bms-790052 and Diabetes-Mellitus--Type-2

The achievement of virological response in the treatment of hepatitis C virus (HCV) can improve the extrahepatic manifestations. The present study aimed to investigate the effect of HCV eradication after sofosbuvir/daclatasvir (SOF/DCV) therapy on hematological and inflammatory biomarkers in type 2 diabetic patients infected with HCV genotype 4. Between October 2017 and August 2018, among 145 patients with HCV genotype 4, 30 patients were enrolled in the study based on the fact that they have type 2 diabetes. Enrolled HCV-diabetic patients were treated for 12 weeks with SOF/DCV regimen. Patients were screened by laboratory investigations before treatment (baseline values) and after HCV treatment (post-treatment values). Additionally, 30 healthy individuals were enrolled as a control group. Among the patient's cohort, the sustained virological response was achieved by 100% of the treated patients after 12 weeks of SOF/DCV therapy. Moreover, the levels of insulin resistance (HOMA-IR), nitric oxide, interleukin-1β, red cell distribution width, platelet distribution width, mean platelet volume were improved significantly (P < 0.001) in treated patients after successful viral clearance compared to baseline values. In addition, virological clearance exhibited positive correlations with interleukin-1β, nitric oxide, leukocytes count, red cell distribution width, and mean platelet volume. In conclusion, the data suggest the potential amelioration effect of HCV eradication after treatment with SOF/DCV regimen on the inflammatory status among HCV-diabetic patients which is reflected by the noticeable improvement of altered hematological indices and inflammatory biomarkers.

Topics: Adult; Antiviral Agents; Biomarkers; Carbamates; Diabetes Mellitus, Type 2; Female; Genotype; Glycated Hemoglobin; Hepacivirus; Hepatitis C; Humans; Imidazoles; Inflammation; Insulin Resistance; Interleukin-1beta; Male; Middle Aged; Pyrrolidines; Sofosbuvir; Sustained Virologic Response; Treatment Outcome; Valine

The aim of the present study was to evaluate the effect of the proposed organic cation transporter (OCT) inhibitor daclatasvir on the pharmacokinetics and pharmacodynamics of the OCT substrate metformin.. This was an open-label, two-period, randomized, crossover trial in 20 healthy subjects. Treatment A consisted of metformin and treatment B consisted of metformin + daclatasvir. Pharmacokinetic curves were recorded at steady-state. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) were calculated for metformin area under the concentration-time curve from 0 h to 12 h (AUC. The GMRs (90% CI) of metformin AUC. Bioequivalence analysis showed that daclatasvir does not influence the pharmacokinetics of metformin in healthy subjects. Pharmacodynamic parameters were also comparable between treatments.

Topics: Administration, Oral; Adult; Area Under Curve; Blood Glucose; Carbamates; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Interactions; Female; Glucose Tolerance Test; Healthy Volunteers; Hepatitis C, Chronic; Humans; Hypoglycemic Agents; Imidazoles; Insulin; Lactic Acid; Male; Metformin; Middle Aged; Octamer Transcription Factor-1; Organic Cation Transporter 2; Pyrrolidines; Therapeutic Equivalency; Valine; Young Adult

To evaluate the effect of generic sofosbuvir and daclatasvir (SOF/DCV) treatment on the glycemic state and insulin resistance as well as lipid profiles of those who achieved sustained virological response (SVR) in diabetic chronic hepatitis C virus (CHC) patients.. We retrospectively reviewed 114 CHC patients with evidence of type 2 diabetes that were treated with generic SOF/DCV between May 2016 and August 2017. Baseline demographic and laboratory data were recorded. At 12-week post end of therapy (SVR12), glycemic state and insulin resistance as well as lipid profiles were re-evaluated and compared with baseline.. A total of 98 diabetic CHC patients were finally included and were responders. A significant decline in the glycemic state as well as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P ≤ 0.0001) was observed, but HOMA-S showed a statistically significant increase (P ≤ 0.0001) at SVR12 in comparison to baseline values. Also, a significant increase in serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels was observed at SVR12 compared to baseline, but serum triglycerides levels showed a significant decrease. Logistic regression showed that the higher baseline HOMA-IR was a significant predictive variable of a decrease ≥20% of HOMA-IR, while higher baseline HOMA-IR and baseline triglycerides emerged as the only significant predictors of the Δ increase LDL-C level at SVR12.. SOF/DCV-based therapy led to an improvement of glycemic state associated with a global worsening of lipid profile. Further studies are strongly warranted to evaluate the cardiovascular balance between amelioration of insulin resistance and negative changes of the lipid profile.

Topics: Antiviral Agents; Carbamates; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Pyrrolidines; Retrospective Studies; Ribavirin; Sofosbuvir; Treatment Outcome; Valine

Background /Introduction: A high prevalence of type 2 diabetes mellitus (T2DM) was seen in association with hepatitis C virus infection; moreover, risk of development of T2DM is increased about 11 folds in patients with risk factors for metabolic syndrome in the presence of chronic hepatitis C virus (HCV) infection. There is a few available data on the effect of HCV eradication by the new direct-acting antiviral drugs (DAAs) on the glycemic control; hence the aim of our study is to evaluate the glycated haemoglobin (HbA1c) level changes in type 2 diabetic chronic HCV non cirrhotic treatment-naïve Egyptian patients after eradication with sofosbuvir (SOV) plus daclatasvir (DCV).. A prospective observational cross-sectional study, included 128 type 2 diabetic HCV patients with easy to treat criteria (non cirrhotic treatment-naïve patients with the following liver biochemical markers; total serum bilirubin ≤ 1.2 mg/dl, serum albumin ≥ 3.5 g/dl, INR≤ 1.2 and Platelet count≥ 150.000/mm3); according to the protocol of the Egyptian National Committee for Controlling HCV and the guidelines of the European Association for the Study of the Liver. HbA1c was done for all patients enrolled in the study before starting antiviral treatment, at the end of treatment and 3 months (12 weeks) after the end of treatment to patients who achieved sustained virological response (SVR) 12 only.. According to their antidiabetic medications, patients were classified to Group I: 70 patients taking oral hypoglycemic drugs, Group II: 58 patients taking insulin therapy +/- oral hypoglycemic drugs. Regarding the glycemic profile, a statistically significant decrease of mean HbA1c % values was found in the studied patients (n=128), over the period of the study with p-value < 0.05. For better evaluation of improvement of glycemic control, we used a composite endpoint given by the reduction of HbA1c % (of a minimum of 0.5%). The endpoint was reached to 79% (101 patients) of all studied patients 3 months after the end of treatment. 75.7% (53 patients) reached the endpoint in group I, while 82.75 % (48 patients) of group II reached the endpoint 3 months after the end of treatment.. This study supports the idea that HCV eradication leads to a reduction in HbA1c in patients with diabetes, which could delay the onset and progression of microvascular diabetes complications.

Topics: Antiviral Agents; Blood Glucose; Carbamates; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Egypt; Female; Glycated Hemoglobin; Hepatitis C, Chronic; Humans; Imidazoles; Male; Middle Aged; Prospective Studies; Pyrrolidines; Risk Factors; Sofosbuvir; Treatment Outcome; Valine