Diabetes Hub

Adults who had metabolic syndrome when they were children were at higher risk for developing type 2 diabetes, especially if the disease was more severe, according to Dr. Mark D. DeBoer of the University of Virginia, Charlottesville, and Matthew J. Gurka, Ph.D., of West Virginia University, Morgantown, and their associates.

A total of 354 people completed the study, which started during 1973-1976 and had two follow-ups, one during 1998-2003 and the second from 2010 to 2014. Average age at baseline was 12.9 years, and average age at study completion was 49.6 years.

Among the individuals who had metabolic syndrome (MetS) at baseline, the odds ratio for developing diabetes at the first follow-up was 4.4, and the OR for diabetes at the second follow-up was 7.8. For each unit increase in MetS severity at baseline, the OR for diabetes development was 2.7 at first follow-up and 2.8 at second follow-up.

“These data provide evidence for a role for MetS severity as a marker of disease risk and suggest potential clinical utility in following MetS severity over time,” the investigators noted. They had no disclosures to report.

Find the full study in Diabetologia (doi: 10.1007/s00125-015-3759-5).

[email protected]

Adults who had metabolic syndrome when they were children were at higher risk for developing type 2 diabetes, especially if the disease was more severe, according to Dr. Mark D. DeBoer of the University of Virginia, Charlottesville, and Matthew J. Gurka, Ph.D., of West Virginia University, Morgantown, and their associates.

A total of 354 people completed the study, which started during 1973-1976 and had two follow-ups, one during 1998-2003 and the second from 2010 to 2014. Average age at baseline was 12.9 years, and average age at study completion was 49.6 years.

Among the individuals who had metabolic syndrome (MetS) at baseline, the odds ratio for developing diabetes at the first follow-up was 4.4, and the OR for diabetes at the second follow-up was 7.8. For each unit increase in MetS severity at baseline, the OR for diabetes development was 2.7 at first follow-up and 2.8 at second follow-up.

“These data provide evidence for a role for MetS severity as a marker of disease risk and suggest potential clinical utility in following MetS severity over time,” the investigators noted. They had no disclosures to report.

Find the full study in Diabetologia (doi: 10.1007/s00125-015-3759-5).

[email protected]

Adults who had metabolic syndrome when they were children were at higher risk for developing type 2 diabetes, especially if the disease was more severe, according to Dr. Mark D. DeBoer of the University of Virginia, Charlottesville, and Matthew J. Gurka, Ph.D., of West Virginia University, Morgantown, and their associates.

A total of 354 people completed the study, which started during 1973-1976 and had two follow-ups, one during 1998-2003 and the second from 2010 to 2014. Average age at baseline was 12.9 years, and average age at study completion was 49.6 years.

Among the individuals who had metabolic syndrome (MetS) at baseline, the odds ratio for developing diabetes at the first follow-up was 4.4, and the OR for diabetes at the second follow-up was 7.8. For each unit increase in MetS severity at baseline, the OR for diabetes development was 2.7 at first follow-up and 2.8 at second follow-up.

“These data provide evidence for a role for MetS severity as a marker of disease risk and suggest potential clinical utility in following MetS severity over time,” the investigators noted. They had no disclosures to report.

Find the full study in Diabetologia (doi: 10.1007/s00125-015-3759-5).

[email protected]

STOCKHOLM – While they are effective glucose-lowering agents, sulfonylureas seem to substantially increase the risk for cardiovascular events relative to other antihyperglycemic agents, according to several presentations given at the annual meeting of the European Association for the Study of Diabetes.

In a systematic review and meta-analysis of 84 randomized controlled trials (RCTs) and 26 observational studies, accounting for more than 36,573 and more than 1.5 million subjects with type 2 diabetes mellitus, respectively, treatment with a sulfonylurea was found to significantly increase all-cause mortality and cardiovascular-related mortality when compared to no active treatment or placebo and to other antidiabetic drugs.

In the RCTs, the hazard ratios comparing sulfonylureas to all treatments combined were 1.26 (95% confidence interval, 1.10-1.44) for all-cause mortality and 1.46 (95% CI, 1.21-1.77) for cardiovascular mortality. HR for CV mortality was highest when comparing sulfonylureas with GLP-1 agonists and SGLT-2 inhibitors, at 45.4 (95% CI, 2.07-362.8) and 42.6 (95% CI, 1.71-359.1), with significantly elevated risk also seen when compared with DPP-4 inhibitors (HR, 4.42; 95% CI, 1.92-13.0), thiazolidinediones (HR, 3.05; 95% CI, 1.79-5.54), and insulin (HR, 1.30; 95% CI, 1.02-1.66).

There was also an increase in the risk for acute myocardial infarction and stroke in some comparisons of sulfonylureas versus other treatments.

“We think this study is the most comprehensive review of RCTs and observational studies to compare CV-related outcomes and all-cause mortality among patients receiving sulfonylureas versus [other] antidiabetic agents,” said Dr. Steve Bain of Abertawe Bro Morgannwg University NHS Trust in Swansea, England.

