Unmet needs among patients with Type 2 diabetes and secondary failure to oral anti-diabetic agents

Abstract

Secondary failure is defined as a deterioration of glucose control in patients with Type 2 diabetes on oral antidiabetic drugs (OAD), mainly due to the progressive decline in beta-cell function and reduction in insulin secretion. The consequent hyperglycemia is the most important determinant for the development of microvascular and macrovascular complications, so that an early recognition of this phenomenon can improve long-term outcomes. The recent lowering of target glycosylated hemoglobin (HbA1c) levels by international guidelines not only emphasises the importance of tight glycemic control, but also means that secondary failure to OAD will occur much sooner and is almost unavoidable. Accordingly, in the last years, new different therapeutic strategies were explored to improve the treatment of this condition. The aim of this review is to examine current approaches for treating patients with secondary failure, barriers to achieving and maintaining glycemic control, and recent evidence for emerging therapies which may represent a valid therapeutic option in subjects failing on oral hypoglycemic agents by acting mainly, but not only, at a beta-cell level. In particular, we will focus on the co-administration of OAD plus a novel drug class known as incretin mimetics (e.g. exenatide and liraglutide), which target insulin secretion, and on thiazolidinediones, which act on insulin resistance. Only incretin-mimetics have a lowering HbA1c action, due to the improvement in beta-cell function, which is coupled to significant weight loss. Even if these new options seem to improve the outcome of secondary failure, further investigation is needed to confirm positive results in the long term.

Cultural adaptation of a patient decision-aid for insulin therapy

“…In addition, the overall Singapore population is ageing rapidly due to declining birth rates and longer average lifespan of the individual. With the expectant increase in the number of years a patient has to live with diabetes, many will develop secondary drug failure over time and will require insulin to maintain normoglycaemia 12. Yet local studies have shown that patients with T2DM are reluctant to initiate insulin due to multiple factors 13 14.…”

Bimagrumab improves body composition and insulin sensitivity in insulin‐resistant individuals

“…Genetic predisposition, age and lifestyle (overweight/obesity and physical inactivity) are risk factors for insulin resistance . Moreover, insulin resistance associated with T2D is responsible for inadequate glycaemic control, leading to failure of oral hypoglycaemic agents and the need for insulin therapy …”

“…11 Moreover, insulin resistance associated with T2D is responsible for inadequate glycaemic control, leading to failure of oral hypoglycaemic agents and the need for insulin therapy. 12 Lifestyle changes through caloric restriction and regular physical activity are the first steps toward weight loss and glycaemic control 9 ; thus, aerobic exercise training improves insulin sensitivity in insulinresistant patients by increasing glycogen synthesis in muscles through the increase in glucose transport/phosphorylation (Glut4) stimulated by insulin. 13 Brown adipose tissue (BAT) also plays an important role in energy expenditure through non-shivering thermogenesis to cold exposure, [14][15][16] a mechanism mediated by abundant mitochondria, 17 which uses intracellular triglycerides as a main substrate.…”

Cardiovascular safety of sulphonylureas: over 40 years of continuous controversy without an answer

“…Sulphonylureas have been used for over 50 years in the management of people with type 2 diabetes around the world . Despite their well‐recognized limitations of hypoglycaemia, weight gain and secondary failure , clinical practice guidelines recommend sulphonylureas as second‐line therapy when metformin fails, and even as first‐line therapy under certain circumstances . Indeed, many studies examining the patterns of antidiabetic drug use have identified that sulphonylureas are commonly used for people with type 2 diabetes, although their use has been declining in recent years .…”