Saxagliptin 2.5mg / Metformin 1g tablets

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and decreased insulin secretion. With its rising global prevalence, effective management strategies are critical to reducing morbidity and mortality. This systematic review compares the efficacy, safety, and long-term outcomes of four major pharmacological treatments for T2DM: sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, and insulin. We focused on randomized controlled trials (RCTs) published within the last five years (2019-2024) to provide an up-to-date assessment of glycemic control, cardiovascular and renal benefits, weight effects, and the risk of hypoglycemia. The review highlights that while all four medication classes effectively reduce HbA1c levels, SGLT2 inhibitors stand out for their additional cardiovascular and renal benefits, including significant reductions in major adverse cardiovascular events and chronic kidney disease progression. Metformin remains a cornerstone first-line therapy due to its safety, efficacy, and affordability. DPP-4 inhibitors are a weight-neutral, well-tolerated option, although their efficacy may diminish over time. Insulin, while the most potent glucose-lowering agent, carries a higher risk of hypoglycemia and weight gain. Our findings emphasize the importance of personalized, patient-centered approaches that account for the distinct therapeutic profiles of these treatments. Future research should prioritize head-to-head comparisons and optimal therapy sequencing to refine treatment guidelines for diverse patient populations.

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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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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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BackgroundTriple oral therapy combining metformin, sodium-glucose cotransporter 2 inhibitor, and a dipeptidyl peptidase-4 inhibitor has been proposed as a synergistic approach to intensify glycemic control in patients with type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of triple therapy compared to dual therapy (metformin plus either sodium-glucose cotransporter 2 or dipeptidyl peptidase-4 inhibitor).MethodsFollowing preferred reporting items for systematic review and meta-analysis guidelines, we searched PubMed, Embase, Scopus, and Web of Science through January 2026. Studies included randomized controlled trials comparing triple versus dual therapy in adults with type 2 diabetes mellitus. Outcomes included hemoglobin A1c (HbA1c), fasting plasma glucose, body weight, achievement of HbA1c ResultsEight studies encompassing 2606 participants were included. Findings indicate triple therapy significantly reduced HbA1c levels compared to dual therapy, with a SMD of - 0.54 (95% confidence interval [CI]: -0.92 to -0.16; P = .005). Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06). Patients on triple therapy were more likely to achieve HbA1c levels below 7% (RR: 2.02; 95% CI: 1.55-2.63; P ConclusionTriple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.

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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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BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by insulin resistance and hyperandrogenism; whether novel antidiabetic drugs differentially improve these metabolic and reproductive disturbances remains uncertain. We performed a network meta-analysis to simultaneously rank the efficacy and safety of sodium–glucose cotransporter-2 inhibitors (SGLT-2i), GLP-1 receptor agonists (GLP-1RAs) and DPP-4 inhibitors (DPP-4i) in women with PCOS. METHODS: We searched PubMed, Web of Science, Medline, Cochrane CENTRAL and Embase to 6 June 2025 for randomized controlled trials (RCTs) that compared SGLT-2i, GLP-1RAs or DPP-4i with placebo or active drugs in women ≥ 18 years with PCOS. Primary endpoints were Body Mass Index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), total testosterone (TT) and free androgen index (FAI); secondary endpoints included waist circumference (WC), Sex Hormone Binding Globulin (SHBG), fasting blood glucose (FBG), lipids and gastrointestinal adverse events. A frequentist random-effects network meta-analysis was conducted in Stata 15.1; treatments were ranked with SUCRA (0–100%) and certainty was appraised with CINeMA. RESULTS: 29 RCTs (1771 participants) were eligible. SGLT-2i yielded the largest reduction in BMI (mean difference vs. placebo − 4.26 kg m⁻², 95% CI − 6.01 to − 2.52; SUCRA 91%) and HOMA-IR (–2.56, − 4.53 to − 0.59; SUCRA 89%). The metformin plus GLP-1RAs combination produced the greatest decrease in TT (–1.35 ng mL⁻¹ vs. placebo, − 2.22 to − 0.48; SUCRA 85%) and FAI (–1.91, − 3.43 to − 0.40; SUCRA 82%), and also led improvements in WC, SHBG and FBG. SGLT-2i ranked first for lowering triglycerides (TG) and total cholesterol (TC). GLP-1RAs monotherapy carried the highest risk of nausea (OR 6.26–9.20), vomiting (OR up to 26.56) and abdominal pain, whereas metformin/DPP-4i markedly increased diarrhoea (OR 2 704 vs. placebo). No statistical inconsistency or publication bias was detected; certainty was high for selected contrasts but moderate to very low for most comparisons. CONCLUSIONS: SGLT-2i provide the most favourable cardiometabolic profile as single agents for weight and insulin resistance in PCOS, whereas metformin combined with GLP-1RAs most effectively attenuates hyperandrogenism at the price of greater gastrointestinal intolerance. The low certainty of much of the evidence underscores the need for large, long-term RCTs to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: CRD420251045700.

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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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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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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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