Hyperglycemia in Cardiac ICU Treated With Exenatide

SAN DIEGO – Intravenous exenatide appeared to be as effective and safe as IV insulin to treat hyperglycemia patients in the cardiac ICU, but caused nausea in a fifth of patients in a small study.

The prospective, open-label study included 40 adults admitted to the cardiac ICU primarily for cardiac reasons who were treated with IV exenatide for fasting blood glucose levels of 140-400 mg/dL. They were compared with two historical control groups: 39 patients who were admitted to a cardiac ICU in 2009-2010 and treated with IV insulin for blood glucose levels greater than 180 mg/dL, and 94 patients in the cardiac ICU before 2009 who were treated under prior protocols for stricter glycemic control that started insulin for blood glucose levels greater than 140 mg/dL.

The exenatide and recent control groups aimed to maintain glucose levels at 100-140 mg/dL. The pre-2009 control group aimed to maintain glucose levels at 90-119 mg/dL.

Mean glucose levels at admission to the cardiac ICU were 199 mg/dL in the exenatide group, significantly lower than mean levels at admission of 240 mg/dL in the recent control group and 218 mg/dL in the pre-2009 control group.

Exenatide was infused at a fixed dose of 0.05 mcg/min for a 30-minute bolus, then 0.025 mcg/min continuously for 24-48 hours.

It took a mean of 3.9 hours for patients in the exenatide group to achieve a first glucose value of 140 mg/dL or lower, significantly faster than the 9.3 hours required in the recent control group and similar to the 3.5 hours required in the pre-2009 control group, Dr. Steven P. Marso and his associates reported at the annual scientific sessions of the American Diabetes Association.

Mean steady state glucose values were 139 mg/dL in the exenatide group, 147 mg/dL in the recent control group, and 115 mg/dL in the pre-2009 control group, said Dr. Marso of St. Luke’s Cardiovascular Consultants, Kansas City, Mo.

Eight patients developed exenatide-related nausea, and six of these discontinued the drug.

The exenatide group had a lower rate of hypoglycemic events and severe hypoglycemic episodes than the other groups, though the differences were not statistically significant.

Blood glucose levels below 70 mg/dL were seen in 0.9% of 668 measurements in the exenatide group, 1.2% of 745 measurements in the recent control group, and 1.6% of 1,651 measurements in the pre-2009 control group. No patients on exenatide developed severe hypoglycemia (blood glucose less than 50 mg/dL), but this was seen in 0.3% of measurements in the recent control group and in 0.06% in the pre-2009 control group.

The findings show that it’s feasible to treat hyperglycemia in the cardiac ICU with fixed-dose IV exenatide and that results are comparable to those with IV insulin without the risk for severe hypoglycemia, Dr. Marso said. The disadvantage of IV exenatide is the risk for treatment-limited nausea.

He cautioned, however, that this is a small, nonrandomized, proof-of-concept study with no active control group and no long-term clinical follow-up.

A significantly greater proportion of patients in the exenatide group had diabetes (75%), compared with patients in the recent control group (67%).

The study included two historical control groups because recommendations for glycemic control in the ICU setting have changed in recent years. Initial clinical trials showed clinical benefit from intensive glucose control for patients with hyperglycemia in the ICU, but later studies reported higher risks for severe hypoglycemia and death with intensive glucose control in these patients, Dr. Marso said. Updated consensus guidelines subsequently called for less tight glycemic control.

A 2009 consensus statement on inpatient glycemic control from the American Diabetes Association and American Association of Clinical Endocrinologists calls for insulin therapy to be initiated in critically ill patients when blood glucose values drop below 180 mg/dL. Glucose should be maintained between 140-180 mg/dL, and targets less than 100 mg/dL are not recommended (Endocr. Pract. 2009;15:353-69).

The statement says that IV insulin is the preferred treatment and that noninsulin antihyperglycemic agents are not appropriate in most hospitalized patients who require therapy for hyperglycemia. But the potential risks with insulin therapy prompted the current study of IV exenatide.

The study excluded patients who were dependent on a ventilator, unconscious on sedation, who had type 1 diabetes, were pregnant, were post-orthotopic heart transplant, had a creatinine clearance less than 30 mL/min, had a history of pancreatitis, or who were being treated with insulin monotherapy other than long-acting basal insulin (glargine or detemir).

The study was funded by Amylin Pharmaceuticals, which markets exenatide with Lilly. Dr. Marso has been a consultant to, or received research support from, Amylin, Abbott Vascular, The Medicines Company, Novo Nordisk, Volcano, Boston Scientific, and Terumo Medical.