“We accept that the confidence intervals were wide, but there is a tendency for all significant results to trend in the same direction.” Results of the observational studies analyses generally supported the results from the RCTs, he added. A notable limitation was that there had been no differentiation between the risk according to different sulfonylureas. Dr. Bain said this was to try to keep the number of patients available for analysis as high as possible in the sulfonylurea group.

Data from the German CREST (CV Risk and Events on SU Treatment) study also showed that there was a higher CV risk associated with sulfonylureas when compared with metformin in patients newly diagnosed with type 2 diabetes mellitus. The retrospective cohort database study included more than 35,000 individuals, of whom 26,883 received no antihyperglycemic treatment or treatment with an antihyperglycemic agent other than a sulfonylurea or metformin between January 2010 and December 2011, leaving 7,874 who were given metformin monotherapy and 904 given sulfonylurea monotherapy. Propensity score matching was used to form the final study groups consisting of 730 patients each.

Crude, propensity-matched, and adjusted HRs for death comparing sulfonylurea with metformin as first-line treatment were 3.32 (95% CI, 2.6-4.3; P less than .001), 1.4 (95% CI, 0.9-2.3; P less than .12), and 2.01 (95% CI, 1.5-2.6; P less than .001), respectively. Corresponding HRs for major cardiovascular events (MACE) were 1.9 (95% CI, 1.4-2.4; P less than .001), 1.4 (95% CI, 0.9-2.2; P less than .14), and 1.3 (95% CI, 1.03-1.74; P less than .05).

Dr. Thomas Wilke of the University of Wismar (Germany) who presented the CREST study findings, noted that there were some differences between the groups in terms of the baseline demographics, with those receiving sulfonylureas being somewhat older and more likely to be women, have comorbid disease, and discontinue monotherapy earlier than patients treated with metformin, or possibly be more likely to have contraindications to the use of metformin.

“Taking these differences into account, patients treated with sulfonylureas seem to be at increased risk of death, MACE, and type 2 diabetes hospitalization, compared with metformin-treated patients,” in this German population, Dr. Wilke concluded.

Finally, Dr. Jan Eriksson of Uppsala (Sweden) University presented findings from an observational study of more than 50,000 patients with type 2 diabetes treated with a combination of two noninsulin antidiabetic agents between 2006 and 2013. Of these, 40,736 had received metformin in combination with a sulfonylurea and 12,024 had received a combination of metformin and a DPP-4 inhibitor and were studied further.

Compared with the patients who received a DPP-4 inhibitor on top of metformin, those who received a sulfonylurea had an increased risk of both fatal and nonfatal cardiovascular disease (HR, 1.17; 95% CI, 1.01-1.37) and death from any cause (HR, 1.25; 95% CI, 1.02-1.54) even in the presence of confounding factors such as age, gender, existing cardiovascular disease, and cardio-preventative medication use.

The risk for severe hypoglycemia was also greater with sulfonylurea than DPP-4 use (HR, 2.07; 95% CI, 1.11-3.86), and experiencing severe hypoglycemia was associated with an increased risk for cardiovascular events (HR, 1.51; 95% CI, 1.21-1.88).

“Hypoglycemia may contribute to the increased CVD risk associated with sulfonylureas,” Dr. Eriksson suggested. He concluded that the results of ongoing and future randomized trials would be important in order to understand the cardiovascular risk associated with sulfonylureas better and try to figure out any underlying mechanisms.

Dr. Raz Itamar, head of the diabetes unit at Hadassah Medical Center in Jerusalem, chaired the session during which all these study findings were presented and provided a general comment in an interview on why the cardiovascular safety of sulfonylureas was a particular issue that these studies looked at.

He noted that a study performed in the United States in the 1970s had raised suspicion that there might be an increased cardiovascular risk associated with the sulfonylureas, but the current concerns really started with findings from the UKPDS [United Kingdom Prospective Diabetes Study] and the Women’s Health Study (WHS), for example.

“In the UKPDS, patients who were on metformin and a sulfonylurea demonstrated a doubling in the cardiovascular event rate,” Dr. Itamar said, adding that the WHS data also showed a doubling of the risk.

There is a lack of head-to-head, randomized, controlled data, he emphasized and commented that there were many limitations to the analyses presented at the session. These included the small sample sizes and short duration of follow-up, among others. There is also evidence in the literature suggesting that the cardiovascular risk of individual sulfonylureas may be different. So the results need to be reviewed with caution, he advised.

“As a clinician, I try to give a sulfonylurea which seems to have a safer cardiovascular profile, like glimepiride and gliclazide,” Dr. Itamar said. He noted that there was a randomized controlled trial currently recruiting a projected 6,000 patients that would compare glimepiride with a DPP-4 inhibitor directly for several years that should provide additional and much needed information on the cardiovascular safety of sulfonylureas.

