Miriam E. Tucker

LISBON – New data on two investigational glucagon receptor antagonists suggest that this novel class of drugs has potential to be an effective treatment for type 2 diabetes, but only if safety can be established, according to two presentations at the meeting.

Both Merck's MK-0893 and Lilly's LY2409021 work by suppressing glucagon action via receptor blockade. Dr. Samuel S. Engel, senior director of clinical research, diabetes, and endocrinology, at Merck presented phase II study data on the efficacy and safety of MK-0893 in combination with metformin or sitagliptin in 146 patients with type 2 diabetes, and Dr. Melvin J. Prince, senior director of medical diabetes and endocrinology at Lilly, presented phase I dose-finding data on LY2409021 in 47 patients.

Both agents produced statistically significant reductions in hemoglobin A_1c. However, both also produced small but significant elevations in liver enzymes, and both carry the theoretical potential for hypoglycemia and hyperglucagonemia. “There is definitely potential for the glucagon receptor antagonists in diabetes, but there is also a risk of hypoglycemia associated with them. Also, it has been noted in the past that the hyperglucagonemia that results when the alpha cells overproduce glucagon has led to pancreas tumors in animal studies, so that's a risk,” session moderator Dr. Finbarr O'Harte, professor of endocrinology and metabolism at the University of Ulster, Derry (Northern Ireland), said in an interview.

In June at the American Diabetes Association's annual scientific sessions, Dr. Engel presented data from a phase II study in which 342 type 2 diabetes patients were randomized to once-daily MK-0893 in four different dosages, metformin 1,000 mg twice daily, or placebo. At 12 weeks, treatment with MK-0893 resulted in significant, dose-dependent reductions in fasting plasma glucose, ranging from 32 mg/dL with a 20-mg dose to 63 mg/dL with 80 mg, from a baseline of 180–193 mg/dL. Metformin reduced FPG by 37 mg/dL, and placebo by just 2 mg/dL from baseline. For HbA_1c, reductions at 12 weeks ranged from 0.6–1.5 percentage points, versus 0.8 percentage points with metformin and 0.5 with placebo.

The current study evaluated 40 mg/day MK-0893 in combination with 2,000 mg/day metformin or 100 mg/day sitagliptin, as well as 100 mg of sitagliptin plus 2,000 mg of metformin. The 146 patients had a mean age of 53 years, HbA_1c of 8.6%, and mean diabetes duration of 7 years. The MK-0893/metformin combination was superior to sitagliptin/metformin in lowering 24-hour weighted mean glucose, with a reduction of 117 mg/dL compared with 85 mg/dL. However, MK-0893/sitagliptin was significantly less effective than sitagliptin/metformin, which produced a 24-hour WMG reduction of 100 mg/dL. This could be because sitagliptin, a DPP-4 inhibitor, also suppresses glucagon and so there could be a threshold effect, Dr. Engel noted.

All treatments were equally well tolerated. However, there was a significantly higher incidence of diarrhea in the two MK-0893 groups (10% vs. 0%). Also, the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were elevated in the MK-0893/metformin group, and total cholesterol and LDL cholesterol were increased from baseline with MK-0893/sitagliptin, relative to reductions with MK-0893/metformin and sitagliptin/metformin, he reported.

In the phase I dose-ranging study of LY-2409021, 47 patients were randomized to one of four doses or metformin. Patients had a mean baseline fasting blood glucose of 148 mg/dL, and a baseline HbA_1c of 8.0%. By day 28, mean reductions in HbA_1c were statistically significant compared with baseline in all treatment groups, ranging from 1.02 percentage points with 60 mg to 0.69 percentage points with 5 mg. In the placebo group, HbA_1c dropped by 0.49 percentage points, Dr. Prince reported.

Fasting glucagon significantly increased by 0.6- to 4.2-fold compared with baseline across the LY dose levels, and fasting active glucagon-like peptide-1 (GLP-1) rose by 59% at the highest dose. Glucagon and GLP-1 returned to baseline levels during follow-up, he said.

The agent was generally well tolerated. Reversible elevations in hepatic transaminases were seen in five of nine patients in the highest-dose group, with no clinical signs or significant elevations in bilirubin or alkaline phosphatase, he reported. In the interview, Dr. O'Harte said that these two agents seem to have already exceeded expectations. “We need toxicity studies, but there's a possibility for a breakthrough, I hope.”

Dr. Engel is an employee of Merck, and Dr. Prince is an employee of Lilly. Dr. O'Harte stated that he had no disclosures.

LISBON – New data on two investigational glucagon receptor antagonists suggest that this novel class of drugs has potential to be an effective treatment for type 2 diabetes, but only if safety can be established, according to two presentations at the meeting.

Both Merck's MK-0893 and Lilly's LY2409021 work by suppressing glucagon action via receptor blockade. Dr. Samuel S. Engel, senior director of clinical research, diabetes, and endocrinology, at Merck presented phase II study data on the efficacy and safety of MK-0893 in combination with metformin or sitagliptin in 146 patients with type 2 diabetes, and Dr. Melvin J. Prince, senior director of medical diabetes and endocrinology at Lilly, presented phase I dose-finding data on LY2409021 in 47 patients.

Both agents produced statistically significant reductions in hemoglobin A_1c. However, both also produced small but significant elevations in liver enzymes, and both carry the theoretical potential for hypoglycemia and hyperglucagonemia. “There is definitely potential for the glucagon receptor antagonists in diabetes, but there is also a risk of hypoglycemia associated with them. Also, it has been noted in the past that the hyperglucagonemia that results when the alpha cells overproduce glucagon has led to pancreas tumors in animal studies, so that's a risk,” session moderator Dr. Finbarr O'Harte, professor of endocrinology and metabolism at the University of Ulster, Derry (Northern Ireland), said in an interview.

In June at the American Diabetes Association's annual scientific sessions, Dr. Engel presented data from a phase II study in which 342 type 2 diabetes patients were randomized to once-daily MK-0893 in four different dosages, metformin 1,000 mg twice daily, or placebo. At 12 weeks, treatment with MK-0893 resulted in significant, dose-dependent reductions in fasting plasma glucose, ranging from 32 mg/dL with a 20-mg dose to 63 mg/dL with 80 mg, from a baseline of 180–193 mg/dL. Metformin reduced FPG by 37 mg/dL, and placebo by just 2 mg/dL from baseline. For HbA_1c, reductions at 12 weeks ranged from 0.6–1.5 percentage points, versus 0.8 percentage points with metformin and 0.5 with placebo.

The current study evaluated 40 mg/day MK-0893 in combination with 2,000 mg/day metformin or 100 mg/day sitagliptin, as well as 100 mg of sitagliptin plus 2,000 mg of metformin. The 146 patients had a mean age of 53 years, HbA_1c of 8.6%, and mean diabetes duration of 7 years. The MK-0893/metformin combination was superior to sitagliptin/metformin in lowering 24-hour weighted mean glucose, with a reduction of 117 mg/dL compared with 85 mg/dL. However, MK-0893/sitagliptin was significantly less effective than sitagliptin/metformin, which produced a 24-hour WMG reduction of 100 mg/dL. This could be because sitagliptin, a DPP-4 inhibitor, also suppresses glucagon and so there could be a threshold effect, Dr. Engel noted.

All treatments were equally well tolerated. However, there was a significantly higher incidence of diarrhea in the two MK-0893 groups (10% vs. 0%). Also, the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were elevated in the MK-0893/metformin group, and total cholesterol and LDL cholesterol were increased from baseline with MK-0893/sitagliptin, relative to reductions with MK-0893/metformin and sitagliptin/metformin, he reported.

In the phase I dose-ranging study of LY-2409021, 47 patients were randomized to one of four doses or metformin. Patients had a mean baseline fasting blood glucose of 148 mg/dL, and a baseline HbA_1c of 8.0%. By day 28, mean reductions in HbA_1c were statistically significant compared with baseline in all treatment groups, ranging from 1.02 percentage points with 60 mg to 0.69 percentage points with 5 mg. In the placebo group, HbA_1c dropped by 0.49 percentage points, Dr. Prince reported.

Fasting glucagon significantly increased by 0.6- to 4.2-fold compared with baseline across the LY dose levels, and fasting active glucagon-like peptide-1 (GLP-1) rose by 59% at the highest dose. Glucagon and GLP-1 returned to baseline levels during follow-up, he said.

The agent was generally well tolerated. Reversible elevations in hepatic transaminases were seen in five of nine patients in the highest-dose group, with no clinical signs or significant elevations in bilirubin or alkaline phosphatase, he reported. In the interview, Dr. O'Harte said that these two agents seem to have already exceeded expectations. “We need toxicity studies, but there's a possibility for a breakthrough, I hope.”

Dr. Engel is an employee of Merck, and Dr. Prince is an employee of Lilly. Dr. O'Harte stated that he had no disclosures.

LISBON – New data on two investigational glucagon receptor antagonists suggest that this novel class of drugs has potential to be an effective treatment for type 2 diabetes, but only if safety can be established, according to two presentations at the meeting.

Both Merck's MK-0893 and Lilly's LY2409021 work by suppressing glucagon action via receptor blockade. Dr. Samuel S. Engel, senior director of clinical research, diabetes, and endocrinology, at Merck presented phase II study data on the efficacy and safety of MK-0893 in combination with metformin or sitagliptin in 146 patients with type 2 diabetes, and Dr. Melvin J. Prince, senior director of medical diabetes and endocrinology at Lilly, presented phase I dose-finding data on LY2409021 in 47 patients.

Both agents produced statistically significant reductions in hemoglobin A_1c. However, both also produced small but significant elevations in liver enzymes, and both carry the theoretical potential for hypoglycemia and hyperglucagonemia. “There is definitely potential for the glucagon receptor antagonists in diabetes, but there is also a risk of hypoglycemia associated with them. Also, it has been noted in the past that the hyperglucagonemia that results when the alpha cells overproduce glucagon has led to pancreas tumors in animal studies, so that's a risk,” session moderator Dr. Finbarr O'Harte, professor of endocrinology and metabolism at the University of Ulster, Derry (Northern Ireland), said in an interview.

In June at the American Diabetes Association's annual scientific sessions, Dr. Engel presented data from a phase II study in which 342 type 2 diabetes patients were randomized to once-daily MK-0893 in four different dosages, metformin 1,000 mg twice daily, or placebo. At 12 weeks, treatment with MK-0893 resulted in significant, dose-dependent reductions in fasting plasma glucose, ranging from 32 mg/dL with a 20-mg dose to 63 mg/dL with 80 mg, from a baseline of 180–193 mg/dL. Metformin reduced FPG by 37 mg/dL, and placebo by just 2 mg/dL from baseline. For HbA_1c, reductions at 12 weeks ranged from 0.6–1.5 percentage points, versus 0.8 percentage points with metformin and 0.5 with placebo.

The current study evaluated 40 mg/day MK-0893 in combination with 2,000 mg/day metformin or 100 mg/day sitagliptin, as well as 100 mg of sitagliptin plus 2,000 mg of metformin. The 146 patients had a mean age of 53 years, HbA_1c of 8.6%, and mean diabetes duration of 7 years. The MK-0893/metformin combination was superior to sitagliptin/metformin in lowering 24-hour weighted mean glucose, with a reduction of 117 mg/dL compared with 85 mg/dL. However, MK-0893/sitagliptin was significantly less effective than sitagliptin/metformin, which produced a 24-hour WMG reduction of 100 mg/dL. This could be because sitagliptin, a DPP-4 inhibitor, also suppresses glucagon and so there could be a threshold effect, Dr. Engel noted.

