Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis

Objective To evaluate the effects of incretin-based therapies on body weight as the primary outcome,as well as on body mass index(BMI)and waist circumference(WC)as secondary outcomes.Methods Databases including Medline,Embase,the Cochrane Library,and clinicaltrials.gov(www.clinicaltrials.gov)were searched for randomized controlled trials(RCTs).Standard pairwise meta-analysis and network meta-analysis(NMA)were both carried out.The risk of bias(ROB)tool recommended by the Cochrane handbook was used to assess the quality of studies.Subgroup analysis,sensitivity analysis,meta-regression,and quality evaluation based on the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)were also performed.Results A total of 292 trials were included in this study.Compared with placebo,dipeptidyl-peptidase IV inhibitors(DPP-4 Is)increased weight slightly by 0.31 kg[95%confidence interval(CI):0.05,0.58]and had negligible effects on BMI and WC.Compared with placebo,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)lowered weight,BMI,and WC by-1.34 kg(95%CI:-1.60,-1.09),-1.10 kg/m2(95%CI:-1.42,-0.78),and-1.28 cm(95%CI:-1.69,-0.86),respectively.Conclusion GLP-1 RAs were more effective than DPP-4 Is in lowering the three indicators.Overall,the effects of GLP-1 RAs on weight,BMI,and WC were favorable.

Comparison between sitagliptin and nateglinide on postprandial lipid levels: The STANDARD study

AIM: To assess the effects of sitagliptin and nateglinide on lipid metabolism. METHODS: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A 1c (HbA 1c ) > 6.5% despite diet and exercise; HbA 1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially. RESULTS: Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m 2 ; the nateglinide group: 21.39 ± 2.24 kg/m 2 ). Fasting levels of HbA 1c , glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P<0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P=0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group. CONCLUSION: Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.

Sitagliptin counteracts seasonal fluctuation of glycemic control

AIM:To assess the effect of sitagliptin therapy on seasonal fluctuation of glycemic control in Japanese type 2 diabetic patients.METHODS:Participating patients(age:29-80 years) had been treated with conventional oral antidiabetic agents and/or diet and exercise therapy for over 6 mo.From December 2009,35 patients were additionally prescribed oral sitagliptin starting from 50 mg once daily,while 19 patients taking-glucosidase inhibitors were switched to sitagliptin.Twenty-four patients who refused sitagliptin formed the control group.Changes of mean monthly hemoglobin A 1c(HbA 1c) during the "winter holiday season" were compared between groups using Student's t-test(2008-2009 vs 2009-2010).Statistical significance was accepted at P < 0.05.Multivariate analysis was performed to assess whether sitagliptin use was associated with deterioration or improvement of glycemic control.RESULTS:Both add-on sitagliptin and switching from-glucosidase inhibitors to sitagliptin prevented the seasonal deterioration of glycemic control and tended to improve HbA 1c.Multivariate analysis revealed that both adding and switching to sitagliptin were negatively correlated with deterioration of glycemic control.In 44 patients who continued sitagliptin therapy for another year,elevation of HbA 1c was suppressed without adverse effects.CONCLUSION:Sitagliptin is a suitable oral agent for preventing deterioration of glycemic control during the winter holiday season.

Vildagliptin vs sulfonylurea in Indian Muslim diabetes patients fasting during Ramadan

AIM:To compare the use of vildagliptin and sulfonylurea with or without metformin in Indian Muslim patients with type 2 diabetes mellitus,fasting during Ramadan.METHODS:This was a 4-wk,multicenter,non-interventional,open-label,observational study.Incidence of hypoglycemic events(HEs),adverse events,and changes in glycosylated hemoglobin A1c(HbA1c),fasting plasma glucose,postprandial plasma glucose and body weight were measured pre-and post-Ramadan.RESULTS:Totally,97 patients were recruited and all completed the study(vildagliptin group,n=55;sulfonylurea group,n=42).HEs were reported in low frequencies in both the vildagliptin and the sulfonylurea groups[0 vs 2(4.8%)patients,respectively].Interestingly,HbA1c reduced by-0.43%(-4.71 mmol/mol)in the vildagliptin group[8.75%(72.10 mmol/mol)to8.32%(67.38 mmol/mol),P=0.009]while in the sulfonylurea group there was a small increase by 0.01%[0.08 mmol/mol;8.64%(70.92 mmol/mol)to 8.65%(71.00 mmol/mol),P=0.958].Higher percentage of vildagliptin-treated patients achieved HbA1c<7.0%(<53 mmol/mol)compared with sulfonylurea(16.4%vs4.8%).Mean decrease in the body weight was 1.2 kg and 0.03 kg,respectively(P<0.001).Both treatment groups were well tolerated during Ramadan.CONCLUSION:Vildagliptin is an attractive treatment option for Indian patients with type 2 diabetes mellitus who are fasting during Ramadan.

Antihyperglycaemic activity of ethylacetate extract of Chlorophytum alismifolium in type 2 diabetes:The involvement of peroxisome proliferator-activated receptor-γand dipeptidyl peptidase-4

Objective:This research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium(EACA)tubers in a type 2 diabetes model.Methods:The tubers were processed and sequentially extracted in hexane followed by ethylacetate,using a Soxhlet apparatus,and subjected to gas chromatography-mass spectrometry(GC–MS).The acute toxicity of EACA was investigated in albino Wistar rats.An antihyperglycaemic study was carried out using high-fat diet(pelletized diet and margarine in the ratio of 10:1 and 20%fructose solution)and streptozotocin-induced hyperglycaemic Wistar rats.The effects of the extract(150,300 and 600 mg/kg)on blood glucose level,insulin,peroxisome proliferator-activated receptor-c(PPAR-c)and dipeptidyl peptidase-4(DPP-4)were evaluated using enzyme-linked immunosorbent assay.Results:The oral median lethal dose in Wistar rats was estimated to be>5000 mg/kg.Treatment with EACA at all doses significantly reduced the fasting blood glucose levels,compared to the hyperglycaemic control,and over time.Administration of EACA increased the serum insulin and PPAR-c levels while decreasing DPP-4 levels.GC–MS analysis revealed the presence of 13 compounds,with isothiazole and isoxazolidine covering total area of 24.6%and 22.69%,respectively.Conclusion:The findings from this study showed that EACA has important compounds with beneficial effect in type 2 diabetes and acts by increasing insulin secretion and PPAR-c level and decreasing DPP-4 activity.