Additive effects of miglitol and anagliptin on insulin-treated type 2 diabetes mellitus: a case study.
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SUBMITTER: Kishimoto M
PROVIDER: S-EPMC4300407 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Recently, we reported that the level of lathosterol, a cholesterol synthesis marker, was suppressed after 1 month of treatment with anagliptin, a dipeptidyl peptidase-4 inhibitor. In this study, we administered either anagliptin or miglitol, an alpha-glucosidase inhibitor, for 3 months in patients with type 2 diabetes and compared the lipid-lowering effects of anagliptin with those of miglitol. Methods:This study was a 12-week, open-label, prospective, randomized, parallel-group comparison trial. Fifty-two patients with type 2 diabetes who aged 20 - 70 years with a low-density lipoprotein cholesterol (LDL-C) level of over 120 mg/dL, and with no history of treatment with antihyperlipidemic drugs were enrolled. Patients were randomly assigned to either the anagliptin group or miglitol group. The 100 mg of anagliptin was administered twice a day for the anagliptin group and 50 mg of miglitol was administered thrice a day for miglitol group. The changes in lipids, cholesterol synthesis, and absorption markers were evaluated after 12 weeks. Results:Fifty-two participants were initially enrolled in the trial, and 47 of them completed the protocol. There was no significant difference in LDL-C, cholesterol synthesis, and the absorption markers between anagliptin and miglitol groups. Conclusions:Anagliptin and miglitol are similarly effective on lipid and glycemic control.
| S-EPMC7011936 | biostudies-literature
Project description:IntroductionBoth dipeptidyl peptidase-4 inhibitors and α-glucosidase inhibitors (α-GI) have been reported to change the incretin and insulin secretion. To examine the effects of acarbose, miglitol, and sitagliptin on glucose metabolism and secretion of gut peptides, we conducted a crossover study in patients with type 2 diabetes mellitus (T2DM).MethodsEleven Japanese patients with T2DM underwent four meal tolerance tests with single administration of acarbose, miglitol, sitagliptin, or nothing. Fasting and postprandial plasma levels of glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ghrelin, and des-acyl ghrelin were measured.ResultsEarly-phase insulin secretion was reduced following acarbose and miglitol, and the areas under the curve (AUC) of insulin at 180 min following acarbose and miglitol were significantly lower than sitagliptin. AUC of plasma glucose at 180 min after acarbose, miglitol, and sitagliptin tended to be lower than in controls, and plasma glucose levels at 30-60 min following miglitol were significantly lower than in controls. Plasma glucagon, ghrelin, and des-acyl ghrelin levels did not differ among the four conditions. Postprandial plasma active GLP-1 levels and AUC of GLP-1 increased significantly in both the sitagliptin and miglitol groups compared to control. Postprandial plasma total GIP levels increased following sitagliptin but decreased after acarbose and miglitol. Changes in incretin levels tended to be greater with miglitol than acarbose.ConclusionThese results showed that sitagliptin and α-GIs, miglitol more so than acarbose, improved hyperglycemia in patients with T2DM after single administration, and had different effects on insulin and incretin secretion.Trial registrationUMIN-CTR number, UMIN000009981.
| S-EPMC4478179 | biostudies-literature
Project description:BackgroundLipohypertrophy (LH) of subcutaneous tissue is an insulin-induced complication occurring in patients with diabetes. We aimed to define the prevalence of LH and identify its risk factors in type 1 diabetes (T1DM) patients treated with continuous subcutaneous insulin infusion (CSII).Materials and methodsThe study included 79 consecutive CSII-treated T1DM patients. The diagnose of LH was based on ultrasonography (US) as a reference method, physical examination was also performed. Clinical characteristics were available from the medical records.ResultsThe median age of patients was 28 years (interquartile range [IQR], 24-30.5) with a body mass index (BMI) of 24.5 ± 3.5 kg/m2, HbA1c 7.1% (IQR, 6.7-8.1), T1DM duration 15 (9-20) years, and CSII use duration of 8 year (IQR, 5-11). LH was detected by US in 75 (94.9%) patients. This value was much higher than this obtained by visual assessment (n = 39, 49.4%) or palpation (n = 59, 74.7%). In univariate analyses, the following risk factors for occurrence of 5 and more LH lesions were identified: the ratio of insulin dose to body mass exceeding 0.7 IU/kg (OR, 3.69; 95% CI, 1.43-10.01) and the total daily insulin dose (OR, 1.05; 95% CI, 1.02-1.09). A higher dose of insulin per kg remained a significant risk factor of LH amount in multivariate analysis.ConclusionThis selected T1DM cohort treated with CSII had a very high prevalence of LH. US assessment should be considered as a reference method for LH screening in T1DM patients. The identified risk factors for the number of LH lesions were related to insulin dosing.