All treatments were equally well tolerated. However, there was a significantly higher incidence of diarrhea in the two MK-0893 groups (10% vs. 0%). Also, the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were elevated in the MK-0893/metformin group, and total cholesterol and LDL cholesterol were increased from baseline with MK-0893/sitagliptin, relative to reductions with MK-0893/metformin and sitagliptin/metformin, he reported.

In the phase I dose-ranging study of LY-2409021, 47 patients were randomized to one of four doses or metformin. Patients had a mean baseline fasting blood glucose of 148 mg/dL, and a baseline HbA_1c of 8.0%. By day 28, mean reductions in HbA_1c were statistically significant compared with baseline in all treatment groups, ranging from 1.02 percentage points with 60 mg to 0.69 percentage points with 5 mg. In the placebo group, HbA_1c dropped by 0.49 percentage points, Dr. Prince reported.

Fasting glucagon significantly increased by 0.6- to 4.2-fold compared with baseline across the LY dose levels, and fasting active glucagon-like peptide-1 (GLP-1) rose by 59% at the highest dose. Glucagon and GLP-1 returned to baseline levels during follow-up, he said.

The agent was generally well tolerated. Reversible elevations in hepatic transaminases were seen in five of nine patients in the highest-dose group, with no clinical signs or significant elevations in bilirubin or alkaline phosphatase, he reported. In the interview, Dr. O'Harte said that these two agents seem to have already exceeded expectations. “We need toxicity studies, but there's a possibility for a breakthrough, I hope.”

Dr. Engel is an employee of Merck, and Dr. Prince is an employee of Lilly. Dr. O'Harte stated that he had no disclosures.

LISBON – Although microcirculation in cardiac surgery patients is impaired during the first few hours in the ICU, the degree of impairment was not great enough to affect the accuracy of continuous glucose monitors in a prospective, observational study of 60 patients.

Hyperglycemia, hypoglycemia, and glucose hypervariability are associated with increased mortality in critically ill patients after cardiac surgery. The accuracy of continuous glucose monitoring (CGM) in critically ill patients has been uncertain, said Dr. J. Hans DeVries, an endocrinologist at the University of Amsterdam.

“These results support CGM use in cardiac surgery patients, with quite good sensor accuracy in patients with a low severity of illness,” he said at the meeting.

The patients had a mean age of 65 years; 48 of the 60 were male. Nearly a third (27%) had diabetes. Thirty-two (53%) of the patients had only coronary artery bypass surgery, 16 (27%) had only valve surgery, and 12 (20%) had both procedures. Their APACHE score predicting mortality was low, 0.01. Total ICU stay was 23 hours. Hemodynamic parameters were fairly good, with a microcirculatory function index of 2.8 (out of 3.0). The proportion of perfused vessels was high, 0.97. The patients' peripheral temperature was low, 32.8 °C.

The Medtronic Guardian REAL-Time and the Abbott FreeStyle Navigator sensors were placed subcutaneously in the abdominal wall of each patient prior to surgery. The Navigator performed slightly better than did the Guardian. Microcirculation was measured by microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging; tissue oxygenation was obtained with near-infrared spectroscopy. Tissue oxygenation and perfused vessel density were impaired in the first hours after surgery, but at no point were any microcirculatory parameters significantly associated with sensor accuracy. For the Navigator CGM, lower peripheral temperature and higher APACHE IV scores were significantly associated with decreased sensor accuracy. For the Guardian, lower peripheral temperature was significantly associated with decreased sensor accuracy.

The EASD's European Foundation for the Study of Diabetes funded the study. Dr. DeVries disclosed ties with Dexcom, Abbott, and Medtronic.

The study results showed 'quite good sensor accuracy in patients with a low severity of illness.'

Source DR.

LISBON – Although microcirculation in cardiac surgery patients is impaired during the first few hours in the ICU, the degree of impairment was not great enough to affect the accuracy of continuous glucose monitors in a prospective, observational study of 60 patients.

Hyperglycemia, hypoglycemia, and glucose hypervariability are associated with increased mortality in critically ill patients after cardiac surgery. The accuracy of continuous glucose monitoring (CGM) in critically ill patients has been uncertain, said Dr. J. Hans DeVries, an endocrinologist at the University of Amsterdam.

“These results support CGM use in cardiac surgery patients, with quite good sensor accuracy in patients with a low severity of illness,” he said at the meeting.

The patients had a mean age of 65 years; 48 of the 60 were male. Nearly a third (27%) had diabetes. Thirty-two (53%) of the patients had only coronary artery bypass surgery, 16 (27%) had only valve surgery, and 12 (20%) had both procedures. Their APACHE score predicting mortality was low, 0.01. Total ICU stay was 23 hours. Hemodynamic parameters were fairly good, with a microcirculatory function index of 2.8 (out of 3.0). The proportion of perfused vessels was high, 0.97. The patients' peripheral temperature was low, 32.8 °C.

The Medtronic Guardian REAL-Time and the Abbott FreeStyle Navigator sensors were placed subcutaneously in the abdominal wall of each patient prior to surgery. The Navigator performed slightly better than did the Guardian. Microcirculation was measured by microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging; tissue oxygenation was obtained with near-infrared spectroscopy. Tissue oxygenation and perfused vessel density were impaired in the first hours after surgery, but at no point were any microcirculatory parameters significantly associated with sensor accuracy. For the Navigator CGM, lower peripheral temperature and higher APACHE IV scores were significantly associated with decreased sensor accuracy. For the Guardian, lower peripheral temperature was significantly associated with decreased sensor accuracy.

The EASD's European Foundation for the Study of Diabetes funded the study. Dr. DeVries disclosed ties with Dexcom, Abbott, and Medtronic.

The study results showed 'quite good sensor accuracy in patients with a low severity of illness.'

Source DR.

LISBON – Although microcirculation in cardiac surgery patients is impaired during the first few hours in the ICU, the degree of impairment was not great enough to affect the accuracy of continuous glucose monitors in a prospective, observational study of 60 patients.

Hyperglycemia, hypoglycemia, and glucose hypervariability are associated with increased mortality in critically ill patients after cardiac surgery. The accuracy of continuous glucose monitoring (CGM) in critically ill patients has been uncertain, said Dr. J. Hans DeVries, an endocrinologist at the University of Amsterdam.

“These results support CGM use in cardiac surgery patients, with quite good sensor accuracy in patients with a low severity of illness,” he said at the meeting.

The patients had a mean age of 65 years; 48 of the 60 were male. Nearly a third (27%) had diabetes. Thirty-two (53%) of the patients had only coronary artery bypass surgery, 16 (27%) had only valve surgery, and 12 (20%) had both procedures. Their APACHE score predicting mortality was low, 0.01. Total ICU stay was 23 hours. Hemodynamic parameters were fairly good, with a microcirculatory function index of 2.8 (out of 3.0). The proportion of perfused vessels was high, 0.97. The patients' peripheral temperature was low, 32.8 °C.

The Medtronic Guardian REAL-Time and the Abbott FreeStyle Navigator sensors were placed subcutaneously in the abdominal wall of each patient prior to surgery. The Navigator performed slightly better than did the Guardian. Microcirculation was measured by microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging; tissue oxygenation was obtained with near-infrared spectroscopy. Tissue oxygenation and perfused vessel density were impaired in the first hours after surgery, but at no point were any microcirculatory parameters significantly associated with sensor accuracy. For the Navigator CGM, lower peripheral temperature and higher APACHE IV scores were significantly associated with decreased sensor accuracy. For the Guardian, lower peripheral temperature was significantly associated with decreased sensor accuracy.

The EASD's European Foundation for the Study of Diabetes funded the study. Dr. DeVries disclosed ties with Dexcom, Abbott, and Medtronic.

The study results showed 'quite good sensor accuracy in patients with a low severity of illness.'

Source DR.

Major Finding: Mean blood glucose levels were nearly identical with and without the LGS (148 vs. 145 mg/dL, respectively), whereas the amount of time spent with blood glucose levels of less than 70 mg/dL and excursions of hypoglycemia below 40 mg/dL were reduced by about 50% with the LGS.

Data Source: A study of 21 children at three German pediatric diabetes centers.

Disclosures: Dr. Danne received funding from Medtronic to conduct this trial.

SAN DIEGO – The “low glucose suspend” insulin pump feature reduced hypoglycemia risk without any severe hyperglycemia or diabetic ketoacidosis in study of 21 children with type 1 diabetes.

Medtronic's sensor-augmented insulin pump, the Paradigm Veo system, comprises an insulin pump, a continuous glucose monitor, and a component that first issues a “pre-alarm” if the sensor detects a reading below a preset level. If there is no response by the patient and the glucose level continues to drop to a second preset level, the pump then alerts again and stops the basal insulin infusion for 2 hours or until there is a response. At 2 hours, the basal infusion resumes. If the glucose level is still too low at 4 hours after resumption, the cycle begins again.

The patient can interrupt the low glucose suspend (LGS) feature at any time, said Dr. Thomas Danne, head of the diabetes center for children and adolescents at the Kinderkrankenhaus auf der Bult in Hanover, Germany.

The Veo system is sold in 45 countries, including Canada and countries in Europe, but it is not currently available in the United States. The Food and Drug Administration recently issued a guidance for manufacturers developing LGS, specifying the testing that must take place to address safety issues, including a concern that the device might overcorrect the hypoglycemia, resulting in hyperglycemia and/or diabetic ketoacidosis (DKA).

The Medtronic-sponsored study, conducted in Germany, initially enrolled 24 patients aged 1–21 years (mean, 10.8 years) who had type 1 diabetes and had been on insulin pump therapy for an average of 3.6 years. After patients wore the Veo without the LGS and pre-alerts for 2 weeks, those features were then turned on for the subsequent 6 weeks. The hypoglycemia alert was set at 75 mg/dL, and the LGS alert at 70 mg/dL. Complete data were available for 21 of the children.

There were 1,298 alerts, of which 66% were shorter than 5 minutes because the patients reacted immediately. The frequency of alerts was 2.56 per patient per day, of which 78% occurred during the day (6:00 a.m.–10:00 p.m.). The frequency of insulin delivery disruptions was more common at night (0.175 vs. 0.032 per patient per day), said Dr. Danne.

During the time of the LGS suspension, glucose levels rose an average of 35 mg/dL per hour, totaling 68.4 mg/dL per hour for the entire 120-minute period. The mean blood glucose level during the 6-week LGS period was 148 mg/dL, which was nearly identical to the 145 mg/dL recorded during the initial 2-week phase without the LGS. The time spent with hyperglycemia also was not significantly different (639 vs. 651 minutes). There were no cases of DKA during either time period, he reported.

But hypoglycemia rates did differ significantly. The amount of time spent with blood glucose levels less than 70 mg/dL was 58 minutes per day with the LGS, compared with 101 minutes without. Excursions of hypoglycemia below 40 mg/dL were also much lower with the LGS (0.13 vs. 0.28 per patient per day) during both the daytime and overnight hours. The LGS cut the time spent with blood glucose levels lower than both 70 mg/dL and 40 mg/dL by about 50%.

Major Finding: Mean blood glucose levels were nearly identical with and without the LGS (148 vs. 145 mg/dL, respectively), whereas the amount of time spent with blood glucose levels of less than 70 mg/dL and excursions of hypoglycemia below 40 mg/dL were reduced by about 50% with the LGS.

