Oral Antidiabetic Agents (oral + antidiabetic_agent)

Distribution by Scientific Domains


Selected Abstracts


Oral antidiabetic agents as cardiovascular drugs

DIABETES OBESITY & METABOLISM, Issue 1 2007
D. P. Macfarlane
The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited. [source]


Mutations in GCK and HNF-1, explain the majority of cases with clinical diagnosis of MODY in Spain

CLINICAL ENDOCRINOLOGY, Issue 4 2007
Itziar Estalella
Summary Objective, The aim of this study was to group patients with MODY (maturity-onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their clinical characteristics. Patients and methods, Molecular analysis of GCK (MODY2), HNF-1, (MODY3), HNF-4, (MODY1) and HNF-1, (MODY5) genes was performed by DNA sequencing in 95 unrelated index probands (47M/48F; mean age 9·9 ± 5·2 years) with clinical diagnosis of MODY. After classification into MODY subtypes according to the genetic alterations, clinical characteristics were compared between the groups. Results, Seventy-six families were shown to carry mutations in GCK (34 of them previously unreported), eight families presented HNF-1, mutations, and a large genomic rearrangement in HNF-1, was found in a family. No alteration was found in HNF-4,. Thus, relative frequencies in the group studied were 80% MODY2, 8·5% MODY3 and 1% MODY5. Comparison of clinical parameters according to genetic status showed significant differences between MODY2 and MODY3 patients in age at diagnosis (9·4 ± 5·4 years vs. 12·7 ± 4·6 years), diagnosis (impaired glucose tolerance vs. diabetes), diagnostic test used (OGTT vs. fasting glucose), treatment (diet and exercise vs. insulin/oral antidiabetic agents) and birth weight (2·96 ± 0·44 kg vs. 3·40 ± 0·67 kg). Conclusion, Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF-1,(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias (paediatric vs. adult). In general, patients with MODY2 were diagnosed at an earlier age in life than MODY3 patients and had a milder form of diabetes. Moreover, the majority of patients with MODY2 mutations were treated with diet whereas half of MODY3 patients received pharmacological treatment. [source]


Adding biphasic insulin aspart 30 once or twice daily is more efficacious than optimizing oral antidiabetic treatment in patients with type 2 diabetes

DIABETES OBESITY & METABOLISM, Issue 5 2007
W. M. W. Bebakar
Aim:, To evaluate the efficacy and safety of adding biphasic insulin aspart 30 (BIAsp30; NovoMix® 30) to existing oral antidiabetic agents (OADs) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy. Methods:, This 26-week, multi-centre, open-labelled, randomized, two-arm parallel trial consisted of a 2-week screening period, followed by 24 weeks of treatment. Subjects randomized to BIAsp30 treatment (n = 129) received BIAsp30 once daily (o.d.) at dinnertime between Week 2 and Week 14, and those not reaching treatment targets were switched to twice daily (b.i.d.) BIAsp30 at Week 14 (n = 50). Subjects randomized to the OAD-only arm (n = 63) continued with their previous OAD treatment and, in an attempt to reach treatment goals, the dose was optimized (but OAD unchanged) in accordance to local treatment practice and labelling. Results:, Significantly greater reductions in HbA1c over Weeks 0,13 with BIAsp30 (o.d.) vs. OAD-only treatment (1.16 vs. 0.58%; p < 0.001), and over Weeks 0,26, with BIAsp30 (o.d.) and BIAsp30 (b.i.d.) treatments vs. OAD-only treatment (1.24 vs. 1.34 vs. 0.67%; p < 0.01). Hypoglycaemic episodes were reported in 54% of the patients in BIAsp30 (o.d. and b.i.d. pooled) and 30% of the patients in OAD-only group. All episodes were minor or symptomatic, except for one in each treatment group, which was major. Conclusions:, Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone. In patients not reaching treatment target on BIAsp30 (o.d.), treatment with BIAsp30 (b.i.d.) should be considered. [source]


Reflecting on Type 2 Diabetes Prevention: More Questions than Answers!

DIABETES OBESITY & METABOLISM, Issue 2007
J. Rosenstock
Given the enormous public health and economic burden posed by the global epidemic of type 2 diabetes mellitus (T2DM), intervention in the prediabetes stage of disease to prevent progression to T2DM and its vascular complications seems the most sensible approach. Precisely how best to intervene remains the subject of much debate. Prudent lifestyle changes have been shown to significantly reduce the risk of progression in individuals with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Although lifestyle modifications are notoriously difficult to maintain, there is evidence that intensive intervention results in continued preventive benefit after the stopping of structured counselling. A number of drug therapies, including metformin, acarbose, orlistat and rosiglitazone, have also been proven effective in preventing progression from IFG/IGT, but unresolved issues still remain. Specifically, whether large numbers of individuals with glucose dysregulation who may never progress to T2DM should be exposed to the risk of pharmacological adverse effects is a topic of discussion and debate. Furthermore, there are limited data on the effectiveness of implementing interventions during the prediabetic state to prevent cardiovascular complications that may be hyperglycaemia related. A recent American Diabetes Association (ADA) consensus statement on IFG/IGT recommends lifestyle modification for individuals with IFG or IGT. Of note, the ADA consensus statement introduces the option of adding metformin treatment to lifestyle changes in those individuals who have combined IFG/IGT plus an additional risk factor for progression and who also have some features that increase the likelihood of benefiting from metformin treatment. The dipeptidyl peptidase-4 inhibitors are a new class of oral antidiabetic agents that, in addition to being effective in improving glycaemic control, may exert beneficial effects in preserving ,-cell function. These characteristics, combined with a low risk of hypoglycaemia, weight neutrality and what appears , so far , to be a relatively benign tolerability profile, make these agents intriguing candidates for preventive treatment. [source]