Merck UK funded the systematic review and meta-analysis. AstraZeneca supported the CREST study and the sulfonylureas versus DPP4 inhibitor comparison study. Dr. Bain disclosed he had received honoraria, teaching, and research sponsorship or grants from multiple pharmaceutical companies including Merck Sharp & Dohme and AstraZeneca. Dr. Wilke did not report his disclosures. Dr. Eriksson disclosed receiving research grants or honoraria from AstraZeneca and Merck Sharp & Dohme, among others, and that he had previously been an employee of AstraZeneca. Dr. Itamar did not report having any relevant disclosures.

STOCKHOLM – While they are effective glucose-lowering agents, sulfonylureas seem to substantially increase the risk for cardiovascular events relative to other antihyperglycemic agents, according to several presentations given at the annual meeting of the European Association for the Study of Diabetes.

In a systematic review and meta-analysis of 84 randomized controlled trials (RCTs) and 26 observational studies, accounting for more than 36,573 and more than 1.5 million subjects with type 2 diabetes mellitus, respectively, treatment with a sulfonylurea was found to significantly increase all-cause mortality and cardiovascular-related mortality when compared to no active treatment or placebo and to other antidiabetic drugs.

In the RCTs, the hazard ratios comparing sulfonylureas to all treatments combined were 1.26 (95% confidence interval, 1.10-1.44) for all-cause mortality and 1.46 (95% CI, 1.21-1.77) for cardiovascular mortality. HR for CV mortality was highest when comparing sulfonylureas with GLP-1 agonists and SGLT-2 inhibitors, at 45.4 (95% CI, 2.07-362.8) and 42.6 (95% CI, 1.71-359.1), with significantly elevated risk also seen when compared with DPP-4 inhibitors (HR, 4.42; 95% CI, 1.92-13.0), thiazolidinediones (HR, 3.05; 95% CI, 1.79-5.54), and insulin (HR, 1.30; 95% CI, 1.02-1.66).

There was also an increase in the risk for acute myocardial infarction and stroke in some comparisons of sulfonylureas versus other treatments.

“We think this study is the most comprehensive review of RCTs and observational studies to compare CV-related outcomes and all-cause mortality among patients receiving sulfonylureas versus [other] antidiabetic agents,” said Dr. Steve Bain of Abertawe Bro Morgannwg University NHS Trust in Swansea, England.

“We accept that the confidence intervals were wide, but there is a tendency for all significant results to trend in the same direction.” Results of the observational studies analyses generally supported the results from the RCTs, he added. A notable limitation was that there had been no differentiation between the risk according to different sulfonylureas. Dr. Bain said this was to try to keep the number of patients available for analysis as high as possible in the sulfonylurea group.

Data from the German CREST (CV Risk and Events on SU Treatment) study also showed that there was a higher CV risk associated with sulfonylureas when compared with metformin in patients newly diagnosed with type 2 diabetes mellitus. The retrospective cohort database study included more than 35,000 individuals, of whom 26,883 received no antihyperglycemic treatment or treatment with an antihyperglycemic agent other than a sulfonylurea or metformin between January 2010 and December 2011, leaving 7,874 who were given metformin monotherapy and 904 given sulfonylurea monotherapy. Propensity score matching was used to form the final study groups consisting of 730 patients each.

Crude, propensity-matched, and adjusted HRs for death comparing sulfonylurea with metformin as first-line treatment were 3.32 (95% CI, 2.6-4.3; P less than .001), 1.4 (95% CI, 0.9-2.3; P less than .12), and 2.01 (95% CI, 1.5-2.6; P less than .001), respectively. Corresponding HRs for major cardiovascular events (MACE) were 1.9 (95% CI, 1.4-2.4; P less than .001), 1.4 (95% CI, 0.9-2.2; P less than .14), and 1.3 (95% CI, 1.03-1.74; P less than .05).

Dr. Thomas Wilke of the University of Wismar (Germany) who presented the CREST study findings, noted that there were some differences between the groups in terms of the baseline demographics, with those receiving sulfonylureas being somewhat older and more likely to be women, have comorbid disease, and discontinue monotherapy earlier than patients treated with metformin, or possibly be more likely to have contraindications to the use of metformin.

“Taking these differences into account, patients treated with sulfonylureas seem to be at increased risk of death, MACE, and type 2 diabetes hospitalization, compared with metformin-treated patients,” in this German population, Dr. Wilke concluded.

Finally, Dr. Jan Eriksson of Uppsala (Sweden) University presented findings from an observational study of more than 50,000 patients with type 2 diabetes treated with a combination of two noninsulin antidiabetic agents between 2006 and 2013. Of these, 40,736 had received metformin in combination with a sulfonylurea and 12,024 had received a combination of metformin and a DPP-4 inhibitor and were studied further.