Data Source: A study of 21 children at three German pediatric diabetes centers.

Disclosures: Dr. Danne received funding from Medtronic to conduct this trial.

SAN DIEGO – The “low glucose suspend” insulin pump feature reduced hypoglycemia risk without any severe hyperglycemia or diabetic ketoacidosis in study of 21 children with type 1 diabetes.

Medtronic's sensor-augmented insulin pump, the Paradigm Veo system, comprises an insulin pump, a continuous glucose monitor, and a component that first issues a “pre-alarm” if the sensor detects a reading below a preset level. If there is no response by the patient and the glucose level continues to drop to a second preset level, the pump then alerts again and stops the basal insulin infusion for 2 hours or until there is a response. At 2 hours, the basal infusion resumes. If the glucose level is still too low at 4 hours after resumption, the cycle begins again.

The patient can interrupt the low glucose suspend (LGS) feature at any time, said Dr. Thomas Danne, head of the diabetes center for children and adolescents at the Kinderkrankenhaus auf der Bult in Hanover, Germany.

The Veo system is sold in 45 countries, including Canada and countries in Europe, but it is not currently available in the United States. The Food and Drug Administration recently issued a guidance for manufacturers developing LGS, specifying the testing that must take place to address safety issues, including a concern that the device might overcorrect the hypoglycemia, resulting in hyperglycemia and/or diabetic ketoacidosis (DKA).

The Medtronic-sponsored study, conducted in Germany, initially enrolled 24 patients aged 1–21 years (mean, 10.8 years) who had type 1 diabetes and had been on insulin pump therapy for an average of 3.6 years. After patients wore the Veo without the LGS and pre-alerts for 2 weeks, those features were then turned on for the subsequent 6 weeks. The hypoglycemia alert was set at 75 mg/dL, and the LGS alert at 70 mg/dL. Complete data were available for 21 of the children.

There were 1,298 alerts, of which 66% were shorter than 5 minutes because the patients reacted immediately. The frequency of alerts was 2.56 per patient per day, of which 78% occurred during the day (6:00 a.m.–10:00 p.m.). The frequency of insulin delivery disruptions was more common at night (0.175 vs. 0.032 per patient per day), said Dr. Danne.

During the time of the LGS suspension, glucose levels rose an average of 35 mg/dL per hour, totaling 68.4 mg/dL per hour for the entire 120-minute period. The mean blood glucose level during the 6-week LGS period was 148 mg/dL, which was nearly identical to the 145 mg/dL recorded during the initial 2-week phase without the LGS. The time spent with hyperglycemia also was not significantly different (639 vs. 651 minutes). There were no cases of DKA during either time period, he reported.

But hypoglycemia rates did differ significantly. The amount of time spent with blood glucose levels less than 70 mg/dL was 58 minutes per day with the LGS, compared with 101 minutes without. Excursions of hypoglycemia below 40 mg/dL were also much lower with the LGS (0.13 vs. 0.28 per patient per day) during both the daytime and overnight hours. The LGS cut the time spent with blood glucose levels lower than both 70 mg/dL and 40 mg/dL by about 50%.

Major Finding: Mean blood glucose levels were nearly identical with and without the LGS (148 vs. 145 mg/dL, respectively), whereas the amount of time spent with blood glucose levels of less than 70 mg/dL and excursions of hypoglycemia below 40 mg/dL were reduced by about 50% with the LGS.

Data Source: A study of 21 children at three German pediatric diabetes centers.

Disclosures: Dr. Danne received funding from Medtronic to conduct this trial.

SAN DIEGO – The “low glucose suspend” insulin pump feature reduced hypoglycemia risk without any severe hyperglycemia or diabetic ketoacidosis in study of 21 children with type 1 diabetes.

Medtronic's sensor-augmented insulin pump, the Paradigm Veo system, comprises an insulin pump, a continuous glucose monitor, and a component that first issues a “pre-alarm” if the sensor detects a reading below a preset level. If there is no response by the patient and the glucose level continues to drop to a second preset level, the pump then alerts again and stops the basal insulin infusion for 2 hours or until there is a response. At 2 hours, the basal infusion resumes. If the glucose level is still too low at 4 hours after resumption, the cycle begins again.

The patient can interrupt the low glucose suspend (LGS) feature at any time, said Dr. Thomas Danne, head of the diabetes center for children and adolescents at the Kinderkrankenhaus auf der Bult in Hanover, Germany.

The Veo system is sold in 45 countries, including Canada and countries in Europe, but it is not currently available in the United States. The Food and Drug Administration recently issued a guidance for manufacturers developing LGS, specifying the testing that must take place to address safety issues, including a concern that the device might overcorrect the hypoglycemia, resulting in hyperglycemia and/or diabetic ketoacidosis (DKA).

The Medtronic-sponsored study, conducted in Germany, initially enrolled 24 patients aged 1–21 years (mean, 10.8 years) who had type 1 diabetes and had been on insulin pump therapy for an average of 3.6 years. After patients wore the Veo without the LGS and pre-alerts for 2 weeks, those features were then turned on for the subsequent 6 weeks. The hypoglycemia alert was set at 75 mg/dL, and the LGS alert at 70 mg/dL. Complete data were available for 21 of the children.

There were 1,298 alerts, of which 66% were shorter than 5 minutes because the patients reacted immediately. The frequency of alerts was 2.56 per patient per day, of which 78% occurred during the day (6:00 a.m.–10:00 p.m.). The frequency of insulin delivery disruptions was more common at night (0.175 vs. 0.032 per patient per day), said Dr. Danne.

During the time of the LGS suspension, glucose levels rose an average of 35 mg/dL per hour, totaling 68.4 mg/dL per hour for the entire 120-minute period. The mean blood glucose level during the 6-week LGS period was 148 mg/dL, which was nearly identical to the 145 mg/dL recorded during the initial 2-week phase without the LGS. The time spent with hyperglycemia also was not significantly different (639 vs. 651 minutes). There were no cases of DKA during either time period, he reported.

But hypoglycemia rates did differ significantly. The amount of time spent with blood glucose levels less than 70 mg/dL was 58 minutes per day with the LGS, compared with 101 minutes without. Excursions of hypoglycemia below 40 mg/dL were also much lower with the LGS (0.13 vs. 0.28 per patient per day) during both the daytime and overnight hours. The LGS cut the time spent with blood glucose levels lower than both 70 mg/dL and 40 mg/dL by about 50%.

LAS VEGAS – Shared medical appointments can be a financially viable way to implement effective diabetes education to a large number of patients in primary care settings, the experience of one practice in south Texas demonstrated.

The premise of the shared medical appointment (SMA), first described in 1974 as a model for well-child consultations, is to provide the educational part of a medical appointment once with a large group of patients rather than repeating the same material over and over again on a one-on-one basis.

“Shared medical appointments are a health care delivery model that provide an opportunity to manage chronic illness, and improve quality and patient self-efficacy and self-management,” said certified diabetes educator Iris Sanchez, DNP, of the Weslaco (Tex.) Medical Clinic.

Weslaco is just to the north of the Mexico border. As such, the population is nearly 100% Hispanic and the diabetes rates are high: In the town's county of Hidalgo, 13.3% of the population has diabetes, compared with 10.3% for the state of Texas and 8.3% for the entire United States. Patients often travel long distances to get to the clinic for medical visits. Based on evidence from a large body of literature, shared medical appointments were seen as a potential way for the clinic to maximize efficiency of delivery of diabetes education while also delivering quality medical care, said Dr. Sanchez, whose report was published online earlier this year (The Diabetes Educator 2011 March 31 [doi:10.1177/0145721711401667).

The program was developed within the context of the chronic care model, a proposed framework for organizing care for patients with chronic conditions that incorporates the elements of community resources and policies, health systems, self-management support, delivery systems design, decision support, and clinical information systems (Milbank Q. 1996;74:511-44).

The clinic employs one physician and two nurse practitioners. The team invited to speak to the group about self-management included a dietician, podiatrist, exercise physiologist, social worker, and others. Flyers were posted in exam rooms and in the lobby to advertise the “Diabetes Days,” and ads were placed in the local newspaper in English and Spanish.

The shared medical appointment, including the educational component plus the medical visit, lasted a total of 90 minutes. Patients were called out during the group education session to see the physician or nurse practitioner for their medical visits, and would then return to the room. To maintain confidentiality, individual cases were not discussed during the educational sessions, Dr. Sanchez noted.

Progress notes were kept, and outcomes tracked using an electronic medical record system. Initially scheduled once a week with 12 people in the group, the SMAs have recently been expanded to twice weekly. It's important to tell patients that the SMAs are not a choice, but are to be kept just as they would a medical appointment. Participation initially varied from 30% to 100%, but now hovers around 90%.

Of 70 patients seen between September and November 2009, 65 had a second visit and 49 a third. Prior to initiation of the program, 75% had not had a urine albumin measurement in the previous 12 months, 34% had not had an eye exam, and 55% were not on daily aspirin. All of these standards of care were implemented as part of the SMA, which resulted in increased revenue from services such as eye exams and urine screens, Dr. Sanchez pointed out.

Average hemoglobin A_1c at initiation was 7.95%. That dropped to 7.48% on second measurement, and rose slightly to 7.51% at a third measurement. For those with a second HbA_1c value, 25 (42%) had an increase and 34 (58%) had a decrease. The differences were not statistically significant, but they were clinically significant, she said. Dr. Sanchez reported having no financial disclosures.

LAS VEGAS – Shared medical appointments can be a financially viable way to implement effective diabetes education to a large number of patients in primary care settings, the experience of one practice in south Texas demonstrated.

The premise of the shared medical appointment (SMA), first described in 1974 as a model for well-child consultations, is to provide the educational part of a medical appointment once with a large group of patients rather than repeating the same material over and over again on a one-on-one basis.

“Shared medical appointments are a health care delivery model that provide an opportunity to manage chronic illness, and improve quality and patient self-efficacy and self-management,” said certified diabetes educator Iris Sanchez, DNP, of the Weslaco (Tex.) Medical Clinic.

Weslaco is just to the north of the Mexico border. As such, the population is nearly 100% Hispanic and the diabetes rates are high: In the town's county of Hidalgo, 13.3% of the population has diabetes, compared with 10.3% for the state of Texas and 8.3% for the entire United States. Patients often travel long distances to get to the clinic for medical visits. Based on evidence from a large body of literature, shared medical appointments were seen as a potential way for the clinic to maximize efficiency of delivery of diabetes education while also delivering quality medical care, said Dr. Sanchez, whose report was published online earlier this year (The Diabetes Educator 2011 March 31 [doi:10.1177/0145721711401667).

The program was developed within the context of the chronic care model, a proposed framework for organizing care for patients with chronic conditions that incorporates the elements of community resources and policies, health systems, self-management support, delivery systems design, decision support, and clinical information systems (Milbank Q. 1996;74:511-44).

The clinic employs one physician and two nurse practitioners. The team invited to speak to the group about self-management included a dietician, podiatrist, exercise physiologist, social worker, and others. Flyers were posted in exam rooms and in the lobby to advertise the “Diabetes Days,” and ads were placed in the local newspaper in English and Spanish.

The shared medical appointment, including the educational component plus the medical visit, lasted a total of 90 minutes. Patients were called out during the group education session to see the physician or nurse practitioner for their medical visits, and would then return to the room. To maintain confidentiality, individual cases were not discussed during the educational sessions, Dr. Sanchez noted.

