ADA Annual Scientific Sessions 2015

BOSTON – Adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin in patients with type 2 diabetes was associated with an increased, earlier need for treatment intensification, compared with adding a sulfonylurea in a large, retrospective, population-based study in the United Kingdom.

Conversely, adding a thiazolidinedione as a second-line glucose-lowering agent resulted in the most durable glycemic response, Jil Mamza reported at the annual scientific sessions of the American Diabetes Association.

Unadjusted survival analysis showed that 23% of 3,080 patients treated with second-line DDP-4 agents experienced treatment failure at 1 year, compared with 15% of 15,508 on a sulfonylurea, and 8% of 1,582 on a thiazolidinedione. The corresponding failure rates at 2 years were 38%, 26% and 12%, said Mr. Mamza, a clinical researcher and doctoral student at the University of Nottingham, Derby, England.

After multivariate adjustment, adding a DPP-4 inhibitor was associated with an increased hazard of intensification of therapy (adjusted hazard ratio, 1.58), while adding a thiazolidinedione was associated with a reduced hazard (adjusted HR, 0.45).

Several baseline factors were also shown to be associated an increased hazard of intensification, including hemoglobin A_1c level, diabetes duration, gender, smoking status, and the use of lipid-lowering medications, he said.

Patients included in this study were adults with a mean age of 60 years and a mean disease duration of 3 years from the The Health Initiative Network (THIN) database of United Kingdom general practice patients. All those included had added a second oral glucose lowering therapy (GLT) to metformin between 2007 and 2014.

Time to dual therapy failure was defined as time to treatment substitution or intensification with a third agent at an HbA_1c level greater than 58 mmol/mol.

The durability of glycemic response for different second-line treatments was previously unclear. These findings suggest that DPP-4 agents provide the least durable response, compared with sulfonylureas and thiazolidinediones as second-line GLTs, Dr. Mamza said.

Mr. Mamza reported having no disclosures.

[email protected]

BOSTON – Adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin in patients with type 2 diabetes was associated with an increased, earlier need for treatment intensification, compared with adding a sulfonylurea in a large, retrospective, population-based study in the United Kingdom.

Conversely, adding a thiazolidinedione as a second-line glucose-lowering agent resulted in the most durable glycemic response, Jil Mamza reported at the annual scientific sessions of the American Diabetes Association.

Unadjusted survival analysis showed that 23% of 3,080 patients treated with second-line DDP-4 agents experienced treatment failure at 1 year, compared with 15% of 15,508 on a sulfonylurea, and 8% of 1,582 on a thiazolidinedione. The corresponding failure rates at 2 years were 38%, 26% and 12%, said Mr. Mamza, a clinical researcher and doctoral student at the University of Nottingham, Derby, England.

After multivariate adjustment, adding a DPP-4 inhibitor was associated with an increased hazard of intensification of therapy (adjusted hazard ratio, 1.58), while adding a thiazolidinedione was associated with a reduced hazard (adjusted HR, 0.45).

Several baseline factors were also shown to be associated an increased hazard of intensification, including hemoglobin A_1c level, diabetes duration, gender, smoking status, and the use of lipid-lowering medications, he said.

Patients included in this study were adults with a mean age of 60 years and a mean disease duration of 3 years from the The Health Initiative Network (THIN) database of United Kingdom general practice patients. All those included had added a second oral glucose lowering therapy (GLT) to metformin between 2007 and 2014.

Time to dual therapy failure was defined as time to treatment substitution or intensification with a third agent at an HbA_1c level greater than 58 mmol/mol.

The durability of glycemic response for different second-line treatments was previously unclear. These findings suggest that DPP-4 agents provide the least durable response, compared with sulfonylureas and thiazolidinediones as second-line GLTs, Dr. Mamza said.

Mr. Mamza reported having no disclosures.

[email protected]

BOSTON – Adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin in patients with type 2 diabetes was associated with an increased, earlier need for treatment intensification, compared with adding a sulfonylurea in a large, retrospective, population-based study in the United Kingdom.

Conversely, adding a thiazolidinedione as a second-line glucose-lowering agent resulted in the most durable glycemic response, Jil Mamza reported at the annual scientific sessions of the American Diabetes Association.

Unadjusted survival analysis showed that 23% of 3,080 patients treated with second-line DDP-4 agents experienced treatment failure at 1 year, compared with 15% of 15,508 on a sulfonylurea, and 8% of 1,582 on a thiazolidinedione. The corresponding failure rates at 2 years were 38%, 26% and 12%, said Mr. Mamza, a clinical researcher and doctoral student at the University of Nottingham, Derby, England.

After multivariate adjustment, adding a DPP-4 inhibitor was associated with an increased hazard of intensification of therapy (adjusted hazard ratio, 1.58), while adding a thiazolidinedione was associated with a reduced hazard (adjusted HR, 0.45).

Several baseline factors were also shown to be associated an increased hazard of intensification, including hemoglobin A_1c level, diabetes duration, gender, smoking status, and the use of lipid-lowering medications, he said.

Patients included in this study were adults with a mean age of 60 years and a mean disease duration of 3 years from the The Health Initiative Network (THIN) database of United Kingdom general practice patients. All those included had added a second oral glucose lowering therapy (GLT) to metformin between 2007 and 2014.

Time to dual therapy failure was defined as time to treatment substitution or intensification with a third agent at an HbA_1c level greater than 58 mmol/mol.

The durability of glycemic response for different second-line treatments was previously unclear. These findings suggest that DPP-4 agents provide the least durable response, compared with sulfonylureas and thiazolidinediones as second-line GLTs, Dr. Mamza said.

Mr. Mamza reported having no disclosures.

[email protected]

BOSTON – Maintaining or improving cardiorespiratory fitness during the year following an intensive lifestyle intervention contributed to the prevention of advanced chronic kidney disease over 4 years among participants in Look AHEAD, according to findings from a substudy of that randomized clinical trial.

During the first 4 years of follow-up in 4,906 of the 5,145 original study subjects, the incidence of advanced chronic kidney disease – after adjustment for age, race, ethnicity, and disease-related baseline covariates – was reduced by nearly 60% in those who received the intervention in the original study, compared with those who received diabetes support and education (hazard ratio, 0.59), Dr. Margareta I. Hellgren reported at the annual scientific sessions of the American Diabetes Association.

At 1-year follow-up, fitness level was unchanged in 77% of the lifestyle intervention group patients, compared with 58% of those in the diabetes support and education group, and in a model that used the same covariates, plus 1-year fitness change, and which included annually updated weight, blood pressure, and hemoglobin A1c, both intervention group participation and unchanged or improved fitness predicted lower incidence of advanced CKD over 4 years (HR, 0.69, 0.49, respectively), said Dr. Hellgren of the University of Gothenburg, Sweden.

