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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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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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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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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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 Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

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