Progress notes were kept, and outcomes tracked using an electronic medical record system. Initially scheduled once a week with 12 people in the group, the SMAs have recently been expanded to twice weekly. It's important to tell patients that the SMAs are not a choice, but are to be kept just as they would a medical appointment. Participation initially varied from 30% to 100%, but now hovers around 90%.

Of 70 patients seen between September and November 2009, 65 had a second visit and 49 a third. Prior to initiation of the program, 75% had not had a urine albumin measurement in the previous 12 months, 34% had not had an eye exam, and 55% were not on daily aspirin. All of these standards of care were implemented as part of the SMA, which resulted in increased revenue from services such as eye exams and urine screens, Dr. Sanchez pointed out.

Average hemoglobin A_1c at initiation was 7.95%. That dropped to 7.48% on second measurement, and rose slightly to 7.51% at a third measurement. For those with a second HbA_1c value, 25 (42%) had an increase and 34 (58%) had a decrease. The differences were not statistically significant, but they were clinically significant, she said. Dr. Sanchez reported having no financial disclosures.

LAS VEGAS – Shared medical appointments can be a financially viable way to implement effective diabetes education to a large number of patients in primary care settings, the experience of one practice in south Texas demonstrated.

The premise of the shared medical appointment (SMA), first described in 1974 as a model for well-child consultations, is to provide the educational part of a medical appointment once with a large group of patients rather than repeating the same material over and over again on a one-on-one basis.

“Shared medical appointments are a health care delivery model that provide an opportunity to manage chronic illness, and improve quality and patient self-efficacy and self-management,” said certified diabetes educator Iris Sanchez, DNP, of the Weslaco (Tex.) Medical Clinic.

Weslaco is just to the north of the Mexico border. As such, the population is nearly 100% Hispanic and the diabetes rates are high: In the town's county of Hidalgo, 13.3% of the population has diabetes, compared with 10.3% for the state of Texas and 8.3% for the entire United States. Patients often travel long distances to get to the clinic for medical visits. Based on evidence from a large body of literature, shared medical appointments were seen as a potential way for the clinic to maximize efficiency of delivery of diabetes education while also delivering quality medical care, said Dr. Sanchez, whose report was published online earlier this year (The Diabetes Educator 2011 March 31 [doi:10.1177/0145721711401667).

The program was developed within the context of the chronic care model, a proposed framework for organizing care for patients with chronic conditions that incorporates the elements of community resources and policies, health systems, self-management support, delivery systems design, decision support, and clinical information systems (Milbank Q. 1996;74:511-44).

The clinic employs one physician and two nurse practitioners. The team invited to speak to the group about self-management included a dietician, podiatrist, exercise physiologist, social worker, and others. Flyers were posted in exam rooms and in the lobby to advertise the “Diabetes Days,” and ads were placed in the local newspaper in English and Spanish.

The shared medical appointment, including the educational component plus the medical visit, lasted a total of 90 minutes. Patients were called out during the group education session to see the physician or nurse practitioner for their medical visits, and would then return to the room. To maintain confidentiality, individual cases were not discussed during the educational sessions, Dr. Sanchez noted.

Progress notes were kept, and outcomes tracked using an electronic medical record system. Initially scheduled once a week with 12 people in the group, the SMAs have recently been expanded to twice weekly. It's important to tell patients that the SMAs are not a choice, but are to be kept just as they would a medical appointment. Participation initially varied from 30% to 100%, but now hovers around 90%.

Of 70 patients seen between September and November 2009, 65 had a second visit and 49 a third. Prior to initiation of the program, 75% had not had a urine albumin measurement in the previous 12 months, 34% had not had an eye exam, and 55% were not on daily aspirin. All of these standards of care were implemented as part of the SMA, which resulted in increased revenue from services such as eye exams and urine screens, Dr. Sanchez pointed out.

Average hemoglobin A_1c at initiation was 7.95%. That dropped to 7.48% on second measurement, and rose slightly to 7.51% at a third measurement. For those with a second HbA_1c value, 25 (42%) had an increase and 34 (58%) had a decrease. The differences were not statistically significant, but they were clinically significant, she said. Dr. Sanchez reported having no financial disclosures.

NEW YORK – For the first time ever, the United Nations formally recognized and set an agenda to reduce the burden of noncommunicable diseases globally. However, to many observers anticipating the historic event, the effort fell short of setting tangible targets for driving change.

At the September meeting of the UN General Assembly – the second high-level meeting ever to address a health issue since a 2001 meeting on HIV/AIDS – the UN issued a consensus document recognizing that "the global burden and threat of NCDs constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world."

In the consensus document, known as a political declaration, UN members pledged to promote the reduction of salts and sugars; to eliminate trans fats in foods; to increase access to affordable, quality-assured medicines and technologies; and to strengthen health care systems so they can address NCD prevention and treatment.

The UN also endorsed WHO efforts to combat smoking, to improve diet and physical activity, to reduce the harmful use of alcohol, and to halt the marketing of unhealthful foods and beverages to children.

The UN Secretary-General Ban Ki-moon urged UN representatives at the meeting to carry out the provisions of the document and to "bring NCDs into our broader global health and development agenda."

Nearly two-thirds (63%) of deaths worldwide result from NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries, according to the WHO. Because half of individuals who die of NCDs are in their working-age years, the issue is recognized as an economic and developmental problem, as well as one of public health. Success will need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade, UN members agreed.

NCDs are "the diseases that break the bank," said Dr. Margaret Chan, WHO’s director general. They are anticipated to cost more than $30 trillion in U.S. dollars over the next 20 years, representing 48% of global gross domestic product in 2010, according to a report issued by the World Economic Forum.

Yet just days before the meeting was held, several contentious revisions to the final draft of the political declaration took place, essentially stripping the document of specific and time-bound targets.

The NCD Alliance, a lobbying coalition of global NCD-related organizations, opposed the removal of the goal to cut by 25% all preventable deaths from cancer, cardiovascular disease, diabetes, and chronic respiratory disease by 2025, an element that did not make it into the final document.

"Emblematic figures have been excised, such as the aim to reduce salt intake to less than 5 g per day," according to an editorial that blamed conflicts of interest for the lack of compulsory targets (Lancet Oncol. 2011 Sept. 22 [doi:10.1016/S1470-2045(11)70272-8]).

"Groups from the food and drink industry ... were invited to participate in the meeting, although they were excluded from any decision-making. Unsurprisingly, these industry representatives urged a voluntary, rather than a regulatory approach," the authors wrote.

Instead of compulsory targets, the UN tasked the WHO to establish a comprehensive global monitoring framework and to prepare recommendations for voluntary global targets before the end of 2012, as well as to report initial progress in 2013, enabling a lack of accountability that the editorial authors deemed "a missed opportunity."

In a similar expression of concern, Paul Lincoln of the National Health Forum in London and colleagues issued a statement calling for the conflicts of interest to be "explicitly recognized and addressed. ...Failure to do this will undermine the development of competent policy; the effectiveness and efficiency of programs; and the confidence the global health community and the public at large have in the UN and WHO’s ability to govern and advance public health, which will severely impair capacity to help member states address NCDs" (Lancet 2011 [doi:10.1016/S0140-6736(11)61463-3]).

Dr. Derek Yach, senior vice president for global health and agriculture policy at PepsiCo, said that industry agrees with the principle of reducing conflicts of interest. But, he noted, "the reality is that conflicts occur not just in relationship between industry and [the UN], but between academic bodies, foundations, and other entities. They all bring their own particular backgrounds, interests, prejudices and perspectives. All forms of conflicts need to be addressed."

Dr. Yach, formerly a professor of public health and head of the division of global health at Yale University in New Haven, Conn., and a former executive director of the WHO, said he disagrees that industry should be barred from policy development. "I think that industry has to be involved in the development of the options for policy, and in the implementation. The middle bit – when final decisions are made on policy – is probably best left in the hand of government and the UN. But if industry is not at the table, even talking about the options, the UN and the government will simply be lost in terms of knowing the full range of possibilities that are out there."

He noted that industry is already committed to reformulating products, to changing food and beverage marketing to children, and to promoting greater physical activity.

In 2012, the UN is slated to address the issues of targets and indicators, as well as establish a postsummit partnership to drive implementation and ensure accountability. There is still a chance that the "25% by 2025" NCD mortality reduction goal and other targets might be reinserted, NCD Alliance CEO Ann Keeling said in an interview.

The Alliance, the main lobbying group that had first initiated the call for the UN high-level meeting, will be urging governments and the UN system to agree to strong outcomes on those issues. "If the outcomes are strong, we will forgive governments for not agreeing to those at the summit," Ms. Keeling said.

The 2-day, high-level meeting of the UN General Assembly was not aimed just at the developing world, although that was a major focus.

Indeed, heads of state from more than 130 member states – including low-, middle- and high-income nations – were each allotted 3 minutes to speak about their own nations’ experiences with NCDs and their national efforts taken to combat them.

The United States, where NCDs account for 7 of 10 deaths, is committed to reducing NCDs, Health and Human Services Secretary Kathleen Sebelius said in her 3-minute address. "For the United States’ part, under President Obama the United States has made taking on chronic disease a major focus."

Among the U.S. initiatives are the recently launched Million Hearts campaign (http://millionhearts.hhs.gov), a public-private sector initiative that aims to prevent 1 million heart attacks and strokes in 5 years by improving aspirin use, blood pressure management, cholesterol control, and smoking prevention. She also pointed to First Lady Michelle Obama’s ongoing efforts in reducing childhood obesity, and the Clinton Global Initiative Commitment, a public-private partnership to support tobacco-cessation efforts using mobile phone technologies.

NEW YORK – For the first time ever, the United Nations formally recognized and set an agenda to reduce the burden of noncommunicable diseases globally. However, to many observers anticipating the historic event, the effort fell short of setting tangible targets for driving change.

At the September meeting of the UN General Assembly – the second high-level meeting ever to address a health issue since a 2001 meeting on HIV/AIDS – the UN issued a consensus document recognizing that "the global burden and threat of NCDs constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world."

In the consensus document, known as a political declaration, UN members pledged to promote the reduction of salts and sugars; to eliminate trans fats in foods; to increase access to affordable, quality-assured medicines and technologies; and to strengthen health care systems so they can address NCD prevention and treatment.

The UN also endorsed WHO efforts to combat smoking, to improve diet and physical activity, to reduce the harmful use of alcohol, and to halt the marketing of unhealthful foods and beverages to children.

The UN Secretary-General Ban Ki-moon urged UN representatives at the meeting to carry out the provisions of the document and to "bring NCDs into our broader global health and development agenda."

Nearly two-thirds (63%) of deaths worldwide result from NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries, according to the WHO. Because half of individuals who die of NCDs are in their working-age years, the issue is recognized as an economic and developmental problem, as well as one of public health. Success will need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade, UN members agreed.

NCDs are "the diseases that break the bank," said Dr. Margaret Chan, WHO’s director general. They are anticipated to cost more than $30 trillion in U.S. dollars over the next 20 years, representing 48% of global gross domestic product in 2010, according to a report issued by the World Economic Forum.

Yet just days before the meeting was held, several contentious revisions to the final draft of the political declaration took place, essentially stripping the document of specific and time-bound targets.

The NCD Alliance, a lobbying coalition of global NCD-related organizations, opposed the removal of the goal to cut by 25% all preventable deaths from cancer, cardiovascular disease, diabetes, and chronic respiratory disease by 2025, an element that did not make it into the final document.