The multicenter Look AHEAD trial included overweight adults with type 2 diabetes who were followed for about 10 years. The findings, which were published in 2013, showed no difference between intensive lifestyle intervention – including physical activity and reduced calorie intake – and diabetes support and education for reducing the incidence of cardiovascular events (the primary outcome measure), but did demonstrate a benefit with intensive lifestyle intervention for a number of secondary outcomes, including nephropathy.

A secondary analysis published in The Lancet in 2014 showed that the incidence of advanced kidney disease was reduced by 31% over 8 years in those in the intervention group, compared with those in the diabetes care and intervention group – an effect that was partly attributable to reductions in body weight, HbA1c, and systolic blood pressure, she noted.

The outcome of the current substudy was very high risk kidney disease (classified according to the Kidney Disease Improving Global Outcomes Guidelines), which is an important cause of disability and high costs and is associated with high mortality, Dr. Hellgren said.

Study subjects had a mean age of 58.6 years at baseline, 59% were women, and 66% were non-Hispanic whites. Known diabetes duration was 6.7 years.

Fitness assessment was based on estimated metabolic equivalents (METs) during a graded treadmill exercise test at baseline and at 1 year. A significant association was seen between baseline fitness and class of chronic kidney disease, Dr. Hellgren said, noting that 31% of those with the lowest fitness level had abnormal kidney function, compared with 14% of those with the highest level.

“Physical fitness at baseline was positively associated with kidney function. Maintaining or improving fitness during the first year was associated with lower incidence of very high risk kidney disease in both intervention groups, with a 51% reduction overall,” she said, adding that the lifestyle intervention effect was only partially attenuated after accounting for fitness change and annually updated wight, blood pressure, and HbA1c, which suggests that an additional unknown mechanism is responsible for the benefits of intervention.

The National Institute of Diabetes and Digestive and Kidney Diseases sponsored Look AHEAD. Dr. Hellgren reported having no disclosures.

[email protected]

BOSTON – Maintaining or improving cardiorespiratory fitness during the year following an intensive lifestyle intervention contributed to the prevention of advanced chronic kidney disease over 4 years among participants in Look AHEAD, according to findings from a substudy of that randomized clinical trial.

During the first 4 years of follow-up in 4,906 of the 5,145 original study subjects, the incidence of advanced chronic kidney disease – after adjustment for age, race, ethnicity, and disease-related baseline covariates – was reduced by nearly 60% in those who received the intervention in the original study, compared with those who received diabetes support and education (hazard ratio, 0.59), Dr. Margareta I. Hellgren reported at the annual scientific sessions of the American Diabetes Association.

At 1-year follow-up, fitness level was unchanged in 77% of the lifestyle intervention group patients, compared with 58% of those in the diabetes support and education group, and in a model that used the same covariates, plus 1-year fitness change, and which included annually updated weight, blood pressure, and hemoglobin A1c, both intervention group participation and unchanged or improved fitness predicted lower incidence of advanced CKD over 4 years (HR, 0.69, 0.49, respectively), said Dr. Hellgren of the University of Gothenburg, Sweden.

The multicenter Look AHEAD trial included overweight adults with type 2 diabetes who were followed for about 10 years. The findings, which were published in 2013, showed no difference between intensive lifestyle intervention – including physical activity and reduced calorie intake – and diabetes support and education for reducing the incidence of cardiovascular events (the primary outcome measure), but did demonstrate a benefit with intensive lifestyle intervention for a number of secondary outcomes, including nephropathy.

A secondary analysis published in The Lancet in 2014 showed that the incidence of advanced kidney disease was reduced by 31% over 8 years in those in the intervention group, compared with those in the diabetes care and intervention group – an effect that was partly attributable to reductions in body weight, HbA1c, and systolic blood pressure, she noted.

The outcome of the current substudy was very high risk kidney disease (classified according to the Kidney Disease Improving Global Outcomes Guidelines), which is an important cause of disability and high costs and is associated with high mortality, Dr. Hellgren said.

Study subjects had a mean age of 58.6 years at baseline, 59% were women, and 66% were non-Hispanic whites. Known diabetes duration was 6.7 years.

Fitness assessment was based on estimated metabolic equivalents (METs) during a graded treadmill exercise test at baseline and at 1 year. A significant association was seen between baseline fitness and class of chronic kidney disease, Dr. Hellgren said, noting that 31% of those with the lowest fitness level had abnormal kidney function, compared with 14% of those with the highest level.

“Physical fitness at baseline was positively associated with kidney function. Maintaining or improving fitness during the first year was associated with lower incidence of very high risk kidney disease in both intervention groups, with a 51% reduction overall,” she said, adding that the lifestyle intervention effect was only partially attenuated after accounting for fitness change and annually updated wight, blood pressure, and HbA1c, which suggests that an additional unknown mechanism is responsible for the benefits of intervention.

The National Institute of Diabetes and Digestive and Kidney Diseases sponsored Look AHEAD. Dr. Hellgren reported having no disclosures.

[email protected]

BOSTON – Maintaining or improving cardiorespiratory fitness during the year following an intensive lifestyle intervention contributed to the prevention of advanced chronic kidney disease over 4 years among participants in Look AHEAD, according to findings from a substudy of that randomized clinical trial.

During the first 4 years of follow-up in 4,906 of the 5,145 original study subjects, the incidence of advanced chronic kidney disease – after adjustment for age, race, ethnicity, and disease-related baseline covariates – was reduced by nearly 60% in those who received the intervention in the original study, compared with those who received diabetes support and education (hazard ratio, 0.59), Dr. Margareta I. Hellgren reported at the annual scientific sessions of the American Diabetes Association.

At 1-year follow-up, fitness level was unchanged in 77% of the lifestyle intervention group patients, compared with 58% of those in the diabetes support and education group, and in a model that used the same covariates, plus 1-year fitness change, and which included annually updated weight, blood pressure, and hemoglobin A1c, both intervention group participation and unchanged or improved fitness predicted lower incidence of advanced CKD over 4 years (HR, 0.69, 0.49, respectively), said Dr. Hellgren of the University of Gothenburg, Sweden.

The multicenter Look AHEAD trial included overweight adults with type 2 diabetes who were followed for about 10 years. The findings, which were published in 2013, showed no difference between intensive lifestyle intervention – including physical activity and reduced calorie intake – and diabetes support and education for reducing the incidence of cardiovascular events (the primary outcome measure), but did demonstrate a benefit with intensive lifestyle intervention for a number of secondary outcomes, including nephropathy.

A secondary analysis published in The Lancet in 2014 showed that the incidence of advanced kidney disease was reduced by 31% over 8 years in those in the intervention group, compared with those in the diabetes care and intervention group – an effect that was partly attributable to reductions in body weight, HbA1c, and systolic blood pressure, she noted.

