Use of continuous subcutaneous insulin infusion pump in patients with type 2 diabetes mellitus

PURPOSE: In patients with type 2 diabetes, the control of hyperglycemia is often difficult despite full doses of oral hypoglycemic agents and extremely large doses of insulin. These patients pose a major management problem. The authors therefore investigated whether insulin given as a subcutaneous continuous infusion of insulin (CSII) would result in an improvement in glucose homeostasis. METHODS: Four patients with badly controlled type 2 diabetes, on treatment with extremely high doses of insulin and oral hypoglycemic agents, were started on CSII. RESULTS: All four patients had a marked improvement in plasma glucose concentrations with a corresponding fall in HbA1c levels. This improvement was associated with a marked fall in the insulin doses necessary to maintain adequate glucose homeostasis. CONCLUSIONS: Since HbA1c levels fell from levels that would be associated with diabetic complications to those at which complications are markedly reduced, we recommend that patients with type 2 diabetes uncontrolled on extremely high doses of insulin be given a trial of treatment with CSII.     

Turning Glucosuria into a Therapy: Efficacy and Safety with SGLT2 Inhibitors

Hyperglycemia is important in the development of microvascular and macrovascular complications from type 2 diabetes. Although there are many oral therapies available to help ameliorate hyperglycemia, it has been found that the competitive inhibition of the sodium-D-glucose cotransporter-2 (SGLT2) in the kidney may be a promising alternative treatment reducing hyperglycemia and potentially helping to lower the risk of diabetes complications. This article reviews clinical trials that have revealed favorable responses to many glycemic and metabolic parameters with SGLT2 inhibition, both as monotherapy and as an adjunct to insulin and oral antidiabetic agents. Additional studies are necessary to further determine the efficacy and long-term safety of SGLT2 inhibitors.     

Fasting hyperglycemia: etiology, diagnosis, and treatment

Suboptimal glycemic control in individuals with type 1 and type 2 diabetes mellitus is associated with an increased risk of microvascular and macrovascular complications. Even brief periods of hyperglycemia increase the risk of complications. Fasting hyperglycemia is a phenomenon that has been observed in essentially all individuals with diabetes and may be due to dysregulation of the normal circadian hormonal patterns resulting in increased hepatic glucose output. Controlling hepatic glucose output and disposal is essential for effectively managing fasting hyperglycemia. Fasting hyperglycemia generally can be attributed to inadequate or inappropriate hepatic insulinization or the dawn phenomenon (fasting hyperglycemia occurring in the absence of antecedent hypoglycemia). Less commonly, the Somogyi effect (marked fasting hyperglycemia following antecedent hypoglycemia) can cause fasting hyperglycemia. Accurate diagnosis with overnight home blood glucose monitoring is important in developing an appropriate treatment strategy. Manipulation of the individual's diet or oral agent therapy may be all that is required in some individuals to reduce fasting hyperglycemia. Hepatic glucose output and disposal in the fasting state may be controlled via bedtime administration of either an intermediate-acting insulin such as NPH or a long-acting true basal insulin such as insulin glargine. Attention to fasting hyperglycemia coupled with appropriate individualization of treatment should improve the long-term outcome of individuals with type 1 and type 2 diabetes by reducing the risk of complications. Normalization of the fasting blood glucose, through whatever strategy, minimizes glucotoxicity and insulin resistance, profoundly influences daytime glycemic control, and profoundly reduces the risk of the complications of diabetes.     

102例酮症倾向2型糖尿病患者的临床特征分析

目的探讨酮症倾向2型糖尿病的临床特征及治疗方法。方法102例酮症倾向2型糖尿病在胰岛素降糖治疗1个月后,停用胰岛素给予口服降糖药单用或联合治疗,接受至少1年的随访。根据最终的治疗方案,分为口服降糖药（OHA）组和胰岛素治疗（INS）组。结果（1）经过1年的随访,77．5％的患者通过口服药物可将血糖得到较满意的控制,22．5％的患者因严重高血糖或酮症需要再次接受胰岛素治疗。（2）酮症倾向的2型糖尿病具有普通2型糖尿病许多类似的临床特点和病理生理特征。（3）与INS组相比,OHA组起病时的血糖、HbA1c、胰岛素强化治疗达标时间、男性构成比较低,而BMI、甘油三酯、糖尿病家族史构成比较高（P〈0．05）。（4）在高血糖得到控制后,OHA组胰岛素分泌指数（MBCI）和MBCI的变化值均大于INS组（P〈0．05）。（5）多元回归分析发现,高血糖控制后的MBCI、：BMI为选择不同治疗方案（口服药治疗或胰岛素治疗）的主要参考因素。结论酮症倾向2型糖尿病可能是2型糖尿病的一个亚型。在短期胰岛素治疗后,大多数可以改用口服降糖药,高血糖控制后的MBCI、：BMI将有助于不同降糖方案的选择。     

