Vildagliptin 50mg / Metformin 850mg tablets

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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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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IntroductionThe management of type 2 diabetes with metformin as the first-line therapy has long been established. However, combination therapy of metformin and other oral antidiabetics became necessary to achieve optimal glycemic targets. Recently, the rising cost of these combinations poses a challenge for the healthcare system and patients, particularly in low- and middle-income settings, highlighting the need to balance clinical benefits with economic considerations to ensure access to treatment while maintaining sustainability in patient care. This review aims to compare the efficacy, safety, and cost-effectiveness of DPP-4 inhibitors with metformin/metformin with other combinations and metformin alone.MethodsA literature search was performed through databases including PubMed, Scopus, Cochrane, clinicaltrials.gov, and Google Scholar using specific keywords on "type 2 diabetes mellitus management," "metformin," "DPP-4 inhibitors," "safety," and "efficacy." The retrieved studies were screened and selected according to eligibility criteria, followed by data extraction and critical appraisal. The extracted data were synthesized and reported according to the PRISMA guidelines.ResultsThirty-five eligible studies were included in the review. From the studies, oral antidiabetic options apart from DPP-4 inhibitors commonly combined with metformin, either as free or fixed-dose combinations, include SGLT-2 inhibitors, sulfonylureas, GLP-1 receptor agonists, insulin, and thiazolidinediones (TZDs). The efficacy of this drug combination is comparable to that of metformin monotherapy, which is more cost-effective, especially at the beginning of treatment. Where metformin monotherapy fails, the efficacy of an add-on therapy as a second line depends on the specific target and individual patient differences, and even triple therapy may be recommended for some individuals. The cost-effectiveness of each combination depended on the cost-effectiveness model used in the assessment and the nature of the healthcare setting.DiscussionDPP-4 inhibitors/metformin demonstrate significant HbA1c reduction, but their low cost-effectiveness hinders patient adherence compared to metformin monotherapy, free drugs, or other combinations. For that, initiating therapy with cost-effective metformin alone is recommended. Manufacturer-funded trials highlight a potential bias, necessitating independent research validations.

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Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are used as second-line drugs in the treatment of type 2 diabetes mellitus (T2DM) patients. They act by preventing the breakdown of incretin hormones, which enhance insulin secretion and reduce glucagon secretion. Vildagliptin and sitagliptin are more commonly used DPP-4 inhibitors. In recent years, the use of DPP-4 inhibitors has been increasing; hence, it is important to evaluate the comparative efficacy and safety of this medication with available evidence. Moreover, this systematic review will evaluate to look for any specific superiority or safety advantage of using Vildagliptin over other DPP-4 inhibitors. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review search with Cochrane and PubMed databases. Two independent reviewers examined randomized controlled trial (RCT) studies against the inclusion criteria. Excluded studies involve type 1 diabetes, gestational diabetes, and severe acute diabetic complications. Finally, five RCT studies were chosen, involving 296 participants overall. Baseline and outcome values with p-values and intergroup differences with their p-value from original studies were gathered to evaluate the significance of using vildagliptin over DPP-4 inhibitors, and findings were provided in a narrative way with available evidence. All five RCT studies have demonstrated a significant reduction in HbA1c from baseline, ranging from -0.3 to -1.34 with p-value 0.05 in other DPP-4 inhibitors, with no significant intergroup differences indicating comparable efficacy between vildagliptin and other DPP-4 inhibitors. Similarly, no significant intergroup differences were observed between vildagliptin and comparator agents in reducing fasting plasma glucose and postprandial glucose. Notably, one study reported a significant reduction favoring vildagliptin, while another showed a greater reduction of FPG with alogliptin; however, intergroup comparisons were not statistically significant. In addition, vildagliptin did not show consistent improvement in lipid profile across the involved studies. Vildagliptin showed a low incidence of hypoglycemic events in comparison with other DPP-4 inhibitors. Overall, this systematic review found no significant superiority of vildagliptin over other DPP-4 inhibitors such as sitagliptin and alogliptin in the management of type 2 diabetes mellitus, whether used as monotherapy or in combination therapy.