"Emblematic figures have been excised, such as the aim to reduce salt intake to less than 5 g per day," according to an editorial that blamed conflicts of interest for the lack of compulsory targets (Lancet Oncol. 2011 Sept. 22 [doi:10.1016/S1470-2045(11)70272-8]).

"Groups from the food and drink industry ... were invited to participate in the meeting, although they were excluded from any decision-making. Unsurprisingly, these industry representatives urged a voluntary, rather than a regulatory approach," the authors wrote.

Instead of compulsory targets, the UN tasked the WHO to establish a comprehensive global monitoring framework and to prepare recommendations for voluntary global targets before the end of 2012, as well as to report initial progress in 2013, enabling a lack of accountability that the editorial authors deemed "a missed opportunity."

In a similar expression of concern, Paul Lincoln of the National Health Forum in London and colleagues issued a statement calling for the conflicts of interest to be "explicitly recognized and addressed. ...Failure to do this will undermine the development of competent policy; the effectiveness and efficiency of programs; and the confidence the global health community and the public at large have in the UN and WHO’s ability to govern and advance public health, which will severely impair capacity to help member states address NCDs" (Lancet 2011 [doi:10.1016/S0140-6736(11)61463-3]).

Dr. Derek Yach, senior vice president for global health and agriculture policy at PepsiCo, said that industry agrees with the principle of reducing conflicts of interest. But, he noted, "the reality is that conflicts occur not just in relationship between industry and [the UN], but between academic bodies, foundations, and other entities. They all bring their own particular backgrounds, interests, prejudices and perspectives. All forms of conflicts need to be addressed."

Dr. Yach, formerly a professor of public health and head of the division of global health at Yale University in New Haven, Conn., and a former executive director of the WHO, said he disagrees that industry should be barred from policy development. "I think that industry has to be involved in the development of the options for policy, and in the implementation. The middle bit – when final decisions are made on policy – is probably best left in the hand of government and the UN. But if industry is not at the table, even talking about the options, the UN and the government will simply be lost in terms of knowing the full range of possibilities that are out there."

He noted that industry is already committed to reformulating products, to changing food and beverage marketing to children, and to promoting greater physical activity.

In 2012, the UN is slated to address the issues of targets and indicators, as well as establish a postsummit partnership to drive implementation and ensure accountability. There is still a chance that the "25% by 2025" NCD mortality reduction goal and other targets might be reinserted, NCD Alliance CEO Ann Keeling said in an interview.

The Alliance, the main lobbying group that had first initiated the call for the UN high-level meeting, will be urging governments and the UN system to agree to strong outcomes on those issues. "If the outcomes are strong, we will forgive governments for not agreeing to those at the summit," Ms. Keeling said.

The 2-day, high-level meeting of the UN General Assembly was not aimed just at the developing world, although that was a major focus.

Indeed, heads of state from more than 130 member states – including low-, middle- and high-income nations – were each allotted 3 minutes to speak about their own nations’ experiences with NCDs and their national efforts taken to combat them.

The United States, where NCDs account for 7 of 10 deaths, is committed to reducing NCDs, Health and Human Services Secretary Kathleen Sebelius said in her 3-minute address. "For the United States’ part, under President Obama the United States has made taking on chronic disease a major focus."

Among the U.S. initiatives are the recently launched Million Hearts campaign (http://millionhearts.hhs.gov), a public-private sector initiative that aims to prevent 1 million heart attacks and strokes in 5 years by improving aspirin use, blood pressure management, cholesterol control, and smoking prevention. She also pointed to First Lady Michelle Obama’s ongoing efforts in reducing childhood obesity, and the Clinton Global Initiative Commitment, a public-private partnership to support tobacco-cessation efforts using mobile phone technologies.

NEW YORK – For the first time ever, the United Nations formally recognized and set an agenda to reduce the burden of noncommunicable diseases globally. However, to many observers anticipating the historic event, the effort fell short of setting tangible targets for driving change.

At the September meeting of the UN General Assembly – the second high-level meeting ever to address a health issue since a 2001 meeting on HIV/AIDS – the UN issued a consensus document recognizing that "the global burden and threat of NCDs constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world."

In the consensus document, known as a political declaration, UN members pledged to promote the reduction of salts and sugars; to eliminate trans fats in foods; to increase access to affordable, quality-assured medicines and technologies; and to strengthen health care systems so they can address NCD prevention and treatment.

The UN also endorsed WHO efforts to combat smoking, to improve diet and physical activity, to reduce the harmful use of alcohol, and to halt the marketing of unhealthful foods and beverages to children.

The UN Secretary-General Ban Ki-moon urged UN representatives at the meeting to carry out the provisions of the document and to "bring NCDs into our broader global health and development agenda."

Nearly two-thirds (63%) of deaths worldwide result from NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries, according to the WHO. Because half of individuals who die of NCDs are in their working-age years, the issue is recognized as an economic and developmental problem, as well as one of public health. Success will need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade, UN members agreed.

NCDs are "the diseases that break the bank," said Dr. Margaret Chan, WHO’s director general. They are anticipated to cost more than $30 trillion in U.S. dollars over the next 20 years, representing 48% of global gross domestic product in 2010, according to a report issued by the World Economic Forum.

Yet just days before the meeting was held, several contentious revisions to the final draft of the political declaration took place, essentially stripping the document of specific and time-bound targets.

The NCD Alliance, a lobbying coalition of global NCD-related organizations, opposed the removal of the goal to cut by 25% all preventable deaths from cancer, cardiovascular disease, diabetes, and chronic respiratory disease by 2025, an element that did not make it into the final document.

"Emblematic figures have been excised, such as the aim to reduce salt intake to less than 5 g per day," according to an editorial that blamed conflicts of interest for the lack of compulsory targets (Lancet Oncol. 2011 Sept. 22 [doi:10.1016/S1470-2045(11)70272-8]).

"Groups from the food and drink industry ... were invited to participate in the meeting, although they were excluded from any decision-making. Unsurprisingly, these industry representatives urged a voluntary, rather than a regulatory approach," the authors wrote.

Instead of compulsory targets, the UN tasked the WHO to establish a comprehensive global monitoring framework and to prepare recommendations for voluntary global targets before the end of 2012, as well as to report initial progress in 2013, enabling a lack of accountability that the editorial authors deemed "a missed opportunity."

In a similar expression of concern, Paul Lincoln of the National Health Forum in London and colleagues issued a statement calling for the conflicts of interest to be "explicitly recognized and addressed. ...Failure to do this will undermine the development of competent policy; the effectiveness and efficiency of programs; and the confidence the global health community and the public at large have in the UN and WHO’s ability to govern and advance public health, which will severely impair capacity to help member states address NCDs" (Lancet 2011 [doi:10.1016/S0140-6736(11)61463-3]).

Dr. Derek Yach, senior vice president for global health and agriculture policy at PepsiCo, said that industry agrees with the principle of reducing conflicts of interest. But, he noted, "the reality is that conflicts occur not just in relationship between industry and [the UN], but between academic bodies, foundations, and other entities. They all bring their own particular backgrounds, interests, prejudices and perspectives. All forms of conflicts need to be addressed."

Dr. Yach, formerly a professor of public health and head of the division of global health at Yale University in New Haven, Conn., and a former executive director of the WHO, said he disagrees that industry should be barred from policy development. "I think that industry has to be involved in the development of the options for policy, and in the implementation. The middle bit – when final decisions are made on policy – is probably best left in the hand of government and the UN. But if industry is not at the table, even talking about the options, the UN and the government will simply be lost in terms of knowing the full range of possibilities that are out there."

He noted that industry is already committed to reformulating products, to changing food and beverage marketing to children, and to promoting greater physical activity.

In 2012, the UN is slated to address the issues of targets and indicators, as well as establish a postsummit partnership to drive implementation and ensure accountability. There is still a chance that the "25% by 2025" NCD mortality reduction goal and other targets might be reinserted, NCD Alliance CEO Ann Keeling said in an interview.

The Alliance, the main lobbying group that had first initiated the call for the UN high-level meeting, will be urging governments and the UN system to agree to strong outcomes on those issues. "If the outcomes are strong, we will forgive governments for not agreeing to those at the summit," Ms. Keeling said.

The 2-day, high-level meeting of the UN General Assembly was not aimed just at the developing world, although that was a major focus.

Indeed, heads of state from more than 130 member states – including low-, middle- and high-income nations – were each allotted 3 minutes to speak about their own nations’ experiences with NCDs and their national efforts taken to combat them.

The United States, where NCDs account for 7 of 10 deaths, is committed to reducing NCDs, Health and Human Services Secretary Kathleen Sebelius said in her 3-minute address. "For the United States’ part, under President Obama the United States has made taking on chronic disease a major focus."

Among the U.S. initiatives are the recently launched Million Hearts campaign (http://millionhearts.hhs.gov), a public-private sector initiative that aims to prevent 1 million heart attacks and strokes in 5 years by improving aspirin use, blood pressure management, cholesterol control, and smoking prevention. She also pointed to First Lady Michelle Obama’s ongoing efforts in reducing childhood obesity, and the Clinton Global Initiative Commitment, a public-private partnership to support tobacco-cessation efforts using mobile phone technologies.

Intensive glycemic lowering did not significantly affect cognition at 40 months in older adults with type 2 diabetes participating in the Action to Control Cardiovascular Risk in Diabetes study.

There were differences in brain structure, however, suggesting that structural changes occur prior to cognitive changes, said Lenore J. Launer, Ph.D., of the National Institute on Aging, Bethesda, Md., and her associates (Lancet Neurol. 2011 [doi:10.1016/S1474-4422[11]70188-0]).

The MIND (Memory in Diabetes) study was a substudy of 2,977 ACCORD participants who had been randomly assigned to receive either intensive glycemic treatment targeting hemoglobin A_1c to less than 6.0% or standard treatment targeting HbA_1c to 7.0%-7.9%. They were also assigned to either intensive or standard lipid- and blood pressure–lowering treatment arms. The intensive glucose-lowering intervention was stopped early, in February 2008, because it was associated with a significant 22% increased cardiovascular mortality. Participants in that group were switched to standard glycemic treatment, and the lipid and blood pressure arms of the study were continued. No significant cardiovascular benefit was seen with intensive glucose lowering during the period it was studied (N. Engl. J. Med. 2008;358:2545-59).

The MIND study – believed to be the first-ever randomized study to examine the effect of intensive glucose lowering on cognition and brain structure in older people with type 2 diabetes – began in August 2003, 34 months into ACCORD, and continued until December 2005. Of the total 2,794 MIND patients who had at least 20-month and 40-month follow-up, 614 underwent successful brain magnetic resonance imaging (MRI).

The patients had a mean age of 62.5 years at study start, and the separation in median HbA_1c achieved between the intensive and standard treatment groups – 6.6% vs. 7.5% – was similar to that of the overall ACCORD study population. At the time the intensive treatment intervention was stopped, the MIND study patients in that group had received treatment for a median of 39 months, and those in the MRI substudy had received 35 months of intensive treatment.

Scores on the primary end point DSST (Digit Symbol Substitution Test), a measure of psychomotor speed that requires reasoning and working memory, declined in both the intensive and standard treatment groups. At 20 months, the difference between the two groups approached statistical significance (P = .076), but by 40 months the difference was attenuated and not significant (P = .23).

