Effects Of Oral Antidiabetic Drugs Research Articles

Association between side effects of oral anti-diabetic drugs and self-reported mental health and quality of life among patients with type 2 diabetes

To examine the association between the side effects of oral anti-diabetic drugs (OAD) and self-reported mental health and quality of life among patients with type 2 diabetes mellitus (T2DM). An observational, cross-sectional multicenter study with a retrospective medical chart review was conducted at 16 medical centers from around China. The T2DM patients were followed-up and treated with OAD alone prior to the index visit from January to September 2007. All subjects were ≥30 years old at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Health-related quality of life was measured by the EuroQol-5D (EQ-5D) and Hypoglycemia Fear Survey (HFS)-II. The symptoms of hypoglycemia were reported by 41.8% (n=203) of participants, and 19.2% (n=93) experienced weight gain. For those reporting hypoglycemia, the scores were higher for HFS-II [7.00 (2.00-19.00) vs 0.00 (0.00-7.00), P<0.01] and lower for EQ-5D (0.90±0.12 vs 0.93±0.13, P=0.003) than those without hypoglycemic symptoms. According to the multivariate linear regression analysis, the symptoms of hypoglycemia were positively correlated with HFS-II (β=5.78, P<0.01) and negatively with EQ-5D (β=-0.04, P<0.05) after adjusting for patient and disease characteristics. There is a high possibility of hypoglycemic risks among T2DM patients on OAD therapy. The self-reported hypoglycemia is associated with health-related quality of life and hypoglycemic fear. They may have an impact on the long-term prognosis.

Therapy with oral antidiabetic drugs: applied pharmacogenetics

Pharmacogenetics focuses on the relationship between individual gene variants and variable drug effects. The present brief review addresses the importance of pharmacogenetic factors for the efficacy and adverse effects of oral antidiabetic drugs in the therapy of type 2 diabetes mellitus. In particular, genetic polymorphisms of cytochrome P450 drug metabolizing enzymes, peroxisome proliferator-activated receptor- γ gene, TCF7L2 gene regulating insulin resistance and secretion and organic cation transporters or organic anion transporting polypeptides modify the individual response to drugs such as metformin, thiazolidinediones, sulphonylureas, meglitinides, and DPP4 inhibitors. However, apart from a complex variety of individual factors, genetic heterogeneity makes assessing the role of genetic factors in diabetes therapy for a single individual highly challenging. Continuing advances in pharmacogenetics will uncover further genetic variants that modify responses to diabetes medications and may offer targeted pharmacotherapy to the patient.

The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort.

Effects of oral antidiabetic drugs (OADs) on lipids may influence cardiovascular outcomes. Our aim was to compare time to initiation of lipid lowering medication (LLM) and 12-month lipid profiles among new OAD users. We identified a retrospective cohort of 17,774 veterans who received care at Veterans Administration (VA) Mid-South Network with a first OAD from 1 January 2000 to 31 December 2007. There were 6917 patients (38.9%) not on a LLM at baseline, and 3871 (56%) had complete covariates. Incident users of sulfonylurea and combination metformin + sulfonylurea were compared to metformin users for time to LLM initiation. Incident users of these OADs and thiazolidendiones were included in comparison of 12-month low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and total cholesterol. All analyses adjusted for demographics, lipids, HbA1C, healthcare utilization, and cardiovascular disease at baseline. The median time to starting LLM was 2.35 years (interquartile range 0.96, 4.6) following metformin initiation and not statistically different for users of sulfonylureas, or combination OADs. Compared to metformin users, 12-month HDL was 1.35 mg/dl (95%CI: -2.01, -0.72) lower and TGs were 5.7% higher (95%CI: 1.5%, 10.0%) for sulfonylurea users; TGs were 24.8% (95%CI: 0.7%, 54.5%) higher for thiazolidinedione users. Statin users had LDL and total cholesterol 16.7 mg/dl (95%CI: -19.9, -13.5) and 18.6 mg/dl (95%CI: -22.1, -15.1) lower than non-statin users, respectively. Time to LLM initiation was similar between OADs. Metformin use resulted in more favorable lipids at 12 months compared to sulfonylureas or thiazolidinediones.