Compared with the patients who received a DPP-4 inhibitor on top of metformin, those who received a sulfonylurea had an increased risk of both fatal and nonfatal cardiovascular disease (HR, 1.17; 95% CI, 1.01-1.37) and death from any cause (HR, 1.25; 95% CI, 1.02-1.54) even in the presence of confounding factors such as age, gender, existing cardiovascular disease, and cardio-preventative medication use.

The risk for severe hypoglycemia was also greater with sulfonylurea than DPP-4 use (HR, 2.07; 95% CI, 1.11-3.86), and experiencing severe hypoglycemia was associated with an increased risk for cardiovascular events (HR, 1.51; 95% CI, 1.21-1.88).

“Hypoglycemia may contribute to the increased CVD risk associated with sulfonylureas,” Dr. Eriksson suggested. He concluded that the results of ongoing and future randomized trials would be important in order to understand the cardiovascular risk associated with sulfonylureas better and try to figure out any underlying mechanisms.

Dr. Raz Itamar, head of the diabetes unit at Hadassah Medical Center in Jerusalem, chaired the session during which all these study findings were presented and provided a general comment in an interview on why the cardiovascular safety of sulfonylureas was a particular issue that these studies looked at.

He noted that a study performed in the United States in the 1970s had raised suspicion that there might be an increased cardiovascular risk associated with the sulfonylureas, but the current concerns really started with findings from the UKPDS [United Kingdom Prospective Diabetes Study] and the Women’s Health Study (WHS), for example.

“In the UKPDS, patients who were on metformin and a sulfonylurea demonstrated a doubling in the cardiovascular event rate,” Dr. Itamar said, adding that the WHS data also showed a doubling of the risk.

There is a lack of head-to-head, randomized, controlled data, he emphasized and commented that there were many limitations to the analyses presented at the session. These included the small sample sizes and short duration of follow-up, among others. There is also evidence in the literature suggesting that the cardiovascular risk of individual sulfonylureas may be different. So the results need to be reviewed with caution, he advised.

“As a clinician, I try to give a sulfonylurea which seems to have a safer cardiovascular profile, like glimepiride and gliclazide,” Dr. Itamar said. He noted that there was a randomized controlled trial currently recruiting a projected 6,000 patients that would compare glimepiride with a DPP-4 inhibitor directly for several years that should provide additional and much needed information on the cardiovascular safety of sulfonylureas.

Merck UK funded the systematic review and meta-analysis. AstraZeneca supported the CREST study and the sulfonylureas versus DPP4 inhibitor comparison study. Dr. Bain disclosed he had received honoraria, teaching, and research sponsorship or grants from multiple pharmaceutical companies including Merck Sharp & Dohme and AstraZeneca. Dr. Wilke did not report his disclosures. Dr. Eriksson disclosed receiving research grants or honoraria from AstraZeneca and Merck Sharp & Dohme, among others, and that he had previously been an employee of AstraZeneca. Dr. Itamar did not report having any relevant disclosures.

STOCKHOLM – While they are effective glucose-lowering agents, sulfonylureas seem to substantially increase the risk for cardiovascular events relative to other antihyperglycemic agents, according to several presentations given at the annual meeting of the European Association for the Study of Diabetes.

In a systematic review and meta-analysis of 84 randomized controlled trials (RCTs) and 26 observational studies, accounting for more than 36,573 and more than 1.5 million subjects with type 2 diabetes mellitus, respectively, treatment with a sulfonylurea was found to significantly increase all-cause mortality and cardiovascular-related mortality when compared to no active treatment or placebo and to other antidiabetic drugs.

In the RCTs, the hazard ratios comparing sulfonylureas to all treatments combined were 1.26 (95% confidence interval, 1.10-1.44) for all-cause mortality and 1.46 (95% CI, 1.21-1.77) for cardiovascular mortality. HR for CV mortality was highest when comparing sulfonylureas with GLP-1 agonists and SGLT-2 inhibitors, at 45.4 (95% CI, 2.07-362.8) and 42.6 (95% CI, 1.71-359.1), with significantly elevated risk also seen when compared with DPP-4 inhibitors (HR, 4.42; 95% CI, 1.92-13.0), thiazolidinediones (HR, 3.05; 95% CI, 1.79-5.54), and insulin (HR, 1.30; 95% CI, 1.02-1.66).

There was also an increase in the risk for acute myocardial infarction and stroke in some comparisons of sulfonylureas versus other treatments.

“We think this study is the most comprehensive review of RCTs and observational studies to compare CV-related outcomes and all-cause mortality among patients receiving sulfonylureas versus [other] antidiabetic agents,” said Dr. Steve Bain of Abertawe Bro Morgannwg University NHS Trust in Swansea, England.

“We accept that the confidence intervals were wide, but there is a tendency for all significant results to trend in the same direction.” Results of the observational studies analyses generally supported the results from the RCTs, he added. A notable limitation was that there had been no differentiation between the risk according to different sulfonylureas. Dr. Bain said this was to try to keep the number of patients available for analysis as high as possible in the sulfonylurea group.