SAN DIEGO – Intravenous exenatide appeared to be as effective and safe as IV insulin to treat hyperglycemia patients in the cardiac ICU, but caused nausea in a fifth of patients in a small study.

The prospective, open-label study included 40 adults admitted to the cardiac ICU primarily for cardiac reasons who were treated with IV exenatide for fasting blood glucose levels of 140-400 mg/dL. They were compared with two historical control groups: 39 patients who were admitted to a cardiac ICU in 2009-2010 and treated with IV insulin for blood glucose levels greater than 180 mg/dL, and 94 patients in the cardiac ICU before 2009 who were treated under prior protocols for stricter glycemic control that started insulin for blood glucose levels greater than 140 mg/dL.

The exenatide and recent control groups aimed to maintain glucose levels at 100-140 mg/dL. The pre-2009 control group aimed to maintain glucose levels at 90-119 mg/dL.

Mean glucose levels at admission to the cardiac ICU were 199 mg/dL in the exenatide group, significantly lower than mean levels at admission of 240 mg/dL in the recent control group and 218 mg/dL in the pre-2009 control group.

Exenatide was infused at a fixed dose of 0.05 mcg/min for a 30-minute bolus, then 0.025 mcg/min continuously for 24-48 hours.

It took a mean of 3.9 hours for patients in the exenatide group to achieve a first glucose value of 140 mg/dL or lower, significantly faster than the 9.3 hours required in the recent control group and similar to the 3.5 hours required in the pre-2009 control group, Dr. Steven P. Marso and his associates reported at the annual scientific sessions of the American Diabetes Association.

Mean steady state glucose values were 139 mg/dL in the exenatide group, 147 mg/dL in the recent control group, and 115 mg/dL in the pre-2009 control group, said Dr. Marso of St. Luke’s Cardiovascular Consultants, Kansas City, Mo.

Eight patients developed exenatide-related nausea, and six of these discontinued the drug.

The exenatide group had a lower rate of hypoglycemic events and severe hypoglycemic episodes than the other groups, though the differences were not statistically significant.

Blood glucose levels below 70 mg/dL were seen in 0.9% of 668 measurements in the exenatide group, 1.2% of 745 measurements in the recent control group, and 1.6% of 1,651 measurements in the pre-2009 control group. No patients on exenatide developed severe hypoglycemia (blood glucose less than 50 mg/dL), but this was seen in 0.3% of measurements in the recent control group and in 0.06% in the pre-2009 control group.

The findings show that it’s feasible to treat hyperglycemia in the cardiac ICU with fixed-dose IV exenatide and that results are comparable to those with IV insulin without the risk for severe hypoglycemia, Dr. Marso said. The disadvantage of IV exenatide is the risk for treatment-limited nausea.

He cautioned, however, that this is a small, nonrandomized, proof-of-concept study with no active control group and no long-term clinical follow-up.

A significantly greater proportion of patients in the exenatide group had diabetes (75%), compared with patients in the recent control group (67%).

The study included two historical control groups because recommendations for glycemic control in the ICU setting have changed in recent years. Initial clinical trials showed clinical benefit from intensive glucose control for patients with hyperglycemia in the ICU, but later studies reported higher risks for severe hypoglycemia and death with intensive glucose control in these patients, Dr. Marso said. Updated consensus guidelines subsequently called for less tight glycemic control.

A 2009 consensus statement on inpatient glycemic control from the American Diabetes Association and American Association of Clinical Endocrinologists calls for insulin therapy to be initiated in critically ill patients when blood glucose values drop below 180 mg/dL. Glucose should be maintained between 140-180 mg/dL, and targets less than 100 mg/dL are not recommended (Endocr. Pract. 2009;15:353-69).

The statement says that IV insulin is the preferred treatment and that noninsulin antihyperglycemic agents are not appropriate in most hospitalized patients who require therapy for hyperglycemia. But the potential risks with insulin therapy prompted the current study of IV exenatide.

The study excluded patients who were dependent on a ventilator, unconscious on sedation, who had type 1 diabetes, were pregnant, were post-orthotopic heart transplant, had a creatinine clearance less than 30 mL/min, had a history of pancreatitis, or who were being treated with insulin monotherapy other than long-acting basal insulin (glargine or detemir).

The study was funded by Amylin Pharmaceuticals, which markets exenatide with Lilly. Dr. Marso has been a consultant to, or received research support from, Amylin, Abbott Vascular, The Medicines Company, Novo Nordisk, Volcano, Boston Scientific, and Terumo Medical.

