Probiotics and smectite absorbent gel formulation reduce liver stiffness, transaminase and cytokine levels in NAFLD associated with type 2 diabetes: a randomized clinical study

Introduction. In double-blind single center randomized clinical trial (RCT), the efficacy of alive probiotics sup­plementation with smectite gel vs. placebo in type 2 diabetes patient with non-alcoholic fatty liver disease (NAFLD) detected on ultrasonography (US) were studied. Material and methods. A total of 50 patients met the criteria for inclusion. They were randomly assigned to receive Symbiter Forte combination of probiotic biomass with smectite gel (250 mg) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) meas­ured by shear wave elastography (SWE). Secondary outcomes were the changes in transaminases activity, serum lipids and cytokines levels. Results. All subjects completed the study and received more than 90% of prescribed sachets. In respect to our primary endpoints, FLI and LS insignificant de­crease in both interventional and placebo groups. However, when we compare mean changes across groups from baseline, expressed in absolute values, the reduction of both LS (–0.254 ± 0.85 vs. 0.262 ± 0.77; p = 0.031) were observed. Analysis of sec­ondary outcomes showed that co-administration of probiotic with smectite lead to significant reduction of alanine aminotransferase (ALT), aspartate amino­transferase (AST), total cholesterol, IL-1b, and tumor necrosis factor (TNF-a) after 8 weeks. Conclusion. In this RCT, we confirmed previously re­ported animal data, showing that co-administration of probiotic with smectite manifested with reduction of LS, liver transaminases and chronic systemic inflam­mation

Probiotics and smectite absorbent gel formulation reduce liver stiffness, transaminase and cytokine levels in NAFLD associated with type 2 diabetes: a randomized clinical study

Introduction. In double-blind single center randomized clinical trial (RCT), the efficacy of alive probiotics sup­plementation with smectite gel vs. placebo in type 2 diabetes patient with non-alcoholic fatty liver disease (NAFLD) detected on ultrasonography (US) were studied. Material and methods. A total of 50 patients met the criteria for inclusion. They were randomly assigned to receive Symbiter Forte combination of probiotic biomass with smectite gel (250 mg) or placebo for 8-weeks. The primary main outcomes were the change in fatty liver index (FLI) and liver stiffness (LS) meas­ured by shear wave elastography (SWE). Secondary outcomes were the changes in transaminases activity, serum lipids and cytokines levels. Results. All subjects completed the study and received more than 90% of prescribed sachets. In respect to our primary endpoints, FLI and LS insignificant de­crease in both interventional and placebo groups. However, when we compare mean changes across groups from baseline, expressed in absolute values, the reduction of both LS (–0.254 ± 0.85 vs. 0.262 ± 0.77; p = 0.031) were observed. Analysis of sec­ondary outcomes showed that co-administration of probiotic with smectite lead to significant reduction of alanine aminotransferase (ALT), aspartate amino­transferase (AST), total cholesterol, IL-1b, and tumor necrosis factor (TNF-a) after 8 weeks. Conclusion. In this RCT, we confirmed previously re­ported animal data, showing that co-administration of probiotic with smectite manifested with reduction of LS, liver transaminases and chronic systemic inflam­mation

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Zmniejszenie sztywności wątroby, aktywności transaminaz i stężenia cytokin w wyniku zastosowania preparatu probiotyków ze smektytem w żelu u pacjentów z cukrzycą typu 2 i niealkoholową stłuszczeniową chorobą wątroby: randomizowane badanie kliniczne

Wstęp. W podwójnie zaślepionej, jednoośrodkowej, randomizowanej próbie klinicznej (RCT) zbadano sku­teczność suplementacji probiotykami ze smektytem w żelu w porównaniu z placebo u pacjentów z cukrzycą typu 2 i niealkoholową stłuszczeniową chorobą wątro­by (NAFLD) wykrytą w badaniu ultrasonograficznym. Materiał i metody. Kryteria włączenia spełniło łącznie 50 chorych, których przypisano losowo do przyjmowa­nia preparatu Symbiter Forte, będącego połączeniem biomasy probiotyku ze smektytem w żelu (250 mg), lub placebo przez 8 tygodni. Głównymi ocenianymi wynikami leczenia były zmiany wskaźnika stłuszczenia wątroby (FLI) oraz sztywności wątroby (LS) mierzonej za pomocą elastografii fali poprzecznej (SWE). Drugo­rzędowymi ocenianymi wynikami leczenia były zmiany aktywności transaminaz oraz stężenia lipidów i cytokin w surowicy. Wyniki. Wszyscy badani ukończyli badanie i przyjęli ponad 90% ogólnej liczby przepisanych saszetek pre­paratu. Oba główne oceniane parametry, tj. FLI i LS, uległy nieistotnemu zmniejszeniu w grupie interwencji, natomiast minimalnie zwiększyły się w grupie placebo. Kiedy jednak porównano zmiany tych parametrów między początkiem obserwacji a końcem leczenia w obu grupach, w grupie interwencji stwierdzono zmniejszenie LS w porównaniu z grupą placebo (–0,254 ± 0,85 w porównaniu z 0,262 ± 0,77; p = 0,031). Ana liza drugorzędowych wyników leczenia wykazała, że podawanie probiotyku ze smektytem spowodowało po 8 tygodniach istotne zmniejszenie aktywności ALT i AST oraz stężeń cholesterolu całkowitego, IL-1b i TNF-a. Wnioski. W przedstawionej RCT autorzy potwierdzili wyniki uzyskane wcześniej wśród zwierząt, wykazując, że podawanie probiotyku ze smektytem powoduje zmniejszenie LS, aktywności transaminaz oraz prze­wlekłego układowego zapalenia