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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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Dipeptidyl peptidase 4 (DPP-4) inhibitors (DPP-4i) are widely used to treat Type 2 diabetes (T2D) and are known for their cardiovascular and renal safety profiles. Systematic reviews have also shown that DPP-4i are associated with reduced dementia risk via unknown mechanisms. To examine vildagliptin (DPP-4i) effects on the intestinal microbiota in T2D patients, plasma metabolomics were conducted and inflammatory profiles collected to investigate correlations with potential neuroprotective effects. We examined 29 patients with T2D (not well controlled with metformin) before, and at 30 and 60 days after vildagliptin was introduced, and investigated intestinal microbiota, plasma metabolomic, and inflammatory profiles. In patients after 2 months, vildagliptin induced mild microbiota changes, represented by significant increases in Bariatricus and Butyricimonas genera and the Marinifilaceae family (short-chain fatty acids producers), reduced insulin, HOMA-IR, MCP1, and interferon (IFN)-γ levels, and elevated interleukin (IL)-4 and IL-10 levels, all of which represented an anti-inflammatory profile. Metabolomics results showed that leucine, 2-oxoisocaproate (branched-chain amino acid metabolite), and inosine were significantly reduced after vildagliptin was introduced. Additionally, choline, dimethylamine, and betaine levels were significantly higher, which may contribute to explain DPP-4i protective effects against dementia, as these metabolites are neuroprotective. In our T2D patient cohort (not well controlled with metformin), vildagliptin, in addition to improved glucose control and improved insulin resistance, modulated the intestinal microbiota, anti-inflammatory cytokine profiles, and metabolomics, and when combined, may contribute to explain DPP-4i's neuroprotective effects.

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Abstract Dipeptidyl peptidase 4 (DPP-4) inhibitors (DPP-4i) are widely used to treat Type 2 diabetes (T2D) and are known for their cardiovascular and renal safety profiles. Systematic reviews have also shown that DPP-4i are associated with reduced dementia risk via unknown mechanisms. To examine vildagliptin (DPP-4i) effects on the intestinal microbiota in T2D patients, plasma metabolomics were conducted and inflammatory profiles collected to investigate correlations with potential neuroprotective effects. We examined 29 patients with T2D (not well controlled with metformin) before, and at 30 and 60 days after vildagliptin was introduced, and investigated intestinal microbiota, plasma metabolomic, and inflammatory profiles. In patients after 2 months, vildagliptin induced mild microbiota changes, represented by significant increases in Bariatricus and Butyricimonas genera and the Marinifilaceae family (short-chain fatty acids (SCFA) producers), reduced insulin, HOMA-IR, MCP1, and interferon (IFN)-γ levels, and elevated interleukin (IL)-4 and IL-10 levels, all of which represented an anti-inflammatory profile. Metabolomics results showed that leucine, 2-oxoisocaproate (branched-chain amino acid (BCAA) metabolite), and inosine were significantly reduced after vildagliptin was introduced. Additionally, choline, dimethylamine, and betaine levels were significantly higher, which may explain DPP-4i protective effects against dementia, as these metabolites are neuroprotective. In our T2D patient cohort (not well controlled with metformin), vildagliptin, in addition to improved glucose control and improved insulin resistance, modulated the intestinal microbiota, anti-inflammatory cytokine profiles, and metabolomics, and when combined, may explain DPP-4i’s neuroprotective effects.

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Metformin is a cheap, orally administered, guideline recommended glucose-lowering drug (GLD), initiated as monotherapy in treatment naïve newly diagnosed type 2 diabetes (T2D), and in combination with other GLDs in T2D not controlled on metformin. The unique Asian T2D phenotype that is markedly different than Western population, and warrants T2D treatment approaches unique to the Asian population. However, the bulk of metformin literature is from Western population and may not be generalizable for Asians. The systematic review evaluated the efficacy and safety of metformin monotherapy and combination therapy in Asians. Literature on other GLDs recommended by the 2023 American Diabetes Association guidelines as add-on therapy to metformin were included from Asia. The systematic review concluded that metformin is effective and safe for long-term T2D control of T2D in Asians. Metformin monotherapy may be initiated and continued in treatment naïve Asian patients with T2D and/or obesity if the monotherapy is adequate for achieving glycemic control. Other GLDs may be added for better glycemic control for those who fail on monotherapy. Patients inadequately controlled on another first-line GLD can achieve glycemic control and target HbA1c of <7% by adding metformin in a once daily dose. The use of metformin reduces the risk of hypoglycemia, and its gastrointestinal side effects are mild and manageable in Asians.

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