Other measures of cognition, the RAVLT (Rey Auditory Verbal Learning Test) and the Stroop test of executive function, also changed similarly in the intensive and standard treatment groups. There were small increases in mean RAVLT scores between groups, but no significant difference between them. Performance on the Stroop test improved slightly in the intensive treatment group and declined slightly in the standard treatment group, but there was no difference between treatments.

"Overall, there is no evidence in this patient group, which had long-standing type 2 diabetes, a high risk of cardiovascular disease, and a mean of 62 years, that an intensive glycemic treatment strategy provides benefit to cognitive function," Dr. Launer and her associates commented.

Differences were seen in brain structure, however. At 40 months, the intensive treatment group had significantly greater total brain volume (TBV), compared with the standard treatment group. Although TBV declined in both groups, the TBV of the intensive treatment group declined less, by 0.41%/year, compared with 0.57%/year. Abnormal white matter (AWM) tissue volume was significantly greater in the intensive treatment group at 40 months (geometric mean 1.89 vs. 1.71 cm³), but this effect seems to be restricted to patients younger than 60 years, they noted.

There was no evidence that measures of peripheral edema or weight gain could explain the differences in TBV or AWM between groups.

"There was a significant but small difference in TBV favoring the intensive strategy. However, this difference does not support the use of intensive treatment to reduce brain atrophy in view of the effects of this intervention in the main ACCORD trial: Raised mortality, no overall benefit on cardiovascular disease events, an increase in hypoglycemic events, and weight gain," the investigators commented.

"Taking the cognitive and MRI findings together, it is reasonable to postulate that, in this age group, structural changes in the brain happen before cognitive changes and that over time cognitive differences between treatment groups would emerge," Dr. Launer and her associates said, noting that ongoing follow-up should be able to establish whether that is the case.

Dr. Launer and all but one of her 21 coauthors declared that they had no conflicts of interest. Dr. Hertzel C. Gerstein, the principal investigator for the overall ACCORD trial, declared that that he has received consulting fees, institutional grant support, and/or lecture fees from numerous pharmaceutical companies including Sanofi-Aventis, GlaxoSmithKline, Eli Lilly, Novo Nordisk, AstraZeneca, and Bristol-Myers Squibb.

Intensive glycemic lowering did not significantly affect cognition at 40 months in older adults with type 2 diabetes participating in the Action to Control Cardiovascular Risk in Diabetes study.

There were differences in brain structure, however, suggesting that structural changes occur prior to cognitive changes, said Lenore J. Launer, Ph.D., of the National Institute on Aging, Bethesda, Md., and her associates (Lancet Neurol. 2011 [doi:10.1016/S1474-4422[11]70188-0]).

The MIND (Memory in Diabetes) study was a substudy of 2,977 ACCORD participants who had been randomly assigned to receive either intensive glycemic treatment targeting hemoglobin A_1c to less than 6.0% or standard treatment targeting HbA_1c to 7.0%-7.9%. They were also assigned to either intensive or standard lipid- and blood pressure–lowering treatment arms. The intensive glucose-lowering intervention was stopped early, in February 2008, because it was associated with a significant 22% increased cardiovascular mortality. Participants in that group were switched to standard glycemic treatment, and the lipid and blood pressure arms of the study were continued. No significant cardiovascular benefit was seen with intensive glucose lowering during the period it was studied (N. Engl. J. Med. 2008;358:2545-59).

The MIND study – believed to be the first-ever randomized study to examine the effect of intensive glucose lowering on cognition and brain structure in older people with type 2 diabetes – began in August 2003, 34 months into ACCORD, and continued until December 2005. Of the total 2,794 MIND patients who had at least 20-month and 40-month follow-up, 614 underwent successful brain magnetic resonance imaging (MRI).

The patients had a mean age of 62.5 years at study start, and the separation in median HbA_1c achieved between the intensive and standard treatment groups – 6.6% vs. 7.5% – was similar to that of the overall ACCORD study population. At the time the intensive treatment intervention was stopped, the MIND study patients in that group had received treatment for a median of 39 months, and those in the MRI substudy had received 35 months of intensive treatment.

Scores on the primary end point DSST (Digit Symbol Substitution Test), a measure of psychomotor speed that requires reasoning and working memory, declined in both the intensive and standard treatment groups. At 20 months, the difference between the two groups approached statistical significance (P = .076), but by 40 months the difference was attenuated and not significant (P = .23).

Other measures of cognition, the RAVLT (Rey Auditory Verbal Learning Test) and the Stroop test of executive function, also changed similarly in the intensive and standard treatment groups. There were small increases in mean RAVLT scores between groups, but no significant difference between them. Performance on the Stroop test improved slightly in the intensive treatment group and declined slightly in the standard treatment group, but there was no difference between treatments.

"Overall, there is no evidence in this patient group, which had long-standing type 2 diabetes, a high risk of cardiovascular disease, and a mean of 62 years, that an intensive glycemic treatment strategy provides benefit to cognitive function," Dr. Launer and her associates commented.

Differences were seen in brain structure, however. At 40 months, the intensive treatment group had significantly greater total brain volume (TBV), compared with the standard treatment group. Although TBV declined in both groups, the TBV of the intensive treatment group declined less, by 0.41%/year, compared with 0.57%/year. Abnormal white matter (AWM) tissue volume was significantly greater in the intensive treatment group at 40 months (geometric mean 1.89 vs. 1.71 cm³), but this effect seems to be restricted to patients younger than 60 years, they noted.

There was no evidence that measures of peripheral edema or weight gain could explain the differences in TBV or AWM between groups.

"There was a significant but small difference in TBV favoring the intensive strategy. However, this difference does not support the use of intensive treatment to reduce brain atrophy in view of the effects of this intervention in the main ACCORD trial: Raised mortality, no overall benefit on cardiovascular disease events, an increase in hypoglycemic events, and weight gain," the investigators commented.

"Taking the cognitive and MRI findings together, it is reasonable to postulate that, in this age group, structural changes in the brain happen before cognitive changes and that over time cognitive differences between treatment groups would emerge," Dr. Launer and her associates said, noting that ongoing follow-up should be able to establish whether that is the case.

Dr. Launer and all but one of her 21 coauthors declared that they had no conflicts of interest. Dr. Hertzel C. Gerstein, the principal investigator for the overall ACCORD trial, declared that that he has received consulting fees, institutional grant support, and/or lecture fees from numerous pharmaceutical companies including Sanofi-Aventis, GlaxoSmithKline, Eli Lilly, Novo Nordisk, AstraZeneca, and Bristol-Myers Squibb.

Intensive glycemic lowering did not significantly affect cognition at 40 months in older adults with type 2 diabetes participating in the Action to Control Cardiovascular Risk in Diabetes study.

There were differences in brain structure, however, suggesting that structural changes occur prior to cognitive changes, said Lenore J. Launer, Ph.D., of the National Institute on Aging, Bethesda, Md., and her associates (Lancet Neurol. 2011 [doi:10.1016/S1474-4422[11]70188-0]).

The MIND (Memory in Diabetes) study was a substudy of 2,977 ACCORD participants who had been randomly assigned to receive either intensive glycemic treatment targeting hemoglobin A_1c to less than 6.0% or standard treatment targeting HbA_1c to 7.0%-7.9%. They were also assigned to either intensive or standard lipid- and blood pressure–lowering treatment arms. The intensive glucose-lowering intervention was stopped early, in February 2008, because it was associated with a significant 22% increased cardiovascular mortality. Participants in that group were switched to standard glycemic treatment, and the lipid and blood pressure arms of the study were continued. No significant cardiovascular benefit was seen with intensive glucose lowering during the period it was studied (N. Engl. J. Med. 2008;358:2545-59).

The MIND study – believed to be the first-ever randomized study to examine the effect of intensive glucose lowering on cognition and brain structure in older people with type 2 diabetes – began in August 2003, 34 months into ACCORD, and continued until December 2005. Of the total 2,794 MIND patients who had at least 20-month and 40-month follow-up, 614 underwent successful brain magnetic resonance imaging (MRI).

The patients had a mean age of 62.5 years at study start, and the separation in median HbA_1c achieved between the intensive and standard treatment groups – 6.6% vs. 7.5% – was similar to that of the overall ACCORD study population. At the time the intensive treatment intervention was stopped, the MIND study patients in that group had received treatment for a median of 39 months, and those in the MRI substudy had received 35 months of intensive treatment.

Scores on the primary end point DSST (Digit Symbol Substitution Test), a measure of psychomotor speed that requires reasoning and working memory, declined in both the intensive and standard treatment groups. At 20 months, the difference between the two groups approached statistical significance (P = .076), but by 40 months the difference was attenuated and not significant (P = .23).

Other measures of cognition, the RAVLT (Rey Auditory Verbal Learning Test) and the Stroop test of executive function, also changed similarly in the intensive and standard treatment groups. There were small increases in mean RAVLT scores between groups, but no significant difference between them. Performance on the Stroop test improved slightly in the intensive treatment group and declined slightly in the standard treatment group, but there was no difference between treatments.

"Overall, there is no evidence in this patient group, which had long-standing type 2 diabetes, a high risk of cardiovascular disease, and a mean of 62 years, that an intensive glycemic treatment strategy provides benefit to cognitive function," Dr. Launer and her associates commented.

Differences were seen in brain structure, however. At 40 months, the intensive treatment group had significantly greater total brain volume (TBV), compared with the standard treatment group. Although TBV declined in both groups, the TBV of the intensive treatment group declined less, by 0.41%/year, compared with 0.57%/year. Abnormal white matter (AWM) tissue volume was significantly greater in the intensive treatment group at 40 months (geometric mean 1.89 vs. 1.71 cm³), but this effect seems to be restricted to patients younger than 60 years, they noted.

There was no evidence that measures of peripheral edema or weight gain could explain the differences in TBV or AWM between groups.

"There was a significant but small difference in TBV favoring the intensive strategy. However, this difference does not support the use of intensive treatment to reduce brain atrophy in view of the effects of this intervention in the main ACCORD trial: Raised mortality, no overall benefit on cardiovascular disease events, an increase in hypoglycemic events, and weight gain," the investigators commented.

"Taking the cognitive and MRI findings together, it is reasonable to postulate that, in this age group, structural changes in the brain happen before cognitive changes and that over time cognitive differences between treatment groups would emerge," Dr. Launer and her associates said, noting that ongoing follow-up should be able to establish whether that is the case.

Dr. Launer and all but one of her 21 coauthors declared that they had no conflicts of interest. Dr. Hertzel C. Gerstein, the principal investigator for the overall ACCORD trial, declared that that he has received consulting fees, institutional grant support, and/or lecture fees from numerous pharmaceutical companies including Sanofi-Aventis, GlaxoSmithKline, Eli Lilly, Novo Nordisk, AstraZeneca, and Bristol-Myers Squibb.

NEW YORK – The United Nations General Assembly has adopted a political declaration on the prevention and control of noncommunicable diseases.

The declaration emerged from a UN high-level meeting that was only the second-ever to address a health issue, the first being on HIV/AIDS in 2001. It states that "the global burden and threat of NCDs [noncommunicable diseases] constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world."

Miriam E. Tucker/Elsevier Global Medical News

According to the World Health Organization, 63% of deaths worldwide are due to NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries.

Although the declaration doesn’t contain everything that noncommunicable disease lobbyists had hoped for, the document is nonetheless seen as a significant first step toward prompting global action to combat NCDs.