The outcome of the current substudy was very high risk kidney disease (classified according to the Kidney Disease Improving Global Outcomes Guidelines), which is an important cause of disability and high costs and is associated with high mortality, Dr. Hellgren said.

Study subjects had a mean age of 58.6 years at baseline, 59% were women, and 66% were non-Hispanic whites. Known diabetes duration was 6.7 years.

Fitness assessment was based on estimated metabolic equivalents (METs) during a graded treadmill exercise test at baseline and at 1 year. A significant association was seen between baseline fitness and class of chronic kidney disease, Dr. Hellgren said, noting that 31% of those with the lowest fitness level had abnormal kidney function, compared with 14% of those with the highest level.

“Physical fitness at baseline was positively associated with kidney function. Maintaining or improving fitness during the first year was associated with lower incidence of very high risk kidney disease in both intervention groups, with a 51% reduction overall,” she said, adding that the lifestyle intervention effect was only partially attenuated after accounting for fitness change and annually updated wight, blood pressure, and HbA1c, which suggests that an additional unknown mechanism is responsible for the benefits of intervention.

The National Institute of Diabetes and Digestive and Kidney Diseases sponsored Look AHEAD. Dr. Hellgren reported having no disclosures.

[email protected]

BOSTON – Psychosocial stress is an independent risk factor for excess weight gain among women with gestational diabetes mellitus, findings from the Gestational Diabetes Effects on Moms (GEM) study suggest.

Among nearly 1,300 women in the cluster randomized trial conducted within Kaiser Permanent Northern California, perceived stress near the time of gestational diabetes diagnosis at around 32 weeks’ gestation was significantly associated with a risk of excess gestational weight gain.

After adjusting for gestational and maternal age at the time of gestational diabetes diagnosis, education level, pregravid body mass index, and race/ethnicity, an upper-quartile score on the Perceived Stress Scale (PSS), compared with a lower score, was associated with a 54% increased odds of weight gain that exceeded Institute of Medicine recommendations (odds ratio, 1.54), Ai Kubo, Ph.D., of Kaiser Permanente in Oakland, Calif., reported at the annual scientific sessions of the American Diabetes Association.

A significant trend between PSS score and gestational weight gain was seen, and the association was not attenuated by inclusion of other lifestyle variables, including diet and physical activity, Dr. Kubo said, noting that no association was seen between PSS and the odds of gaining weight at a level below the IOM recommendations.

Dr. Kubo and her colleagues examined the relationship between stress and weight gain using baseline data from the GEM study. Subjects were women who delivered a term singleton at greater than 37 weeks’ gestation. Total gestational weight gain (about 20 pounds on average) and prepregnancy body mass index were obtained from electronic health records. Weight gain was categorized according to 2009 IOM recommendations.

Women with lower socioeconomic status tended to be in the highest stress group, and although there was no significant differences in prepregnancy weight between the highest and lowest stress groups, more of those with BMIs over 35 were in the highest stress group, she noted.

“Excess gestational weight gain has become an important public health concern,” Dr. Kubo said, noting that nearly 60% of women exceed IOM recommendations for weight gain, which increases the risk of adverse health outcomes, including obesity, in both women and their offspring.

Gestational diabetes mellitus occurs in about 8% of all pregnant women and also increases the risk of adverse outcomes in both mothers and offspring, she said.

The current findings suggest that stress reduction interventions may be warranted in women with gestational diabetes mellitus to optimize weight gain and possibly reduce the risks to both mother and offspring, she said, noting that the study is limited by a lack of assessment regarding the timing of stress relative to weight gain and gestational diabetes diagnosis.

“For future studies, use of a [non–gestational diabetes] population, and assessment of stress at the beginning of the pregnancy or even prior to the pregnancy would help us better understand the role of psychosocial stress on weight gain during pregnancy,” she said.

Dr. Kubo reported having no disclosures.

[email protected]

BOSTON – Psychosocial stress is an independent risk factor for excess weight gain among women with gestational diabetes mellitus, findings from the Gestational Diabetes Effects on Moms (GEM) study suggest.

Among nearly 1,300 women in the cluster randomized trial conducted within Kaiser Permanent Northern California, perceived stress near the time of gestational diabetes diagnosis at around 32 weeks’ gestation was significantly associated with a risk of excess gestational weight gain.

After adjusting for gestational and maternal age at the time of gestational diabetes diagnosis, education level, pregravid body mass index, and race/ethnicity, an upper-quartile score on the Perceived Stress Scale (PSS), compared with a lower score, was associated with a 54% increased odds of weight gain that exceeded Institute of Medicine recommendations (odds ratio, 1.54), Ai Kubo, Ph.D., of Kaiser Permanente in Oakland, Calif., reported at the annual scientific sessions of the American Diabetes Association.

A significant trend between PSS score and gestational weight gain was seen, and the association was not attenuated by inclusion of other lifestyle variables, including diet and physical activity, Dr. Kubo said, noting that no association was seen between PSS and the odds of gaining weight at a level below the IOM recommendations.

Dr. Kubo and her colleagues examined the relationship between stress and weight gain using baseline data from the GEM study. Subjects were women who delivered a term singleton at greater than 37 weeks’ gestation. Total gestational weight gain (about 20 pounds on average) and prepregnancy body mass index were obtained from electronic health records. Weight gain was categorized according to 2009 IOM recommendations.

Women with lower socioeconomic status tended to be in the highest stress group, and although there was no significant differences in prepregnancy weight between the highest and lowest stress groups, more of those with BMIs over 35 were in the highest stress group, she noted.

“Excess gestational weight gain has become an important public health concern,” Dr. Kubo said, noting that nearly 60% of women exceed IOM recommendations for weight gain, which increases the risk of adverse health outcomes, including obesity, in both women and their offspring.

Gestational diabetes mellitus occurs in about 8% of all pregnant women and also increases the risk of adverse outcomes in both mothers and offspring, she said.

The current findings suggest that stress reduction interventions may be warranted in women with gestational diabetes mellitus to optimize weight gain and possibly reduce the risks to both mother and offspring, she said, noting that the study is limited by a lack of assessment regarding the timing of stress relative to weight gain and gestational diabetes diagnosis.

“For future studies, use of a [non–gestational diabetes] population, and assessment of stress at the beginning of the pregnancy or even prior to the pregnancy would help us better understand the role of psychosocial stress on weight gain during pregnancy,” she said.

Dr. Kubo reported having no disclosures.

[email protected]

BOSTON – Psychosocial stress is an independent risk factor for excess weight gain among women with gestational diabetes mellitus, findings from the Gestational Diabetes Effects on Moms (GEM) study suggest.

Among nearly 1,300 women in the cluster randomized trial conducted within Kaiser Permanent Northern California, perceived stress near the time of gestational diabetes diagnosis at around 32 weeks’ gestation was significantly associated with a risk of excess gestational weight gain.