SAN DIEGO – Intravenous exenatide appeared to be as effective and safe as IV insulin to treat hyperglycemia patients in the cardiac ICU, but caused nausea in a fifth of patients in a small study.

The prospective, open-label study included 40 adults admitted to the cardiac ICU primarily for cardiac reasons who were treated with IV exenatide for fasting blood glucose levels of 140-400 mg/dL. They were compared with two historical control groups: 39 patients who were admitted to a cardiac ICU in 2009-2010 and treated with IV insulin for blood glucose levels greater than 180 mg/dL, and 94 patients in the cardiac ICU before 2009 who were treated under prior protocols for stricter glycemic control that started insulin for blood glucose levels greater than 140 mg/dL.

The exenatide and recent control groups aimed to maintain glucose levels at 100-140 mg/dL. The pre-2009 control group aimed to maintain glucose levels at 90-119 mg/dL.

Mean glucose levels at admission to the cardiac ICU were 199 mg/dL in the exenatide group, significantly lower than mean levels at admission of 240 mg/dL in the recent control group and 218 mg/dL in the pre-2009 control group.

Exenatide was infused at a fixed dose of 0.05 mcg/min for a 30-minute bolus, then 0.025 mcg/min continuously for 24-48 hours.

It took a mean of 3.9 hours for patients in the exenatide group to achieve a first glucose value of 140 mg/dL or lower, significantly faster than the 9.3 hours required in the recent control group and similar to the 3.5 hours required in the pre-2009 control group, Dr. Steven P. Marso and his associates reported at the annual scientific sessions of the American Diabetes Association.

Mean steady state glucose values were 139 mg/dL in the exenatide group, 147 mg/dL in the recent control group, and 115 mg/dL in the pre-2009 control group, said Dr. Marso of St. Luke’s Cardiovascular Consultants, Kansas City, Mo.

Eight patients developed exenatide-related nausea, and six of these discontinued the drug.

The exenatide group had a lower rate of hypoglycemic events and severe hypoglycemic episodes than the other groups, though the differences were not statistically significant.

Blood glucose levels below 70 mg/dL were seen in 0.9% of 668 measurements in the exenatide group, 1.2% of 745 measurements in the recent control group, and 1.6% of 1,651 measurements in the pre-2009 control group. No patients on exenatide developed severe hypoglycemia (blood glucose less than 50 mg/dL), but this was seen in 0.3% of measurements in the recent control group and in 0.06% in the pre-2009 control group.

The findings show that it’s feasible to treat hyperglycemia in the cardiac ICU with fixed-dose IV exenatide and that results are comparable to those with IV insulin without the risk for severe hypoglycemia, Dr. Marso said. The disadvantage of IV exenatide is the risk for treatment-limited nausea.

He cautioned, however, that this is a small, nonrandomized, proof-of-concept study with no active control group and no long-term clinical follow-up.

A significantly greater proportion of patients in the exenatide group had diabetes (75%), compared with patients in the recent control group (67%).

The study included two historical control groups because recommendations for glycemic control in the ICU setting have changed in recent years. Initial clinical trials showed clinical benefit from intensive glucose control for patients with hyperglycemia in the ICU, but later studies reported higher risks for severe hypoglycemia and death with intensive glucose control in these patients, Dr. Marso said. Updated consensus guidelines subsequently called for less tight glycemic control.

A 2009 consensus statement on inpatient glycemic control from the American Diabetes Association and American Association of Clinical Endocrinologists calls for insulin therapy to be initiated in critically ill patients when blood glucose values drop below 180 mg/dL. Glucose should be maintained between 140-180 mg/dL, and targets less than 100 mg/dL are not recommended (Endocr. Pract. 2009;15:353-69).

The statement says that IV insulin is the preferred treatment and that noninsulin antihyperglycemic agents are not appropriate in most hospitalized patients who require therapy for hyperglycemia. But the potential risks with insulin therapy prompted the current study of IV exenatide.

The study excluded patients who were dependent on a ventilator, unconscious on sedation, who had type 1 diabetes, were pregnant, were post-orthotopic heart transplant, had a creatinine clearance less than 30 mL/min, had a history of pancreatitis, or who were being treated with insulin monotherapy other than long-acting basal insulin (glargine or detemir).

The study was funded by Amylin Pharmaceuticals, which markets exenatide with Lilly. Dr. Marso has been a consultant to, or received research support from, Amylin, Abbott Vascular, The Medicines Company, Novo Nordisk, Volcano, Boston Scientific, and Terumo Medical.