Discussion
hepatic cholestasis, diabetic nephropathy, diabetic, microalbuminuria, diabetic kidney diseases
DIABETIC NEPHROPATHY
Since there were several studies on the effectiveness or ineffectiveness of linagliptin on albumin excretion in urineOn the other hand, FPG and HbA1C had a significant decrease in both linagliptin and control groups. A study, conducted by Ito et al. indicated that the mean level of HbA1C in the two groups with and without receiving linagliptin was not significantly differentThe results of the present study revealed that triglyceride were significantly reduced in each group over 24 weeks from the beginning of the intervention, however the decreases were not significantly different between two groups. Howevere, the results of Monami et al. study showed that DPP-4 inhibitors had a reducing effect on triglyceridesIn the present study, cholesterol change was not significantly different between the two groups.In addition to our study, among liver enzymes, ALP was significantly higher in the linagliptin group as compared with the control group 12 weeks after the intervention. In this respect, the results of the repeated measures ANOVA indicated the significant effect of the intervention. It is important to note that the increase in ALP was not significant between two groups 24 weeks after the beginning of the intervention. The reason for the transient increase in alkaline phosphatase in the twelfth week of the study in the linagliptin group may be due to the effect of linagliptin on bone metabolism or indicate hepatic cholestasis. As we had not measured GGT (Gama-Glutamyl Transferase), we cannot determine the alkaline phosphataseʼ origin. However, the effects of DPP-4 inhibitors, including linagliptin, on bone metabolism are still unknown. One study by Kanda et al. showed a protective effect of linagliptin on the bones of diabetic ratsThe results of the evaluation of renal function factors as well as microalbuminuria also showed that although there was a significant decrease in GFR and a significant increase in Cr in the linagliptin group, the effect of the intervention and the interactive effect of time and intervention were still not significant. Moreover the rate of decrease in GFR and increase in creatinine was not more than 30% and the effect of the intervention was not significant, it is necessary to examine this finding with more participants and longer follow-up period. In this regard, Nishida et al. conducted a study to investigate the effects of DPP-4 inhibition on diabetic patients and noted a negative brief effect on creatinineIt should be noted that this study was also associated with some limitations and strengths. The investigation area of the present study, which was the evaluation of the effect of linagliptin on microalbuminuria in patients with diabetic nephropathy, can be considered novel as few studies have been performed with this aim. The mentioned point can be regarded as one of the strong points of this study. However, this study was only been performed on patients with diabetic nephropathy (microalbuminuria with mild reduced GFR), so it is imprecise whether the findings can be generalized to patients with more advanced diabetic kidney diseases. In addition, the small number of participants and the short follow-up period can be regarded as another limitation of this study.