- CADTH Canadian Drug Expert Committee Recommendation: Ertugliflozin/Metformin (Segluromet — Merck Canada Inc.): Indication: Diabetes mellitus, type 2 [BOOK]
- BOOKCanadian Agency for Drugs and Technologies in Health: Ottawa (ON)
- Clinical Review Report: Ertugliflozin (Steglatro): (Merck Canada Inc.): Indication: Type 2 Diabetes Mellitus [BOOK]
- BOOKCanadian Agency for Drugs and Technologies in Health: Ottawa (ON)
- Diabetes mellitus is a metabolic disease that is characterized by persistent elevations in blood glucose (hyperglycemia). This persistent elevated blood glucose causes damage to blood vessels on a mi…
Diabetes mellitus is a metabolic disease that is characterized by persistent elevations in blood glucose (hyperglycemia). This persistent elevated blood glucose causes damage to blood vessels on a microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (peripheral artery disease, cardiovascular [CV] disease) level. Diabetes is one of the most common chronic diseases in Canada. Diabetes Canada estimated that there were 3.4 million people (9.3% of the population) with diabetes in 2015, and by 2025 this number will have increased to five million people (12.1%). The objective was to perform a systematic review of the beneficial and harmful effects of ertugliflozin (ERT) 5 mg and 15 mg tablets to improve glycemic control in adult patients with type 2 diabetes mellitus for whom metformin is inappropriate due to contraindications or intolerance (as monotherapy); or in combination with metformin, or metformin and sitagliptin, when these therapies, along with diet and exercise, do not provide adequate glycemic control. This review was conducted in tandem with an evaluation of the ERT/metformin fixed-dose combination product, Segluromet.
- Bioequivalence of Ertugliflozin/Metformin Fixed-Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components. [Journal Article]
- CPClin Pharmacol Drug Dev 2019 Jun 17
- A fixed-dose combination (FDC) of ertugliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and immediate-release metformin is approved for the treatment of type 2 diabetes mellitus in the…
A fixed-dose combination (FDC) of ertugliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and immediate-release metformin is approved for the treatment of type 2 diabetes mellitus in the United States and European Union. Four open-label, randomized, 2-period, single-dose, crossover studies were conducted under fasted conditions in healthy subjects to demonstrate bioequivalence of the ertugliflozin/metformin FDC tablets and coadministration of the individual components at respective strengths. In each study, 32 or 34 subjects received an ertugliflozin/metformin FDC tablet (2.5 mg/500 mg, 7.5 mg/850 mg, or 7.5 mg/1000 mg) and the respective doses of individual components (ertugliflozin with US- or EU-sourced metformin [Glucophage]). Plasma samples for ertugliflozin and metformin concentrations were collected for 72 hours in each period. For both ertugliflozin and metformin, the 90% confidence intervals for the adjusted geometric mean ratio (FDC : coadministration) for area under the plasma concentration-time profile from time zero extrapolated to infinity and maximum observed plasma concentration were within acceptance criteria for bioequivalence. The majority of adverse events were mild in intensity. The studies demonstrated that each strength of FDC tablet is bioequivalent to respective doses of coadministered individual components, supporting that safety and efficacy can be bridged to the individual components used in phase 3 studies evaluating ertugliflozin in combination with metformin.
- Prevalence of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in a tertiary institution, South-South Nigeria. [Journal Article]
- SOSAGE Open Med 2019; 7:2050312119853433
- CONCLUSIONS: The prevalence of vitamin B12 deficiency was significantly high in diabetics, especially the metformin-treated patients. We advocate for vitamin B12 supplementation among this group of patients in order to prevent the occurrence of vitamin B12 deficiency complications such as macro-ovalocytic anemia, impaired immunity with hypersegmented neutrophils, peripheral neuropathy and subacute degeneration of the spinal cord.
