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European Association for the Study of Diabetes (EASD): Annual Meeting
ED in type 1 diabetes often resolves
BARCELONA – If a man with type 1 diabetes develops erectile dysfunction, the first appearance spontaneously resolves more than half the time, according to data collected from nearly 700 men followed for 16 years.
But of those men whose first erectile dysfunction (ED) episode resolves, more than half will experience a recurrence. Furthermore, although these recurrences may resolve as well, the likelihood of resolution falls over time, and the chance of resolution also drops as repeated cycles of ED and resolution accumulate, Dr. Hunter Wessells said at the annual meeting of the European Association for the Study of Diabetes.
Factors affecting this pattern of ED onset and resolution appear to include modifiable risks such as glycemic control, blood pressure, and body mass index, and a "point of no return" for ED resolution "may be postulated based on patient’s age, level of hemoglobin A1c, and duration of ED," said Dr. Wessells, professor and chairman of urology at the University of Washington in Seattle.
The findings suggest that a window of opportunity exists when ED first appears to boost the chance of resolution through improved glycemic control and other interventions.
"I counsel men with type 1 diabetes and new-onset ED that with increased exercise, better blood pressure control, weight loss, and better glycemic control they have a good chance of reversing their ED," Dr. Wessells said in an interview. "It’s an opportunity to intervene. We don’t yet have firm evidence for this, but as a clinician I give this advice. We need to run a clinical trial to show whether, for example, lowering HbA1c can reverse ED. If you have a man with ED and an HbA1c of 10%, if you bring him down to 7% I think you could probably reverse his ED, but currently that is just my speculation."
Dr. Wessells and his associates used data collected from men during the Diabetes Control and Complications Trial (DCCT) – which enrolled 1,441 men and women with type 1 diabetes starting in 1983 at 29 centers in the United States and Canada – and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, which extended the follow-up of more than 90% of the originally-enrolled patients.
Their new analysis focused on 683 men who were followed for 16 years; their average age at their most recent follow-up was 50 years. During follow-up, the men completed an annual survey, which included a question that asked whether or not they had impotence, and a second question of whether or not they were using a drug for ED. Men who answered yes to either question were considered to have ED.
In this cohort, 326 men (48%) never developed ED, 77 (11%) had a single episode during follow-up that later resolved, 158 (23%) had two or more episodes of ED occurrences followed by resolution, and 122 men (18%) developed ED and never had resolution. By the end of the 16 years of follow-up, the majority of men who had multiple episodes of ED onset and resolution had progressed to unremitting ED.
The results showed that among the 357 men in this cohort who developed ED, 235 (66%) had resolution of their first episode.
To explore potential correlates of ED onset and resolution, they further analyzed the subgroup of 333 men from this group with at least 7 years of completed information on their ED status (although all men were followed for 16 years, many had years when they did not supply survey information). The researchers found that, on average, the men whose ED resolved were slightly younger than those whose ED did not resolve, and they had a lower BMI. In addition, men with a single ED episode had an average HbA1c of 8.1%, compared with 8.4% among those with multiple episodes of ED and resolution, and an average 8.8% level in men whose ED never resolved. The prevalence of an HbA1c level of 8% or higher was 47% in men with a single, transient episode, 66% in those with multiple transient episodes, and 71% among men whose ED never resolved.
The results also showed that when ED persisted for more than a year, the chance of subsequent resolution fell with time. Men with 2 consecutive years of reporting ED had a 50% rate of resolution the next year. The resolution rate continued to fall as the duration of ED increased, and when men had 5 consecutive years reporting ED, 25% had resolution the following year. "By the fifth year, ED status was essentially set," Dr. Wessells said.
Dr. Wessells said that he had no disclosures. The DCCT and EDIC trials were sponsored by the National Institutes of Health
On Twitter @mitchelzoler
BARCELONA – If a man with type 1 diabetes develops erectile dysfunction, the first appearance spontaneously resolves more than half the time, according to data collected from nearly 700 men followed for 16 years.
But of those men whose first erectile dysfunction (ED) episode resolves, more than half will experience a recurrence. Furthermore, although these recurrences may resolve as well, the likelihood of resolution falls over time, and the chance of resolution also drops as repeated cycles of ED and resolution accumulate, Dr. Hunter Wessells said at the annual meeting of the European Association for the Study of Diabetes.
Factors affecting this pattern of ED onset and resolution appear to include modifiable risks such as glycemic control, blood pressure, and body mass index, and a "point of no return" for ED resolution "may be postulated based on patient’s age, level of hemoglobin A1c, and duration of ED," said Dr. Wessells, professor and chairman of urology at the University of Washington in Seattle.
The findings suggest that a window of opportunity exists when ED first appears to boost the chance of resolution through improved glycemic control and other interventions.
"I counsel men with type 1 diabetes and new-onset ED that with increased exercise, better blood pressure control, weight loss, and better glycemic control they have a good chance of reversing their ED," Dr. Wessells said in an interview. "It’s an opportunity to intervene. We don’t yet have firm evidence for this, but as a clinician I give this advice. We need to run a clinical trial to show whether, for example, lowering HbA1c can reverse ED. If you have a man with ED and an HbA1c of 10%, if you bring him down to 7% I think you could probably reverse his ED, but currently that is just my speculation."
Dr. Wessells and his associates used data collected from men during the Diabetes Control and Complications Trial (DCCT) – which enrolled 1,441 men and women with type 1 diabetes starting in 1983 at 29 centers in the United States and Canada – and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, which extended the follow-up of more than 90% of the originally-enrolled patients.
Their new analysis focused on 683 men who were followed for 16 years; their average age at their most recent follow-up was 50 years. During follow-up, the men completed an annual survey, which included a question that asked whether or not they had impotence, and a second question of whether or not they were using a drug for ED. Men who answered yes to either question were considered to have ED.
In this cohort, 326 men (48%) never developed ED, 77 (11%) had a single episode during follow-up that later resolved, 158 (23%) had two or more episodes of ED occurrences followed by resolution, and 122 men (18%) developed ED and never had resolution. By the end of the 16 years of follow-up, the majority of men who had multiple episodes of ED onset and resolution had progressed to unremitting ED.
The results showed that among the 357 men in this cohort who developed ED, 235 (66%) had resolution of their first episode.
To explore potential correlates of ED onset and resolution, they further analyzed the subgroup of 333 men from this group with at least 7 years of completed information on their ED status (although all men were followed for 16 years, many had years when they did not supply survey information). The researchers found that, on average, the men whose ED resolved were slightly younger than those whose ED did not resolve, and they had a lower BMI. In addition, men with a single ED episode had an average HbA1c of 8.1%, compared with 8.4% among those with multiple episodes of ED and resolution, and an average 8.8% level in men whose ED never resolved. The prevalence of an HbA1c level of 8% or higher was 47% in men with a single, transient episode, 66% in those with multiple transient episodes, and 71% among men whose ED never resolved.
The results also showed that when ED persisted for more than a year, the chance of subsequent resolution fell with time. Men with 2 consecutive years of reporting ED had a 50% rate of resolution the next year. The resolution rate continued to fall as the duration of ED increased, and when men had 5 consecutive years reporting ED, 25% had resolution the following year. "By the fifth year, ED status was essentially set," Dr. Wessells said.
Dr. Wessells said that he had no disclosures. The DCCT and EDIC trials were sponsored by the National Institutes of Health
On Twitter @mitchelzoler
BARCELONA – If a man with type 1 diabetes develops erectile dysfunction, the first appearance spontaneously resolves more than half the time, according to data collected from nearly 700 men followed for 16 years.
But of those men whose first erectile dysfunction (ED) episode resolves, more than half will experience a recurrence. Furthermore, although these recurrences may resolve as well, the likelihood of resolution falls over time, and the chance of resolution also drops as repeated cycles of ED and resolution accumulate, Dr. Hunter Wessells said at the annual meeting of the European Association for the Study of Diabetes.