After adjusting for gestational and maternal age at the time of gestational diabetes diagnosis, education level, pregravid body mass index, and race/ethnicity, an upper-quartile score on the Perceived Stress Scale (PSS), compared with a lower score, was associated with a 54% increased odds of weight gain that exceeded Institute of Medicine recommendations (odds ratio, 1.54), Ai Kubo, Ph.D., of Kaiser Permanente in Oakland, Calif., reported at the annual scientific sessions of the American Diabetes Association.

A significant trend between PSS score and gestational weight gain was seen, and the association was not attenuated by inclusion of other lifestyle variables, including diet and physical activity, Dr. Kubo said, noting that no association was seen between PSS and the odds of gaining weight at a level below the IOM recommendations.

Dr. Kubo and her colleagues examined the relationship between stress and weight gain using baseline data from the GEM study. Subjects were women who delivered a term singleton at greater than 37 weeks’ gestation. Total gestational weight gain (about 20 pounds on average) and prepregnancy body mass index were obtained from electronic health records. Weight gain was categorized according to 2009 IOM recommendations.

Women with lower socioeconomic status tended to be in the highest stress group, and although there was no significant differences in prepregnancy weight between the highest and lowest stress groups, more of those with BMIs over 35 were in the highest stress group, she noted.

“Excess gestational weight gain has become an important public health concern,” Dr. Kubo said, noting that nearly 60% of women exceed IOM recommendations for weight gain, which increases the risk of adverse health outcomes, including obesity, in both women and their offspring.

Gestational diabetes mellitus occurs in about 8% of all pregnant women and also increases the risk of adverse outcomes in both mothers and offspring, she said.

The current findings suggest that stress reduction interventions may be warranted in women with gestational diabetes mellitus to optimize weight gain and possibly reduce the risks to both mother and offspring, she said, noting that the study is limited by a lack of assessment regarding the timing of stress relative to weight gain and gestational diabetes diagnosis.

“For future studies, use of a [non–gestational diabetes] population, and assessment of stress at the beginning of the pregnancy or even prior to the pregnancy would help us better understand the role of psychosocial stress on weight gain during pregnancy,” she said.

Dr. Kubo reported having no disclosures.

[email protected]

BOSTON – Most children diagnosed with type 1 diabetes who develop celiac disease test positive for celiac autoimmunity at the time of their first screen; thus annual rescreening is necessary only in those with a positive first screen and in those who develop celiac disease symptoms, findings from a retrospective records review suggest.

Of 758 children with new-onset type 1 diabetes between August 2007 and March 2012, 69 had celiac autoimmunity, and 96.1% of those were already positive on their first screen, Dr. Rebecca L. Schaub, a pediatric endocrinologist in San Antonio, Texas, reported at the annual scientific sessions of the American Diabetes Association.

Of the children with celiac autoimmunity, 28 underwent small bowel biopsy. Biopsy was strongly recommended in 12 others, but their families refused; some families elected to initiate a gluten-free diet without a biopsy. In children with only minor elevations in titer levels, physicians did not recommend biopsy, Dr. Schaub said.

The probability of biopsy being performed became more likely with increasing tissue transglutaminase (tTG) antibody titers levels, but age, race/ethnicity, and sex did not significantly affect the likelihood of biopsy, she noted.

Celiac disease was diagnosed in 15 children (2% of the overall study population, which is lower than in some other studies), including 54% of those who underwent small bowel biopsy, and 21% of those with celiac autoimmunity.

Only one child who was seronegative at diagnosis later tested positive for celiac autoimmunity and celiac disease on repeat testing, Dr. Schaub said, noting that celiac disease occurred significantly more often in non-Hispanic white children (2.9%), than in Hispanic children (0.7%) or African American children (0%).

Of note, those with autoimmunity had lower body mass index, compared with those without celiac autoimmunity – a finding that did not change when those with celiac disease were excluded from the analysis, said Dr. Schaub.

On multivariate analysis, only tTG levels and race/ethnicity were independent predictors of celiac disease.

A little more than a third (34.8%) of those with celiac autoimmunity at onset of type 1 diabetes became seronegative at 18 months. Many of those patients had very mildly elevated titers, Dr. Schaub said.

The age at onset of type 1 diabetes among the children included in the study was 9.8 years (range of 6 months to 18 years; 61% were between ages 7 and 11 years), and most (58.6%) were non-Hispanic white children, 20.9% were Hispanic, 15.6% were African American, 3.9% were Asian, and 3.7% were mixed race.

Most of the children (95%) underwent tTG immunoglobulin A testing (or tTG immunoglobulin G testing if IgA was deficient) within 3 months of diabetes onset. Repeat screens were conducted in 35.6% of the children; 270 had follow-up screens at more than 18 months after diabetes diagnosis, and 70 had a repeat screens at 36 months or more after diagnosis.

Celiac disease is known to occur more often in patients with type 1 diabetes, Dr. Schaub said, explaining that reported incidence ranges from 1% to 10%, compared with 0.3% to 1% in the general population.

Untreated celiac disease can result in poor growth, difficult glycemic control – including problematic hyperglycemia – and long-term complications including an increased risk of intestinal lymphoproliferative disorder, she said.

A recent paper in Diabetes Care showed that celiac disease is an independent risk factor for the development of nephropathy and retinopathy in patients with type 1 diabetes, she added.

However, current guidelines are inconsistent. For example, current ADA guidelines call for screening at diagnosis, but they state that the effectiveness and optimal frequency of repeat screening remains unclear in asymptomatic patients; some others recommend screening at diagnosis, and repeat screening every 1-2 years thereafter.

The findings suggest that while some children without celiac autoimmunity at the time of type 1 diabetes diagnosis may require annual rescreening, such rescreening “might not be a good use of resources” in those who are asymptomatic, she said, noting that race, tTG titers, and some other factors such as genetics might play a role in recommendations for biopsy.

Also, the findings of lower BMI in children with celiac autoimmunity “certainly warrant further investigation,” she concluded.

Dr. Schaub reported having no disclosures.

BOSTON – Most children diagnosed with type 1 diabetes who develop celiac disease test positive for celiac autoimmunity at the time of their first screen; thus annual rescreening is necessary only in those with a positive first screen and in those who develop celiac disease symptoms, findings from a retrospective records review suggest.

Of 758 children with new-onset type 1 diabetes between August 2007 and March 2012, 69 had celiac autoimmunity, and 96.1% of those were already positive on their first screen, Dr. Rebecca L. Schaub, a pediatric endocrinologist in San Antonio, Texas, reported at the annual scientific sessions of the American Diabetes Association.

Of the children with celiac autoimmunity, 28 underwent small bowel biopsy. Biopsy was strongly recommended in 12 others, but their families refused; some families elected to initiate a gluten-free diet without a biopsy. In children with only minor elevations in titer levels, physicians did not recommend biopsy, Dr. Schaub said.

