Critical evaluation of the role of acarbose in the treatment of diabetes: patient considerations.

The alpha-glucosidase inhibitor acarbose has been used for more than 20 years in the management of hyperglycemia. Owing to its unique mode of action in the gastrointestinal tract, its properties are very different from other antidiabetic medications. Patients on long-term treatment to control a chronic disease are not only interested in good treatment efficacy, but are also even more interested in the safety and side effects of their medications. Significant aspects of acarbose predominantly regarding safety and tolerability in the management of type 2 diabetes and prediabetes are reviewed. It is concluded that acarbose is a convenient long-term treatment option, with benefits for both type 2 diabetics and patients in a prediabetic state.

Effects of acarbose on proinsulin and insulin secretion and their potential significance for the intermediary metabolism and cardiovascular system.

The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ss-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ss-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.

Improvement in glycemic control in morbidly obese type 2 diabetic subjects by gastric stimulation.

BACKGROUND: Gastric electrical stimulation synchronized to the refractory period of gastric electrical activity and applied during meals was evaluated for safety and for improvement of body weight and glycemic control in obese type 2 diabetes. METHODS: The study involved obese diabetic type 2 (ODM) patients in a multicenter open-label European feasibility trial. A total of 24 ODM (nine males, 15 females) treated with insulin and/or oral hyperglycemic agents and body mass index between 33.3 to 49.7 kg/m(2) were implanted laparoscopically with a TANTALUS system. RESULTS: There were 18 adverse events related to the implant procedure or the device reported in 12 subjects. All were short lived and resolved with no sequelae. In the 21 subjects that reached the 1-year visit weight was reduced by 4.5 +/- 2.7 kg (p < 0.05) and HbA1c by 0.5 +/- 0.3% (p < 0.05). In a subgroup (n = 11) on stable or reduced oral medication, weight was reduced by 6.3 +/- 3.4 kg (p < 0.05) and HbA1c by 0.9 +/- 0.4% (p < 0.05). The group on insulin (n = 6) had no significant changes in weight and HbA1c. CONCLUSIONS: The TANTALUS system is well tolerated in obese type 2 diabetic subjects. Gastric electrical stimulation can potentially improve glucose metabolism and induce weight loss in obese diabetic patients, who are not well controlled on oral antidiabetic therapy. Further evaluation is required to determine whether this effect is due to induced weight loss and/or to direct signal dependent mechanisms.

A randomized clinical trial comparing breakfast, dinner, or bedtime administration of insulin glargine in patients with type 1 diabetes.

OBJECTIVE: Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes on basal-bolus therapy (n = 378, 18-68 years, HbA(1c) 5.5-9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks. RESULTS: Baseline characteristics were similar in the three groups (overall age 40.9 +/- 11.9 years, diabetes duration 17.3 +/- 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine-to-total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA(1c) from baseline to end point occurred in all patients (7.6-7.4, 7.6-7.5, and 7.6-7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA(1c) <7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P = 0.005). CONCLUSIONS: These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.

[Non-insulin therapy in diabetes mellitus]. / Nicht-Insulin-Therapie des Diabetes mellitus.

Changes to nutritional habits, including the reduction of weight, are basic therapy principles for the treatment of diabetes mellitus. With overweight patients a reduction of energy intake is important. Patients with diabetes mellitus should eat plenty of carbohydrates, the intake of fat should be limited to a maximum of 35%. Patients treated with insulin must be made to calculate carbohydrate exchange units. Unless there are contraindications, diabetic patients should be encouraged to engage in physical exercise. Educating the patients is of major importance in the treatment of diabetics; this must be undertaken by trained personnel. All diabetic patients treated with oral antidiabetic drugs or insulin should be encouraged to measure their blood glucose levels themselves, in cases of insulin therapy this is an absolutely necessity. If with the aid of basic therapy measures, which include the control of fasting blood glucose, postprandial blood glucose and HbA1c levels, the aims of the therapy are not reached, this is an indication for the use of oral antidiabetic drugs. The drug should be chosen with the dominant pathophysiological disturbance in mind. In the case of increased fasting blood glucose values (hepatic insulin resistance leading to increased glucose production by the liver), after contraindications have been excluded, the use of metformin is recommended. If there are significantly increased postprandial blood glucose values (due to an early-insulin-secretion deficiency or severe insulin resistance), the use of alpha-glucosidase-inhibitors, metformin, sulphonylureas or glinides is indicated. With obese patients alphaglucosidaseinhibitors and metformin are the drugs of choice, with patients with BMI < 25 kg/m2 these are sulfonylureas or glinides. In cases of severe insulin resistance the use of glitazones in conjunction with metformin or sulphonylureas may be indicated.

The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents.

Type 2 diabetes results from the abnormal resistance of peripheral tissues to insulin and from the progressive insulin secretory failure of the pancreatic beta-cells. Treatment of type 2 diabetes has greatly improved due to the availability of new classes of oral antidiabetic drugs (OADs) and new insulin analogs. Three types of oral medications exert their antidiabetic action without directly stimulating insulin release: alpha-glucosidase inhibitors (e.g., acarbose) interfere with the digestion of dietary glucose precursors and the absorption of glucose; biguanides (e.g., metformin) inhibit hepatic gluconeogenesis, thereby lowering fasting blood glucose concentrations and increasing peripheral insulin sensitivity; and thiazolidinediones (e.g., rosiglitazone) improve the sensitivity of tissues to insulin-stimulated glucose disposal. In contrast, two classes of OADs stimulate insulin release from pancreatic beta-cells. Sulfonylureas (e.g., glyburide) have been used successfully for many years to treat type 2 diabetes, but their prolonged action may result in hypoglycemia. The third-generation sulfonylurea glimepiride is associated with a reduced risk of hypoglycemia and less weight gain than other sulfonylureas. Finally, the meglitinides (e.g., repaglinide) and D-phenylalanine derivatives (e.g., nateglinide) are powerful prandial insulin secretagogues. If the pancreatic beta-cells deteriorate to such an extent that insulin secretion is significantly impaired, treatment with additional exogenous insulin may be required.