Cardiovascular prevention in type 2 diabetes mellitus patients: the role of oral glucose-lowering agents

Diabetes mellitus (DM) is a metabolic disorder that requires medical diagnosis and treatment. Type 2 DM is due to a combination of defective secretion of and responsiveness to insulin. In early stages, the predominant abnormality is reduced insulin sensitivity, and hyperglycemia can be reversed by a variety of measures and medications. In this stage, the cornerstone of glucose-lowering therapy is lifestyle modification, but when counseling does not adequately achieve the recommended glycemic targets, at least five classes of oral drugs are available. In general, alpha-glucosidase inhibitors delay carbohydrate absorption, metiglinides and sulfonylureas increase insulin supply, and biguanides and thiazolidinediones enhance insulin action. Given the high cardiovascular morbidity and mortality in type 2 DM patients, the attempt to reduce cardiovascular complications, beyond the glucose lowering itself, is an extremely relevant task. Indeed, the role of oral glucose-lowering agents concerning hyperglycemia reduction is defined; however, they have not clearly demonstrated to reduce micro- and macrovascular disease, and hitherto, no firm evidence favors one pharmacological treatment over another. The aim of this update is to describe the existing experiences with oral glucose-lowering agents for type 2 DM treatment with respect to cardiovascular prevention.     

Statin therapy for the treatment of diabetic dyslipidemia

The increasing prevalence of type 2 diabetes is a major problem for healthcare providers globally, since it is associated with serious microvascular and macrovascular complications. Although microvascular complications can be largely reduced with strict glycemic control, prevention of macrovascular disease involves a multifaceted approach that addresses all major risk factors, including dyslipidemia, hypertension, and insulin insensitivity. In particular, the treatment of diabetic dyslipidemia is a major challenge for diabetologists and cardiologists, as it is characterized by an array of lipid abnormalities. The management of diabetic dyslipidemia should initially include lifestyle approaches such as improved nutrition and weight reduction; however, the majority of patients require the addition of pharmacotherapy. Whilst insulin and/or oral hypoglycemic drugs are generally prescribed for the treatment of hyperglycemia, the addition of lipid-lowering drugs may be necessary for the control of diabetic dyslipidemia. The American Diabetes Association guidelines recommend lowering of low-density lipoprotein cholesterol (LDL-C) as a first priority. Hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) are recommended for first-line therapy in diabetic patients, since these agents are effective at reducing LDL-C levels. Whilst statins provide effective control of dyslipidemia in the majority of patients, more efficacious treatment regimens would provide greater benefit to more patients. Combination therapies may provide one solution to obtaining maximal lipid profile modifications, although the introduction of new, more efficacious agents for use as monotherapy may provide a more acceptable option, as drug combinations are often associated with poor tolerability and patient compliance.     

Pathogenesis of type 2 diabetes mellitus

"Common" type 2 diabetes mellitus is a multifactorial disease. Hyperglycemia is related to a decrease in glucose peripheral uptake, and to an increase in hepatic glucose production, due to reduced insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including loss of basal pulsatility, lack of early phase of insulin secretion after intravenous glucose administration, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. These genetically determined abnormalities appear early in the course of the disease. Insulin resistance affects muscle, liver, and adipose tissue. For the same plasma insulin levels, peripheral glucose uptake and hepatic glucose production suppressibility are lower in diabetic patients than in controls. It results from aging of the population and from "western" lifestyle, with progressive increase in mean body weight, due to excess in energy intake, decreased energy expenses and low physical activity level. NEW ASPECTS: The role of beta-cell dysfunction, as well as the interplay between insulin secretory defect and insulin resistance are now better understood. In subjects with normal beta-cell function, increase in insulin needs secondary to insulin resistance is compensated by an increase in insulin secretion adjusted to maintain plasma glucose levels to normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate for increased needs is responsible for a progressive elevation in plasma glucose levels, then for overt type 2 diabetes. This adaptative phenomenon is called beta-cell compensation of insulin resistance. The lack of compensation is responsible for type 2 diabetes. When permanent hyperglycemia is present, progressive insulin secretory failure with time ensues, due to glucotoxicity and to lipotoxicity. PERSPECTIVES: Simple changes in lifestyle, such regular moderate physical activity, and control of body weight, should permit to avoid the explosion in prevalence of type 2 diabetes. This has been evidenced by the results of prospective studies aiming at preventing conversion from impaired glucose tolerance to diabetes. In patients with permanent hyperglycemia not controlled by lifestyle changes, metabolic defects are the targets of specific therapy intervention with antidiabetic oral agents, such as insulin secretagogues, insulin sensitizers, and inhibitors of hepatic glucose production.     