Initial short‐term intensive insulin therapy as a strategy for evaluating the preservation of beta‐cell function with oral antidiabetic medications: a pilot study with sitagliptin

Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0-2 OADs were switched to 4-8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUC(Cpep) to AUC(gluc) over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUC(Cpep/gluc) /HOMA-IR)] on 4-h meal tests. During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUC(Cpep/gluc) /HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function.

Nutzen und Risiken oraler Antidiabetika hinsichtlich kardialer Endpunkte

The reduction of cardiovascular risk in patients with type 2 diabetes poses a major challenge in internal medicine these days. The present review will focus on the role of glucose lowering therapies in this context and in particular elucidate the effect of oral anti-diabetic drugs on cardiovascular morbidity and mortality.

Focussed Section “Effect of Oral Antidiabetic Drugs on Micro- and Macrovascular Complications in Patients with Diabetes Mellitus – Update 2008”

Patients with diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. In addition, these patients have an increased risk to develop both microand macrovascular complications. Recent data suggest that this increase in cardiovascular risk is due to a clustering of risk factors in these patients like hypertension, dyslipidemia, increased platelet aggregation, endothelial dysfunction and inflammation [1]. Each of these factors is independently associated with an increased risk for cardiovascular events. Over the last years many clinical trials have focused on the reduction of cardiovascular risk in these diabetic patients. As such, studies have shown that reducing low-density lipoprotein cholesterol by a statin therapy has a major impact on the incidence of myocardial infarction and stroke [2]. In addition, lowering blood pressure is also a major tool to decrease cardiovascular morbidity and mortality in this high risk population [3]. In this context, it has been shown that some antihypertensive drugs may be more favourable in this particular population than others but overall, tight blood pressure control is one of the cornerstones to modify cardiovascular risk in patients with diabetes [4]. In addition, good evidence exists that the initiation of anti-platelet therapy decreases cardiovascular events [5]. But what about blood glucose control? Data from the United Kingdom Prospective Diabetes Study suggest that a reduction of HbA1C levels by 1% decreases the risk for both myocardial infarction and stroke by about 12–14% [6]. However, the effect of intensive glucose control on the incidence of myocardial infarction was barely significant while the effect on microvascular complications was much more pronounced [7]. The results of this landmark trial in diabetology has led to the conclusion that blood glucose lowering is also crucial to reduce cardiovascular risk in diabetic patients. Still, in contrast to many large hypertension and lipid trials, the number of clinical studies investigating the effect of anti-diabetic drugs on the incidence of macrovascular events is pretty scarce. Only a few trials directly assessed the effect of certain anti-diabetic drugs on cardiovascular morbidity and mortality and we are still lacking strong evidence that lowering HbA1C will significantly decrease cardiovascular events in diabetic patients. Given the clinical importance of this question we decided to dedicate the current issue of Current Drug Targets to the effects of different oral antidiabetic drugs and insulin on microand macrovascular complications in patients with diabetes. Five review articles address the clinical evidence of a treatment with sulfonylurea, metformin, glitazones, acarbose, or insulin and summarize the current knowledge on this topic. Overall, future studies are warranted to determine the clinical benefit of HbA1C lowering in particular with respect to macrovascular endpoints; within the next few years data from on-going trials will increase our knowledge concerning this question. Hopefully, these studies will close the gap and clarify whether glucose lowering—in addition to lipid lowering, blood pressure lowering and anti-platelet therapy—is the fourth “tool” to modify cardiovascular risk in diabetic patients. Cardiovasc Drugs Ther (2008) 22:205–206 DOI 10.1007/s10557-008-6102-2

Effect of oral antidiabetic drugs on blood-sugar and inorganic phosphate curves in oral and intravenous glucosetolerance tests.

Effect of oral antidiabetic drugs on blood-sugar and inorganic phosphate curves in oral and intravenous glucosetolerance tests.