Factors affecting this pattern of ED onset and resolution appear to include modifiable risks such as glycemic control, blood pressure, and body mass index, and a "point of no return" for ED resolution "may be postulated based on patient’s age, level of hemoglobin A1c, and duration of ED," said Dr. Wessells, professor and chairman of urology at the University of Washington in Seattle.
The findings suggest that a window of opportunity exists when ED first appears to boost the chance of resolution through improved glycemic control and other interventions.
"I counsel men with type 1 diabetes and new-onset ED that with increased exercise, better blood pressure control, weight loss, and better glycemic control they have a good chance of reversing their ED," Dr. Wessells said in an interview. "It’s an opportunity to intervene. We don’t yet have firm evidence for this, but as a clinician I give this advice. We need to run a clinical trial to show whether, for example, lowering HbA1c can reverse ED. If you have a man with ED and an HbA1c of 10%, if you bring him down to 7% I think you could probably reverse his ED, but currently that is just my speculation."
Dr. Wessells and his associates used data collected from men during the Diabetes Control and Complications Trial (DCCT) – which enrolled 1,441 men and women with type 1 diabetes starting in 1983 at 29 centers in the United States and Canada – and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, which extended the follow-up of more than 90% of the originally-enrolled patients.
Their new analysis focused on 683 men who were followed for 16 years; their average age at their most recent follow-up was 50 years. During follow-up, the men completed an annual survey, which included a question that asked whether or not they had impotence, and a second question of whether or not they were using a drug for ED. Men who answered yes to either question were considered to have ED.
In this cohort, 326 men (48%) never developed ED, 77 (11%) had a single episode during follow-up that later resolved, 158 (23%) had two or more episodes of ED occurrences followed by resolution, and 122 men (18%) developed ED and never had resolution. By the end of the 16 years of follow-up, the majority of men who had multiple episodes of ED onset and resolution had progressed to unremitting ED.
The results showed that among the 357 men in this cohort who developed ED, 235 (66%) had resolution of their first episode.
To explore potential correlates of ED onset and resolution, they further analyzed the subgroup of 333 men from this group with at least 7 years of completed information on their ED status (although all men were followed for 16 years, many had years when they did not supply survey information). The researchers found that, on average, the men whose ED resolved were slightly younger than those whose ED did not resolve, and they had a lower BMI. In addition, men with a single ED episode had an average HbA1c of 8.1%, compared with 8.4% among those with multiple episodes of ED and resolution, and an average 8.8% level in men whose ED never resolved. The prevalence of an HbA1c level of 8% or higher was 47% in men with a single, transient episode, 66% in those with multiple transient episodes, and 71% among men whose ED never resolved.
The results also showed that when ED persisted for more than a year, the chance of subsequent resolution fell with time. Men with 2 consecutive years of reporting ED had a 50% rate of resolution the next year. The resolution rate continued to fall as the duration of ED increased, and when men had 5 consecutive years reporting ED, 25% had resolution the following year. "By the fifth year, ED status was essentially set," Dr. Wessells said.
Dr. Wessells said that he had no disclosures. The DCCT and EDIC trials were sponsored by the National Institutes of Health
On Twitter @mitchelzoler
AT THE EASD ANNUAL MEETING
Major finding: Two-thirds of men with type 1 diabetes who developed erectile dysfunction later recovered sexual function, but many had subsequent recurrences.
Data source: The DCCT and EDIC trials, which followed 683 men with type 1 diabetes for 16 years.
Disclosures: Dr. Wessells said that he had no disclosures. The DCCT and EDIC trials were sponsored by the National Institutes of Health.
After 15 years, UKPDS sulfonylurea-metformin combo shows no mortality bump
BARCELONA – It’s taken 15 years, but newly released data are finally clearing the last shadow of doubt over metformin’s safety in type 2 diabetes.
Patients in the groundbreaking U.K. Prospective Diabetes Study (UKPDS) who took the drug along with a sulfonylurea don’t appear to have any long-term increases in the risk of diabetes-related death, all-cause mortality, or cardiovascular events, Dr. Rury R. Holman said at the annual meeting of the European Association for the Study of Diabetes.
However, although they are strongly reassuring, these data can’t yet be considered ironclad, said Dr. Holman, a primary UKPDS investigator and director of the University of Oxford Diabetes Trials Unit. "What we have here is comforting, but it is not proof positive. It’s not a second trial, but it does suggest that [the apparent early risk] may have evened out over time."
The Sulfonylurea and Metformin Substudy was designed to investigate the combination’s effect on patients in UKPDS who had not achieved the target glucose goal of 6 mmol/L (108 mg/dL), despite being on sulfonylurea monotherapy for the entire 7-year study. This group of 537 patients was secondarily randomized to either staying with the sulfonylurea monotherapy or adding metformin. "The impact of this was actually to add glycemic rescue therapy at 6 mmol/L rather than 15 mmol/L [270 mg/dL]," the level built into UKPDS, Dr. Holman said.
The substudy patients were a fairly representative mix of those in the larger study. They were a mean of 64 years old, with a mean body mass index of about 28 kg/m2. They did differ significantly in two major categories, however, Dr. Holman pointed out. Patients in the combination therapy group had lower fasting plasma glucose (9 vs. 10 mmol/L; 162 vs. 180 mg/dL), hemoglobin A1c (8.3% vs. 7.9%) and lower LDL cholesterol (3.4 vs. 3.2 mmol/L; 61.2 mg/dL vs. 57.6 mg/dL). These baseline differences could have helped set the stage for the differences in mortality outcomes, he suggested.
After the secondary randomization, those who got the addition of metformin showed an immediate, significant, decrease in fasting plasma glucose. This was a very encouraging finding, he said, because it broke the disappointing pattern of improvement followed eventually by beta-cell deterioration, which UKPDS characterized in all of its treatment arms. But, Dr. Holman said, after reaching a nadir at about 18 months, glucose levels in the dual-therapy patients did begin to creep back up, taking a parallel – although less pronounced – track to the monotherapy group.
The glucose response was encouraging, but clouded by an unexpected finding. By 6 years, those taking the drug combination were almost twice as likely to have died from a diabetes-related complication as were those in the monotherapy group (risk ratio, 1.96). The overall risk of death from any cause was also significantly increased in those taking the combination (RR, 0.60). However, there were no differences in fatal or nonfatal stroke or myocardial infarction.
"There was a separation of the mortality curves at around 3 years" that continued to separate through the entire study period, Dr. Holman said. "This was contrary to everything else UKPDS had shown, and raised considerable concern and alarm. It looked horrific and it could potentially have been horrific."
The investigators tried to make sense of the results, without much luck. Matching the cohorts with similar groups in other studies shed no light on the matter. The disconnect between the increase in all-cause mortality and stable cardiovascular events remained a puzzle. Because only 40 patients had died at that point – a reflection of the relative good baseline health of the UKPDS group – there was limited power to fully explore the finding.
Nonetheless, "when we found this, we said that these results could be real and that the addition of metformin to patients on sulfonylureas required more study, which is what we now have done."
At the meeting, Dr. Holman reported the most recent, yet-unpublished, data on these patients, who were followed for up to 15 years. In 1997, the hazard ratio for diabetes-related deaths was 1.96, with a high level of statistical significance (P = .039). It hovered near that point until 2001, when it began to decline. By 2003, it dropped to about 1.50, and was no longer statistically significant. Since then, the risk has declined close to null; it has never regained a significant value.
"Over time, the combination of sulfonylurea and metformin does not appear to have any continued adverse effect," Dr. Holman said. "We saw a diminishing risk ratio and at this point, close to 15 years after we started UKPDS, there appears to be no evidence of harm."
All-cause mortality showed a similar pattern, with a 60% increased risk in 1997 and a gradual improvement. "Although it’s still on the wrong side of 1.0, it’s not close to being statistically significant."