Where thiazolidinediones will fit

Individuals with type 2 diabetes have two defects: insulin resistance, which occurs in the first stages of disease progression, and pancreatic beta-cell failure, which occurs later in the disease. Insulin resistance is the major pathological defect. During the course of the disease, insulin levels are initially elevated to compensate for the increased insulin resistance and then decline as the disease progresses and beta-cells become less responsive. It is necessary to change antidiabetic therapies to address this progression. Current management of type 2 diabetes follows a stepwise treatment program of diet and exercise, monotherapy with oral antidiabetic agents, combination oral therapy and, ultimately, combination therapy with insulin to control blood glucose levels. While control of blood glucose will reduce the risk of microvascular complications, such as microalbuminuria and retinopathy, the incidence of macrovascular complications is not significantly reduced. The introduction of the thiazolidinediones (TZDs) or 'glitazones', a class of agents that offer effective glycemic control and work through the reduction of insulin resistance, offers a new strategy in the management of this condition. These agents have beneficial effects on the pancreatic beta-cell and, in addition, may have potential benefits on the macrovascular complications that commonly occur in these patients.     

Pharmacologic therapy for type 2 diabetes mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.     

Effects of macronutrient excess and composition on oxidative stress: Relevance to diabetes and cardiovascular disease

Type 2 diabetes is a disease that is increasing in prevalence worldwide. In genetically predisposed patients, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When β-cells are not able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance occurs, which is characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These three conditions (ie, insulin resistance, impaired glucose tolerance, and overt diabetes) are associated with an increased risk of cardiovascular disease. Intervention trials have demonstrated that diabetes can be prevented by means of lifestyle modifications, antidiabetic drugs directed against insulin resistance or simply postprandial hyperglycemia, and cardiovascular drugs devoid of effects on blood glucose levels. All of these have intracellular antioxidant effects. Evidence on the efficacy of antioxidant interventions is accumulating, and oxidative stress may be a therapeutic target to prevent diabetes as well as cardiovascular complications.     

Exploring the pharmacotherapeutic options for treating type 2 diabetes

There has been a dramatic increase in the prevalence of the most common form of diabetes, with approximately 14.6 million diagnosed and 6.2 million undiagnosed cases of type 2 (non-insulin-dependent) diabetes in the United States since 2005. If diabetes is not diagnosed early and managed properly, patients are at greater risk for microvascular and macrovascular complications, such as nerve damage, heart disease, blindness, and kidney damage. The pathogenesis of type 2 diabetes includes impaired insulin secretion, increased hepatic and muscle/fat insulin resistance, and increased glucagon secretion. Problems commonly associated with type 2 diabetes and consequent hyperglycemia are weight gain, hypertension, and dyslipidemia. The natural progression of type 2 diabetes involves increased insulin deficiency as a result of decreased beta cell function over time, which can raise glycosylated hemoglobin to dangerous levels and consequently increase the risk of death. Lifestyle modifications (eg, diet changes and increased physical activity) remain the cornerstone of early treatment, but glycemic control may worsen despite behavior changes and treatment with oral hypoglycemic agents. Historically, upon failure to maintain glucose levels with exercise and oral medication, insulin was the second-line treatment option. Current treatment algorithms include a new class of agents, incretin mimetics, such as the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide. Exenatide mimics the actions of the hormone GLP-1 that occurs naturally in the gastrointestinal tract and has emerged as an efficacious therapy adjunct to 1 or more oral hypoglycemic agent(s).     

The role of glimepiride in the effective management of Type 2 diabetes

Type 2 diabetes mellitus, a disorder of impaired insulin secretion and insulin resistance, has reached epidemic proportions. The effective management of Type 2 diabetes is of vital concern to clinicians. The identification of high-risk individuals and lifestyle management can help control diabetes; however, most patients require pharmacologic intervention. The goals of pharmacologic therapy are to achieve adequate glycemic control while avoiding hypoglycemia and weight gain and to minimize the risk of future micro- and macrovascular complications. There are a number of available glucose-lowering agents from which to choose. This review focuses on the sulfonylureas, the first oral agents introduced for the management of Type 2 diabetes, which are effective, well-tolerated, and well-established drugs, Second-generation sulfonylureas are now widely used in the management of Type 2 diabetes. The most recent addition, glimepiride, can be used in combination with metformin, the thiazolidinediones, -glucosidase inhibitors, and insulin. The unique properties of glimepiride may provide advantages over other currently available insulin secretagogues.     

