Sitagliptin vs. Sulfonylureas in Elderly Patients With T2DM
Sitagliptin vs. Sulfonylureas in Elderly Patients With T2DM
Introduction In the USA, 45% of patients with type 2 diabetes mellitus (T2DM) are elderly (≥ 65 years old). In general, use of sulfonylurea increases with patient age as does the associated risk for hypoglycaemia, and the consequences of hypoglycaemia can be more pronounced in elderly patients. Sitagliptin, a DPP-4 inhibitor, improves glycaemic control in adult patients of all ages with T2DM, with a low risk of hypoglycaemia when used alone or in combination with other antidiabetic agents that are not generally associated with hypoglycaemia when used independently.
Methods In a post hoc analysis, pooled data from elderly patients who participated in one of three double-blind studies comparing the effects of therapy with sitagliptin (100 mg/day) vs. sulfonylurea (in titrated doses) were analysed for changes from baseline in HbA1c, fasting plasma glucose (FPG), and body weight and for the incidence of reported symptomatic hypoglycaemia. In these studies, patients on diet alone or metformin were randomised to sitagliptin or glipizide for 104 weeks (studies 1 and 2) or glimepiride for 30 weeks (study 3). The analysis included 372 elderly patients who completed a trial through 25 or 30 weeks.
Results Both HbA1c and FPG decreased from baseline with each treatment, with no statistically significant differences between treatments. A significantly lower incidence of reported hypoglycaemia was observed with sitagliptin compared with sulfonylurea (6.2% vs. 27.8%; p < 0.001). Body weight decreased significantly with sitagliptin but not with sulfonylurea. Significantly more patients on sitagliptin than on sulfonylureas achieved a composite end-point of >0.5% HbA1c reduction with no reported hypoglycaemia or increase in body weight (44.1% vs. 16.0%; p < 0.001).
Conclusion In this analysis of elderly patients with T2DM, compared with sulfonylurea, sitagliptin provided similar glycaemic efficacy with less hypoglycaemia and with body weight loss.
The global prevalence of type 2 diabetes mellitus (T2DM) in the population aged 20–79 years is expected to increase from 8.3% (382 million patients) in 2013 to 10.1% (592 million patients) in 2035. The fraction of these patients who are elderly (≥ 65 years of age) is anticipated to increase disproportionately because of increases in the proportion of elderly people in the overall population, the prevalence of T2DM in elderly people population, and the longevity of patients diagnosed with T2DM at ages < 65 years. It is predicted that the number of elderly patients with T2DM will increase from nearly 60 million in 2000 to over 120 million by 2030.
As in all patients with T2DM, poor glucose control is associated with microvascular complications in elderly patients necessitating the achievement and maintenance of glycaemic control in this population. However, improving glycaemic control in elderly people with T2DM presents unique challenges, in part because of the increased risk of hypoglycaemia in older patients. Hypoglycaemia is associated with increased morbidity and, in some studies, with increased mortality and is known to have a deleterious effect on patients' quality of life. Elderly patients have compromised counter-regulatory hormone response to hypoglycaemia and decreased awareness of hypoglycaemia. This may make the use of sulfonylureas, which lower glucose in a non-glucose-dependent manner and thus causing hypoglycaemia, particularly problematic for elderly patients.
In an observational study of 3810 patients in primary care, Bramlage et al. found that patients ≥ 70 years of age with T2DM were more frequently treated with sulfonylurea and less frequently treated with metformin, thiazolidinediones or DPP-4 inhibitors, that higher rates of hypoglycaemia were observed in the oldest group of patients analysed, and that use of sulfonylurea was associated with hypoglycaemic events. In addition, in a study of 130 hospitalised patients, Deusenberry et al. observed that elderly patients were at increased risk, compared with younger patients, for sulfonylurea-related hypoglycaemia during hospitalisation.
Many effective oral antihyperglycaemic medications, including metformin, thiazolidinediones and sulfonylureas, may be contraindicated in some elderly patients because of comorbid conditions. Thus, there is a clear need for improvement in the glycaemic control of hyperglycaemia in elderly patients with T2DM using safe and effective agents, and in particular, agents that improve glycaemic control with a low incidence of hypoglycaemia.
Sitagliptin is a selective, oral, DPP-4 inhibitor that improves glycaemic control with a low risk of hypoglycaemia when used alone, or in combination with metformin or pioglitazone. Here, we used pooled data from three clinical trials to compare glycaemic efficacy, reported adverse events of hypoglycaemia, and changes in body weight in elderly (≥ 65 years of age) patients with T2DM who received either sitagliptin or a sulfonylurea.