Overall, 226 patients have now died: 107 in the monotherapy group (40%) and 119 in the combination group (44%). Death from a diabetes-related cause has occurred in 57 of the monotherapy group (21%) and 60 of the combination therapy group (22%), for a nonsignificant risk ratio of 1.18.
There is no significant increase in the risk of myocardial infarction (1.09) or stroke (0.86), whether fatal or nonfatal.
Two more studies are in the works to try and sort out the sulfonylurea-metformin mash-up, Dr. Holman said: GRADE and GLINT. GRADE (Glycemic Reduction Approaches in Diabetes) is a four-arm comparative effectiveness study sponsored by the National Institutes of Health. It will randomize 6,000 patients with type 2 diabetes to metformin and either a sulfonylurea (glimepiride), a DPP-4 inhibitor (sitagliptin), a GLP-1 agonist (liraglutide), or insulin glargine. The groups will be followed for 5 years, Dr. Holman said. "Certainly, if there is a doubling in the risk of death in the sulfonylurea/metformin group, we will see it."
The second study, called GLINT (Glucose Lowering in Non-diabetic Hyperglycemia Trial), is just getting ramped up in the United Kingdom. It’s aimed at patients whose HbA1c is elevated, but not yet in the diabetic range of 6.5%.
The 5-year GLINT aims to recruit nearly 12,000 people aged 40 years and older, who have a 10-year calculated cardiovascular disease risk of at least 20%. Subjects will be randomized to metformin or placebo. The primary endpoint is a composite cardiovascular outcome of death or nonfatal MI or stroke. The first patients are being seen this month, Dr. Holman noted.
The study is also well powered to look at the increased risk of bowel and breast cancers among diabetes patients, he added
"Perhaps this will be the pivotal second study that will help confirm the preeminence of metformin as first-line therapy."
Becton Dickinson, Boehringer Mannheim, Bristol Myers Squibb, Hoechst, Lilly, Lipha, and Novo Nordisk contributed to the funding for the UKPDS study. Dr. Holman had no financial disclosures.
On Twitter @Alz_gal
BARCELONA – It’s taken 15 years, but newly released data are finally clearing the last shadow of doubt over metformin’s safety in type 2 diabetes.
Patients in the groundbreaking U.K. Prospective Diabetes Study (UKPDS) who took the drug along with a sulfonylurea don’t appear to have any long-term increases in the risk of diabetes-related death, all-cause mortality, or cardiovascular events, Dr. Rury R. Holman said at the annual meeting of the European Association for the Study of Diabetes.
However, although they are strongly reassuring, these data can’t yet be considered ironclad, said Dr. Holman, a primary UKPDS investigator and director of the University of Oxford Diabetes Trials Unit. "What we have here is comforting, but it is not proof positive. It’s not a second trial, but it does suggest that [the apparent early risk] may have evened out over time."
The Sulfonylurea and Metformin Substudy was designed to investigate the combination’s effect on patients in UKPDS who had not achieved the target glucose goal of 6 mmol/L (108 mg/dL), despite being on sulfonylurea monotherapy for the entire 7-year study. This group of 537 patients was secondarily randomized to either staying with the sulfonylurea monotherapy or adding metformin. "The impact of this was actually to add glycemic rescue therapy at 6 mmol/L rather than 15 mmol/L [270 mg/dL]," the level built into UKPDS, Dr. Holman said.
The substudy patients were a fairly representative mix of those in the larger study. They were a mean of 64 years old, with a mean body mass index of about 28 kg/m2. They did differ significantly in two major categories, however, Dr. Holman pointed out. Patients in the combination therapy group had lower fasting plasma glucose (9 vs. 10 mmol/L; 162 vs. 180 mg/dL), hemoglobin A1c (8.3% vs. 7.9%) and lower LDL cholesterol (3.4 vs. 3.2 mmol/L; 61.2 mg/dL vs. 57.6 mg/dL). These baseline differences could have helped set the stage for the differences in mortality outcomes, he suggested.
After the secondary randomization, those who got the addition of metformin showed an immediate, significant, decrease in fasting plasma glucose. This was a very encouraging finding, he said, because it broke the disappointing pattern of improvement followed eventually by beta-cell deterioration, which UKPDS characterized in all of its treatment arms. But, Dr. Holman said, after reaching a nadir at about 18 months, glucose levels in the dual-therapy patients did begin to creep back up, taking a parallel – although less pronounced – track to the monotherapy group.
The glucose response was encouraging, but clouded by an unexpected finding. By 6 years, those taking the drug combination were almost twice as likely to have died from a diabetes-related complication as were those in the monotherapy group (risk ratio, 1.96). The overall risk of death from any cause was also significantly increased in those taking the combination (RR, 0.60). However, there were no differences in fatal or nonfatal stroke or myocardial infarction.
"There was a separation of the mortality curves at around 3 years" that continued to separate through the entire study period, Dr. Holman said. "This was contrary to everything else UKPDS had shown, and raised considerable concern and alarm. It looked horrific and it could potentially have been horrific."
The investigators tried to make sense of the results, without much luck. Matching the cohorts with similar groups in other studies shed no light on the matter. The disconnect between the increase in all-cause mortality and stable cardiovascular events remained a puzzle. Because only 40 patients had died at that point – a reflection of the relative good baseline health of the UKPDS group – there was limited power to fully explore the finding.
Nonetheless, "when we found this, we said that these results could be real and that the addition of metformin to patients on sulfonylureas required more study, which is what we now have done."
At the meeting, Dr. Holman reported the most recent, yet-unpublished, data on these patients, who were followed for up to 15 years. In 1997, the hazard ratio for diabetes-related deaths was 1.96, with a high level of statistical significance (P = .039). It hovered near that point until 2001, when it began to decline. By 2003, it dropped to about 1.50, and was no longer statistically significant. Since then, the risk has declined close to null; it has never regained a significant value.
"Over time, the combination of sulfonylurea and metformin does not appear to have any continued adverse effect," Dr. Holman said. "We saw a diminishing risk ratio and at this point, close to 15 years after we started UKPDS, there appears to be no evidence of harm."
All-cause mortality showed a similar pattern, with a 60% increased risk in 1997 and a gradual improvement. "Although it’s still on the wrong side of 1.0, it’s not close to being statistically significant."
Overall, 226 patients have now died: 107 in the monotherapy group (40%) and 119 in the combination group (44%). Death from a diabetes-related cause has occurred in 57 of the monotherapy group (21%) and 60 of the combination therapy group (22%), for a nonsignificant risk ratio of 1.18.
There is no significant increase in the risk of myocardial infarction (1.09) or stroke (0.86), whether fatal or nonfatal.
Two more studies are in the works to try and sort out the sulfonylurea-metformin mash-up, Dr. Holman said: GRADE and GLINT. GRADE (Glycemic Reduction Approaches in Diabetes) is a four-arm comparative effectiveness study sponsored by the National Institutes of Health. It will randomize 6,000 patients with type 2 diabetes to metformin and either a sulfonylurea (glimepiride), a DPP-4 inhibitor (sitagliptin), a GLP-1 agonist (liraglutide), or insulin glargine. The groups will be followed for 5 years, Dr. Holman said. "Certainly, if there is a doubling in the risk of death in the sulfonylurea/metformin group, we will see it."
The second study, called GLINT (Glucose Lowering in Non-diabetic Hyperglycemia Trial), is just getting ramped up in the United Kingdom. It’s aimed at patients whose HbA1c is elevated, but not yet in the diabetic range of 6.5%.
The 5-year GLINT aims to recruit nearly 12,000 people aged 40 years and older, who have a 10-year calculated cardiovascular disease risk of at least 20%. Subjects will be randomized to metformin or placebo. The primary endpoint is a composite cardiovascular outcome of death or nonfatal MI or stroke. The first patients are being seen this month, Dr. Holman noted.