- Metformin Induces Apoptosis and Inhibits Proliferation through the AMP-Activated Protein Kinase and Insulin-like Growth Factor 1 Receptor Pathways in the Bile Duct Cancer Cells. [Journal Article]
- JCJ Cancer 2019; 10(7):1734-1744
- CONCLUSIONS: Metformin has antineoplastic effects in bile duct cancer, and hyperglycemic environment interrupts the effect of metformin. In addition, AMPK and IGF-1R play a key role in the proliferation of bile duct cancer cells.
- Mechanism of Metformin on LPS-Induced Bacterial Myocarditis. [Journal Article]
- DRDose Response 2019 Apr-Jun; 17(2):1559325819847409
- CONCLUSIONS: We demonstrate that LPS stimulation may activate intracellular MAPK/JNK and NF-κB signaling pathways and thus induce cell apoptosis. In contrast, metformin reduced apoptosis by inhibiting this signaling pathway and increasing the expression level of Bcl-2. Moreover, it was found that metformin could enhance the ability of cells to antagonize redox damage by regulating the activities of superoxide dismutase and lactate dehydrogenase and subsequently promote the recovery of cardiomyocyte function.
- Preparation, Diagnosis, Biological Activity, and Theoretical Studies of Some Mixed Drug Complexes. [Journal Article]
- SScientificWorldJournal 2019; 2019:8962923
- This paper includes synthesis and characterization of mixed ligand complexes derived from mefenamic acid and metformin using transition metal ions such as Co(II) and Cu(II). These complexes have been…
This paper includes synthesis and characterization of mixed ligand complexes derived from mefenamic acid and metformin using transition metal ions such as Co(II) and Cu(II). These complexes have been characterized by magnetic susceptibility, molar conductance, TG analyses, and spectral techniques such as FTIR and UV spectra. The theoretical study of the ligands and their complexes using semiempirical (PM6) method was used to measure IR and UV spectroscopy, HOMO-LUMO categories of the ligands. These synthesized complexes are also studied for their biological activities. The studies made on these complexes proposed a six octahedral geometry.
- Effects of vildagliptin, a DPP-4 inhibitor, in elderly diabetic patients with mild cognitive impairment. [Journal Article]
- AGArch Gerontol Geriatr 2019 Jun 03
- CONCLUSIONS: Vildagliptin in addition to metformin resulted in the maintenance of MMSE score, showing a protecting role on cognitive functioning compared to the metformin only group.
- Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium. [Journal Article]
- DDiabetologia 2019 Jun 15
- CONCLUSIONS: The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.
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- Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways. [Journal Article]
- IIInt Immunopharmacol 2019 Jun 13; 74:105693
- Metformin (Met) has been found to modify the methylation of H19 and to alter its expression. In addition, IL-27, one of the downstream factors in the H19 signaling pathway, plays an important role in…
Metformin (Met) has been found to modify the methylation of H19 and to alter its expression. In addition, IL-27, one of the downstream factors in the H19 signaling pathway, plays an important role in the pathogenesis of pre-eclampsia (PE). In this study, we investigated the molecular mechanism underlying the therapeutic effect of Met in the management of PE both in vivo and in vitro. The role of H19 signaling pathway in PE was validated using online bioinformatics tools, luciferase assays, real-time PCR and Western Blot. A tail-cuff method was used to examine the blood pressures in PE rats with or without Met treatment. Cells exhibited a dose-dependent increase of H19 methylation, which inhibited the expression of H19. Additionally, upon the Met treatment, levels of miR-148-5p and miR-216-3p were both elevated in a dose-dependent manner while levels of p28 mRNA and EBI3 mRNA were both inhibited by Met treatment. Also, H19 was found to regulate the expression of miR-148a-5p and miR-216-3p, while P28 and EBI3 were respectively identified as target genes of miR-148a-5p and miR-216-3p. Therefore, the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways were implicated in the pathogenesis of PE. Met was implicated in the pathogenesis of PE via modulating the H19 signaling pathway. The methylation of H19 reduced H19 expression, which in turn could up-regulate the expression of miR-148-5p/miR-216-3p. And the expressions of subunits of IL-27, P28 and EBI3, were thus suppressed. Therefore, Met-induced inhibition of H19 also led to the reduction of IL-27 expression, TNF-α and IL-6 in vivo.