Abstract and Introduction
Abstract
Introduction In the USA, 45% of patients with type 2 diabetes mellitus (T2DM) are elderly (≥ 65 years old). In general, use of sulfonylurea increases with patient age as does the associated risk for hypoglycaemia, and the consequences of hypoglycaemia can be more pronounced in elderly patients. Sitagliptin, a DPP-4 inhibitor, improves glycaemic control in adult patients of all ages with T2DM, with a low risk of hypoglycaemia when used alone or in combination with other antidiabetic agents that are not generally associated with hypoglycaemia when used independently.
Methods In a post hoc analysis, pooled data from elderly patients who participated in one of three double-blind studies comparing the effects of therapy with sitagliptin (100 mg/day) vs. sulfonylurea (in titrated doses) were analysed for changes from baseline in HbA1c, fasting plasma glucose (FPG), and body weight and for the incidence of reported symptomatic hypoglycaemia. In these studies, patients on diet alone or metformin were randomised to sitagliptin or glipizide for 104 weeks (studies 1 and 2) or glimepiride for 30 weeks (study 3). The analysis included 372 elderly patients who completed a trial through 25 or 30 weeks.
Results Both HbA1c and FPG decreased from baseline with each treatment, with no statistically significant differences between treatments. A significantly lower incidence of reported hypoglycaemia was observed with sitagliptin compared with sulfonylurea (6.2% vs. 27.8%; p < 0.001). Body weight decreased significantly with sitagliptin but not with sulfonylurea. Significantly more patients on sitagliptin than on sulfonylureas achieved a composite end-point of >0.5% HbA1c reduction with no reported hypoglycaemia or increase in body weight (44.1% vs. 16.0%; p < 0.001).
Conclusion In this analysis of elderly patients with T2DM, compared with sulfonylurea, sitagliptin provided similar glycaemic efficacy with less hypoglycaemia and with body weight loss.
Introduction
The global prevalence of type 2 diabetes mellitus (T2DM) in the population aged 20–79 years is expected to increase from 8.3% (382 million patients) in 2013 to 10.1% (592 million patients) in 2035. The fraction of these patients who are elderly (≥ 65 years of age) is anticipated to increase disproportionately because of increases in the proportion of elderly people in the overall population, the prevalence of T2DM in elderly people population, and the longevity of patients diagnosed with T2DM at ages < 65 years. It is predicted that the number of elderly patients with T2DM will increase from nearly 60 million in 2000 to over 120 million by 2030.
As in all patients with T2DM, poor glucose control is associated with microvascular complications in elderly patients necessitating the achievement and maintenance of glycaemic control in this population. However, improving glycaemic control in elderly people with T2DM presents unique challenges, in part because of the increased risk of hypoglycaemia in older patients. Hypoglycaemia is associated with increased morbidity and, in some studies, with increased mortality and is known to have a deleterious effect on patients' quality of life. Elderly patients have compromised counter-regulatory hormone response to hypoglycaemia and decreased awareness of hypoglycaemia. This may make the use of sulfonylureas, which lower glucose in a non-glucose-dependent manner and thus causing hypoglycaemia, particularly problematic for elderly patients.
In an observational study of 3810 patients in primary care, Bramlage et al. found that patients ≥ 70 years of age with T2DM were more frequently treated with sulfonylurea and less frequently treated with metformin, thiazolidinediones or DPP-4 inhibitors, that higher rates of hypoglycaemia were observed in the oldest group of patients analysed, and that use of sulfonylurea was associated with hypoglycaemic events. In addition, in a study of 130 hospitalised patients, Deusenberry et al. observed that elderly patients were at increased risk, compared with younger patients, for sulfonylurea-related hypoglycaemia during hospitalisation.
Many effective oral antihyperglycaemic medications, including metformin, thiazolidinediones and sulfonylureas, may be contraindicated in some elderly patients because of comorbid conditions. Thus, there is a clear need for improvement in the glycaemic control of hyperglycaemia in elderly patients with T2DM using safe and effective agents, and in particular, agents that improve glycaemic control with a low incidence of hypoglycaemia.
Sitagliptin is a selective, oral, DPP-4 inhibitor that improves glycaemic control with a low risk of hypoglycaemia when used alone, or in combination with metformin or pioglitazone. Here, we used pooled data from three clinical trials to compare glycaemic efficacy, reported adverse events of hypoglycaemia, and changes in body weight in elderly (≥ 65 years of age) patients with T2DM who received either sitagliptin or a sulfonylurea.
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