The study is also well powered to look at the increased risk of bowel and breast cancers among diabetes patients, he added
"Perhaps this will be the pivotal second study that will help confirm the preeminence of metformin as first-line therapy."
Becton Dickinson, Boehringer Mannheim, Bristol Myers Squibb, Hoechst, Lilly, Lipha, and Novo Nordisk contributed to the funding for the UKPDS study. Dr. Holman had no financial disclosures.
On Twitter @Alz_gal
BARCELONA – It’s taken 15 years, but newly released data are finally clearing the last shadow of doubt over metformin’s safety in type 2 diabetes.
Patients in the groundbreaking U.K. Prospective Diabetes Study (UKPDS) who took the drug along with a sulfonylurea don’t appear to have any long-term increases in the risk of diabetes-related death, all-cause mortality, or cardiovascular events, Dr. Rury R. Holman said at the annual meeting of the European Association for the Study of Diabetes.
However, although they are strongly reassuring, these data can’t yet be considered ironclad, said Dr. Holman, a primary UKPDS investigator and director of the University of Oxford Diabetes Trials Unit. "What we have here is comforting, but it is not proof positive. It’s not a second trial, but it does suggest that [the apparent early risk] may have evened out over time."
The Sulfonylurea and Metformin Substudy was designed to investigate the combination’s effect on patients in UKPDS who had not achieved the target glucose goal of 6 mmol/L (108 mg/dL), despite being on sulfonylurea monotherapy for the entire 7-year study. This group of 537 patients was secondarily randomized to either staying with the sulfonylurea monotherapy or adding metformin. "The impact of this was actually to add glycemic rescue therapy at 6 mmol/L rather than 15 mmol/L [270 mg/dL]," the level built into UKPDS, Dr. Holman said.
The substudy patients were a fairly representative mix of those in the larger study. They were a mean of 64 years old, with a mean body mass index of about 28 kg/m2. They did differ significantly in two major categories, however, Dr. Holman pointed out. Patients in the combination therapy group had lower fasting plasma glucose (9 vs. 10 mmol/L; 162 vs. 180 mg/dL), hemoglobin A1c (8.3% vs. 7.9%) and lower LDL cholesterol (3.4 vs. 3.2 mmol/L; 61.2 mg/dL vs. 57.6 mg/dL). These baseline differences could have helped set the stage for the differences in mortality outcomes, he suggested.
After the secondary randomization, those who got the addition of metformin showed an immediate, significant, decrease in fasting plasma glucose. This was a very encouraging finding, he said, because it broke the disappointing pattern of improvement followed eventually by beta-cell deterioration, which UKPDS characterized in all of its treatment arms. But, Dr. Holman said, after reaching a nadir at about 18 months, glucose levels in the dual-therapy patients did begin to creep back up, taking a parallel – although less pronounced – track to the monotherapy group.
The glucose response was encouraging, but clouded by an unexpected finding. By 6 years, those taking the drug combination were almost twice as likely to have died from a diabetes-related complication as were those in the monotherapy group (risk ratio, 1.96). The overall risk of death from any cause was also significantly increased in those taking the combination (RR, 0.60). However, there were no differences in fatal or nonfatal stroke or myocardial infarction.
"There was a separation of the mortality curves at around 3 years" that continued to separate through the entire study period, Dr. Holman said. "This was contrary to everything else UKPDS had shown, and raised considerable concern and alarm. It looked horrific and it could potentially have been horrific."
The investigators tried to make sense of the results, without much luck. Matching the cohorts with similar groups in other studies shed no light on the matter. The disconnect between the increase in all-cause mortality and stable cardiovascular events remained a puzzle. Because only 40 patients had died at that point – a reflection of the relative good baseline health of the UKPDS group – there was limited power to fully explore the finding.
Nonetheless, "when we found this, we said that these results could be real and that the addition of metformin to patients on sulfonylureas required more study, which is what we now have done."
At the meeting, Dr. Holman reported the most recent, yet-unpublished, data on these patients, who were followed for up to 15 years. In 1997, the hazard ratio for diabetes-related deaths was 1.96, with a high level of statistical significance (P = .039). It hovered near that point until 2001, when it began to decline. By 2003, it dropped to about 1.50, and was no longer statistically significant. Since then, the risk has declined close to null; it has never regained a significant value.
"Over time, the combination of sulfonylurea and metformin does not appear to have any continued adverse effect," Dr. Holman said. "We saw a diminishing risk ratio and at this point, close to 15 years after we started UKPDS, there appears to be no evidence of harm."
All-cause mortality showed a similar pattern, with a 60% increased risk in 1997 and a gradual improvement. "Although it’s still on the wrong side of 1.0, it’s not close to being statistically significant."
Overall, 226 patients have now died: 107 in the monotherapy group (40%) and 119 in the combination group (44%). Death from a diabetes-related cause has occurred in 57 of the monotherapy group (21%) and 60 of the combination therapy group (22%), for a nonsignificant risk ratio of 1.18.
There is no significant increase in the risk of myocardial infarction (1.09) or stroke (0.86), whether fatal or nonfatal.
Two more studies are in the works to try and sort out the sulfonylurea-metformin mash-up, Dr. Holman said: GRADE and GLINT. GRADE (Glycemic Reduction Approaches in Diabetes) is a four-arm comparative effectiveness study sponsored by the National Institutes of Health. It will randomize 6,000 patients with type 2 diabetes to metformin and either a sulfonylurea (glimepiride), a DPP-4 inhibitor (sitagliptin), a GLP-1 agonist (liraglutide), or insulin glargine. The groups will be followed for 5 years, Dr. Holman said. "Certainly, if there is a doubling in the risk of death in the sulfonylurea/metformin group, we will see it."
The second study, called GLINT (Glucose Lowering in Non-diabetic Hyperglycemia Trial), is just getting ramped up in the United Kingdom. It’s aimed at patients whose HbA1c is elevated, but not yet in the diabetic range of 6.5%.
The 5-year GLINT aims to recruit nearly 12,000 people aged 40 years and older, who have a 10-year calculated cardiovascular disease risk of at least 20%. Subjects will be randomized to metformin or placebo. The primary endpoint is a composite cardiovascular outcome of death or nonfatal MI or stroke. The first patients are being seen this month, Dr. Holman noted.
The study is also well powered to look at the increased risk of bowel and breast cancers among diabetes patients, he added
"Perhaps this will be the pivotal second study that will help confirm the preeminence of metformin as first-line therapy."
Becton Dickinson, Boehringer Mannheim, Bristol Myers Squibb, Hoechst, Lilly, Lipha, and Novo Nordisk contributed to the funding for the UKPDS study. Dr. Holman had no financial disclosures.
On Twitter @Alz_gal
AT THE EASD ANNUAL MEETING
Major finding: A UKPDS substudy with up to 15 years of follow-up found no increased risk of diabetes-related or all-cause mortality in patients taking the combination of sulfonylurea and metformin.
Data source: The Sulfonylurea and Metformin Substudy comprising 537 patients from UKPDS who did not achieve the blood glucose target despite 7 years of sulfonylurea monotherapy.
Disclosures: Becton Dickinson, Boehringer Mannheim, Bristol Myers Squibb, Hoechst, Lilly, Lipha, and Novo Nordisk contributed to the funding for the UKPDS study. Dr. Holman had no financial disclosures.
Albiglutide shows safety, efficacy, slight weight loss in pivotal diabetes trial
BARCELONA – Treatment of patients with type 2 diabetes with albiglutide plus metformin produced a significantly greater rate of glycemic control compared with three other oral regimens in a pivotal trial with more than 1,000 patients treated and followed for up to 2 years.
