[Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: Rationale for the active-comparator CAROLINA® trial]. / Kardiovaskuläre Studien-Endpunkte bei Typ-2-Diabetes und die Sulfonylharnstoff-Kontroverse: Rationale für die aktiv kontrollierte CAROLINA®-Studie.

Sulphonylureas (SUs) are antidiabetic agents widely used in patients with Type 2 Diabetes Mellitus (T2DM). Observational retrospective studies have raised concerns regarding the cardiovascular (CV) safety of this class of drugs, and data from observational and registry studies are conflicting. To address the SU controversy, this review looked at longer-term RCTs, where SUs were compared in a head-to-head fashion with active comparators. An analysis of 18 studies did not find any increase in the incidence of CV events with SU therapy. However, the available data are limited and most importantly, there is a lack of prospective, adequately powered, formal head-to-head CV outcome trials. Since SUs are still being used as second-line therapy in combination with metformin and in some cases as first-line treatment of T2DM, there is a definite need for CV safety data from a prospective RCT. The CAROLINA(®) study is currently the largest CV outcome study with a direct comparison of an SU and a dipeptidyl peptidase-4 inhibitor (DPP-4). Based on the study design and statistical power of CAROLINA(®), its results will provide a unique perspective regarding CV outcomes of these 2 commonly used agents.

Diabetes mellitus and gastric emptying: questions and issues in clinical practice.

It is long known that both type 1 and type 2 diabetes can be associated with changes in gastric emptying; a number of publications have linked diabetes to delayed gastric emptying of variable severity and often with poor relationship to gastrointestinal symptomatology. In contrast, more recent studies have reported accelerated gastric emptying when adjusted for glucose concentration in patients with diabetes, indicating a reciprocal relationship between gastric emptying and ambient glucose concentrations. This review proposes that gastroparesis or gastroparesis diabeticorum, a severe condition characterized by a significant impairment of gastric emptying accompanied by severe nausea, vomiting, and malnutrition, is often overdiagnosed and not well contrasted with delays in gastric emptying. The article offers a clinically relevant definition of gastroparesis that should help differentiate this rare condition from (often asymptomatic) delays in gastric emptying. The fact that delayed gastric emptying can also be observed in non-diabetic individuals under experimental conditions in which hyperglycaemia is artificially induced suggests that a delay in gastric emptying rate when blood glucose concentrations are high is actually an appropriate physiological response to hyperglycaemia, slowing further increases in blood glucose. The article discusses the strengths and weaknesses of various methodologies for assessing gastric emptying, especially with respect to the diabetes population, and reviews newer diabetes therapies that decelerate the rate of gastric emptying. These therapies may be a beneficial tool in managing postprandial hyperglycaemia because they attenuate rapid surges in glucose concentrations by slowing the delivery of meal-derived glucose.