Liraglutide, The Once-Daily Human GLP-1 Analog, in the Treatment of Type 2 Diabetes
Liraglutide, The Once-Daily Human GLP-1 Analog, in the Treatment of Type 2 Diabetes
Type 2 diabetes is a progressive disorder characterized by continuous deterioration in β-cell function requiring an escalation of therapeutic efforts in order to maintain glycemic control. Recent studies have demonstrated that the current antidiabetic treatments, including metformin, sulfonylureas and thiazolidinediones, are not durable, resulting in an increase of hemoglobin A1c over time with all three therapies. Many current antidiabetic treatments (sulfonylureas, thiazolidinediones and insulin) are associated with the undesirable feature of weight gain. In addition, sulfonylureas and insulin are associated with an increased risk for hypoglycemia. The unsatisfactory results with the current pharmacological therapies for Type 2 diabetes have encouraged the development of a number of novel treatments. Among these are the incretin-based therapies, which include glucagon-like peptide (GLP)-1 receptor agonists; this article focuses on one of these agonists, the human GLP-1 analog liraglutide. Liraglutide has been approved for use in Type 2 diabetic individuals in several countries, including Europe, the USA and Japan.
Type 2 diabetes is an increasingly common chronic disease, affecting more than 200 million people worldwide. It is a progressive disorder, characterized by a more-or-less constant degree of insulin resistance associated with declining β-cell function, leading to multiple, potentially life-threatening, comorbidities, including micro- and macro-vascular complications. According to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) joint consensus statement, the first approach to Type 2 diabetes treatment should be intervention at the time of diagnosis with metformin (Met) in combination with lifestyle changes, followed by the timely augmentation of therapy with additional agents as a means of achieving and maintaining recommended levels of glycemic control (i.e., hemoglobin A1c [HbA1c] <7%). However, despite the availability of drugs belonging to ten different medication classes, at present, a considerable number of patients with Type 2 diabetes do not achieve glycemic targets with standard treatment. A survey examining trends in glycemic control among 1334 Type 2 diabetic patients in the USA between 1999 and 2004 demonstrated that, although the percentage of patients that did achieve glycemic targets significantly increased from 37% in 1999–2000 to 57% in 2003–2004 (p < 0.0001), 43% of patients still did not reach it. Although the cardiovascular (CV) disease benefits of very aggressive glucose-lowering interventions have recently been brought into question, it is well established that achieving and maintaining tight glycemic control soon after the diagnosis of diabetes is crucial to reduce the risk of diabetes-related complications. An additional limitation of standard diabetes treatments, particularly sulfonylurea (SU) and insulin, is that they are associated with an increased risk of hypoglycemia. This side effect is particularly worrisome to both patients and physicians, as major hypoglycemic events can lead to unconsciousness, brain damage and death, when left untreated. Furthermore, a number of the currently available treatments, in particular, insulin, thiazolidinediones (TZDs) and SU, are associated with weight gain over time; this represents an additional problem, especially since Type 2 diabetic subjects are often already overweight or obese. Treatments that minimize the risk of hypoglycemia and weight gain may, therefore, have a positive impact on patients' adherence to therapy. Finally, CV risk management is a very important part of Type 2 diabetes care as CV risk factors, such as hypertension, are often associated with diabetes and obesity. It is well known that systolic blood pressure (SBP) increases with the duration of diabetes and a decrease in SBP of only 5.6 mmHg has been associated with a significant reduction of 18% in the relative risk of death from CV disease. Treatments that improve CV risk factors are thus actively sought after.
Abstract and Introduction
Abstract
Type 2 diabetes is a progressive disorder characterized by continuous deterioration in β-cell function requiring an escalation of therapeutic efforts in order to maintain glycemic control. Recent studies have demonstrated that the current antidiabetic treatments, including metformin, sulfonylureas and thiazolidinediones, are not durable, resulting in an increase of hemoglobin A1c over time with all three therapies. Many current antidiabetic treatments (sulfonylureas, thiazolidinediones and insulin) are associated with the undesirable feature of weight gain. In addition, sulfonylureas and insulin are associated with an increased risk for hypoglycemia. The unsatisfactory results with the current pharmacological therapies for Type 2 diabetes have encouraged the development of a number of novel treatments. Among these are the incretin-based therapies, which include glucagon-like peptide (GLP)-1 receptor agonists; this article focuses on one of these agonists, the human GLP-1 analog liraglutide. Liraglutide has been approved for use in Type 2 diabetic individuals in several countries, including Europe, the USA and Japan.
Introduction
Type 2 diabetes is an increasingly common chronic disease, affecting more than 200 million people worldwide. It is a progressive disorder, characterized by a more-or-less constant degree of insulin resistance associated with declining β-cell function, leading to multiple, potentially life-threatening, comorbidities, including micro- and macro-vascular complications. According to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) joint consensus statement, the first approach to Type 2 diabetes treatment should be intervention at the time of diagnosis with metformin (Met) in combination with lifestyle changes, followed by the timely augmentation of therapy with additional agents as a means of achieving and maintaining recommended levels of glycemic control (i.e., hemoglobin A1c [HbA1c] <7%). However, despite the availability of drugs belonging to ten different medication classes, at present, a considerable number of patients with Type 2 diabetes do not achieve glycemic targets with standard treatment. A survey examining trends in glycemic control among 1334 Type 2 diabetic patients in the USA between 1999 and 2004 demonstrated that, although the percentage of patients that did achieve glycemic targets significantly increased from 37% in 1999–2000 to 57% in 2003–2004 (p < 0.0001), 43% of patients still did not reach it. Although the cardiovascular (CV) disease benefits of very aggressive glucose-lowering interventions have recently been brought into question, it is well established that achieving and maintaining tight glycemic control soon after the diagnosis of diabetes is crucial to reduce the risk of diabetes-related complications. An additional limitation of standard diabetes treatments, particularly sulfonylurea (SU) and insulin, is that they are associated with an increased risk of hypoglycemia. This side effect is particularly worrisome to both patients and physicians, as major hypoglycemic events can lead to unconsciousness, brain damage and death, when left untreated. Furthermore, a number of the currently available treatments, in particular, insulin, thiazolidinediones (TZDs) and SU, are associated with weight gain over time; this represents an additional problem, especially since Type 2 diabetic subjects are often already overweight or obese. Treatments that minimize the risk of hypoglycemia and weight gain may, therefore, have a positive impact on patients' adherence to therapy. Finally, CV risk management is a very important part of Type 2 diabetes care as CV risk factors, such as hypertension, are often associated with diabetes and obesity. It is well known that systolic blood pressure (SBP) increases with the duration of diabetes and a decrease in SBP of only 5.6 mmHg has been associated with a significant reduction of 18% in the relative risk of death from CV disease. Treatments that improve CV risk factors are thus actively sought after.