After 2 years of treatment, 59% of patients randomized to albiglutide, an investigational glucagonlike peptide–1 (GLP-1) receptor agonist, and metformin had a hemoglobin A1c level below 7.5%, compared with 49% of patients randomized to glimepiride plus metformin, 44% of patients randomized to sitagliptin plus metformin, and 28% who received metformin plus placebo. The differences between albiglutide and each of the three other study groups were statistically significant, Dr. Murray W. Stewart reported at the annual meeting of the European Association for the Study of Diabetes.
In addition, albiglutide treatment produced no severe hypoglycemic episodes and resulted in a relatively modest 5% incidence of nausea and vomiting during the first 8 weeks on treatment, "generally consistent with the known profile" of GLP-1 receptor agonists, Dr. Stewart said. During the second year of treatment, the incidence of nausea or vomiting in albiglutide-treated patients declined to a steady rate of about 1%-2%, similar to that of patients on sitagliptin or metformin plus placebo, and less than the 3%-4% rate seen among patients on glimepiride during the final 6 months of the study, he said. Dr. Stewart is senior vice president for metabolic pathways and cardiovascular therapy at GlaxoSmithKline, the company developing albiglutide.
The HARMONY 3 trial randomized 1,049 patients with type 2 diabetes and hyperglycemia, with an average HbA1c level of 8.1%. The study started all patients on metformin and up-titrated their regimen to a maximum tolerated dosage over 2 weeks, and also started all patients on a diet and exercise regimen for a week prior to randomization. After these two run-in treatments began, the investigators randomized patients to receive either 30 mg of albiglutide by injection once a week, sitagliptin (Januvia, a dipeptidyl peptidase–4 inhibitor) at 100 mg orally once per day, glimepiride (Amaryl, a sulfonylurea) at 2-4 mg orally once a day, or a weekly placebo injection. About two thirds of patients completed the study’s full 2 years of treatment. Study patients averaged about 55 years old, their mean body mass index was 33 kg/m2, and they had type 2 diabetes for an average of about 6 years.
After 2 years, the average HbA1c level was about 7.5% in the patients on albiglutide, 7.8% in the patients on sitagliptin or glimepiride, and 8.4% among those on metformin plus placebo. All patients lost an average of about 1 kg of weight at 2 years compared with baseline except those who receive glimepiride, whose weight increased by an average of about 1 kg. The incidence of patients having their HbA1c rise to 8.5%, requiring the initiation of insulin therapy, was 26% in patients on albiglutide, 33% of those on glimepiride, 36% among those on sitagliptin, and 59% of those on metformin plus placebo, all significant differences between albiglutide and each of the three comparator arms.
Symptomatic hypoglycemia occurred in 3% of the albiglutide patients, similar to the rates in the sitagliptin and placebo subgroups, and less than the 18% rate among patients who received glimepiride. Injection-site reactions occurred in 17% of the albiglutide patients, but these were mostly mild or moderate, and 21 patients on this drug developed antialbiglutide antibodies. Two patients on albiglutide had probable pancreatitis that was at least possibly related to their treatment, and one patient developed thyroid cancer.
The HARMONY 3 trial is one of several pivotal trials recently completed for albiglutide. GlaxoSmithKline initially filed an application with the Food and Drug Administration for approval of albiglutide last January. The goal date for an FDA decision is currently next April.
HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
[email protected]
On Twitter @mitchelzoler
In this study, albiglutide showed less weight loss than we have seen in the results from studies of other GLP-1 receptor agonists; on the other hand, it was relatively free of adverse events other than some episodes of nausea and vomiting, which may be an attractive feature for some patients.
It is still too soon to know how this entire class of drugs will fit into the algorithm for treating patients with type 2 diabetes. The GLP-1 receptor agonists seem to produce glycemic control that is at least as good as that produced by insulin, but without causing severe hypoglycemia or much hypoglycemia of any kind, and also leading to a small amount of weight loss. The potential exists for the GLP-1 receptor agonists to supplant metformin as a first-line drug, but with a few qualifications.
 |
|
First, the most convincing evidence to support early use of the GLP-1 receptor agonists would be if they are shown in the future to be significantly better at preventing complications than metformin, especially cardiovascular and microvascular events.
There is also the issue of administration by injection. Some patients don’t like injections, and others may hesitate until they try it and find it is not very difficult. But patients who accept this route of delivery may find the GLP-1 receptor agonists to be effective and relatively safe. Of course, there is also the issue of the drug’s costs. Generic metformin will hold a price edge over all these new drugs for many years to come.
Dr. Michael A. Nauck is head of the Diabetes Center in Bad Lauterberg, Germany. He made these comments in an interview. He has been a coinvestigator on other trials of albiglutide and a consultant to GlaxoSmithKline, the company developing this drug, as well as a consultant to several other companies that are developing or that market drugs for patients with diabetes.
In this study, albiglutide showed less weight loss than we have seen in the results from studies of other GLP-1 receptor agonists; on the other hand, it was relatively free of adverse events other than some episodes of nausea and vomiting, which may be an attractive feature for some patients.
It is still too soon to know how this entire class of drugs will fit into the algorithm for treating patients with type 2 diabetes. The GLP-1 receptor agonists seem to produce glycemic control that is at least as good as that produced by insulin, but without causing severe hypoglycemia or much hypoglycemia of any kind, and also leading to a small amount of weight loss. The potential exists for the GLP-1 receptor agonists to supplant metformin as a first-line drug, but with a few qualifications.
|
|
First, the most convincing evidence to support early use of the GLP-1 receptor agonists would be if they are shown in the future to be significantly better at preventing complications than metformin, especially cardiovascular and microvascular events.
There is also the issue of administration by injection. Some patients don’t like injections, and others may hesitate until they try it and find it is not very difficult. But patients who accept this route of delivery may find the GLP-1 receptor agonists to be effective and relatively safe. Of course, there is also the issue of the drug’s costs. Generic metformin will hold a price edge over all these new drugs for many years to come.
Dr. Michael A. Nauck is head of the Diabetes Center in Bad Lauterberg, Germany. He made these comments in an interview. He has been a coinvestigator on other trials of albiglutide and a consultant to GlaxoSmithKline, the company developing this drug, as well as a consultant to several other companies that are developing or that market drugs for patients with diabetes.
In this study, albiglutide showed less weight loss than we have seen in the results from studies of other GLP-1 receptor agonists; on the other hand, it was relatively free of adverse events other than some episodes of nausea and vomiting, which may be an attractive feature for some patients.
It is still too soon to know how this entire class of drugs will fit into the algorithm for treating patients with type 2 diabetes. The GLP-1 receptor agonists seem to produce glycemic control that is at least as good as that produced by insulin, but without causing severe hypoglycemia or much hypoglycemia of any kind, and also leading to a small amount of weight loss. The potential exists for the GLP-1 receptor agonists to supplant metformin as a first-line drug, but with a few qualifications.
|
|
First, the most convincing evidence to support early use of the GLP-1 receptor agonists would be if they are shown in the future to be significantly better at preventing complications than metformin, especially cardiovascular and microvascular events.
There is also the issue of administration by injection. Some patients don’t like injections, and others may hesitate until they try it and find it is not very difficult. But patients who accept this route of delivery may find the GLP-1 receptor agonists to be effective and relatively safe. Of course, there is also the issue of the drug’s costs. Generic metformin will hold a price edge over all these new drugs for many years to come.
Dr. Michael A. Nauck is head of the Diabetes Center in Bad Lauterberg, Germany. He made these comments in an interview. He has been a coinvestigator on other trials of albiglutide and a consultant to GlaxoSmithKline, the company developing this drug, as well as a consultant to several other companies that are developing or that market drugs for patients with diabetes.
BARCELONA – Treatment of patients with type 2 diabetes with albiglutide plus metformin produced a significantly greater rate of glycemic control compared with three other oral regimens in a pivotal trial with more than 1,000 patients treated and followed for up to 2 years.