The probability of biopsy being performed became more likely with increasing tissue transglutaminase (tTG) antibody titers levels, but age, race/ethnicity, and sex did not significantly affect the likelihood of biopsy, she noted.

Celiac disease was diagnosed in 15 children (2% of the overall study population, which is lower than in some other studies), including 54% of those who underwent small bowel biopsy, and 21% of those with celiac autoimmunity.

Only one child who was seronegative at diagnosis later tested positive for celiac autoimmunity and celiac disease on repeat testing, Dr. Schaub said, noting that celiac disease occurred significantly more often in non-Hispanic white children (2.9%), than in Hispanic children (0.7%) or African American children (0%).

Of note, those with autoimmunity had lower body mass index, compared with those without celiac autoimmunity – a finding that did not change when those with celiac disease were excluded from the analysis, said Dr. Schaub.

On multivariate analysis, only tTG levels and race/ethnicity were independent predictors of celiac disease.

A little more than a third (34.8%) of those with celiac autoimmunity at onset of type 1 diabetes became seronegative at 18 months. Many of those patients had very mildly elevated titers, Dr. Schaub said.

The age at onset of type 1 diabetes among the children included in the study was 9.8 years (range of 6 months to 18 years; 61% were between ages 7 and 11 years), and most (58.6%) were non-Hispanic white children, 20.9% were Hispanic, 15.6% were African American, 3.9% were Asian, and 3.7% were mixed race.

Most of the children (95%) underwent tTG immunoglobulin A testing (or tTG immunoglobulin G testing if IgA was deficient) within 3 months of diabetes onset. Repeat screens were conducted in 35.6% of the children; 270 had follow-up screens at more than 18 months after diabetes diagnosis, and 70 had a repeat screens at 36 months or more after diagnosis.

Celiac disease is known to occur more often in patients with type 1 diabetes, Dr. Schaub said, explaining that reported incidence ranges from 1% to 10%, compared with 0.3% to 1% in the general population.

Untreated celiac disease can result in poor growth, difficult glycemic control – including problematic hyperglycemia – and long-term complications including an increased risk of intestinal lymphoproliferative disorder, she said.

A recent paper in Diabetes Care showed that celiac disease is an independent risk factor for the development of nephropathy and retinopathy in patients with type 1 diabetes, she added.

However, current guidelines are inconsistent. For example, current ADA guidelines call for screening at diagnosis, but they state that the effectiveness and optimal frequency of repeat screening remains unclear in asymptomatic patients; some others recommend screening at diagnosis, and repeat screening every 1-2 years thereafter.

The findings suggest that while some children without celiac autoimmunity at the time of type 1 diabetes diagnosis may require annual rescreening, such rescreening “might not be a good use of resources” in those who are asymptomatic, she said, noting that race, tTG titers, and some other factors such as genetics might play a role in recommendations for biopsy.

Also, the findings of lower BMI in children with celiac autoimmunity “certainly warrant further investigation,” she concluded.

Dr. Schaub reported having no disclosures.

BOSTON – Most children diagnosed with type 1 diabetes who develop celiac disease test positive for celiac autoimmunity at the time of their first screen; thus annual rescreening is necessary only in those with a positive first screen and in those who develop celiac disease symptoms, findings from a retrospective records review suggest.

Of 758 children with new-onset type 1 diabetes between August 2007 and March 2012, 69 had celiac autoimmunity, and 96.1% of those were already positive on their first screen, Dr. Rebecca L. Schaub, a pediatric endocrinologist in San Antonio, Texas, reported at the annual scientific sessions of the American Diabetes Association.

Of the children with celiac autoimmunity, 28 underwent small bowel biopsy. Biopsy was strongly recommended in 12 others, but their families refused; some families elected to initiate a gluten-free diet without a biopsy. In children with only minor elevations in titer levels, physicians did not recommend biopsy, Dr. Schaub said.

The probability of biopsy being performed became more likely with increasing tissue transglutaminase (tTG) antibody titers levels, but age, race/ethnicity, and sex did not significantly affect the likelihood of biopsy, she noted.

Celiac disease was diagnosed in 15 children (2% of the overall study population, which is lower than in some other studies), including 54% of those who underwent small bowel biopsy, and 21% of those with celiac autoimmunity.

Only one child who was seronegative at diagnosis later tested positive for celiac autoimmunity and celiac disease on repeat testing, Dr. Schaub said, noting that celiac disease occurred significantly more often in non-Hispanic white children (2.9%), than in Hispanic children (0.7%) or African American children (0%).

Of note, those with autoimmunity had lower body mass index, compared with those without celiac autoimmunity – a finding that did not change when those with celiac disease were excluded from the analysis, said Dr. Schaub.

On multivariate analysis, only tTG levels and race/ethnicity were independent predictors of celiac disease.

A little more than a third (34.8%) of those with celiac autoimmunity at onset of type 1 diabetes became seronegative at 18 months. Many of those patients had very mildly elevated titers, Dr. Schaub said.

The age at onset of type 1 diabetes among the children included in the study was 9.8 years (range of 6 months to 18 years; 61% were between ages 7 and 11 years), and most (58.6%) were non-Hispanic white children, 20.9% were Hispanic, 15.6% were African American, 3.9% were Asian, and 3.7% were mixed race.

Most of the children (95%) underwent tTG immunoglobulin A testing (or tTG immunoglobulin G testing if IgA was deficient) within 3 months of diabetes onset. Repeat screens were conducted in 35.6% of the children; 270 had follow-up screens at more than 18 months after diabetes diagnosis, and 70 had a repeat screens at 36 months or more after diagnosis.

Celiac disease is known to occur more often in patients with type 1 diabetes, Dr. Schaub said, explaining that reported incidence ranges from 1% to 10%, compared with 0.3% to 1% in the general population.

Untreated celiac disease can result in poor growth, difficult glycemic control – including problematic hyperglycemia – and long-term complications including an increased risk of intestinal lymphoproliferative disorder, she said.

A recent paper in Diabetes Care showed that celiac disease is an independent risk factor for the development of nephropathy and retinopathy in patients with type 1 diabetes, she added.

However, current guidelines are inconsistent. For example, current ADA guidelines call for screening at diagnosis, but they state that the effectiveness and optimal frequency of repeat screening remains unclear in asymptomatic patients; some others recommend screening at diagnosis, and repeat screening every 1-2 years thereafter.

The findings suggest that while some children without celiac autoimmunity at the time of type 1 diabetes diagnosis may require annual rescreening, such rescreening “might not be a good use of resources” in those who are asymptomatic, she said, noting that race, tTG titers, and some other factors such as genetics might play a role in recommendations for biopsy.

Also, the findings of lower BMI in children with celiac autoimmunity “certainly warrant further investigation,” she concluded.

Dr. Schaub reported having no disclosures.

