treatment on miRNA were included, encompassing a total of 1093 patients. Key findings included treatment-associated changes in miRNA expression and their potential utility for the prediction of clinical outcomes. Conclusions: Current evidence supports the hypothesis that antidiabetic treatments modulate miRNA expression, with some findings showing predictive value for metabolic outcomes. However, the available data remain limited and of low grade of certainty, and further large-scale clinical studies are needed to provide deeper insights into these associations.

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This review evaluates the available pharmacokinetic data on the plasma-to-breastmilk transfer of first- and second-line T2DM drugs against available clinical guideline recommendations. A list of drug therapies for treating T2DM was generated from national and international clinical guidelines. A systematic search of research articles reporting human plasma and breastmilk drug concentrations was conducted in Scopus, PubMed, Google Scholar, and LactMed® in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating breastmilk drug transfer in T2DM, with fully accessible abstract and main text reported in English, were included. Study quality was evaluated using the ClinPK checklist. Authors evaluated clinical guideline recommendations on the use of T2DM drugs in lactation and the basis upon which such recommendations were made. Only 5 out of 20 drugs (metformin, glyburide, glipizide, tolbutamide, and semaglutide) have clinical data on plasma-to-breastmilk transfer. Metformin and tolbutamide were detectable in maternal plasma and breastmilk. Half (51.7%) of guideline recommendations provide explicit guidance. Only 4.4% of recommendations were based on clinical evidence. Over half (57.8%) of recommendations were accessible online, and most guideline recommendations (78%) were against the use of antiglycemic agents while breastfeeding. The scarce clinical evidence to guide T2DM drug therapy during breastfeeding available has several design and methodological limitations. Published recommendations remain largely inconsistent, thus perpetuating uncertainty in the use of T2DM drug therapies in lactation. Addressing knowledge gaps is critical in developing clinical consensus to optimize T2DM drug therapy among breastfeeding mothers.

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Alzheimer's disease (AD) and mild cognitive impairment (MCI) are major causes of cognitive decline. Antidiabetic medications such as metformin, pioglitazone, and GLP-1 receptor agonists have been proposed as potential neuroprotective therapies. We assessed whether these agents slow cognitive decline or disease progression in people with AD or MCI. PubMed, Embase, and Cochrane Central were searched for randomized controlled trials and observational studies of metformin, pioglitazone, or GLP-1 receptor agonists in AD/MCI. Results were synthesized narratively by drug class. Eleven studies met the inclusion criteria. Metformin, particularly in early-stage disease and metabolically vulnerable groups, demonstrated improvements in episodic memory and selective executive outcomes. Observational data in diabetic MCI suggested improved cognition and preservation of hippocampal and cortical structure, with limited amyloid-β and tau changes. Pioglitazone findings varied. Benefits were mainly reported in mild AD with type-2 diabetes, but not in non-diabetic AD/MCI. GLP-1 receptor agonists demonstrated preserved cerebral glucose metabolism and improved blood-to-brain glucose transport but did not improve cognitive function. Current evidence does not support antidiabetic therapies as effective treatments in AD/MCI. Any benefits appear to depend on disease stage and metabolic status, with metformin being the most promising candidate. Larger, longer-duration biomarker-defined trials are needed to determine whether any sustained clinical benefit is observed.