| S-EPMC8803446 | biostudies-literature
Project description:The effects of antidiabetic agents on lipoprotein subclasses are assumed to be pivotal, but this assumption has not been studied. We evaluated lipoprotein subclasses in patients, randomly selected from REASON (Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes) Trial participants, with type-2 diabetes treated with either anagliptin or sitagliptin. We measured total cholesterol (TC) and triglycerides (TG) in 4 (chylomicron (CM), very low-density lipoprotein (VLDL), low density lipoprotein (LDL), and high-density lipoprotein (HDL)) lipoprotein classes and 20 (2 CM, 5 VLDL, 6 LDL, and 7 HDL) lipoprotein subclasses. Between 0 and 52 weeks, TC and TG in lipoprotein and the lipoprotein subclass were distributed differently in patients treated with anagliptin and sitagliptin. The preferable changes in TC and TG levels were observed dominantly in the anagliptin-treated group under standard statin therapy, but the benefits were observed in both the anagliptin- and sitagliptin-treated groups, at least partially under strong statin therapy. In future studies, the atherogenic properties of lipoprotein subclasses might be considered when employing antidiabetic dipeptidyl peptidase-4 (DPP-4) inhibitors, especially in patients with type-2 diabetes who are at risk of atherosclerotic cardiovascular disease (ASCVD) or are undergoing statin treatment.
| S-EPMC7019317 | biostudies-literature
Project description:Microorganisms within the gastrointestinal tract significantly influence metabolic processes within their mammalian host, and recently several groups have sought to characterise the gastrointestinal microbiota of individuals affected by metabolic disease. Differences in the composition of the gastrointestinal microbiota have been reported in mouse models of type 2 diabetes mellitus, as well as in human patients. Diabetes mellitus in cats has many similarities to type 2 diabetes in humans. No studies of the gastrointestinal microbiota of diabetic cats have been previously published. The objectives of this study were to compare the composition of the faecal microbiota of diabetic and non-diabetic cats, and secondarily to determine if host signalment and dietary factors influence the composition of the faecal microbiota in cats. Faecal samples were collected from insulin-treated diabetic and non-diabetic cats, and Illumina sequencing of the 16S rRNA gene and quantitative PCR were performed on each sample. ANOSIM based on the unweighted UniFrac distance metric identified no difference in the composition of the faecal microbiota between diabetic and non-diabetic cats, and no significant differences in the proportions of dominant bacteria by phylum, class, order, family or genus as determined by 16S rRNA gene sequencing were identified between diabetic and non-diabetic cats. qPCR identified a decrease in Faecalibacterium spp. in cats aged over ten years. Cat breed or gender, dietary carbohydrate, protein or fat content, and dietary formulation (wet versus dry food) did not affect the composition of the faecal microbiota. In conclusion, the composition of the faecal microbiota was not altered by the presence of diabetes mellitus in cats. Additional studies that compare the functional products of the microbiota in diabetic and non-diabetic cats are warranted to further investigate the potential impact of the gastrointestinal microbiota on metabolic diseases such as diabetes mellitus in cats.
| S-EPMC4184829 | biostudies-literature
Project description:BackgroundChronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.ObjectivesTo assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.Search strategyWe searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.Selection criteriaAll randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.Data collection and analysisTwo authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.Main resultsThis review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.Authors' conclusionsOur analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.