BOSTON – Most children diagnosed with type 1 diabetes who develop celiac disease test positive for celiac autoimmunity at the time of their first screen; thus annual rescreening is necessary only in those with a positive first screen and in those who develop celiac disease symptoms, findings from a retrospective records review suggest.

Of 758 children with new-onset type 1 diabetes between August 2007 and March 2012, 69 had celiac autoimmunity, and 96.1% of those were already positive on their first screen, Dr. Rebecca L. Schaub, a pediatric endocrinologist in San Antonio, Texas, reported at the annual scientific sessions of the American Diabetes Association.

Of the children with celiac autoimmunity, 28 underwent small bowel biopsy. Biopsy was strongly recommended in 12 others, but their families refused; some families elected to initiate a gluten-free diet without a biopsy. In children with only minor elevations in titer levels, physicians did not recommend biopsy, Dr. Schaub said.

The probability of biopsy being performed became more likely with increasing tissue transglutaminase (tTG) antibody titers levels, but age, race/ethnicity, and sex did not significantly affect the likelihood of biopsy, she noted.

Celiac disease was diagnosed in 15 children (2% of the overall study population, which is lower than in some other studies), including 54% of those who underwent small bowel biopsy, and 21% of those with celiac autoimmunity.

Only one child who was seronegative at diagnosis later tested positive for celiac autoimmunity and celiac disease on repeat testing, Dr. Schaub said, noting that celiac disease occurred significantly more often in non-Hispanic white children (2.9%), than in Hispanic children (0.7%) or African American children (0%).

Of note, those with autoimmunity had lower body mass index, compared with those without celiac autoimmunity – a finding that did not change when those with celiac disease were excluded from the analysis, said Dr. Schaub.

On multivariate analysis, only tTG levels and race/ethnicity were independent predictors of celiac disease.

A little more than a third (34.8%) of those with celiac autoimmunity at onset of type 1 diabetes became seronegative at 18 months. Many of those patients had very mildly elevated titers, Dr. Schaub said.

The age at onset of type 1 diabetes among the children included in the study was 9.8 years (range of 6 months to 18 years; 61% were between ages 7 and 11 years), and most (58.6%) were non-Hispanic white children, 20.9% were Hispanic, 15.6% were African American, 3.9% were Asian, and 3.7% were mixed race.

Most of the children (95%) underwent tTG immunoglobulin A testing (or tTG immunoglobulin G testing if IgA was deficient) within 3 months of diabetes onset. Repeat screens were conducted in 35.6% of the children; 270 had follow-up screens at more than 18 months after diabetes diagnosis, and 70 had a repeat screens at 36 months or more after diagnosis.

Celiac disease is known to occur more often in patients with type 1 diabetes, Dr. Schaub said, explaining that reported incidence ranges from 1% to 10%, compared with 0.3% to 1% in the general population.

Untreated celiac disease can result in poor growth, difficult glycemic control – including problematic hyperglycemia – and long-term complications including an increased risk of intestinal lymphoproliferative disorder, she said.

A recent paper in Diabetes Care showed that celiac disease is an independent risk factor for the development of nephropathy and retinopathy in patients with type 1 diabetes, she added.

However, current guidelines are inconsistent. For example, current ADA guidelines call for screening at diagnosis, but they state that the effectiveness and optimal frequency of repeat screening remains unclear in asymptomatic patients; some others recommend screening at diagnosis, and repeat screening every 1-2 years thereafter.

The findings suggest that while some children without celiac autoimmunity at the time of type 1 diabetes diagnosis may require annual rescreening, such rescreening “might not be a good use of resources” in those who are asymptomatic, she said, noting that race, tTG titers, and some other factors such as genetics might play a role in recommendations for biopsy.

Also, the findings of lower BMI in children with celiac autoimmunity “certainly warrant further investigation,” she concluded.

Dr. Schaub reported having no disclosures.

[email protected]

BOSTON – Most children diagnosed with type 1 diabetes who develop celiac disease test positive for celiac autoimmunity at the time of their first screen; thus annual rescreening is necessary only in those with a positive first screen and in those who develop celiac disease symptoms, findings from a retrospective records review suggest.

Of 758 children with new-onset type 1 diabetes between August 2007 and March 2012, 69 had celiac autoimmunity, and 96.1% of those were already positive on their first screen, Dr. Rebecca L. Schaub, a pediatric endocrinologist in San Antonio, Texas, reported at the annual scientific sessions of the American Diabetes Association.

Of the children with celiac autoimmunity, 28 underwent small bowel biopsy. Biopsy was strongly recommended in 12 others, but their families refused; some families elected to initiate a gluten-free diet without a biopsy. In children with only minor elevations in titer levels, physicians did not recommend biopsy, Dr. Schaub said.

The probability of biopsy being performed became more likely with increasing tissue transglutaminase (tTG) antibody titers levels, but age, race/ethnicity, and sex did not significantly affect the likelihood of biopsy, she noted.

Celiac disease was diagnosed in 15 children (2% of the overall study population, which is lower than in some other studies), including 54% of those who underwent small bowel biopsy, and 21% of those with celiac autoimmunity.

Only one child who was seronegative at diagnosis later tested positive for celiac autoimmunity and celiac disease on repeat testing, Dr. Schaub said, noting that celiac disease occurred significantly more often in non-Hispanic white children (2.9%), than in Hispanic children (0.7%) or African American children (0%).

Of note, those with autoimmunity had lower body mass index, compared with those without celiac autoimmunity – a finding that did not change when those with celiac disease were excluded from the analysis, said Dr. Schaub.

On multivariate analysis, only tTG levels and race/ethnicity were independent predictors of celiac disease.

A little more than a third (34.8%) of those with celiac autoimmunity at onset of type 1 diabetes became seronegative at 18 months. Many of those patients had very mildly elevated titers, Dr. Schaub said.

The age at onset of type 1 diabetes among the children included in the study was 9.8 years (range of 6 months to 18 years; 61% were between ages 7 and 11 years), and most (58.6%) were non-Hispanic white children, 20.9% were Hispanic, 15.6% were African American, 3.9% were Asian, and 3.7% were mixed race.

Most of the children (95%) underwent tTG immunoglobulin A testing (or tTG immunoglobulin G testing if IgA was deficient) within 3 months of diabetes onset. Repeat screens were conducted in 35.6% of the children; 270 had follow-up screens at more than 18 months after diabetes diagnosis, and 70 had a repeat screens at 36 months or more after diagnosis.

Celiac disease is known to occur more often in patients with type 1 diabetes, Dr. Schaub said, explaining that reported incidence ranges from 1% to 10%, compared with 0.3% to 1% in the general population.

Untreated celiac disease can result in poor growth, difficult glycemic control – including problematic hyperglycemia – and long-term complications including an increased risk of intestinal lymphoproliferative disorder, she said.