Oral antidiabetic agents as cardiovascular drugs

DIABETES OBESITY & METABOLISM, Issue 1 2007
D. P. Macfarlane
The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited. [source]


Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study

DIABETES OBESITY & METABOLISM, Issue 5 2006
M. Hausmann
Aim:, This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:, Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:, INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (,2.7 vs. ,3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (,1.23 vs. ,1.05%), body weight (,1.9 vs. ,2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (,1.15 ,mol/l; p < 0.001) but not with GLA [,0.52 ,mol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:, In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies. [source]


Different effects of pioglitazone and rosiglitazone on lipid metabolism in mouse cultured liver explants

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2010
Louiza Djaouti
Abstract Background Pioglitazone (PIO) and rosiglitazone (ROSI) are widely used as oral antidiabetic agents for treatment of type 2 diabetes. Although these medications exert similar effects on blood glucose, recent clinical studies indicated that PIO has a more pronounced beneficial effect on lipid parameters than ROSI. In order to get further insight into the lipid effects of both drugs, we tested whether PIO, compared to ROSI, could exert direct effects on lipid liver metabolism in relation with plasma lipids. Methods We performed in vitro studies using mice liver slices incubated 21 h either with ROSI (1 µmol/L) or PIO (7.5 µmol/L). Results We showed that both glitazones slightly reduced HMG-CoA reductase mRNA levels at the same degree but only PIO reduced intracellular cholesterol content, suggesting an alteration of cholesterol uptake rather than an inhibition of cholesterol biosynthesis. This concept was supported by the reduction of scavenger receptor class B type I expression, hepatic lipase activity and high-density lipoprotein cholesterol uptake in PIO-treated liver explants. Conversely, hepatic lipase mRNA levels were increased 3.5-fold. ROSI, but not PIO, induced acetyl-CoA carboxylase and fatty acid synthase gene expression and increased apoB secretion suggesting a stimulation of lipogenesis. Concurrently, peroxisome proliferator-activated receptor-, mRNA levels were induced by ROSI and not significantly changed by PIO. Besides, PIO appeared to be a more potent activator of AMP-Activated Protein Kinase than ROSI. Conclusions PIO and ROSI exert specific direct effects on liver and extrapolating these data to humans could explain the significant improvements in plasma lipids observed in diabetic patients treated with PIO. Copyright © 2010 John Wiley & Sons, Ltd. [source]


Metformin decreases platelet superoxide anion production in diabetic patients

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2002
P. Gargiulo
Abstract Background Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans. Methods We studied 60 patients with type 2 diabetes mellitus, divided into three groups on the basis of hypoglycaemic treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All patients were followed for at least 1 year. The three subgroups had similar clinical characteristics. Twenty healthy subjects, of comparable sex and age, were enrolled as controls. In each subject, platelet production of superoxide anion (O2,) elicited by collagen, was determined by lucigenin assay. Results Patients with diabetes had higher platelet O2, production than controls; no correlation was observed between blood glucose and platelet O2, production. Group A patients had platelet O2, production similar to that of healthy subjects but lower than Group B and Group C patients. Conclusion The present findings suggest an in vivo antioxidant activity of metformin and warrant prospective studies to further explore this hypothesis. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Statin use in Type 2 diabetes mellitus is associated with a delay in starting insulin

DIABETIC MEDICINE, Issue 9 2004
A. Yee
Abstract Aims It has been suggested that HMG Co-A reductase inhibitors (,statins') may reduce the risk of developing Type 2 diabetes mellitus. This study was designed to evaluate whether use of statins would also delay progression to insulin therapy. Methods This was a retrospective cohort study using Saskatchewan Health databases to identify subjects newly started on oral antidiabetic agents from 1991 to 1996. Subjects < 30 years of age or with previous lipid-lowering drug use were excluded. Medications known to influence glycaemic control, co-morbidity, and demographic data were collected. Statin exposure was defined as at least 1 year of use. Primary outcome was starting insulin treatment. Multivariate Cox proportional hazards models were used to examine the association between statin use and starting insulin. Results The final cohort included 10 996 new users of oral antidiabetic agents, of which 484 (4.4%) used statins. Mean age was 64 years and 55% were male. Mean duration of follow-up was 5.1 years; 11.1% (n = 1221) eventually started insulin treatment. Statin users were no less likely than non-users to start insulin treatment eventually (11.6% vs. 11.1%, P = 0.74). After multivariate adjustment, however, statin use was associated with a 10-month delay before newly treated diabetic subjects needed to start insulin treatment (adjusted hazard ratio 0.74; 95% confidence interval 0.56, 0.97, P = 0.028). Conclusion The use of statins is associated with a delay in starting insulin treatment in patients with Type 2 diabetes initially treated with oral antidiabetic agents. Whether this relationship exists for patients at high risk of developing diabetes should be examined in a randomized trial. [source]