Progression from IGT to type 2 diabetes mellitus: the central role of impaired early insulin secretion

Impaired glucose tolerance (IGT) is characterized by plasma glucose responses to an oral glucose challenge that are above normal but not at the level defining diabetes. IGT is a common condition that greatly increases risk for the subsequent development of type 2 diabetes. Individuals with IGT manifest abnormalities in both insulin action and early insulin secretion similar to those seen in patients with type 2 diabetes. These abnormalities not only precede diabetes, they predict it as well. Furthermore, the progression from IGT to diabetes is characterized by a dramatic decline in early insulin secretion. It is now evident that early insulin secretion plays an important role in the rapid and efficient suppression of endogenous glucose production following a meal. Loss of early insulin secretion initially leads to post-prandial hyperglycemia which, as the disease progresses, worsens to clinical hyperglycemia. Obesity and a high fat diet may contribute to the development of both insulin resistance and insulin secretory dysfunction in susceptible individuals. Strategies that improve insulin resistance and enhance early insulin secretion may prevent the progression from IGT to diabetes. Already, there is substantial evidence the weight loss and exercise may reduce the risk of developing diabetes by up to 58%. Other trials using pharmacologic agents to decrease insulin resistance and increase early insulin secretion are underway. Prevention remains the best hope for a long-term solution to the worldwide epidemic of diabetes.     

Development of oral insulin: progress and current status

NOBEX oral drug delivery technology is centered on modification of peptides, proteins and small organic molecules by attachment of one or more amphiphilic oligomers. Attachment of these oligomers results in stability to enzymatic degradation, improved solubility to allow optimized formulation, and modification of pharmacology to prolong circulating half-life and activity. NOBEX has applied this technology to insulin, creating an orally absorbed, bioactive conjugate which is safe and rapidly absorbed and which demonstrates dose-dependent, glucose-lowering effects in animal models, healthy volunteers and type 1 diabetic patients. Results of recently completed and ongoing studies in both type 1 and type 2 diabetes suggest a promising role for conjugated insulin in the management of fasting and post-prandial hyperglycemia. Orally administered conjugated insulin is delivered first to the liver through the portal circulation, similar to the physiological route of insulin secretion in non-diabetic individuals. Potential benefits from this route of insulin delivery include improved disease management and reduction of long-term complications of diabetes. Further studies with oral conjugated insulin are planned in both type 1 and type 2 diabetic patients.     

Atherogenicity of postprandial hyperglycemia and lipotoxicity

Type 2 diabetes is characterized by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose regulation. However, physicians continue to rely on fasting plasma glucose and glycated hemoglobin to guide management. There is a linear relationship between the risk of cardiovascular death and the 2-h oral glucose tolerance test, while a study confirms postprandial hyperglycemia as independent risk factor for cardiovascular disease in type 2 diabetes. At the same time, several studies show that postprandial hypertriglyceridemia may also be a cardiovascular risk factor. Interestingly, the simultaneous presence of postprandial hyperglycemia and postprandial hypertriglyceridemia has an additive effect in worsening endothelial function and inflammation. Evidence supports the hypothesis glucose postprandial hyperglycemia and hypertriglyceridemia may favor the appearance of the cardiovascular disease through the generation of an oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycemia is a common phenomenon even in patients who may be considered in “good metabolic control”. Therefore, physicians should consider monitoring and targeting postprandial plasma glucose, as well as glycated hemoglobin and fasting plasma glucose, in patients with type 2 diabetes.     

Cystic fibrosis-related diabetes: a frequent co-morbidity

Cystic fibrosis-related diabetes (CFRD) is a major co-morbidity generally affecting patients over 15 years old and it is associated with increased morbidity and mortality. The pathophysiology includes exocrine tissue destruction, insulin deficiency and insulin resistance; the carbohydrate metabolism dysfunction begins with an altered kinetic in insulin secretion followed by a progressive insulin deficiency. Postprandial hyperglycemia is the first abnormality seen in CF patients and the classical symptoms of diabetes may not be recognized. The screening strategy proposed is annual random plasma glucose or fasting plasma glucose investigation, as well as the performance the oral glucose tolerance test (OGTT). Two categories of diabetes are related to CF: CFRD without fasting hyperglycemia (fasting glucose < 126 mg/dL and 2h OGTT glucose > 200 mg/dL) and CFRD with fasting hyperglycemia (fasting glucose > 126 mg/dL). Nutritional management and hyperglycemia control are the CFRD treatment goals. Insulin control is the standard medical therapy for CFRD with fasting hyperglycemia and the benefits of oral insulin secretagogue and sensitizing agents are still controversial.     