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IntroductionAchieving and sustaining target glycated haemoglobin (HbA1c) levels is fundamental in the management of type 2 diabetes (T2D). We here aimed to assess whether initial dual oral therapy outperforms monotherapy in reaching glycaemic targets in patients with treatment-naive or early-stage T2D.MethodsThis systematic review and meta-analysis were registered with PROSPERO (CRD420251111096). Parallel-group randomised controlled trials with a duration of at least 12 weeks were identified through searches of PubMed and the Cochrane Library spanning 2005 to 2025. Data at the trial arm level, including baseline and endpoint HbA1c values, were extracted for seven predefined comparisons and combined using a random-effects inverse-variance meta-analysis in R version 4.3.1 (meta package). The primary outcome was the proportion of treatment arms achieving an HbA1c level of ≤7.5% (58 mmol/mol). Secondary outcomes included the proportions achieving HbA1c levels of ≤7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol), as well as mean differences in HbA1c levels.ResultsA total of 20 trials, encompassing 37 treatment arms, were analysed. Dual combination therapy consistently demonstrated superior efficacy compared to monotherapy. The proportion of patients achieving HbA1c levels of ≤7.5% (58 mmol/mol) was 86% with initial dual therapy versus 82% with initial monotherapy (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.20-1.47, p = 0.002). At the more stringent threshold of ≤7.0% (53 mmol/mol), the rates were 69% versus 64% (OR 1.27, p = 0.003), and at ≤6.5% (48 mmol/mol), 42% versus 39% (OR 1.18, p = 0.056). When comparing initial dual therapy to metformin monotherapy, the respective achievement rates were 86% versus 81% (OR 1.41, p = 0.001) for a target of ≤7.0% (53 mmol/mol). The combination of metformin with a sodium-glucose cotransporter 2 inhibitor (SGLT2-i) resulted in 88% reaching ≤7.5% (58 mmol/mol), compared to 81% with metformin alone (OR 1.55, p ≤ 0.001), a difference significant across all thresholds. Dual therapy containing SGLT-2i achieved 87% at ≤7.5% (58 mmol/mol), compared with 82% with all monotherapies (OR 1.43, p ≤ 0.001). SGLT-2i monotherapy itself led to 89% reaching the target, compared with 81% with metformin (OR 1.73, p ≤ 0.001). No significant difference in outcome was observed between dual and monotherapy involving SGLT2-is (OR 0.87, p = 0.480). The pooled final HbA1c values were 6.7% (50 mmol/mol) for dual therapy and 7.9% (63 mmol/mol) for monotherapy, corresponding to a mean difference of -0.45% (95% CI -0.60 to -0.25, p ≤ 0.001). Heterogeneity among studies was low to moderate (I2 25%-50%), and results remained consistent after excluding rosiglitazone arms.ConclusionsInitial dual therapy, particularly combining metformin with an SGLT2-i, results in superior achievement of HbA1c targets across various thresholds compared to monotherapy. SGLT2-i alone surpasses metformin alone in efficacy. Adding a second agent to SGLT2-i did not provide additional glucose-lowering benefit to SGLT2-i monotherapy. Early initiation of SGLT2-i monotherapy or combination therapy should be considered upon diagnosis of T2D.

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BackgroundDiabetes is significantly associated with cognitive impairment, particularly the risk of developing dementia. However, the impact of antidiabetic drugs on dementia risk remains unclear. This study aims to comprehensively evaluate the effects of different antidiabetic drugs on dementia risk using Bayesian network analysis.MethodsThe study systematically searched databases including PubMed, Embase, and the Cochrane Library to identify relevant publications up to September 5, 2025. Eligible randomized controlled trials, cohort studies, and case-control studies were selected. We employed a Bayesian network meta-analysis model to quantitatively assess the relationship between antidiabetic drugs and dementia risk. Data analysis was performed using R version 4.4.1.ResultsA total of 28 articles (involving 4,382,897 patients), network meta-analysis results indicates that compared with placebo, Insulin [OR = 0.11, 95% CrI (0.1, 0.12)], Metformin [OR = 0.79, 95% CrI (0.77, 0.81)], and Pioglitazone [OR = 0.69, 95% CrI (0.56, 0.86)] all reduced the incidence of dementia compared to placebo, a higher incidence of Alzheimer's dementia[OR = 1.78, 95% CrI (1.66, 1.91)] and Vascular dementia[OR = 2.59, 95% CrI (2.33, 2.88)] with DPP4i compared to SGLT_2i.ConclusionThis study indicate that insulin demonstrates the most pronounced efficacy in reducing the incidence risk of dementia and vascular dementia. Furthermore, SGLT_2i and GLP1 exhibit certain therapeutic benefits in the management of Alzheimer's disease.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251172386.

