Alogliptin 12.5mg / Metformin 1g tablets

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.

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The adherence to oral antidiabetic drugs (OADs) among people with type 2 diabetes (T2D) is suboptimal. However, new OADs have been marketed within the last 10 years. As these new drugs differ in mechanism of action, treatment complexity, and side effects, they may influence adherence. Thus, the aim of this study was to assess the adherence to newer second-line OADs, defined as drugs marketed in 2012-2022, among people with T2D. A systematic review was performed in CINAHL, Cochrane Trials, Embase, PubMed, PsycINFO, and Scopus. Articles were included if they were original research of adherence to newer second-line OADs and reported objective adherence quantification. The quality of the articles was assessed using JBI's critical appraisal tools. The overall findings were reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and summarized in a narrative synthesis. All seven included articles were European retrospective cohort studies investigating alogliptin, canagliflozin, dapagliflozin, empagliflozin, and unspecified types of SGLT2i. Treatment discontinuation and medication possession ratio (MPR) were the most frequently reported adherence quantification measures. Within the first 12 months of treatment, 29%-44% of subjects on SGLT2i discontinued the treatment. In terms of MPR, 61.7%-94.9% of subjects on either alogliptin, canagliflozin, dapagliflozin, empagliflozin or an unspecified SGLT2i were adherent. The two investigated adherence quantification measures, treatment discontinuation and MPR, suggest that adherence to the newer second-line OADs may be better than that of older OADs. However, a study directly comparing older and newer OADs should be done to verify this.

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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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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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BackgroundAbdominal aortic aneurysm (AAA) is a life-threatening condition with no proven pharmacological treatment to halt its progression. While animal models offer insights into pathophysiology and drug response, clinical translation remains limited.MethodsWe conducted a systematic review of repurposed drugs, classified by Anatomical Therapeutic Chemical (ATC) codes, tested in animal models for their effects on AAA progression. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a PROSPERO-registered protocol (CRD42024323430), we screened 14,127 articles and included 144 studies across 13 of the 14 ATC categories.ResultsMost drug classes, particularly cardiovascular, metabolic, and immunomodulatory agents-including statins, angiotensin II receptor blockers (ARBs), metformin, and rapamycin-showed a reduced aneurysm diameter. However, high heterogeneity in models, treatment timing, and methodological shortcomings, including a lack of blinding and power calculations, limit translational value. The predominance of positive findings suggests potential publication bias.ConclusionsNevertheless, drugs effective post-aneurysm initiation may offer the greatest clinical promise. Our findings underscore the need for standardized, high-quality, preclinical research to support future human trials.

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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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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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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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IntroductionDPP-4 inhibitors use has been reported to cause heart failure events in patients with type-2 diabetes. The FDA had also issued warnings concerning increased risk of heart failure events for alogliptin, saxagliptin and their combination with metformin.MethodsRandomized controlled trials (RCTs) involving adult patients with type-2 diabetes patients with or without history of cardio-vascular disorders were included in the review. Cohort studies, case-control studies and other non-RCTs, and studies involving paediatric patients were excluded. Data bases searched were PubMed/Medline, DOAJ, MDPI, Google Scholar and clinicaltrails.gov. The search was conducted in late January of 2026. Risk of bias was assessed using RoB-2 tool for RCTs. Individual study outcomes were tabulated and summary measure was synthesized by meta-analysis under random effect model; GRADE certainty of evidence was used; sub-group analysis based on individual DPP-4 inhibitors, follow-up duration and placebo or other controls was done; systematic review was done under PRISMA 2020 Guidelines.ResultsThe meta-analysis was done under random effect computation model for all 29 included studies. The analysis for total of pooled 67,873 patients showed statistically insignificant association between the use of DPP-4 inhibitors and heart failure with Risk Ratio (RR) = 1.06, 95% Confidence Interval (CI) 0.94-1.12. Sub-group analysis found significant association of saxagliptin use with increased heart failure risk.ConclusionResults should be interpreted with caution because of several limitations of the study.Trial registrationPROSPERO, CRD420261288081.

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