| S-EPMC6486036 | biostudies-literature
Project description:AimIntermittent fasting, a dietary intervention of alternate eating and fasting, has gained popularity in people trying to lose weight. Intermittent fasting could provide an alternative to classic caloric restriction in people with type 2 diabetes mellitus. The aim of the study is to determine the impact of a 12-week intermittent fasting regimen compared with usual care in people with type 2 diabetes mellitus receiving insulin therapy.MethodsThis open, single-centre, randomized controlled trial investigates participants with type 2 diabetes mellitus on insulin therapy and a glycated haemoglobin A1c (HbA1c) of ≥53 mmol/mol (≥7.0%) and a minimum insulin dose of 0.3 IU/kg body weight per day. Participants are randomized in a 1:1 ratio to either 12 weeks of intermittent fasting or the standard care group. All participants receive dietary counselling, continuous glucose monitoring, measurement of the resting metabolic rate, an oral glucose tolerance test, body composition measurement via dual-energy X-ray absorptiometry and stool samples for microbiome analyses at the beginning and at the end of the intervention. Two co-primary outcomes (analysed in hierarchical order) were chosen for the study: (i) the difference in the change of HbA1c from baseline to 12 weeks and (ii) the difference in the number of participants achieving a combined end point encompassing a body weight reduction of at least 2%, an insulin dose reduction of at least 10% and an absolute HbA1c reduction of at least 3 mmol/mol (0.3%) between the two groups.
| S-EPMC9304224 | biostudies-literature
Project description:AimProprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial.MethodsPCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin (n=122) or sitagliptin (n=128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization.ResultsBaseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P=0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P=0.07).ConclusionsPCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor.
| S-EPMC8737073 | biostudies-literature
Project description:AimsTo assess associations between hypoglycaemia and risk of accidents resulting in hospital visits among people with type 2 diabetes receiving antidiabetes drugs without insulin.MethodsPeople with type 2 diabetes who were not treated with insulin were identified from a US-based employer claims database (1998-2010). Following initiation of an antidiabetes drug, the occurrence of accidents resulting in hospital visits was compared between people with, and without, claims for hypoglycaemia using multivariable Cox proportional hazard models adjusted for demographics, comorbidities, prior treatments and prior medical service use. Additional analyses were stratified by age 65?years or older.ResultsA total of N?=?5582 people with claims for hypoglycaemia and N?=?27,910 with no such claims were included. Accidents resulting in hospital visits occurred in 5.5 and 2.8% of people with, and without, hypoglycaemia, respectively. After adjusting for baseline characteristics, hypoglycaemia was associated with significantly increased hazards for any accident [hazard ratio (HR) 1.39, 95% CI 1.21-1.59, p?<?0.001], accidental falls (HR 1.36, 95% CI 1.13-1.65, p?<?0.001) and motor vehicle accidents (HR 1.82, 95% CI 1.18-2.80, p?=?0.007). In age-stratified analyses, hypoglycaemia was associated with greater hazards of driving-related accidents in people younger than age 65 and falls in people aged 65 or older.ConclusionsIn people with type 2 diabetes receiving antidiabetes drugs without insulin, hypoglycaemia was associated with a significantly higher risk of accidents resulting in hospital visits, including accidents related to driving and falls.
| S-EPMC3593162 | biostudies-literature
Project description:AimTo explore the chronic effects of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).MethodsThis is a secondary analysis of a real-world study evaluating the efficacy and safety of premixed insulin treatment in patients with T2DM via 3-month intermittent flash glucose monitoring. Male patients aged 18-60 who were using metformin during the 3-month study period were included as the metformin group. The control group included males without metformin therapy by propensity score matching analysis with age as a covariate. Testosterone levels were measured at baseline and after 3-month treatment.ResultsAfter 3-month treatment, the control group had higher levels of total testosterone, free and bioavailable testosterone than those at baseline (P<0.05). Compared with the control group, the change of total (-0.82 ± 0.59 vs. 0.99 ± 0.59 nmol/L) and bioavailable (-0.13 ± 0.16 vs. 0.36 ± 0.16 nmol/L) testosterone levels in the metformin group significantly decreased (P=0.036 and 0.029, respectively). In Glycated Albumin (GA) improved subgroup, the TT, FT, and Bio-T levels in the control subgroup were higher than their baseline levels (P < 0.05). Compared with the metformin subgroup, TT level in the control subgroup also increased significantly (P=0.044). In GA unimproved subgroup, the change of TT level in the metformin subgroup was significantly lower than that in the control subgroup (P=0.040).ConclusionIn men with T2DM, 3-month metformin therapy can reduce testosterone levels, and counteract the testosterone elevation that accompanied with the improvement of blood glucose.Clinical trial registrationhttps://www.clinicaltrials.gov/ct2/show/NCT04847219?term=04847219&draw=2&rank=1.
| S-EPMC8740051 | biostudies-literature