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Objective: To compare the safety and efficacy of linagliptin with pioglitazone in combination therapy of metformin for the management of type2 diabetes mellitus (T2DM). Materials and Methods: A meta-analayis research design is applied to evaluate the primary and secondary outcomes. Literature search was carried out using databases such as PubMed, Cochrane Library, MEDLINE Complete, Scopus, Clinical Trial Registry, and Web of Science. Studies were considered eligible if the eligibility criteria were met. Cochrane Collaboration Tool was used to assess the risk of bias in randomized clinical trials. Results: A total of 170 citations were identified during the database search. Further evaluation of articles confirmed 16 clinical trials suitable for the research which were randomized, double-blinded, and published as full articles. The articles were evaluated with low risk of bias and high-quality evidence. The mean baseline hemoglobin A1c(HbA1c) ranged from 6.93% to 9.99% and 7.1% to 8.89% for linagliptin with metformin and pioglitazone with metformin groups, respectively. Two among the 12 groups show a slight increase in the mean HbA1c levels which is nonsignificant due to their sample size. Overall, the combination therapy of linagliptin with metformin led to a reduction of 1.35% which is significantly higher than pioglitazone combined with metformin which led to a 1.27% reduction. The mean baseline values of fasting plasma glucose levels varied from 158.2 mg/dl to 198.0 mg/dl in linagliptin plus metformin group, whereas in pioglitazone plus metformin group, the values varied from 137.0 mg/dL to 212.4 mg/dL. The high heterogeneity could refer to the inconsistencies between the studies. The combination of linagliptin with metformin showed a significant reduction of 0.56% in body mass index, whereas pioglitazone with metformin led to a 0.37% reduction.Conclusion: The findings showed better efficacy profiling of lingaliptin–metformin combination compared with pioglitazone combination therapy.
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ABSTRACT Aim: The aim of the study is to evaluate the effect of linagliptin versus metformin on insulin secretion, insulin sensitivity and glucose control in patients with impaired glucose tolerance (IGT). Patients and methods: A randomized, double-blind, clinical trial with parallel groups was per-formed on 16 adults with IGT. Lipid profile and haemoglobin (HbA1c) were evaluated prior to and after the intervention. Glucose and insulin were measured at 0, 30, 60, 90 and 120 minutes after a 75-g oral dextrose load. Eight patients received metformin (500 mg) twice a day before meals for three months. The remaining eight patients received placebo (500 mg) in the morning and linagliptin (5 mg) in the evening before meals. The area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were assessed. Results: After linagliptin administration, a significant decrease in glucose at 90 minutes (10.8 ± 2.6 vs 7.9 ± 2.2 mmol/L, p < 0.05), 120 minutes (8.8 ± 0.9 vs 6.5 ± 2.1 mmol/L, p < 0.05) and AUC of glucose (1168 ± 210 vs 953 ± 207 mmol/L, p < 0.05) were observed. Metformin administration decreased insulin significantly at 0 minutes (94.8 ± 25.8 vs 73.8 ± 24.6 pmol/L, p < 0.05). Conclusion: Three-month administration of linagliptin in patients with IGT decreased glucose at 90 and 120 minutes after a 75-g oral dextrose load and AUC of glucose. Metformin decreased insulin at 0 minutes.
RESUMEN Objetivo: El objetivo del estudio es evaluar el efecto de la linagliptina frente a la metformina en la secreción de insulina, la sensibilidad a la insulina, y el control de la glucosa en pacientes con intolerancia a la glucosa (IG). Pacientes y métodos: Se realizó un ensayo clínico aleatorio de doble ciego con grupos paralelos a 16 adultos con IG. El perfil lipídico y la hemoglobina (Hba1C) se evaluaron antes y después de la intervención. La glucosa y la insulina se midieron a los 0, 30, 60, 90 y 120 minutos después de un carga oral de 75-g dextrosa. Ocho pacientes recibieron metformina (500 mg) dos veces al día antes de las comidas por tres meses. Los ocho pacientes restantes recibieron placebo (500 mg) por la mañana y linagliptina (5 mg) por la noche antes de las comidas. El área bajo la curva (ABC) de la glucosa y la insulina, la secreción total de insulina, la primera fase de la secreción de insulina, y la sensibilidad a la insulina, fueron evaluadas. Resultados: Luego de la administración de la linagliptina, se observó una disminución significativa de la glucosa a los 90 minutos (10.8 ± 2.6 vs 7.9 ± 2.2 mmol/L, p < 0.05), 120 minutos (8.8 ± 0.9 mmol/L p < 0.05) y el ABC de la glucosa (1168 ± 210 vs 953 ± 207 mmol/L, p < 0.05). La administración de metformina redujo significativamente la insulina a los 0 minutos (94.8 ± 25.8 vs 73.8 ± 24.6 pmol/L, p < 0.05). Conclusión: Tres meses de administración de linagliptina en pacientes con IG disminuyó la glucosa a los 90 y 120 minutos después de una carga oral de dextrosa de 75-g y el ABC de la glucosa. La metformina disminuyó la insulina en 0 minutos.