After 2 years of treatment, 59% of patients randomized to albiglutide, an investigational glucagonlike peptide–1 (GLP-1) receptor agonist, and metformin had a hemoglobin A1c level below 7.5%, compared with 49% of patients randomized to glimepiride plus metformin, 44% of patients randomized to sitagliptin plus metformin, and 28% who received metformin plus placebo. The differences between albiglutide and each of the three other study groups were statistically significant, Dr. Murray W. Stewart reported at the annual meeting of the European Association for the Study of Diabetes.
In addition, albiglutide treatment produced no severe hypoglycemic episodes and resulted in a relatively modest 5% incidence of nausea and vomiting during the first 8 weeks on treatment, "generally consistent with the known profile" of GLP-1 receptor agonists, Dr. Stewart said. During the second year of treatment, the incidence of nausea or vomiting in albiglutide-treated patients declined to a steady rate of about 1%-2%, similar to that of patients on sitagliptin or metformin plus placebo, and less than the 3%-4% rate seen among patients on glimepiride during the final 6 months of the study, he said. Dr. Stewart is senior vice president for metabolic pathways and cardiovascular therapy at GlaxoSmithKline, the company developing albiglutide.
The HARMONY 3 trial randomized 1,049 patients with type 2 diabetes and hyperglycemia, with an average HbA1c level of 8.1%. The study started all patients on metformin and up-titrated their regimen to a maximum tolerated dosage over 2 weeks, and also started all patients on a diet and exercise regimen for a week prior to randomization. After these two run-in treatments began, the investigators randomized patients to receive either 30 mg of albiglutide by injection once a week, sitagliptin (Januvia, a dipeptidyl peptidase–4 inhibitor) at 100 mg orally once per day, glimepiride (Amaryl, a sulfonylurea) at 2-4 mg orally once a day, or a weekly placebo injection. About two thirds of patients completed the study’s full 2 years of treatment. Study patients averaged about 55 years old, their mean body mass index was 33 kg/m2, and they had type 2 diabetes for an average of about 6 years.
After 2 years, the average HbA1c level was about 7.5% in the patients on albiglutide, 7.8% in the patients on sitagliptin or glimepiride, and 8.4% among those on metformin plus placebo. All patients lost an average of about 1 kg of weight at 2 years compared with baseline except those who receive glimepiride, whose weight increased by an average of about 1 kg. The incidence of patients having their HbA1c rise to 8.5%, requiring the initiation of insulin therapy, was 26% in patients on albiglutide, 33% of those on glimepiride, 36% among those on sitagliptin, and 59% of those on metformin plus placebo, all significant differences between albiglutide and each of the three comparator arms.
Symptomatic hypoglycemia occurred in 3% of the albiglutide patients, similar to the rates in the sitagliptin and placebo subgroups, and less than the 18% rate among patients who received glimepiride. Injection-site reactions occurred in 17% of the albiglutide patients, but these were mostly mild or moderate, and 21 patients on this drug developed antialbiglutide antibodies. Two patients on albiglutide had probable pancreatitis that was at least possibly related to their treatment, and one patient developed thyroid cancer.
The HARMONY 3 trial is one of several pivotal trials recently completed for albiglutide. GlaxoSmithKline initially filed an application with the Food and Drug Administration for approval of albiglutide last January. The goal date for an FDA decision is currently next April.
HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
[email protected]
On Twitter @mitchelzoler
BARCELONA – Treatment of patients with type 2 diabetes with albiglutide plus metformin produced a significantly greater rate of glycemic control compared with three other oral regimens in a pivotal trial with more than 1,000 patients treated and followed for up to 2 years.
After 2 years of treatment, 59% of patients randomized to albiglutide, an investigational glucagonlike peptide–1 (GLP-1) receptor agonist, and metformin had a hemoglobin A1c level below 7.5%, compared with 49% of patients randomized to glimepiride plus metformin, 44% of patients randomized to sitagliptin plus metformin, and 28% who received metformin plus placebo. The differences between albiglutide and each of the three other study groups were statistically significant, Dr. Murray W. Stewart reported at the annual meeting of the European Association for the Study of Diabetes.
In addition, albiglutide treatment produced no severe hypoglycemic episodes and resulted in a relatively modest 5% incidence of nausea and vomiting during the first 8 weeks on treatment, "generally consistent with the known profile" of GLP-1 receptor agonists, Dr. Stewart said. During the second year of treatment, the incidence of nausea or vomiting in albiglutide-treated patients declined to a steady rate of about 1%-2%, similar to that of patients on sitagliptin or metformin plus placebo, and less than the 3%-4% rate seen among patients on glimepiride during the final 6 months of the study, he said. Dr. Stewart is senior vice president for metabolic pathways and cardiovascular therapy at GlaxoSmithKline, the company developing albiglutide.
The HARMONY 3 trial randomized 1,049 patients with type 2 diabetes and hyperglycemia, with an average HbA1c level of 8.1%. The study started all patients on metformin and up-titrated their regimen to a maximum tolerated dosage over 2 weeks, and also started all patients on a diet and exercise regimen for a week prior to randomization. After these two run-in treatments began, the investigators randomized patients to receive either 30 mg of albiglutide by injection once a week, sitagliptin (Januvia, a dipeptidyl peptidase–4 inhibitor) at 100 mg orally once per day, glimepiride (Amaryl, a sulfonylurea) at 2-4 mg orally once a day, or a weekly placebo injection. About two thirds of patients completed the study’s full 2 years of treatment. Study patients averaged about 55 years old, their mean body mass index was 33 kg/m2, and they had type 2 diabetes for an average of about 6 years.
After 2 years, the average HbA1c level was about 7.5% in the patients on albiglutide, 7.8% in the patients on sitagliptin or glimepiride, and 8.4% among those on metformin plus placebo. All patients lost an average of about 1 kg of weight at 2 years compared with baseline except those who receive glimepiride, whose weight increased by an average of about 1 kg. The incidence of patients having their HbA1c rise to 8.5%, requiring the initiation of insulin therapy, was 26% in patients on albiglutide, 33% of those on glimepiride, 36% among those on sitagliptin, and 59% of those on metformin plus placebo, all significant differences between albiglutide and each of the three comparator arms.
Symptomatic hypoglycemia occurred in 3% of the albiglutide patients, similar to the rates in the sitagliptin and placebo subgroups, and less than the 18% rate among patients who received glimepiride. Injection-site reactions occurred in 17% of the albiglutide patients, but these were mostly mild or moderate, and 21 patients on this drug developed antialbiglutide antibodies. Two patients on albiglutide had probable pancreatitis that was at least possibly related to their treatment, and one patient developed thyroid cancer.
The HARMONY 3 trial is one of several pivotal trials recently completed for albiglutide. GlaxoSmithKline initially filed an application with the Food and Drug Administration for approval of albiglutide last January. The goal date for an FDA decision is currently next April.
HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
[email protected]
On Twitter @mitchelzoler
AT THE EASD ANNUAL MEETING
Major finding: Treatment with metformin plus albiglutide dropped HbA1c below 7.5% in 59% of patients, compared with 28% for metformin plus placebo.
Data source: HARMONY 3, which randomized 1,049 patients with type 2 diabetes to treatment with metformin plus albiglutide, sitagliptin, glimepiride, or placebo and followed them for up to 2 years.
Disclosures: HARMONY 3 was sponsored by GlaxoSmithKline. Dr. Stewart is an employee of the company.
Continuous glucose monitoring keeps ICU patients steady
BARCELONA – Use of a subcutaneous continuous glucose monitoring system translated into better glycemic control for critically ill patients in intensive care, a study has shown.
Compared with those monitored by point-of-care testing, patients with continuous monitoring spent significantly more time in their target blood glucose range, Daphne Boom reported at the annual meeting of the European Association for the Study of Diabetes.
The implantable device also markedly reduced the need for blood samples, said Ms. Boom, a medical student at the Onze Lieve Vrouwe Gasthuis, Amsterdam. Nurses obtained a mean of just two samples over a 24-hour period for these patients, compared with 12 over the same time for point-of-care patients.
