Saxagliptin 5mg tablets

Disease modifying therapies aiming to preserve β-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking. Here, we conducted a multi-centre, randomized, controlled trial to assess the β-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes. In this 3-arm trial, 301 participants were randomly assigned to a 24-month course of the conventional therapy (metformin with or without insulin) or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy. The primary endpoint was the change from baseline to 24 months in the fasting C-peptide. The secondary endpoints included the area under the concentration-time curve (AUC) for C-peptide level in a 2-h mixed-meal tolerance test, glycemic control, total daily insulin use and safety, respectively. The primary endpoint was not achieved in saxagliptin plus vitamin D group (P = 0.18) and saxagliptin group (P = 0.26). However, compared with the conventional therapy, 2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D (-276 pmol/L vs. -419 pmol/L; P = 0.01), and not to the same degree with saxagliptin alone (-314 pmol/L; P = 0.14). Notably, for participants with higher glutamic acid decarboxylase antibody (GADA) levels, the decline of β-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group (P = 0.001). Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control. In conclusion, the combination of saxagliptin and vitamin D preserves pancreatic β-cell function in adult-onset autoimmune type 1 diabetes, an effect especially efficacious in individuals with higher GADA levels. Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes. (ClinicalTrials.gov identifier: NCT02407899).

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INTRODUCTION: Effects of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34 + Hematopoetic Stem Cells (HSCs) as a cellular CVD biomarker. Both Dapa (a sodium-glucose co-transporter 2 or SGLT2, receptor inhibitor) and Saxagliptin (a Di-peptydl-peptidase-4 or DPP4 enzyme inhibitor) are commonly used type 2 diabetes mellitus or T2DM medications, however the benefit of using the combination has not been evaluated for cardio-renal risk assessment, in a real-life practice setting, compared to a placebo. HYPOTHESIS: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial. METHODS: This is a pilot study evaluating low dose Dapagliflozin 10 mg or low dose Dapa + low dose Saxagliptin combination. 15 subjects were enrolled in 16 weeks, double-blind, three-arm, randomized placebo matched trial, with 10mg Dapa + Saxa placebo (n = 4), 10 mg Dapa + 5 mg Saxa (n = 5) Combo, And Dapa placebo + Saxa placebo (n = 6), Placebo groups. T2DM subjects (age 30-70 yrs) with HbA1c of 7-10%, were included. CD34 + HSC number, migration, mRNA expression along with biochemistry and urine exosomes were measured. Data were collected at week 0, 8, and 16. For statistics, a mixed model regression analysis was used. RESULTS: Significant HbA1c (p = 0.0357) reduction was noted in Combo group versus Dapa alone and Placebo. hsCRP levels (P = 0.0317) and IL-6, two important inflammatory molecules, were significantly reduced in both Dapa and Combo vs. Placebo. Leptin levels decreased significantly in both Dapa alone (p = 0.035) and Combo group(p = 0.015), vs. Placebo, however the Adiponectin levels were higher in Dapa alone group. Dapagliflozin alone reduced lipid parameters significantly particularly triglyceride (TG) when compared to placebo, with resultant visit 3 values at 99.5 ± 7.2 vs. 129 ± 12.3 and LDL/HDL ratio values were similar at 2.18 ± 0.08 vs. 2.13 ± 0.15. CD34 + cell migration improved significantly in both Dapa alone (p = 0.05) and Combo group (p = 0.05) vs. Placebo. CONCLUSIONS: Several parameters showed significant improvement with both Dapa alone and Combo compared to placebo. However, when all outcome measures were taken into account, other than glycemic control the Combo didn't seem to offer any further benefit, over Dapa alone. Therefore, contrary to our initial hypothesis we do not believe the more expensive Dapa + Saxa combination offers any specific cardiovascular benefit compared to Dapagliflozin alone. However it is noteworthy that both Dapa and its combination with Saxagliptin showed significant improvement compared to placebo in T2DM, particularly when progenitor cell based numbers and function were analyzed and taken into account. TRIAL REGISTRATION: The trial was registered with Clinical Trials.gov number NCT03660683, last updated 06052023.

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BACKGROUND: This post-hoc analysis of the DELIGHT trial assessed effects of the SGLT2 inhibitor dapagliflozin on iron metabolism and markers of inflammation. METHODS: Patients with type 2 diabetes and albuminuria were randomized to dapagliflozin, dapagliflozin and saxagliptin, or placebo. We measured hemoglobin, iron markers (serum iron, transferrin saturation, and ferritin), plasma erythropoietin, and inflammatory markers (urinary MCP-1 and urinary/serum IL-6) at baseline and week 24. RESULTS: 360/461 (78.1%) participants had available biosamples. Dapagliflozin and dapagliflozin-saxagliptin, compared to placebo, increased hemoglobin by 5.7 g/L (95%CI 4.0, 7.3; p < 0.001) and 4.4 g/L (2.7, 6.0; p < 0.001) and reduced ferritin by 18.6% (8.7, 27.5; p < 0.001) and 18.4% (8.7, 27.1; p < 0.001), respectively. Dapagliflozin reduced urinary MCP-1/Cr by 29.0% (14.6, 41.0; p < 0.001) and urinary IL-6/Cr by 26.6% (9.1, 40.7; p = 0.005) with no changes in other markers. CONCLUSIONS: Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02547935.

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Abstract: Background and Aim: Qternmet XR® consisting of dapagliflozin (10 mg), saxagliptin (5 mg), and metformin hydrochloride (1000 mg), is a fixed-dose combination (tablets) that improves glycemic control in individuals with diabetes mellitus (type 2). The projected work presents four spectrophotometric methods that are eco-friendly, quick, effortless, accurate and reproducible for the concurrent assessment of the ternary mixture. Materials and Methods: The 1st approach works on the notion of unravelling pre-existing equations (simultaneous) by measuring absorbance at 223, 212 and 232.6 nm for dapagliflozin, saxagliptin and metformin hydrochloride, sequentially. The second method namely ratio difference spectroscopy works by evaluating the variation in amplitude at two dissimilar wavelengths in the ratio spectra. Whereas the derivative ratio spectrum zero-crossing approach (third approach) relied on the utilization of the derivative ratio signals at zero-crossing locations. The fourth approach is the double divisor-ratio spectra derivative approach in which the first derivative of ratio spectrum was acquired and the concentrations of all 3 drugs in their combination were quantified. Results and Discussion: All the three drugs exhibited excellent linear correlation in the concentration series of 2-10 μg/mL for simultaneous equation method and 0.5-10 μg/mL for all the other methods with an exceptional correlation coefficient value. Furthermore, the projected approaches were authenticated in line with ICH strategies and which displayed suitable precision, accuracy and sensitivity. Conclusion: The developed spectrophotometric approaches when compared to other analytical procedures are regarded to be more cost-effective because they do not require expensive solvents or sophisticated instruments. Therefore, the projected methods could be effectively employed for the concurrent assessment of dapagliflozin, saxagliptin and metformin hydrochloride in ternary mixture. Keywords: Dapagliflozin, Saxagliptin, Metformin, Simultaneous Equation Method, Ratio Difference Spectroscopic approach, Derivative Ratio Spectrum-Zero crossing approach, Double Divisor Ratio Spectra Derivative approach, Ternary mixture.

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