Data from the German CREST (CV Risk and Events on SU Treatment) study also showed that there was a higher CV risk associated with sulfonylureas when compared with metformin in patients newly diagnosed with type 2 diabetes mellitus. The retrospective cohort database study included more than 35,000 individuals, of whom 26,883 received no antihyperglycemic treatment or treatment with an antihyperglycemic agent other than a sulfonylurea or metformin between January 2010 and December 2011, leaving 7,874 who were given metformin monotherapy and 904 given sulfonylurea monotherapy. Propensity score matching was used to form the final study groups consisting of 730 patients each.

Crude, propensity-matched, and adjusted HRs for death comparing sulfonylurea with metformin as first-line treatment were 3.32 (95% CI, 2.6-4.3; P less than .001), 1.4 (95% CI, 0.9-2.3; P less than .12), and 2.01 (95% CI, 1.5-2.6; P less than .001), respectively. Corresponding HRs for major cardiovascular events (MACE) were 1.9 (95% CI, 1.4-2.4; P less than .001), 1.4 (95% CI, 0.9-2.2; P less than .14), and 1.3 (95% CI, 1.03-1.74; P less than .05).

Dr. Thomas Wilke of the University of Wismar (Germany) who presented the CREST study findings, noted that there were some differences between the groups in terms of the baseline demographics, with those receiving sulfonylureas being somewhat older and more likely to be women, have comorbid disease, and discontinue monotherapy earlier than patients treated with metformin, or possibly be more likely to have contraindications to the use of metformin.

“Taking these differences into account, patients treated with sulfonylureas seem to be at increased risk of death, MACE, and type 2 diabetes hospitalization, compared with metformin-treated patients,” in this German population, Dr. Wilke concluded.

Finally, Dr. Jan Eriksson of Uppsala (Sweden) University presented findings from an observational study of more than 50,000 patients with type 2 diabetes treated with a combination of two noninsulin antidiabetic agents between 2006 and 2013. Of these, 40,736 had received metformin in combination with a sulfonylurea and 12,024 had received a combination of metformin and a DPP-4 inhibitor and were studied further.

Compared with the patients who received a DPP-4 inhibitor on top of metformin, those who received a sulfonylurea had an increased risk of both fatal and nonfatal cardiovascular disease (HR, 1.17; 95% CI, 1.01-1.37) and death from any cause (HR, 1.25; 95% CI, 1.02-1.54) even in the presence of confounding factors such as age, gender, existing cardiovascular disease, and cardio-preventative medication use.

The risk for severe hypoglycemia was also greater with sulfonylurea than DPP-4 use (HR, 2.07; 95% CI, 1.11-3.86), and experiencing severe hypoglycemia was associated with an increased risk for cardiovascular events (HR, 1.51; 95% CI, 1.21-1.88).

“Hypoglycemia may contribute to the increased CVD risk associated with sulfonylureas,” Dr. Eriksson suggested. He concluded that the results of ongoing and future randomized trials would be important in order to understand the cardiovascular risk associated with sulfonylureas better and try to figure out any underlying mechanisms.

Dr. Raz Itamar, head of the diabetes unit at Hadassah Medical Center in Jerusalem, chaired the session during which all these study findings were presented and provided a general comment in an interview on why the cardiovascular safety of sulfonylureas was a particular issue that these studies looked at.

He noted that a study performed in the United States in the 1970s had raised suspicion that there might be an increased cardiovascular risk associated with the sulfonylureas, but the current concerns really started with findings from the UKPDS [United Kingdom Prospective Diabetes Study] and the Women’s Health Study (WHS), for example.

“In the UKPDS, patients who were on metformin and a sulfonylurea demonstrated a doubling in the cardiovascular event rate,” Dr. Itamar said, adding that the WHS data also showed a doubling of the risk.

There is a lack of head-to-head, randomized, controlled data, he emphasized and commented that there were many limitations to the analyses presented at the session. These included the small sample sizes and short duration of follow-up, among others. There is also evidence in the literature suggesting that the cardiovascular risk of individual sulfonylureas may be different. So the results need to be reviewed with caution, he advised.

“As a clinician, I try to give a sulfonylurea which seems to have a safer cardiovascular profile, like glimepiride and gliclazide,” Dr. Itamar said. He noted that there was a randomized controlled trial currently recruiting a projected 6,000 patients that would compare glimepiride with a DPP-4 inhibitor directly for several years that should provide additional and much needed information on the cardiovascular safety of sulfonylureas.

Merck UK funded the systematic review and meta-analysis. AstraZeneca supported the CREST study and the sulfonylureas versus DPP4 inhibitor comparison study. Dr. Bain disclosed he had received honoraria, teaching, and research sponsorship or grants from multiple pharmaceutical companies including Merck Sharp & Dohme and AstraZeneca. Dr. Wilke did not report his disclosures. Dr. Eriksson disclosed receiving research grants or honoraria from AstraZeneca and Merck Sharp & Dohme, among others, and that he had previously been an employee of AstraZeneca. Dr. Itamar did not report having any relevant disclosures.