Member states agreed to measures such as reducing salts and sugars and eliminating industrially produced trans fats in all foods, increasing access to affordable, quality-assured medicines and technologies, and strengthening health care systems to include integration of NCD prevention and treatment. Beyond the health sector, there was also general agreement that success would need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade.

The U.N. General Assembly also tasked the World Health Organization with setting up a comprehensive global monitoring framework and preparing recommendations for voluntary global targets before the end of 2012.

The NCD community, led by the nongovernmental coalition called the NCD Alliance, had pushed for specific targets, including a 25% reduction of NCD deaths by 2025. But the current declaration isn’t the last step. There will be another evaluation in 2014, just in advance of the scheduled 2015 revision of the Millennium Development Goals, according to the alliance’s director Ann Keeling.

NEW YORK – The United Nations General Assembly has adopted a political declaration on the prevention and control of noncommunicable diseases.

The declaration emerged from a UN high-level meeting that was only the second-ever to address a health issue, the first being on HIV/AIDS in 2001. It states that "the global burden and threat of NCDs [noncommunicable diseases] constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world."

Miriam E. Tucker/Elsevier Global Medical News

According to the World Health Organization, 63% of deaths worldwide are due to NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries.

Although the declaration doesn’t contain everything that noncommunicable disease lobbyists had hoped for, the document is nonetheless seen as a significant first step toward prompting global action to combat NCDs.

Member states agreed to measures such as reducing salts and sugars and eliminating industrially produced trans fats in all foods, increasing access to affordable, quality-assured medicines and technologies, and strengthening health care systems to include integration of NCD prevention and treatment. Beyond the health sector, there was also general agreement that success would need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade.

The U.N. General Assembly also tasked the World Health Organization with setting up a comprehensive global monitoring framework and preparing recommendations for voluntary global targets before the end of 2012.

The NCD community, led by the nongovernmental coalition called the NCD Alliance, had pushed for specific targets, including a 25% reduction of NCD deaths by 2025. But the current declaration isn’t the last step. There will be another evaluation in 2014, just in advance of the scheduled 2015 revision of the Millennium Development Goals, according to the alliance’s director Ann Keeling.

NEW YORK – The United Nations General Assembly has adopted a political declaration on the prevention and control of noncommunicable diseases.

The declaration emerged from a UN high-level meeting that was only the second-ever to address a health issue, the first being on HIV/AIDS in 2001. It states that "the global burden and threat of NCDs [noncommunicable diseases] constitutes one of the major challenges for development in the twenty-first century, which undermines social and economic development throughout the world."

Miriam E. Tucker/Elsevier Global Medical News

According to the World Health Organization, 63% of deaths worldwide are due to NCDs such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer, and nearly 80% of those deaths occur in developing countries.

Although the declaration doesn’t contain everything that noncommunicable disease lobbyists had hoped for, the document is nonetheless seen as a significant first step toward prompting global action to combat NCDs.

Member states agreed to measures such as reducing salts and sugars and eliminating industrially produced trans fats in all foods, increasing access to affordable, quality-assured medicines and technologies, and strengthening health care systems to include integration of NCD prevention and treatment. Beyond the health sector, there was also general agreement that success would need to involve many sectors beyond health, including finance, agriculture, transportation, urban development, and trade.

The U.N. General Assembly also tasked the World Health Organization with setting up a comprehensive global monitoring framework and preparing recommendations for voluntary global targets before the end of 2012.

The NCD community, led by the nongovernmental coalition called the NCD Alliance, had pushed for specific targets, including a 25% reduction of NCD deaths by 2025. But the current declaration isn’t the last step. There will be another evaluation in 2014, just in advance of the scheduled 2015 revision of the Millennium Development Goals, according to the alliance’s director Ann Keeling.

LISBON – New data on two investigational glucagon receptor antagonists suggest that this novel class of drugs has potential to be an effective treatment for type 2 diabetes, but only if safety can be established, according to two presentations at the annual meeting of the European Society for the Study of Diabetes.

Both Merck’s MK-0893 and Eli Lilly’s LY2409021 work by suppressing glucagon action via receptor blockade. Dr. Samuel S. Engel, senior director of clinical research, diabetes and endocrinology, at Merck presented phase II study data on the efficacy and safety of MK-0893 in combination with metformin or sitagliptin in 146 patients with type 2 diabetes, and Dr. Melvin J. Prince, senior director of medical diabetes and endocrinology at Eli Lilly, presented phase I dose-finding data on LY2409021 in 47 patients.

Both agents produced statistically significant reductions in hemoglobin A_1c. However, both also produced small but significant elevations in liver enzymes, and both carry the theoretical potential for hypoglycemia and hyperglucagonemia. "I think there is definitely potential for the glucagon receptor antagonists in diabetes, but there is also a risk of hypoglycemia associated with them. Also, it has been noted in the past that the hyperglucagonemia that results when the alpha cells overproduce glucagon has led to pancreas tumors in animal studies, so that’s a risk," session moderator Dr. Finbarr O’Harte, professor of endocrinology and metabolism at the University of Ulster, Derry (Northern Ireland), said in an interview.

In June at the American Diabetes Association’s annual scientific sessions, Dr. Engel presented data from a phase II study in which 342 type 2 diabetes patients were randomized to once-daily MK-0893 in four different dosages, metformin 1,000 mg twice daily, or placebo. At 12 weeks, treatment with MK-0893 resulted in significant, dose-dependent reductions in fasting plasma glucose, ranging from 32 mg/dL with a 20-mg dose to 63 mg/dL with 80 mg, from a baseline of 180-193 mg/dL. Metformin reduced FPG by 37 mg/dL, and placebo by just 2 mg/dL from baseline. For HbA_1c, reductions at 12 weeks ranged from 0.6 to 1.5 percentage points, compared with 0.8 percentage points with metformin and 0.5 with placebo.

The current study evaluated 40-mg/day MK-0893 in combination with 2,000-mg/day metformin or 100-mg/day sitagliptin, as well as 100 mg of sitagliptin plus 2,000 mg of metformin. The 146 patients had a mean age of 53 years, HbA_1c of 8.6%, and mean diabetes duration of 7 years. The MK-0893/metformin combination was superior to sitagliptin/metformin in lowering 24-hour weighted mean glucose, with a reduction of 117 mg/dL compared with 85 mg/dL. However, MK-0893/sitagliptin was significantly less effective than sitagliptin/metformin, which produced a 24-hour WMG reduction of 100 mg/dL. This could be because sitagliptin, a DPP-4 inhibitor, also suppresses glucagon and so there could be a threshold effect, Dr. Engel noted.

All treatments were equally well tolerated. However, there was a significantly higher incidence of diarrhea in the two MK-0893 groups (10% vs. 0%). In addition, the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were elevated in the MK-0893/metformin group, and total cholesterol and LDL-cholesterol were increased from baseline with MK-0893/sitagliptin, relative to reductions with MK-0893/metformin and sitagliptin/metformin, he reported.

In the phase I dose-ranging study of LY-2409021, 47 patients were randomized to one of four doses or metformin. Patients had a mean baseline fasting blood glucose of 148 mg/dL, and a baseline HbA_1c of 8.0%. By day 28, mean reductions in HbA_1c were statistically significant compared with baseline in all treatment groups, ranging from 1.02 percentage points with 60 mg to 0.69 percentage points with 5 mg. In the placebo group, HbA_1c dropped by 0.49 percentage points, Dr. Prince reported.

Fasting glucagon significantly increased by 0.6- to 4.2-fold compared with baseline across the LY dose levels, and fasting active glucagon-like peptide-1 (GLP-1) rose by 59% at the highest dose. Glucagon and GLP-1 returned to baseline levels during follow-up, he said.

The agent was generally well tolerated. Reversible elevations in hepatic transaminases were seen in five of nine patients in the highest-dose group, with no clinical signs or significant elevations in bilirubin or alkaline phosphatase, he reported. In the interview, Dr. O’Harte said that these two agents seem to have already exceeded expectations based on previous experience with other small-molecule glucagon antagonists that have been tested and have failed due to toxicity issues. "A lot of these small-molecule drugs have fallen by the wayside, and these two are still in there. We need toxicity studies, but there’s a possibility for a breakthrough, I hope."

Dr. Engel is an employee of Merck, and Dr. Prince is an employee of Eli Lilly. Dr. O’Harte stated that he had no disclosures.

LISBON – New data on two investigational glucagon receptor antagonists suggest that this novel class of drugs has potential to be an effective treatment for type 2 diabetes, but only if safety can be established, according to two presentations at the annual meeting of the European Society for the Study of Diabetes.

Both Merck’s MK-0893 and Eli Lilly’s LY2409021 work by suppressing glucagon action via receptor blockade. Dr. Samuel S. Engel, senior director of clinical research, diabetes and endocrinology, at Merck presented phase II study data on the efficacy and safety of MK-0893 in combination with metformin or sitagliptin in 146 patients with type 2 diabetes, and Dr. Melvin J. Prince, senior director of medical diabetes and endocrinology at Eli Lilly, presented phase I dose-finding data on LY2409021 in 47 patients.

Both agents produced statistically significant reductions in hemoglobin A_1c. However, both also produced small but significant elevations in liver enzymes, and both carry the theoretical potential for hypoglycemia and hyperglucagonemia. "I think there is definitely potential for the glucagon receptor antagonists in diabetes, but there is also a risk of hypoglycemia associated with them. Also, it has been noted in the past that the hyperglucagonemia that results when the alpha cells overproduce glucagon has led to pancreas tumors in animal studies, so that’s a risk," session moderator Dr. Finbarr O’Harte, professor of endocrinology and metabolism at the University of Ulster, Derry (Northern Ireland), said in an interview.

In June at the American Diabetes Association’s annual scientific sessions, Dr. Engel presented data from a phase II study in which 342 type 2 diabetes patients were randomized to once-daily MK-0893 in four different dosages, metformin 1,000 mg twice daily, or placebo. At 12 weeks, treatment with MK-0893 resulted in significant, dose-dependent reductions in fasting plasma glucose, ranging from 32 mg/dL with a 20-mg dose to 63 mg/dL with 80 mg, from a baseline of 180-193 mg/dL. Metformin reduced FPG by 37 mg/dL, and placebo by just 2 mg/dL from baseline. For HbA_1c, reductions at 12 weeks ranged from 0.6 to 1.5 percentage points, compared with 0.8 percentage points with metformin and 0.5 with placebo.

The current study evaluated 40-mg/day MK-0893 in combination with 2,000-mg/day metformin or 100-mg/day sitagliptin, as well as 100 mg of sitagliptin plus 2,000 mg of metformin. The 146 patients had a mean age of 53 years, HbA_1c of 8.6%, and mean diabetes duration of 7 years. The MK-0893/metformin combination was superior to sitagliptin/metformin in lowering 24-hour weighted mean glucose, with a reduction of 117 mg/dL compared with 85 mg/dL. However, MK-0893/sitagliptin was significantly less effective than sitagliptin/metformin, which produced a 24-hour WMG reduction of 100 mg/dL. This could be because sitagliptin, a DPP-4 inhibitor, also suppresses glucagon and so there could be a threshold effect, Dr. Engel noted.

All treatments were equally well tolerated. However, there was a significantly higher incidence of diarrhea in the two MK-0893 groups (10% vs. 0%). In addition, the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were elevated in the MK-0893/metformin group, and total cholesterol and LDL-cholesterol were increased from baseline with MK-0893/sitagliptin, relative to reductions with MK-0893/metformin and sitagliptin/metformin, he reported.