A recent paper in Diabetes Care showed that celiac disease is an independent risk factor for the development of nephropathy and retinopathy in patients with type 1 diabetes, she added.

However, current guidelines are inconsistent. For example, current ADA guidelines call for screening at diagnosis, but they state that the effectiveness and optimal frequency of repeat screening remains unclear in asymptomatic patients; some others recommend screening at diagnosis, and repeat screening every 1-2 years thereafter.

The findings suggest that while some children without celiac autoimmunity at the time of type 1 diabetes diagnosis may require annual rescreening, such rescreening “might not be a good use of resources” in those who are asymptomatic, she said, noting that race, tTG titers, and some other factors such as genetics might play a role in recommendations for biopsy.

Also, the findings of lower BMI in children with celiac autoimmunity “certainly warrant further investigation,” she concluded.

Dr. Schaub reported having no disclosures.

[email protected]

BOSTON – Most children diagnosed with type 1 diabetes who develop celiac disease test positive for celiac autoimmunity at the time of their first screen; thus annual rescreening is necessary only in those with a positive first screen and in those who develop celiac disease symptoms, findings from a retrospective records review suggest.

Of 758 children with new-onset type 1 diabetes between August 2007 and March 2012, 69 had celiac autoimmunity, and 96.1% of those were already positive on their first screen, Dr. Rebecca L. Schaub, a pediatric endocrinologist in San Antonio, Texas, reported at the annual scientific sessions of the American Diabetes Association.

Of the children with celiac autoimmunity, 28 underwent small bowel biopsy. Biopsy was strongly recommended in 12 others, but their families refused; some families elected to initiate a gluten-free diet without a biopsy. In children with only minor elevations in titer levels, physicians did not recommend biopsy, Dr. Schaub said.

The probability of biopsy being performed became more likely with increasing tissue transglutaminase (tTG) antibody titers levels, but age, race/ethnicity, and sex did not significantly affect the likelihood of biopsy, she noted.

Celiac disease was diagnosed in 15 children (2% of the overall study population, which is lower than in some other studies), including 54% of those who underwent small bowel biopsy, and 21% of those with celiac autoimmunity.

Only one child who was seronegative at diagnosis later tested positive for celiac autoimmunity and celiac disease on repeat testing, Dr. Schaub said, noting that celiac disease occurred significantly more often in non-Hispanic white children (2.9%), than in Hispanic children (0.7%) or African American children (0%).

Of note, those with autoimmunity had lower body mass index, compared with those without celiac autoimmunity – a finding that did not change when those with celiac disease were excluded from the analysis, said Dr. Schaub.

On multivariate analysis, only tTG levels and race/ethnicity were independent predictors of celiac disease.

A little more than a third (34.8%) of those with celiac autoimmunity at onset of type 1 diabetes became seronegative at 18 months. Many of those patients had very mildly elevated titers, Dr. Schaub said.

The age at onset of type 1 diabetes among the children included in the study was 9.8 years (range of 6 months to 18 years; 61% were between ages 7 and 11 years), and most (58.6%) were non-Hispanic white children, 20.9% were Hispanic, 15.6% were African American, 3.9% were Asian, and 3.7% were mixed race.

Most of the children (95%) underwent tTG immunoglobulin A testing (or tTG immunoglobulin G testing if IgA was deficient) within 3 months of diabetes onset. Repeat screens were conducted in 35.6% of the children; 270 had follow-up screens at more than 18 months after diabetes diagnosis, and 70 had a repeat screens at 36 months or more after diagnosis.

Celiac disease is known to occur more often in patients with type 1 diabetes, Dr. Schaub said, explaining that reported incidence ranges from 1% to 10%, compared with 0.3% to 1% in the general population.

Untreated celiac disease can result in poor growth, difficult glycemic control – including problematic hyperglycemia – and long-term complications including an increased risk of intestinal lymphoproliferative disorder, she said.

A recent paper in Diabetes Care showed that celiac disease is an independent risk factor for the development of nephropathy and retinopathy in patients with type 1 diabetes, she added.

However, current guidelines are inconsistent. For example, current ADA guidelines call for screening at diagnosis, but they state that the effectiveness and optimal frequency of repeat screening remains unclear in asymptomatic patients; some others recommend screening at diagnosis, and repeat screening every 1-2 years thereafter.

The findings suggest that while some children without celiac autoimmunity at the time of type 1 diabetes diagnosis may require annual rescreening, such rescreening “might not be a good use of resources” in those who are asymptomatic, she said, noting that race, tTG titers, and some other factors such as genetics might play a role in recommendations for biopsy.

Also, the findings of lower BMI in children with celiac autoimmunity “certainly warrant further investigation,” she concluded.

Dr. Schaub reported having no disclosures.

[email protected]

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

[email protected]

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

[email protected]

BOSTON – The glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide does not increase the risk for cardiovascular problems in diabetic patients, according to findings from the first cardiovascular disease outcomes trial for this widely prescribed class of glucose-lowering drugs.

The findings of the randomized, placebo-controlled Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the annual scientific sessions of the American Diabetes Association, dissipate the “cloud of suspicion” that has cast a shadow over GLP-1 agonists with regard to their possible effects on cardiovascular risk, the investigators said.

“We have shown that patients and their health care providers should have no cause for concern, even if they are at high risk of heart-related problems,” said principal investigator Dr. Marc Pfeffer, professor of medicine at Harvard University and senior physician in the division of cardiology at Brigham and Women’s Hospital, Boston.

Dr. Pfeffer and his colleagues studied 6,068 patients who were randomized to receive placebo or lixisenatide (Lyxumia), which is investigational in the United States but approved in more than 50 countries worldwide. The study subjects were followed for a mean of 2.1 years.

The composite primary outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina occurred in 399 of 3,304 placebo-group patients (13.2%) and in 406 of 3,034 treatment-group patients (13.4%; hazard ratio, 1.02), Dr. Pfeffer said.

No difference was seen between the groups for any of the individual components of the composite outcome (HR: 0.98 for cardiovascular death, 1.03 for MI, 1.12 for stroke, and 1.11 for unstable angina), and no differences were seen based on sex, age, race, or region.

“No sign of interactions, and no patterns emerged in older patients or sicker patients,” Dr. Pfeffer added.

Heart failure, which is “a very important outcome,” did occur more often in those with heart failure prior to randomization, but again, the outcomes did not differ between the placebo and treatment group (HR, 0.97 for cardiovascular death plus heart failure hospitalization), he noted.

All-cause death also occurred at a similar rate in both groups: 7.4% and 7% for the placebo vs. treatment groups (HR, 0.94).

Treatment can confidently be said to be safe, as well as neutral, with respect to the various outcome measures, he said.