LONDON – Drinking three or more cups of caffeinated espresso per day predicted increasing blood pressure and rising blood glucose, according to the results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter, observational study that began in Italy in 1990 and recruited more than 1,000 patients aged 18-45 years who had stage I hypertension and did not have diabetes.

Further, the risk of a cardiovascular event was increased by 50% in these study participants based on a total of 60 events during a mean of 12.5 years of follow-up.

“Controversy still exists about the long-term cardiovascular and metabolic effects of coffee consumption in hypertension,” Dr. Lucio Mos of Hospital San Daniele del Friuli in Udine, Italy, said during a press conference at the annual congress of the European Society of Cardiology.

Stage 1 hypertension was defined as a diastolic blood pressure of 90-99 mm Hg and a systolic blood pressure of 140-159 mm Hg and diagnosed on the basis of six office-based readings obtained on two separate visits. Enrolled participants underwent ambulatory blood pressure monitoring and three office-based measurements were repeated at 1, 2, 3 and 6 months, and at 6-month intervals thereafter. The endpoint was hypertension requiring any antihypertensive treatment according to international guidelines.

During the study, 24-hour urine samples were collected to assess catecholamine levels. Lifestyle factors such as body weight, physical activity, smoking status, and blood glucose were measured. Patients underwent echocardiography.

They were divided into three groups according to their caffeinated coffee intake: 316 (26%) were designated as abstainers because they did not drink coffee; 767 (64%) drank 1-2 cups a day and were categorized as moderate drinkers; and 119 (10%) drank three or more cups of coffee a day and were defined as heavy drinkers.

“I want to underline that, in this part of Italy, we have a population that drinks mainly espresso coffee and drinking American-style coffee is not usual,” Dr. Mos said.

Around 70% of the study population was male, with similar baseline blood pressures and heart rates among the groups. Heavy coffee drinkers tended to be older (37 years) than those who were more moderate drinkers (34 years) or those who abstained (31 years). They had significantly higher body weights (P less than .001), with a body mass index of 26.1 kg/m² vs. 25.7 kg/m² and 24.6 kg/m², respectively.

Dr. Mos reported that in multivariate analysis, coffee consumption was a significant predictor for developing hypertension that required antihypertensive therapy, with a hazard ratio (HR) of 1.5 (95% confidence interval [CI], 1.1-1.19) for heavy drinkers and 1.1 (95% confidence interval, 1.1-1.19) for moderate drinkers, compared to abstainers. The difference was significant (P = .004) only for heavy coffee consumption.

“Coffee consumption was also a predictor of future prediabetes,” Dr. Mos reported. Indeed, the incidence of prediabetes was highest in the heavy coffee drinkers, and significantly predicted the risk of developing prediabetes compared to abstainers (HR, 2, 95% CI, 1.3-3.1. P = .0017). There was a nonsignificant trend for moderate drinkers also to be at risk for prediabetes when compared to nondrinkers (HR, 1.3, 95% CI 0.9-1.7).

Looking at the risk for prediabetes in relation to caffeine metabolism by analyzing patients by their CYP1A2 genotype, it was found that heavy coffee drinkers who were slow metabolizers of caffeine were at highest risk, with a HR of 2.78 (95% CI, 1.32-5.88). Furthermore, individuals were particularly at risk if they were also overweight or obese.

There was a significant (P = .0017) linear relationship found after multivariate adjustment between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake. Even moderate coffee intake, defined as one to three cups per day, could up the risk of a cardiovascular event when compared to that of non–coffee drinkers.

“The coffee story was very topical a couple of years ago so it is interesting to see it revisited,” said Dr. Ian Graham of Trinity College Dublin and one of the experts who chaired the press briefing on the study results. “We need a randomized controlled trial,” Dr. Graham suggested, noting that there were several prior studies that suggested there were beneficial effects of coffee.

Cochair Dr. José Gonzalez-Juanatey of Hospital Clínico Universitario de Santiago de Compostela in Spain observed: “The recommendation could be that if you are a young or middle-aged, stage 1 hypertensive patient probably you have to reduce your coffee intake. This is the take-home message based on the results of an observational study well performed and well conducted.”

LONDON – Drinking three or more cups of caffeinated espresso per day predicted increasing blood pressure and rising blood glucose, according to the results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter, observational study that began in Italy in 1990 and recruited more than 1,000 patients aged 18-45 years who had stage I hypertension and did not have diabetes.

Further, the risk of a cardiovascular event was increased by 50% in these study participants based on a total of 60 events during a mean of 12.5 years of follow-up.

“Controversy still exists about the long-term cardiovascular and metabolic effects of coffee consumption in hypertension,” Dr. Lucio Mos of Hospital San Daniele del Friuli in Udine, Italy, said during a press conference at the annual congress of the European Society of Cardiology.