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BackgroundPrediabetes refers to the transitional stage from normal glucose metabolism to diabetes. The International Diabetes Federation guidelines reported that, as of 2024, approximately 1.12 billion people globally were in the prediabetes stage. Without intervention, individuals with prediabetes are highly likely to progress to type 2 diabetes mellitus. It can be seen that prediabetes is posing a threat to human health and life and leads to a significant global public health concern.MethodsPubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched before March 29, 2025. Eligible randomized controlled trials (RCTs) enrolled adults with prediabetes, compared the efficacy and safety of placebo and anti-prediabetic drugs (e.g., metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinedione) with a follow-up duration of at least 12 weeks. Bayesian network meta-analysis was employed in statistical analysis.ResultsFifty-five eligible RCTs involving 37 interventions with 16,610 participants were included in this study. Compared with placebo, most anti-prediabetic drugs significantly reduced levels of hemoglobin A1c (HbA1c) (mean difference (MD), - 0.94 ~ - 0.27%), fasting plasma glucose (FPG) (MD, - 26.42 ~ - 0.15 mg/dL), weight loss (WL) (MD, - 13.59 ~ - 5.99 kg) and body mass index (BMI) (MD, - 4.50 ~ - 0.08 kg/m2). Specifically, 2.4 mg of semaglutide SC demonstrated the most optimal efficacy in WL (MD - 13.59 kg; 95% confidence interval (CI) - 17.30 to - 9.91) and favorable efficacy in lowering HbA1c (MD - 0.39%; 95% CI - 0.55 to - 0.25); 15 mg of tirzepatide showed significant efficacy in lowering FPG (MD - 9.58 mg/dL; 95% CI - 12.00 to - 7.15), and potent efficacy in lowering BMI. Thirty milligrams of pioglitazone showed excellent efficacy in lowering lipid and FPG. Among the interventions, there was no significant difference in the incidence of adverse events (AEs), while 100 mg of sitagliptin demonstrated higher incidence of serious adverse events (SAEs).ConclusionsAmong all the included interventions, GLP-1RAs, GIP/GLP-1RAs, and TZDs demonstrated favorable anti-prediabetic efficacy and acceptable safety. 2.4 mg of semaglutide SC and 15 mg of tirzepatide were the best option among the included interventions considering favorable glucose and BMI control.Systematic review registrationPROSPERO CRD42025636991.

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BackgroundThe study aimed to provide evidence to support optimal interventions for alleviating anxiety and depression symptoms in patients with polycystic ovarian syndrome (PCOS) through a systematic review and network meta-analysis.MethodsA comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science from their inceptions to January 2, 2025 was performed. The criteria for inclusion defined were as follows: (1) The study population consisted of female PCOS patients; (2) interventions included psychological therapy, exercise, drug treatment, or digital intervention; (3) studies that reported changes in anxiety and depression scores; and (4) randomized controlled trials (RCTs). Two reviewers independently screened the literature and extracted the data. Disagreements were resolved by consulting a third party. Standardized mean difference (SMD) was used for data recording in this study. The analysis of data was carried out based on a random-effects model, while network meta-analysis was implemented through R 4.4.0 and Just Another Gibbs Sampler (JAGS) 4.3.1. We conducted a Bayesian random-effects network meta-analysis (NMA) and ranked interventions using the surface under the cumulative ranking curve (SUCRA).ResultsThis study included a total of 25 RCTs, involving 1,453 female PCOS patients, to evaluate the effects of various interventions in alleviating anxiety and depression symptoms. Effective interventions included emotion-focused therapy (EFT), peer support (PS), omega-3 plus vitamin E (O3+VE), and mindfulness stress management (MSM). Other interventions, such as metformin and vitamin D plus probiotics (VD+Pro), showed no significant benefit compared with control. Data on PS for anxiety were not analyzed in the present network meta-analysis because relevant trials could not be connected within the network structure.ConclusionOur study demonstrates that EFT and PS emerge as promising interventions in alleviating anxiety and depression symptoms in PCOS patients. Interventions such as O3+VE and MSM also showed potential in improving emotional states.Review registration: PROSPERO CRD420250655513.

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