Ms. Boom and her colleagues compared the two monitoring regimens in a group of 177 patients who were admitted to intensive care with an expected stay of at least 24 hours; 87 were randomized to continuous subcutaneous glucose monitoring and 90 to point-of-care monitoring. The target glucose range for each group was 5-9 mmol/L. The continuous monitoring system measured glucose every 10 minutes, and sounded an alarm whenever it registered outside this parameter. Blood samples were drawn every 2 hours for the point-of-care patients. A computer algorithm made insulin dosing recommendations for patients in both groups, based on the monitoring system level or the results of finger-stick samples.
In both groups, an arterial blood sample provided a reference glucose range every 6 hours; however, the samples were blinded to clinicians and used only for calibrating medications.
The primary endpoints were the incidence of severe hypoglycemia (below 2.2 mmol/L) and severe hyperglycemia (above 25 mmol/L). The measure of efficacy was the total time spent within the blood glucose target range. Nursing workload was assessed by the number of blood samples drawn every 24 hours.
Most patients were from the medical service; 13% were complicated cardiac surgery patients. The majority (92%) were mechanically ventilated. The investigators looked at 1,358 paired measurements.
There were five incidents of severe hypoglycemia in the intervention group and two in the control group, but the difference was not statistically significant. There were no cases of severe hyperglycemia in either group.
There was one case of mild hypoglycemia in each group. There was one case of mild hyperglycemia in the intervention group and two in the control group.
The mean study duration was 73 hours for the intervention group, of which 58 (79%) were spent within the target glucose range. The mean study duration for the control group was 59 hours, of which 43 (73%) were spent in the target range. This difference was statistically significant.
Significantly fewer blood samples were drawn from the intervention group (2 vs. 12 every 24 hours), showing that the continuous monitoring system was a more efficient use of nursing time, Ms. Boom added.
She said she had no relevant financial disclosures.
BARCELONA – Use of a subcutaneous continuous glucose monitoring system translated into better glycemic control for critically ill patients in intensive care, a study has shown.
Compared with those monitored by point-of-care testing, patients with continuous monitoring spent significantly more time in their target blood glucose range, Daphne Boom reported at the annual meeting of the European Association for the Study of Diabetes.
The implantable device also markedly reduced the need for blood samples, said Ms. Boom, a medical student at the Onze Lieve Vrouwe Gasthuis, Amsterdam. Nurses obtained a mean of just two samples over a 24-hour period for these patients, compared with 12 over the same time for point-of-care patients.
Ms. Boom and her colleagues compared the two monitoring regimens in a group of 177 patients who were admitted to intensive care with an expected stay of at least 24 hours; 87 were randomized to continuous subcutaneous glucose monitoring and 90 to point-of-care monitoring. The target glucose range for each group was 5-9 mmol/L. The continuous monitoring system measured glucose every 10 minutes, and sounded an alarm whenever it registered outside this parameter. Blood samples were drawn every 2 hours for the point-of-care patients. A computer algorithm made insulin dosing recommendations for patients in both groups, based on the monitoring system level or the results of finger-stick samples.
In both groups, an arterial blood sample provided a reference glucose range every 6 hours; however, the samples were blinded to clinicians and used only for calibrating medications.
The primary endpoints were the incidence of severe hypoglycemia (below 2.2 mmol/L) and severe hyperglycemia (above 25 mmol/L). The measure of efficacy was the total time spent within the blood glucose target range. Nursing workload was assessed by the number of blood samples drawn every 24 hours.
Most patients were from the medical service; 13% were complicated cardiac surgery patients. The majority (92%) were mechanically ventilated. The investigators looked at 1,358 paired measurements.
There were five incidents of severe hypoglycemia in the intervention group and two in the control group, but the difference was not statistically significant. There were no cases of severe hyperglycemia in either group.
There was one case of mild hypoglycemia in each group. There was one case of mild hyperglycemia in the intervention group and two in the control group.
The mean study duration was 73 hours for the intervention group, of which 58 (79%) were spent within the target glucose range. The mean study duration for the control group was 59 hours, of which 43 (73%) were spent in the target range. This difference was statistically significant.
Significantly fewer blood samples were drawn from the intervention group (2 vs. 12 every 24 hours), showing that the continuous monitoring system was a more efficient use of nursing time, Ms. Boom added.
She said she had no relevant financial disclosures.
BARCELONA – Use of a subcutaneous continuous glucose monitoring system translated into better glycemic control for critically ill patients in intensive care, a study has shown.
Compared with those monitored by point-of-care testing, patients with continuous monitoring spent significantly more time in their target blood glucose range, Daphne Boom reported at the annual meeting of the European Association for the Study of Diabetes.
The implantable device also markedly reduced the need for blood samples, said Ms. Boom, a medical student at the Onze Lieve Vrouwe Gasthuis, Amsterdam. Nurses obtained a mean of just two samples over a 24-hour period for these patients, compared with 12 over the same time for point-of-care patients.
Ms. Boom and her colleagues compared the two monitoring regimens in a group of 177 patients who were admitted to intensive care with an expected stay of at least 24 hours; 87 were randomized to continuous subcutaneous glucose monitoring and 90 to point-of-care monitoring. The target glucose range for each group was 5-9 mmol/L. The continuous monitoring system measured glucose every 10 minutes, and sounded an alarm whenever it registered outside this parameter. Blood samples were drawn every 2 hours for the point-of-care patients. A computer algorithm made insulin dosing recommendations for patients in both groups, based on the monitoring system level or the results of finger-stick samples.
In both groups, an arterial blood sample provided a reference glucose range every 6 hours; however, the samples were blinded to clinicians and used only for calibrating medications.
The primary endpoints were the incidence of severe hypoglycemia (below 2.2 mmol/L) and severe hyperglycemia (above 25 mmol/L). The measure of efficacy was the total time spent within the blood glucose target range. Nursing workload was assessed by the number of blood samples drawn every 24 hours.
Most patients were from the medical service; 13% were complicated cardiac surgery patients. The majority (92%) were mechanically ventilated. The investigators looked at 1,358 paired measurements.
There were five incidents of severe hypoglycemia in the intervention group and two in the control group, but the difference was not statistically significant. There were no cases of severe hyperglycemia in either group.
There was one case of mild hypoglycemia in each group. There was one case of mild hyperglycemia in the intervention group and two in the control group.
The mean study duration was 73 hours for the intervention group, of which 58 (79%) were spent within the target glucose range. The mean study duration for the control group was 59 hours, of which 43 (73%) were spent in the target range. This difference was statistically significant.
Significantly fewer blood samples were drawn from the intervention group (2 vs. 12 every 24 hours), showing that the continuous monitoring system was a more efficient use of nursing time, Ms. Boom added.
She said she had no relevant financial disclosures.
AT THE EASD ANNUAL MEETING
Major finding: ICU patients with continuous subcutaneous glucose monitoring remained in their blood glucose target range for 79% of their stay, compared with 73% for patients who had point-of-care monitoring.
Data source: A study that randomized 87 ICU patients to continuous subcutaneous glucose monitoring and 90 to point-of-care monitoring.
Disclosures: Ms. Boom said she had no relevant financial disclosures.
Diabetes, pro-BNP a bad mix for cardiac health
BARCELONA – High levels of pro-B-type natriuretic peptide significantly predicted cardiovascular events in patients with type 2 diabetes, a prospective study has found.
Over 6 years, patients with diabetes and high levels of the cardiac protein were more than 50% as likely to have an acute cardiovascular event than were patients without diabetes who had low pro-BNP levels, Dr. Christoph H. Saely said at the annual meeting of the European Association for the Study of Diabetes.
The finding could be useful in risk stratification of patients with diabetes, said Dr. Saely of the Academic Teaching Hospital Feldkirch, Austria.