In the phase I dose-ranging study of LY-2409021, 47 patients were randomized to one of four doses or metformin. Patients had a mean baseline fasting blood glucose of 148 mg/dL, and a baseline HbA_1c of 8.0%. By day 28, mean reductions in HbA_1c were statistically significant compared with baseline in all treatment groups, ranging from 1.02 percentage points with 60 mg to 0.69 percentage points with 5 mg. In the placebo group, HbA_1c dropped by 0.49 percentage points, Dr. Prince reported.

Fasting glucagon significantly increased by 0.6- to 4.2-fold compared with baseline across the LY dose levels, and fasting active glucagon-like peptide-1 (GLP-1) rose by 59% at the highest dose. Glucagon and GLP-1 returned to baseline levels during follow-up, he said.

The agent was generally well tolerated. Reversible elevations in hepatic transaminases were seen in five of nine patients in the highest-dose group, with no clinical signs or significant elevations in bilirubin or alkaline phosphatase, he reported. In the interview, Dr. O’Harte said that these two agents seem to have already exceeded expectations based on previous experience with other small-molecule glucagon antagonists that have been tested and have failed due to toxicity issues. "A lot of these small-molecule drugs have fallen by the wayside, and these two are still in there. We need toxicity studies, but there’s a possibility for a breakthrough, I hope."

Dr. Engel is an employee of Merck, and Dr. Prince is an employee of Eli Lilly. Dr. O’Harte stated that he had no disclosures.

LISBON – New data on two investigational glucagon receptor antagonists suggest that this novel class of drugs has potential to be an effective treatment for type 2 diabetes, but only if safety can be established, according to two presentations at the annual meeting of the European Society for the Study of Diabetes.

Both Merck’s MK-0893 and Eli Lilly’s LY2409021 work by suppressing glucagon action via receptor blockade. Dr. Samuel S. Engel, senior director of clinical research, diabetes and endocrinology, at Merck presented phase II study data on the efficacy and safety of MK-0893 in combination with metformin or sitagliptin in 146 patients with type 2 diabetes, and Dr. Melvin J. Prince, senior director of medical diabetes and endocrinology at Eli Lilly, presented phase I dose-finding data on LY2409021 in 47 patients.

Both agents produced statistically significant reductions in hemoglobin A_1c. However, both also produced small but significant elevations in liver enzymes, and both carry the theoretical potential for hypoglycemia and hyperglucagonemia. "I think there is definitely potential for the glucagon receptor antagonists in diabetes, but there is also a risk of hypoglycemia associated with them. Also, it has been noted in the past that the hyperglucagonemia that results when the alpha cells overproduce glucagon has led to pancreas tumors in animal studies, so that’s a risk," session moderator Dr. Finbarr O’Harte, professor of endocrinology and metabolism at the University of Ulster, Derry (Northern Ireland), said in an interview.

In June at the American Diabetes Association’s annual scientific sessions, Dr. Engel presented data from a phase II study in which 342 type 2 diabetes patients were randomized to once-daily MK-0893 in four different dosages, metformin 1,000 mg twice daily, or placebo. At 12 weeks, treatment with MK-0893 resulted in significant, dose-dependent reductions in fasting plasma glucose, ranging from 32 mg/dL with a 20-mg dose to 63 mg/dL with 80 mg, from a baseline of 180-193 mg/dL. Metformin reduced FPG by 37 mg/dL, and placebo by just 2 mg/dL from baseline. For HbA_1c, reductions at 12 weeks ranged from 0.6 to 1.5 percentage points, compared with 0.8 percentage points with metformin and 0.5 with placebo.

The current study evaluated 40-mg/day MK-0893 in combination with 2,000-mg/day metformin or 100-mg/day sitagliptin, as well as 100 mg of sitagliptin plus 2,000 mg of metformin. The 146 patients had a mean age of 53 years, HbA_1c of 8.6%, and mean diabetes duration of 7 years. The MK-0893/metformin combination was superior to sitagliptin/metformin in lowering 24-hour weighted mean glucose, with a reduction of 117 mg/dL compared with 85 mg/dL. However, MK-0893/sitagliptin was significantly less effective than sitagliptin/metformin, which produced a 24-hour WMG reduction of 100 mg/dL. This could be because sitagliptin, a DPP-4 inhibitor, also suppresses glucagon and so there could be a threshold effect, Dr. Engel noted.

All treatments were equally well tolerated. However, there was a significantly higher incidence of diarrhea in the two MK-0893 groups (10% vs. 0%). In addition, the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were elevated in the MK-0893/metformin group, and total cholesterol and LDL-cholesterol were increased from baseline with MK-0893/sitagliptin, relative to reductions with MK-0893/metformin and sitagliptin/metformin, he reported.

In the phase I dose-ranging study of LY-2409021, 47 patients were randomized to one of four doses or metformin. Patients had a mean baseline fasting blood glucose of 148 mg/dL, and a baseline HbA_1c of 8.0%. By day 28, mean reductions in HbA_1c were statistically significant compared with baseline in all treatment groups, ranging from 1.02 percentage points with 60 mg to 0.69 percentage points with 5 mg. In the placebo group, HbA_1c dropped by 0.49 percentage points, Dr. Prince reported.

Fasting glucagon significantly increased by 0.6- to 4.2-fold compared with baseline across the LY dose levels, and fasting active glucagon-like peptide-1 (GLP-1) rose by 59% at the highest dose. Glucagon and GLP-1 returned to baseline levels during follow-up, he said.

The agent was generally well tolerated. Reversible elevations in hepatic transaminases were seen in five of nine patients in the highest-dose group, with no clinical signs or significant elevations in bilirubin or alkaline phosphatase, he reported. In the interview, Dr. O’Harte said that these two agents seem to have already exceeded expectations based on previous experience with other small-molecule glucagon antagonists that have been tested and have failed due to toxicity issues. "A lot of these small-molecule drugs have fallen by the wayside, and these two are still in there. We need toxicity studies, but there’s a possibility for a breakthrough, I hope."

Dr. Engel is an employee of Merck, and Dr. Prince is an employee of Eli Lilly. Dr. O’Harte stated that he had no disclosures.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes during pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, the first such one to adjust for possible confounders, the increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m², but not below.

Moreover, hypertension and smoking during pregnancy were stronger risk factors than GDM for later CVD. "Preventive strategies after pregnancy might need to be individualized depending on each woman’s characteristics and risk profile," said Dr. Erik Schwarcz, an endocrinologist and senior physician at University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish National Healthcare Quality registers from 1991 through 2008, were 4,590 women diagnoses with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19-61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls. Ischemic heart disease and stroke were the most common diagnoses, affecting 56% and 35%, respectively.

A history of GDM was present for 2.4% of the cases, compared with 1.2% of the controls, a significant difference. Also significantly increased among the cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. Using BMI of 20-25 as the referent, a BMI of 25-29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20-24) versus overweight (BMI 25 or greater), only the overweight women had an increased risk for CVD events (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn’t add any risk above and beyond that of smoking, Dr. Schwarcz explained, adding that the numbers for hypertension were too small to stratify.

In response to an audience member’s question about how many women developed diabetes after pregnancy, Dr. Schwarcz replied that the only available information on that is for prescribed medications and that he is currently analyzing those data.

Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes during pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, the first such one to adjust for possible confounders, the increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m², but not below.

Moreover, hypertension and smoking during pregnancy were stronger risk factors than GDM for later CVD. "Preventive strategies after pregnancy might need to be individualized depending on each woman’s characteristics and risk profile," said Dr. Erik Schwarcz, an endocrinologist and senior physician at University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish National Healthcare Quality registers from 1991 through 2008, were 4,590 women diagnoses with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19-61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls. Ischemic heart disease and stroke were the most common diagnoses, affecting 56% and 35%, respectively.

A history of GDM was present for 2.4% of the cases, compared with 1.2% of the controls, a significant difference. Also significantly increased among the cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. Using BMI of 20-25 as the referent, a BMI of 25-29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20-24) versus overweight (BMI 25 or greater), only the overweight women had an increased risk for CVD events (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn’t add any risk above and beyond that of smoking, Dr. Schwarcz explained, adding that the numbers for hypertension were too small to stratify.

In response to an audience member’s question about how many women developed diabetes after pregnancy, Dr. Schwarcz replied that the only available information on that is for prescribed medications and that he is currently analyzing those data.

Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.

LISBON – Women with a history of gestational diabetes had an overall 50% elevated risk for cardiovascular events later in life, with a doubled risk among those who were overweight, in a large, case-control, population-based Swedish study.

It is well known that women who have gestational diabetes during pregnancy are at increased risk for type 2 diabetes later in life, but the relationship between gestational diabetes mellitus (GDM) and later cardiovascular disease (CVD) has been less well studied. In this analysis, the first such one to adjust for possible confounders, the increased risk for CVD among women with previous GDM was significant among women with body mass indexes (BMIs) of at least 25 kg/m², but not below.

Moreover, hypertension and smoking during pregnancy were stronger risk factors than GDM for later CVD. "Preventive strategies after pregnancy might need to be individualized depending on each woman’s characteristics and risk profile," said Dr. Erik Schwarcz, an endocrinologist and senior physician at University Hospital Orebro, Sweden.

Cases in the study, which used data from Swedish National Healthcare Quality registers from 1991 through 2008, were 4,590 women diagnoses with cardiovascular death or a first cardiovascular event – ischemic heart disease, ischemic stroke, peripheral arterial disease, or atherosclerosis – and who gave birth to at least one child during the study period. Those women were each matched with about five age-matched controls – total 22,398 – who did not have cardiovascular disease who gave birth to a child during the same year. Complete data on BMI and smoking were available for 2,660 cases and 13,357 controls.

At the time of the CVD event, the cases had a mean age of 41 years (range 19-61), with a mean of 9 years between the pregnancy and the event. There were 130 deaths among the 2,660 cases, compared with just 2 in the 13,357 controls. Ischemic heart disease and stroke were the most common diagnoses, affecting 56% and 35%, respectively.

A history of GDM was present for 2.4% of the cases, compared with 1.2% of the controls, a significant difference. Also significantly increased among the cases were chronic hypertension (2.1% vs. 0.3%), smoking (35.3% vs. 18.1%), non-Nordic ethnicity (14.1% vs. 11.5%), mean BMI (25.4 vs. 23.9), and low education (23.4% vs. 15.1%).

After adjustment for hypertension, smoking, BMI, parity, education level, and ethnicity, all of the risk factors remained significant except for non-Nordic ethnicity, with odds ratios of 1.50 for GDM, 5.15 for chronic hypertension, and 2.24 for smoking. Using BMI of 20-25 as the referent, a BMI of 25-29 gave an odds ratio of 1.32, while a BMI of 30 or greater doubled the risk (OR, 2.00).

When divided into normal weight (BMI 20-24) versus overweight (BMI 25 or greater), only the overweight women had an increased risk for CVD events (OR, 2.35), while there was no excess CVD risk among those with normal BMI (0.48). When stratified for smoking, GDM was not a risk factor for CVD. In other words, GDM didn’t add any risk above and beyond that of smoking, Dr. Schwarcz explained, adding that the numbers for hypertension were too small to stratify.

In response to an audience member’s question about how many women developed diabetes after pregnancy, Dr. Schwarcz replied that the only available information on that is for prescribed medications and that he is currently analyzing those data.

Dr. Schwarcz disclosed that he has received lecture fees and has conducted clinical trials for Sanofi-Aventis, Novo-Nordisk, and AstraZeneca.