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Humans , Male , Female , Adult , Middle Aged , Blood Glucose/drug effects , Linagliptin/pharmacology , Metformin/pharmacology , Double-Blind Method , Sensitivity and Specificity , Glucose Intolerance/drug therapy , Glucose Intolerance/blood , Glucose Tolerance Test , Insulin/metabolismABSTRACT
Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment (MCI) in elderly type 2 diabetes mellitus (T2DM) patients.Methods Montreal Cognitive Assessment(MoCA)scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited.They were randomly divided into the linagliptin group(Linagliptin + metformin,n=50)and the non-linagliptin group(gliclazide + metformin,n =48).Serum fasting plasma glucose (FPG),glycosylated hemoglobin(HbAlc),blood lipids and amyloid β-protein 1-42 (Aβ1-42) levels were determined,and MoCA score and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated,and were compared between the two groups before and after 24 weeks of treatment.Results In the linagliptin group,serum FPG,HbA1c,HOMA-IR,Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [(7.29± 1.00) mmol/L vs.(9.16 ± 1.60) mmol/L,(7.19 ± 0.99) ％ vs.(9.36 ± 1.07) ％,(3.05 ± 1.12) vs.(4.05±1.30),(0.463±0.093)g/L vs.(0.528±0.110)g/L,(24.48± 1.18) vs.(23.22± 1.37),all P＜0.05].In the non-linagliptin group as control,FPG and HbA1c levels were decreased after 24 weeks of treatment as compared with pre-treatment[(7.23±1.09)mmol/L vs.(9.20± 1.75) mmol/L,(7.23±1.03)％ vs.(9.69± 1.18)％,both P ＜ 0.05],while there was no significant difference in HOMA IR,Aβ1-42 level and MoCA score[(3.95 ± 1.00) vs.(4.19± 1.13),(0.517± 0.113)g/L vs.(0.526±0.119)g/L,(23.21±1.18) vs.(23.00±1.32),all P＞0.05].It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment(all P＜0.05).Conclusions Linagliptin as one of DPP-4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR.DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.
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Objective To evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitor,linagliptin,in subjects aged 60 years or older with type 2 diabetes mellitus (T2DM).Methods Data from eight 24-week,multinational,multicenter,randomized,double-blind,placebo-controlled,parallel-group studies were analyzed.Patients aged 60 years or older with T2DM were received oral linagliptin (5 mg/d) or placebo in combination with mefformin,or metformin plus sulfonylurea.Efficacy was assessed by the changes in glycosylated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) from baseline to 24 weeks of treatment.Safety endpoint included the frequency and intensity of adverse events.Results A total of 1 421 patients (placebo 429,linagliptin 992) were included in the full analysis set (FAS).Mean ages of the subjects were (67.4 ± 5.6) years in the linagliptin group and (66.7-± 5.6) years in the placebo group.Baseline HbA1c was (8.0 ±0.8) ％ in the linagliptin group and (8.1 ±0.9) ％ in the placebo group.At the end of 24-week,placebo-adjusted reduction in HbAlc in subjects with linagliptin was (0.7 ±0.1)％ (95％ CI 0.6-0.8,P ＜0.000 1),and placebo-adjusted reduction in FPG in subjects with linagliptin was (0.88 ±0.12) mmol/L(95％ CI 0.65-1.11,P ＜0.000 1).Overall safety and tolerability in the two groups were similar.Adverse events occurred in 57.1％ of patients in the placebo group and 61.1％ of patients in the linagliptin group,and the incidence of adverse events leading to discontinuation was 3.2％ in the placebo group and 3.8％ in the linagliptin group.Serious adverse events occurred in 1.6％ of patients in the placebo group and 2.8％ of patients in the linagliptin group.Investigator-defined hypoglycaemia occurred in 7.3％ of patients in the placebo group and 11.9％ of patients in the linagliptin group.Among them,most were mild or moderate hypoglycaemia,and severe hypoglycaemia only occurred in 0.2％ of patients in the placebo and 0.5％ in the linagliptin groups.Overall incidence of hypoglycaemia in linagliptin group was slightly higher than that in placebo group,which might be due to the fact that more patients were taking sulfonylureas in linagliptin group than in placebo group (26.8％ linagliptin;18.4％ placebo).No difference could be viewed in hypoglycaemia between the two groups in patients without sulfonylureas (1.2％ linagliptin,1.1％ placebo)Moreover,no severe hypoglycaemia was reported in subjects without sulfonylureas.The incidences of other adverse events were similar in both groups.Conclusion Linagliptin was efficacious in lowering glucose with a safety profile similar to placebo in type 2 diabetic patients aged 60 years or older.