He and his colleagues followed 750 patients who underwent coronary angiography for the evaluation of established or suspected stable coronary artery disease for a mean of 6 years.
At baseline, the patients’ mean age was 66 years. Most (64%) were men. About 60% were current or past smokers, and 24% had type 2 diabetes.
Generally, those with diabetes had worse markers of cardiac health, including a higher incidence of hypertension (91% vs. 79%); a higher body mass index (29 vs. 27 kg/m2); and worse lipid measurements. At baseline, 65% of those with diabetes had marked coronary artery disease, compared with 50% of those without diabetes – a significant difference.
The baseline pro-BNP level was also significantly higher in the patients with diabetes (mean of 750 pg/mL vs. 500 pg/mL).
Over the follow-up period, there were 119 coronary events (16%), including cardiovascular death (24), nonfatal heart attack (18), and nonfatal stroke (12). There were also 10 coronary artery bypass grafts, 27 percutaneous coronary interventions, and 28 noncoronary revascularizations.
To evaluate the impact of pro-BNP levels on cardiovascular risk, Dr. Saely divided the cohort into four groups according to diabetes and either high or low pro-BNP levels; a low level was less than 314 pg/mL, while a high level was 314 pg/mL or more. Patients were classified into nondiabetes with low pro-BNP (391); nondiabetes with high pro-BNP (182); diabetes with low pro-BNP (109); and diabetes with high pro-BNP (68).
By the end of the study, there had been significantly fewer cardiovascular events among patients with low pro-BNP; 95% of those without diabetes and 90% of those with diabetes were free of such events.
Among those patients who had no diabetes but had a high pro-BNP, 80% were event free by 6 years. But the picture was much worse for patients who had diabetes coupled with a high pro-BNP level, Dr. Saely said. By 6 years, about half had experienced some kind of major cardiovascular event; the excess risk associated with high levels was more than 50%, he said, even after adjustment for age, gender, hypertension, body mass index, and smoking status.
The protein is generally thought of as a marker for heart failure, he added. In patients with long-standing diabetes, he said, it may be associated with metabolically induced cardiac fibrosis.
Dr. Saely had no financial disclosures.
BARCELONA – High levels of pro-B-type natriuretic peptide significantly predicted cardiovascular events in patients with type 2 diabetes, a prospective study has found.
Over 6 years, patients with diabetes and high levels of the cardiac protein were more than 50% as likely to have an acute cardiovascular event than were patients without diabetes who had low pro-BNP levels, Dr. Christoph H. Saely said at the annual meeting of the European Association for the Study of Diabetes.
The finding could be useful in risk stratification of patients with diabetes, said Dr. Saely of the Academic Teaching Hospital Feldkirch, Austria.
He and his colleagues followed 750 patients who underwent coronary angiography for the evaluation of established or suspected stable coronary artery disease for a mean of 6 years.
At baseline, the patients’ mean age was 66 years. Most (64%) were men. About 60% were current or past smokers, and 24% had type 2 diabetes.
Generally, those with diabetes had worse markers of cardiac health, including a higher incidence of hypertension (91% vs. 79%); a higher body mass index (29 vs. 27 kg/m2); and worse lipid measurements. At baseline, 65% of those with diabetes had marked coronary artery disease, compared with 50% of those without diabetes – a significant difference.
The baseline pro-BNP level was also significantly higher in the patients with diabetes (mean of 750 pg/mL vs. 500 pg/mL).
Over the follow-up period, there were 119 coronary events (16%), including cardiovascular death (24), nonfatal heart attack (18), and nonfatal stroke (12). There were also 10 coronary artery bypass grafts, 27 percutaneous coronary interventions, and 28 noncoronary revascularizations.
To evaluate the impact of pro-BNP levels on cardiovascular risk, Dr. Saely divided the cohort into four groups according to diabetes and either high or low pro-BNP levels; a low level was less than 314 pg/mL, while a high level was 314 pg/mL or more. Patients were classified into nondiabetes with low pro-BNP (391); nondiabetes with high pro-BNP (182); diabetes with low pro-BNP (109); and diabetes with high pro-BNP (68).
By the end of the study, there had been significantly fewer cardiovascular events among patients with low pro-BNP; 95% of those without diabetes and 90% of those with diabetes were free of such events.
Among those patients who had no diabetes but had a high pro-BNP, 80% were event free by 6 years. But the picture was much worse for patients who had diabetes coupled with a high pro-BNP level, Dr. Saely said. By 6 years, about half had experienced some kind of major cardiovascular event; the excess risk associated with high levels was more than 50%, he said, even after adjustment for age, gender, hypertension, body mass index, and smoking status.
The protein is generally thought of as a marker for heart failure, he added. In patients with long-standing diabetes, he said, it may be associated with metabolically induced cardiac fibrosis.
Dr. Saely had no financial disclosures.
BARCELONA – High levels of pro-B-type natriuretic peptide significantly predicted cardiovascular events in patients with type 2 diabetes, a prospective study has found.
Over 6 years, patients with diabetes and high levels of the cardiac protein were more than 50% as likely to have an acute cardiovascular event than were patients without diabetes who had low pro-BNP levels, Dr. Christoph H. Saely said at the annual meeting of the European Association for the Study of Diabetes.
The finding could be useful in risk stratification of patients with diabetes, said Dr. Saely of the Academic Teaching Hospital Feldkirch, Austria.
He and his colleagues followed 750 patients who underwent coronary angiography for the evaluation of established or suspected stable coronary artery disease for a mean of 6 years.
At baseline, the patients’ mean age was 66 years. Most (64%) were men. About 60% were current or past smokers, and 24% had type 2 diabetes.
Generally, those with diabetes had worse markers of cardiac health, including a higher incidence of hypertension (91% vs. 79%); a higher body mass index (29 vs. 27 kg/m2); and worse lipid measurements. At baseline, 65% of those with diabetes had marked coronary artery disease, compared with 50% of those without diabetes – a significant difference.
The baseline pro-BNP level was also significantly higher in the patients with diabetes (mean of 750 pg/mL vs. 500 pg/mL).
Over the follow-up period, there were 119 coronary events (16%), including cardiovascular death (24), nonfatal heart attack (18), and nonfatal stroke (12). There were also 10 coronary artery bypass grafts, 27 percutaneous coronary interventions, and 28 noncoronary revascularizations.
To evaluate the impact of pro-BNP levels on cardiovascular risk, Dr. Saely divided the cohort into four groups according to diabetes and either high or low pro-BNP levels; a low level was less than 314 pg/mL, while a high level was 314 pg/mL or more. Patients were classified into nondiabetes with low pro-BNP (391); nondiabetes with high pro-BNP (182); diabetes with low pro-BNP (109); and diabetes with high pro-BNP (68).
By the end of the study, there had been significantly fewer cardiovascular events among patients with low pro-BNP; 95% of those without diabetes and 90% of those with diabetes were free of such events.
Among those patients who had no diabetes but had a high pro-BNP, 80% were event free by 6 years. But the picture was much worse for patients who had diabetes coupled with a high pro-BNP level, Dr. Saely said. By 6 years, about half had experienced some kind of major cardiovascular event; the excess risk associated with high levels was more than 50%, he said, even after adjustment for age, gender, hypertension, body mass index, and smoking status.
The protein is generally thought of as a marker for heart failure, he added. In patients with long-standing diabetes, he said, it may be associated with metabolically induced cardiac fibrosis.
Dr. Saely had no financial disclosures.
AT THE EASD ANNUAL MEETING
Major finding: Patients with type 2 diabetes and high levels of pro-B-type natriuretic peptide were 50% more likely to have a serious cardiovascular event over 6 years than were patients without diabetes who had low pro-BNP.
Data source: A prospective study of 750 patients who underwent coronary angiography.
Disclosures: Dr. Saely had no financial disclosures.