Stage 1 hypertension was defined as a diastolic blood pressure of 90-99 mm Hg and a systolic blood pressure of 140-159 mm Hg and diagnosed on the basis of six office-based readings obtained on two separate visits. Enrolled participants underwent ambulatory blood pressure monitoring and three office-based measurements were repeated at 1, 2, 3 and 6 months, and at 6-month intervals thereafter. The endpoint was hypertension requiring any antihypertensive treatment according to international guidelines.

During the study, 24-hour urine samples were collected to assess catecholamine levels. Lifestyle factors such as body weight, physical activity, smoking status, and blood glucose were measured. Patients underwent echocardiography.

They were divided into three groups according to their caffeinated coffee intake: 316 (26%) were designated as abstainers because they did not drink coffee; 767 (64%) drank 1-2 cups a day and were categorized as moderate drinkers; and 119 (10%) drank three or more cups of coffee a day and were defined as heavy drinkers.

“I want to underline that, in this part of Italy, we have a population that drinks mainly espresso coffee and drinking American-style coffee is not usual,” Dr. Mos said.

Around 70% of the study population was male, with similar baseline blood pressures and heart rates among the groups. Heavy coffee drinkers tended to be older (37 years) than those who were more moderate drinkers (34 years) or those who abstained (31 years). They had significantly higher body weights (P less than .001), with a body mass index of 26.1 kg/m² vs. 25.7 kg/m² and 24.6 kg/m², respectively.

Dr. Mos reported that in multivariate analysis, coffee consumption was a significant predictor for developing hypertension that required antihypertensive therapy, with a hazard ratio (HR) of 1.5 (95% confidence interval [CI], 1.1-1.19) for heavy drinkers and 1.1 (95% confidence interval, 1.1-1.19) for moderate drinkers, compared to abstainers. The difference was significant (P = .004) only for heavy coffee consumption.

“Coffee consumption was also a predictor of future prediabetes,” Dr. Mos reported. Indeed, the incidence of prediabetes was highest in the heavy coffee drinkers, and significantly predicted the risk of developing prediabetes compared to abstainers (HR, 2, 95% CI, 1.3-3.1. P = .0017). There was a nonsignificant trend for moderate drinkers also to be at risk for prediabetes when compared to nondrinkers (HR, 1.3, 95% CI 0.9-1.7).

Looking at the risk for prediabetes in relation to caffeine metabolism by analyzing patients by their CYP1A2 genotype, it was found that heavy coffee drinkers who were slow metabolizers of caffeine were at highest risk, with a HR of 2.78 (95% CI, 1.32-5.88). Furthermore, individuals were particularly at risk if they were also overweight or obese.

There was a significant (P = .0017) linear relationship found after multivariate adjustment between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake. Even moderate coffee intake, defined as one to three cups per day, could up the risk of a cardiovascular event when compared to that of non–coffee drinkers.

“The coffee story was very topical a couple of years ago so it is interesting to see it revisited,” said Dr. Ian Graham of Trinity College Dublin and one of the experts who chaired the press briefing on the study results. “We need a randomized controlled trial,” Dr. Graham suggested, noting that there were several prior studies that suggested there were beneficial effects of coffee.

Cochair Dr. José Gonzalez-Juanatey of Hospital Clínico Universitario de Santiago de Compostela in Spain observed: “The recommendation could be that if you are a young or middle-aged, stage 1 hypertensive patient probably you have to reduce your coffee intake. This is the take-home message based on the results of an observational study well performed and well conducted.”

LONDON – Drinking three or more cups of caffeinated espresso per day predicted increasing blood pressure and rising blood glucose, according to the results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter, observational study that began in Italy in 1990 and recruited more than 1,000 patients aged 18-45 years who had stage I hypertension and did not have diabetes.

Further, the risk of a cardiovascular event was increased by 50% in these study participants based on a total of 60 events during a mean of 12.5 years of follow-up.

“Controversy still exists about the long-term cardiovascular and metabolic effects of coffee consumption in hypertension,” Dr. Lucio Mos of Hospital San Daniele del Friuli in Udine, Italy, said during a press conference at the annual congress of the European Society of Cardiology.

Stage 1 hypertension was defined as a diastolic blood pressure of 90-99 mm Hg and a systolic blood pressure of 140-159 mm Hg and diagnosed on the basis of six office-based readings obtained on two separate visits. Enrolled participants underwent ambulatory blood pressure monitoring and three office-based measurements were repeated at 1, 2, 3 and 6 months, and at 6-month intervals thereafter. The endpoint was hypertension requiring any antihypertensive treatment according to international guidelines.

During the study, 24-hour urine samples were collected to assess catecholamine levels. Lifestyle factors such as body weight, physical activity, smoking status, and blood glucose were measured. Patients underwent echocardiography.

