In insulin dependent patients with type 2 diabetes, especially with obesity, control of glycemia is a challenging issue (Hood et al, 2006). Intensification of insulin therapy to achieve target levels of glycosylated hemoglobin leads to further weight gain. Infact, one of main anxieties with insulin therapy in this population is poor weight gain (Nayak et al, 2010). In several developed countries like UK, there are recommendations for obesity surgery, along with exercise, diet and drug control of diabetes. However, obesity surgery is associated with significant risk. Exenatide, when given as an adjunct to insulin therapy, has been proven to not only achieve better control of blood glucose levels, but also decrease the chances of gaining weight. Infact, some studies have demonstrated weight loss with exenatide therapy. In this article, evidence to support the prescription of exenatide, as an adjunct to insulin therapy will be discussed through review of suitable literature.
Understanding the pathophysiology and treatment basis of diabetes type-2
Diabetes mellitus can be defined as a group of clinical syndromes characterized by hyperglycemia arising as a result of absolute or relative insulin deficiency (Edwards et al, 2002). There are basically 2 types of diabetes mellitus. While type-1 is due to absolute insulin deficiency as a result of pancreatic beta-cell destruction, there is relative insulin deficiency in type-2 as a result of combination of peripheral resistance to insulin action and an inadequate secretory response by the beta cells (Kumar et al, 2007). Type 2 diabetes is the most common form of diabetes constituting 90% of diabetic population (Ramachandran et al, 2002). In a classic definition, type 2 diabetes has been defined as a triad of 3 etiologies, namely, resistance to insulin, progressive failure or exhausion of beta cells, and increased gluconeogenesis at liver. However, there is another pathophysiologic abnormality that is worth mentioning and that is decreased activity of GLP-1 (Jellinger, 2011). The impaired insulin secretion in type-2 diabetes is due to beta cell dysfunction (DeFronzo, 1997). The beta cells fail to adapt themselves for the long-term demands of peripheral insulin resistance and increased insulin secretion (Kumaret al, 2007). In type-2, this dysfunction is both quantitative and qualitative. There is loss of normal pulsatile, oscillating pattern of insulin secretion and the rapid first phase of insulin secretion which is a normal response to elevated plasma glucose is attenuated. There is also decrease in beta cell mass, islet degeneration and deposition of islet amyloid (Kumaret al, 2007). Infact, studies have established the onset of insulin resistance much before the manifestations of hyperglycemia (DeFronzo, 1997). The pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia (Stumvoll et al, 2005). The factors which probably lead to insulin resistance are increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction (Stumvoll et al,