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Objective To investigate the clinical effect and safety of linagliptin combined with insulin aspart 50 in the treatment of hepatogenous diabetes (HD).Methods A total of 57 patients with HD who visited The People's Hospital of Liaoning Province from October 2014 to February 2016 were enrolled and randomly divided into insulin aspart 50 group (group A,28 patients) and linagliptin combined with insulin aspart 50 group (group B,29 patients).The two groups were compared in terms of blood glucose,insulin,C-peptide,glucose disposition index (DI),glycosylated hemoglobin A1c (HbA1c),glucagon,and daily insulin dose at baseline and after 12 weeks of treatment.The adverse events including hypoglycemia were observed.The paired t-test was used for comparison of continuous data within one group,and the independent-samples t test was used for comparison of continuous data between groups;the chi-square test was used for comparison of categorical data between groups.Results After 12 weeks of treatment,both groups had significant reductions in blood glucose at four time points (t =5.357-21.380,all P ＜ 0.05) and significant increases in the insulin level at 30,60,and 120 minutes (t =2.222-6.491,all P ＜0.05).Compared with group A,group B had significantly lower levels of HbA1c and glucagon,daily insulin dose,and blood glucose and insulin levels at 30,60,and 120 minutes (t =3.136-15.096,all P ＜ 0.05),as well as significantly higher DI and levels of C-peptide at four time points (t =2.994-10.813,all P ＜ 0.05).Group A had a significantly higher incidence rate of hypoglycemia than group B (28.6％ vs 3.4％,x2 =5.005,P ＜ 0.05).Conclusion Linagliptin combined with insulin aspart 50 can effectively control blood glucose in patients with HD and has good safety.
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In order to find more potential DPP-IV inhibitor, a series of xanthine-scaffold analogs of linagliptin, an approved antidiabetes drug, were designed and synthesized for SAR study. All compounds with a concentration of 50 nmol·L-1 showed the inhibitory activity against DPP-IV enzyme in vitro, and the inhibition rate of compounds 1a, 1d and 1f was over 50%. Virtual docking was also performed to facilitate the SAR analysis of these substituted xanthines.
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BACKGROUND: The use of dipeptidyl peptidase-4 (DPP-4) inhibitors is increasing among renal transplant patients with diabetes. However, the glucose-lowering efficacies of various DPP-4 inhibitors and their effects on blood cyclosporine levels have not been fully investigated. We compared the glucose-lowering efficacies of DPP 4 inhibitors and evaluate their effects on the blood levels of cyclosporine in renal transplant recipients with diabetes. METHODS: Sixty-five renal allograft recipients who received treatment with DPP-4 inhibitors (vildagliptin, sitagliptin, or linagliptin) following kidney transplant were enrolled. The glucose-lowering efficacies of the DPP-4 inhibitors were compared according to the changes in the hemoglobin A1c (HbA1c) levels after 3 months of treatment. Changes in the trough levels of the cyclosporine were also assessed 2 months after treatment with each DPP-4 inhibitor. RESULTS: HbA1c significantly decreased in the linagliptin group in comparison with other DPP-4 inhibitors (vildagliptin –0.38%±1.03%, sitagliptin –0.53%±0.95%, and linagliptin –1.40±1.34; P=0.016). Cyclosporine trough levels were significantly increased in the sitagliptin group compared with vildagliptin group (30.62±81.70 ng/mL vs. –24.22±53.54 ng/mL, P=0.036). Cyclosporine trough levels were minimally changed in patients with linagliptin. CONCLUSION: Linagliptin demonstrates superior glucose-lowering efficacy and minimal effect on cyclosporine trough levels in comparison with other DPP-4 inhibitors in kidney transplant patients with diabetes.
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Humans , Allografts , Cyclosporine , Diabetes Mellitus , Dipeptidyl-Peptidase IV Inhibitors , Hyperglycemia , Kidney , Kidney Transplantation , Pilot Projects , TransplantationABSTRACT
Objective To explore the efficacy and safety of Linagliptin in combination with Metformin in newly diagnosed T2DM patients. Methods A total of 140 newly diagnosed T2DM patients were enrolled in this study. All the patients were admitted in the Endocrinology and Metabolism department of our hospital from January 2013 to October 2013. Random number table method was used in patients’ selection. All the patients were divided into two groups :Linagliptin plus Metformin group (Linagliptin group ,n=70) and Glipizide plus Metformin group (Glipizide group ,n=70) ,and followed up for 12 weeks. Efficacy and safety of treatment were compared between the two groups. Results The difference of FPG ,2 hPG and HbA1 c did not reach the statistical significance between the two groups at baseline treatment (P>0.05). FPG ,2 hPG and HbA1 c were significantly lower after treatment compared with baseline in both groups (P 0.05 ). All these indicators were improved after treatment in both groups (P< 0.05) ,and were significant better in Linagliptin group than in Glipizide group. Adverse events rate were significantly higher in Glipizide group than in Linagliptin group (18.57%vs 5.71% ,χ2 = 5.423 ,P= 0.020 ). Conclusion The efficacy of Linagliptin in combination with Metformin in newly diagnosed T2DM patients was similar with Glipizide plus Metformin. The β cell function improvement was better and APN level was higher after Linagliptin treatment.