Saxagliptin 2.5mg / Metformin 1g tablets

BACKGROUND: Triple 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). METHODS: Following 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 < 7%, and adverse events (AEs). Pooled standardized mean differences (SMDs) and risk ratios (RRs) were calculated using random-effects models. RESULTS: Eight 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 < .0001). Weight reduction was modest, with an SMD: -0.14 (95% CI: -0.22 to -0.07; P = .0002). No significant differences were found in total AEs (RR = 0.97; P = .69) or hypoglycemia (RR = 1.32; P = .32), although there was higher discontinuation due to AEs (RR = 2.62; P = .03). CONCLUSION: Triple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.

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BACKGROUND: Prediabetes 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. METHODS: PubMed, 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. RESULTS: ). 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). CONCLUSIONS: Among 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 REGISTRATION: PROSPERO CRD42025636991.

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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. 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. 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. 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. CRD420251045700.

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AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.

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Saxagliptin is a DPP-4 inhibitor widely used to manage type 2 diabetes, though genetic contributors to variability in response remain unclear. This study aimed to identify genetic variants associated with the efficacy and safety of saxagliptin using genome-wide association studies (GWAS) with data from randomized controlled trials. GWAS were conducted on glycated hemoglobin (HbA1c) levels and hypoglycemic events in saxagliptin-treated individuals from 12 phase II or III clinical trials. Additional exploratory traits included fasting glucose, weight, body mass index, systolic and diastolic blood pressure, heartbeat, and renal function. Primary analyses focused on participants of European ancestry, followed by analyses in the overall multi-ancestry cohort. Linear mixed models for continuous traits and Cox proportional hazards models for time-to-event analyses were used, including gene-by-sex and gene-by-treatment interactions. We also performed a transcriptome-wide association study (TWAS) to identify genes whose predicted expression is associated with the response to saxagliptin using the S-PrediXcan framework. Among 1 016 European and 1 826 multi-ancestry saxagliptin-treated participants, no genome-wide significant associations were observed. Suggestive associations included rs2168426:T > C near UBE2E1 for HbA1c (p = 1.0 × 10⁻⁷) and rs138558907:C > T near CCSER2 for hypoglycemia (p = 6.1 × 10⁻⁸). Treatment interaction analyses showed a stronger rs2168426 effect on HbA1c among saxagliptin users compared with non-users (pint = 9.2 × 10⁻³). The TWAS revealed three genes that significantly associated with HbA1c in human tissues: OGFOD3 in aorta (p = 8.3 × 10⁻⁷), TBC1D3D in coronary artery (p = 3.3 × 10⁻⁶), and TYSND1 in amygdala (p = 3.9 × 10⁻⁶). In the multi-ancestry cohort, KDM7A in whole blood was significantly associated with HbA1c (p = 3.6 × 10⁻⁶). Larger, diverse studies are needed to identify pharmacogenomic determinants of responses to saxagliptin.

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OBJECTIVE: This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, or 10 mg once daily) or placebo plus a stable dose of metformin (1,500-2,500 mg) in 743 patients (A1C > or =7.0 and < or =10.0%). Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary (A1C) and secondary (fasting plasma glucose [FPG] and postprandial glucose [PPG] area under the curve [AUC]) end points. RESULTS: Saxagliptin (2.5, 5, and 10 mg) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C (-0.59, -0.69, and -0.58 vs. +0.13%; all P < 0.0001), FPG (-14.31, -22.03, and -20.50 vs. +1.24 mg/dl; all P < 0.0001), and PPG AUC (-8,891, -9,586, and -8,137 vs. -3,291 mg . min/dl; all P < 0.0001). More than twice as many patients achieved A1C <7.0% with 2.5, 5, and 10 mg saxagliptin versus placebo (37, 44, and 44 vs. 17%; all P < 0.0001). beta-Cell function and postprandial C-peptide, insulin, and glucagon AUCs improved in all saxagliptin treatment groups at week 24. Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo. CONCLUSIONS: Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone.

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At the start of the COVID-19 pandemic, there were concerns that some antidiabetic medications might worsen outcomes, though anti-inflammatory properties suggested possible benefits. Many observational studies examined antidiabetic medications use and COVID-19 outcomes. Meta-analyses showed that insulin was linked to worse outcomes, while metformin, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) agonists were associated with better outcomes. Findings on dipeptidyl peptidase-4 (DPP-4) inhibitors, pioglitazone, and sulfonylureas were mixed-showing neutral, beneficial, or negative effects. However, randomized controlled trials (RCTs) testing these medications after SARS-CoV-2 infection found no effect on COVID-19 outcomes, implying that their anti-inflammatory effects do not translate into meaningful clinical benefits during acute infection. This discrepancy prompts questioning what observational studies actually measured. Given that many studies applied robust statistical methods, their results are unlikely solely due to confounding or indication bias. We hypothesize that these studies reveal broader cardiovascular effects and illuminate diabetes management more than they inform COVID-19 pathology. Their findings align with current 2022 American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) consensus guidelines for the management of type 2 diabetes mellitus endorsing metformin, SGLT-2 inhibitors, and GLP-1 agonists as first-line therapies, recommending cautious early insulin use, and reserving DPP-4 inhibitors, sulfonylureas, and pioglitazone for selective cases. This is applicable regardless of COVID-19 status. Further research should determine whether infection-related clinical endpoints, such as mortality or hospitalization from COVID-19 or other infections, might serve as valid surrogate markers for cardiovascular outcomes.

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