Dr. Matthew Riddle of Oregon Health and Science University, Portland, further reported that patients in the lixisenatide group were more likely than those who received placebo to experience a modest benefit in terms of weight. Those in the treatment group did not gain weight, while those in the placebo group did (–0.7 kg between-group difference from baseline), he said, noting that this is a finding that “has some possibility of clinical relevance.”

A similar pattern was seen with systolic blood pressure, with treatment-group patients experiencing a modest but statistically significant improvement (–0.8 mm Hg between-group difference from baseline).

The treatment-group patients were not more likely than those who received placebo to experience hypoglycemia, despite better glucose control, nor were they more likely to experience pancreatitis or pancreatic cancer, he said.

A modest significant difference was seen with respect to HbA_1c levels and fasting plasma glucose with treatment vs. placebo (–0.27% mean postbaseline difference for each).

Patients included in the ELIXA trial were adults over age 30 years who had experienced a recent acute coronary syndrome event. They were enrolled from 782 sites in 49 countries within 180 days (mean, 72 days) of the event, which was MI in most cases.

Patients received a single injection each day of either lixisenatide or volume-matched placebo before breakfast. The dosage could be titrated up from 10 mcg to 20 mcg, or down for those not able to tolerate the full dose. Other than adjustments to prevent hypoglycemia, local standards of care for lifestyle, glycemic targets, and risk factor management were followed.

At least one adverse event was reported by 77% and 81% of placebo and treatment-group patients, with nausea and vomiting – common side effects for GLP-1 agonists – accounting for most of the difference. No difference was seen between the groups with respect to serious adverse events (22% in each arm reported serious events).

Adverse events, however, led to treatment discontinuation in 7.2% of placebo-group patients, compared with 11.4% of lixisenatide-group patients.

The findings confirm that lixisenatide does not increase the risk of major adverse cardiac events, and no signal was seen for pancreatic cancer, pancreatitis, other cancers, or heart failure, said discussant Dr. Silvio Inzucchi, professor of medicine and director of the Yale Diabetes Center at Yale University in New Haven, Conn., who was invited by the ADA to comment on the findings.

As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.

Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.

According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.

In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.

In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA_1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.

Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).

Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.

Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.

[email protected]

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – The glucose-lowering drug sitagliptin, part of a class of drugs whose cardiovascular safety has been cast into doubt based on findings in trials of similar agents, was shown not to increase the risk of heart failure or other adverse cardiovascular outcomes in a large randomized trial.

Results presented June 8 at the annual scientific sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine (doi:10.1056/NEJMoa1501352) revealed “no evidence of harm one way or another” for cardiovascular events or heart failure, Dr. Rury F. Holman, professor of diabetic medicine and diabetes trials unit director at the Oxford (England) Centre for Diabetes, Endocrinology & Metabolism, the study’s corresponding author, said at a press conference.

Though the manufacturer announced the main cardiovascular findings on sitagliptin (Januvia), earlier this year, the details of this trial – driven by concerns about a signal for increased risk of heart failure in two earlier trials of dipeptidyl peptidase 4 (DPP-4) inhibitors – were presented for the first time.

TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) enrolled 14,671 patients with type 2 diabetes in combination with cardiovascular disease who were age 50 years or older. Patients were recruited in 38 countries and randomized to add-on therapy with

sitagliptin or placebo in addition to other antihyperglycemic therapies used openly at physician discretion. At mean 3 years’ follow-up, sitagliptin was noninferior to placebo for a combined cardiovascular endpoint comprising first time to CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09, P < .001).

Hospitalizations for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.83-1.20, P = .98), and no significant differences were seen in rates of pancreatitis or pancreatic cancer.

All patients in both the control and intervention arms were treated to similar glucose targets by their physicians. Levels of glycated hemoglobin between the groups were close throughout the study period, with a difference of –0.29 for the sitagliptin arm (95% CI, –0.32 to –0.27). “That’s important because we didn’t want a glucose difference that might have influenced the cardiovascular outcomes one way or another,” Dr. Holman commented.

Dr. Eric D. Peterson, executive director of the Duke Clinical Research Institute as well as professor in the departments of medicine and cardiology and the Fred Cobb, MD, Distinguished Professor of Medicine of Duke University, Durham, N.C., who was a coauthor on the study, commented on its heart failure finding. TECOS had been prompted by unexpected

heart-failure signals seen in two earlier trials of DPP-4 inhibitors, saxagliptin and alogliptin.

“Given the size of our study, and the longer duration of follow-up, as well as the higher risk of our population, we feel that this puts to bed the question – at least with sitagliptin – that there’s any risk for heart failure increases,” Dr. Peterson said.

The investigators were careful to assert that few conclusions could be drawn for the class of drugs as a whole based on the TECOS findings but suggested chance could have played a role in the earlier studies.

The study was funded by sitagliptin’s manufacturer, Merck Sharp & Dohme. Dr. Holman disclosed a financial relationship with the study sponsor. Dr. Peterson disclosed financial relationships with other manufacturers.

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

[email protected]

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

[email protected]

BOSTON – Weight loss was greater with laparoscopic adjustable gastric banding than with an intensive lifestyle intervention among obese patients with type 2 diabetes in a randomized clinical trial, but the effects on diabetes control, cardiometabolic risk, and quality of life were comparable.

Weight loss in 18 patients randomized to undergo the bariatric surgery was an average of 13.5 lb at 12 months’ follow-up, compared with 8.5 lb in those randomized to the active component of the study: a 12-week lifestyle intervention (Weight Achievement and Intensive Treatment–the Why WAIT program), Dr. Osama Hamdy reported in a poster at the annual scientific sessions of the American Diabetes Association.

However, hemogobin A_1c reduction was similar in the two groups at –1.2% vs. –1%, respectively. Further, improvements in blood pressure, triglycerides, and low-density lipoprotein levels did not differ between the groups, said Dr. Hamdy, medical director of the obesity clinical program, and director of the inpatient program at Joslin Diabetes Clinic, Harvard Medical School, Boston.

The risk of fatal coronary heart disease events also decreased in both groups, from 6.5% to 5.9% in the bariatric surgery group, and from 5.8% to 5.5% in the Why WAIT group; the difference between the groups was not statistically significant, he said.

Quality of life as assessed by the 36-item Short Form Survey’s physical and mental health summary measures changed only slightly from baseline in both groups, with no between-group differences. Similarly, scores on the Impact of Weight on Quality of Life and on Problem Areas in Diabetes improved significantly in both groups, but no between-group differences were seen.

“These findings suggest that the Why WAIT program and laparoscopic adjustable gastric banding have similar benefits for diabetes control, cardiometabolic risk, and quality of life parameters,” according to Dr. Hamdy, who noted that the findings may be useful for guiding obese patients with type 2 diabetes as they explore weight management options.

Dr. Hamdy reported that he has received research support and is an advisory panel member and author for Metagenics, that he is a consultant and author for Abbott Nutrition and Merck, and that he has received research support and is an author for Neurometrix.

[email protected]