Clinical thiazolidinediones as PPARgamma ligands with the potential for the prevention of cardiovascular disease in diabetes

Thiazolidinediones (TZDs) are PPARgamma ligands and the newest class of agents in routine clinical practice for the treatment of hyperglycemia in type 2 diabetes. The prime reason for treating hyperglycemia and related aspects of the metabolic syndrome is to prevent accelerated cardiovascular disease (CVD) in diabetes. The formation and subsequent rupture of atherosclerotic "plaques", establishes CVD as the major cause of premature mortality in diabetes. Metabolically, TZDs act as insulin sensitizers resulting in improved glucose uptake, lower blood glucose and reduced hyperinsulinemia, however, they also appear to have beneficial direct vascular actions. TZDs have a range of actions directly on vascular cells and the predominance of the reported actions is potentially beneficial. TZDs inhibit vascular smooth muscle cell proliferation, inhibit the expression of adhesion molecules and modify the structure of vascular proteoglycans in a manner that results in reduced lipid binding. These actions manifest as reduced lipid deposition in the vessels of animals with experimental diabetes and atherosclerosis. Early clinical data indicates that TZDs may prevent or delay CVD including atherosclerosis and restenosis following coronary angiography. TZDs may be the first class of oral hypoglycemic agents with significant anti atherogenic effects to combat one of the major complications of diabetes.     

Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus

The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes.     

Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection

Up to 75% of adults with diabetes also have hypertension, and patients with hypertension alone often show evidence of insulin resistance. Thus, hypertension and diabetes are common, intertwined conditions that share a significant overlap in underlying risk factors (including ethnicity, familial, dyslipidemia, and lifestyle determinants) and complications. These complications include microvascular and macrovascular disorders. The macrovascular complications, which are well recognized in patients with longstanding diabetes or hypertension, include coronary artery disease, myocardial infarction, stroke, congestive heart failure, and peripheral vascular disease. Although microvascular complications (retinopathy, nephropathy, and neuropathy) are conventionally linked to hyperglycemia, studies have shown that hypertension constitutes an important risk factor, especially for nephropathy. The familial predisposition to diabetes and hypertension appears to be polygenic in origin, which militates against the feasibility of a "gene therapy" approach to the control or prevention of these conditions. On the other hand, the shared lifestyle factors in the etiology of hypertension and diabetes provide ample opportunity for nonpharmacologic intervention. Thus, the initial approach to the management of both diabetes and hypertension must emphasize weight control, physical activity, and dietary modification. Interestingly, lifestyle intervention is remarkably effective in the primary prevention of diabetes and hypertension. These principles also are pertinent to the prevention of downstream macrovascular complications of the two disorders. In addition to lifestyle modification, most patients will require specific medications to achieve national treatment goals for hypertension and diabetes. Management of hyperglycemia, hypertension, dyslipidemia, and the underlying hypercoagulable and proinflammatory states requires the use of multiple medications in combination.     

Metabolic syndrome therapy: Prevention of vascular injury by antidiabetic agents

More than 65 million Americans are currently obese. Type 2 diabetes mellitus, frequently seen in obese subjects, affects 17 million adults in the United States, with a continuous and alarmingly increasing rate. To prevent development of diabetes in those who are at high risk, it is recommended to optimize meal planning and enhance physical activity to make sustained weight reduction possible. In addition to lifestyle changes, various oral antidiabetic agents are available, with diverse mechanisms of action. Some target defective insulin secretion (sulphonylureas, benzoic acid derivatives) or glucose absorption (glycosidase inhibitors), whereas others target insulin resistance (metformin, thiazolidinediones). Patients with metabolic syndrome and diabetes have an increased risk for cardiovascular disease linked to a higher prevalence of hypertension, dyslipidemia, microalbuminuria, and altered hemostasis—parameters that may be modified by antidiabetic agents. In this article, we review the oral agents used to treat type 2 diabetes and the metabolic syndrome, and their effects on vascular tissue.