The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

RESUMO OBJETIVO Investigar a eficácia clínica e os possíveis mecanismos da saxagliptina no tratamento do diabetes mellitus tipo 2 (DM2) associado à doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS Um total de 95 DM2 combinados com pacientes com DHGNA foram aleatoriamente divididos em grupo A (grupo saxagliptina), grupo B (grupo glimepirida) e grupo C (glimepirida combinado com grupo fosfatidilcolina polienizada). RESULTADOS Após a intervenção tratamento por 24 w, índice de massa corporal (IMC), relação cintura-quadril (RCQ), hemoglobina glicada (HbA1c), glicemia de jejum (FPG), insulina de jejum (Fins), avaliação do modelo homeostático de insulina resistência (Homa-IR), interleucina-6 (IL-6), triglicérides (TG), colesterol total (CT), alanina aminotransferase (ALT), aspartato aminotransferase (AST), γ-glutamiltransferase (γ-GT) e detecção de esteatose hepática dos sujeitos do estudo foram observados. Ação de esteatose hepática de indivíduos nos grupos A e C foram significativamente diferentes do grupo B; no entanto, não houve diferenças entre os grupos A e C. Os grupos Fins, Homa-IR e IL-6 dos participantes do grupo A foram menores que os dos grupos B e C; no entanto, não houve diferenças significativas entre os dois últimos grupos. CONCLUSÃO Para o DM2 combinado com pacientes com DHGNA, o tratamento com saxagliptina pode não apenas controlar efetivamente a glicemia, mas também atenuar a resistência à insulina e a lesão inflamatória do fígado para melhorar ainda mais o fígado gorduroso.

Effect of exogenous lecithin on ethanol-induced testicular injuries in Wistar rats.

Infertility is well-established harmful effect in chronic alcoholism and so far, there is no effective treatment for this condition. The study was conducted to determine the effects of lecithin, a known hepatoprotective on ethanol induced testicular injuries in male albino rats of Wistar strain. Five groups (n=6) of animals were used. Group I served as control. Group II received daily 1.6 g ethanol/kg body weight/day for 4 weeks orally. Group III received 1.6 g ethanol + 500 mg lecithin/kg body weight/day for four weeks orally. Group IV received 1.6 g ethanol/kg body weight for/day 4 weeks and followed by 500 mg lecithin/kg body weight/ day for four weeks orally. Group V received 1.6 g ethanol/kg body weight/ day orally for 4 weeks, followed by 4 weeks abstinence. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and used for the estimation of extent of lipid peroxidation and tissue levels of antioxidants and steroidogenic enzymes. Lecithin protected testes from ethanol induced oxidative stress. However, the drug did not show any considerable effect on the activities of testicular delta5, 3beta-HSD and 17beta-HSD. In conclusion, ethanol induced oxidative stress can be reversed by treatment with lecithin. However the effect of lecithin on steroidogenesis was not promising.

Amphotericin B lipid complex in the management of antimony unresponsive Indian visceral leishmaniasis.

Fifty-eight Indian patients with visceral leishmaniasis who did not respond or relapsed after 30 days of consecutive sodium stibogluconate therapy were randomised to treatment with amphotericin B lipid complex (ABLC) using a total dose of 7.5 or 10 mg/kg. Treatment induced a prompt clinical response in all patients with resolution of fever and regression in spleen size. Fever and chills developed during ABLC infusion, but it diminished with successive infusions. Fourteen days after treatment, 26 of 28 (93%) patients in the 7.5 mg/kg group and all 30 (100%) in the 10 mg/kg group had splenic aspirate parasite density scores of 0 and were considered apparent clinical and parasitologic responders. Four and three patients in the 7.5 and 10 mg/kg groups respectively relapsed during six months of followup; thus, overall 22 of 28 (79%) patients treated with 7.5 mg/kg and 27 of 30 (90%) treated with 10 mg/kg were definitive cures. All initial non-responders and relapses were retreated successfully with higher dose of ABLC. These results confirm the efficacy of short-course ABLC therapy for antimony-unresponsive Indian patients with visceral leishmaniasis. Since treatment with a total dose of 7.5 mg/kg did not appear to increase efficacy (79% vs. 84% induced by 5 mg/kg in a prior study), initial treatment with a total dose of 5 mg/kg followed by retreatment of any non-responders represents a potentially less costly approach in patients who fail antimony therapy. Though high cure rates are achieved with > or = 10 mg/kg total dose of ABLC, treatment using lower doses with retreatment of non-responders or relapses with higher dose can result in considerable savings.

A pilot study of polyunsaturated phosphatidyl choline in fulminant and subacute hepatic failure.

Present pilot study was conducted to evaluate efficacy and safety of polyunsaturated phosphatidyl choline (PPC) in a phase III clinical trial in patients of fulminant and subacute hepatic failure over one year period in a prospective randomised blinded controlled design. We found that in patients of fulminant hepatic failure, recovery period from encephalopathy was faster and mortality rate lower in the test group of patients who received PPC in a dose of 350 mg thrice daily for 6 to 8 weeks as compared to the control groups who did not receive it. In the patients of subacute hepatic failure, recovery from encephalopathy was faster, mortality rate lower and regression of ascites was significantly higher (P = 0.0022) in test group of patients who received PPC as compared to the control group. However, as the number of patients in the present pilot study is small, we propose that larger clinical trials are warranted in this direction to prove the efficacy and safety of PPC in fulminant and subacute hepatic failure.