They were divided into three groups according to their caffeinated coffee intake: 316 (26%) were designated as abstainers because they did not drink coffee; 767 (64%) drank 1-2 cups a day and were categorized as moderate drinkers; and 119 (10%) drank three or more cups of coffee a day and were defined as heavy drinkers.

“I want to underline that, in this part of Italy, we have a population that drinks mainly espresso coffee and drinking American-style coffee is not usual,” Dr. Mos said.

Around 70% of the study population was male, with similar baseline blood pressures and heart rates among the groups. Heavy coffee drinkers tended to be older (37 years) than those who were more moderate drinkers (34 years) or those who abstained (31 years). They had significantly higher body weights (P less than .001), with a body mass index of 26.1 kg/m² vs. 25.7 kg/m² and 24.6 kg/m², respectively.

Dr. Mos reported that in multivariate analysis, coffee consumption was a significant predictor for developing hypertension that required antihypertensive therapy, with a hazard ratio (HR) of 1.5 (95% confidence interval [CI], 1.1-1.19) for heavy drinkers and 1.1 (95% confidence interval, 1.1-1.19) for moderate drinkers, compared to abstainers. The difference was significant (P = .004) only for heavy coffee consumption.

“Coffee consumption was also a predictor of future prediabetes,” Dr. Mos reported. Indeed, the incidence of prediabetes was highest in the heavy coffee drinkers, and significantly predicted the risk of developing prediabetes compared to abstainers (HR, 2, 95% CI, 1.3-3.1. P = .0017). There was a nonsignificant trend for moderate drinkers also to be at risk for prediabetes when compared to nondrinkers (HR, 1.3, 95% CI 0.9-1.7).

Looking at the risk for prediabetes in relation to caffeine metabolism by analyzing patients by their CYP1A2 genotype, it was found that heavy coffee drinkers who were slow metabolizers of caffeine were at highest risk, with a HR of 2.78 (95% CI, 1.32-5.88). Furthermore, individuals were particularly at risk if they were also overweight or obese.

There was a significant (P = .0017) linear relationship found after multivariate adjustment between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake. Even moderate coffee intake, defined as one to three cups per day, could up the risk of a cardiovascular event when compared to that of non–coffee drinkers.

“The coffee story was very topical a couple of years ago so it is interesting to see it revisited,” said Dr. Ian Graham of Trinity College Dublin and one of the experts who chaired the press briefing on the study results. “We need a randomized controlled trial,” Dr. Graham suggested, noting that there were several prior studies that suggested there were beneficial effects of coffee.

Cochair Dr. José Gonzalez-Juanatey of Hospital Clínico Universitario de Santiago de Compostela in Spain observed: “The recommendation could be that if you are a young or middle-aged, stage 1 hypertensive patient probably you have to reduce your coffee intake. This is the take-home message based on the results of an observational study well performed and well conducted.”

LONDON – The combination of two old diuretics – amiloride and hydrochlorothiazide – at half-doses provides synergistic blood pressure lowering beyond the full doses of either drug alone while neutralizing the thiazide diuretic’s blood glucose– and uric acid–raising side effects, according to the results of the PATHWAY-3 trial.

“We think this combination of amiloride and hydrochlorothiazide at equipotent doses is a ‘win win,’ ” Dr. Morris J. Brown said in presenting the study findings at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

“Since unlocking the data, we’ve scarcely been able to contain our excitement at the results. I believe these results will return potassium-sparing diuretics to prominence,” said Dr. Brown, professor of clinical pharmacology at the University of Cambridge (England).

The thiazide diuretics as a group have fallen out of favor because of their adverse metabolic effects, including increased risks of diabetes and gout. But the PATHWAY-3 trial demonstrates that, with the half-dose combination approach, amiloride cancels those side effects, while hydrochlorothiazide (HCTZ) neutralizes amiloride’s tendency to boost serum potassium, he explained.

PATHWAY-3 was a 13-center, 24-week randomized trial involving 399 hypertensive patients with at least one additional component of the metabolic syndrome. They were assigned to 12 weeks of amiloride at 10 mg/day, HCTZ at 25 mg/day, or the combination at half-doses, followed by another 12 weeks at twice the dose in all three groups.

The primary outcome was a safety endpoint: the change from baseline in 2-hour oral glucose tolerance tests conducted at 12 and 24 weeks. Blood glucose levels rose in patients on HCTZ and fell significantly in patients on amiloride or the combination. At 24 weeks, the 2-hour blood glucose level was 0.71 mmol/L lower in the amiloride group and 0.58 mmol/L lower in the combination group than in the HCTZ group.

A key secondary endpoint was change in home systolic blood pressure levels. Averaged over 24 weeks, systolic blood pressure was reduced from baseline by 14.7 mm Hg with amiloride monotherapy, by 14.0 mm Hg with HCTZ, and by 17.5 mm Hg with half-dose combination therapy.

Serum potassium levels rose over time with amiloride, fell with HCTZ, and remained unchanged with combination therapy. But full-dose amiloride monotherapy was well tolerated, with no instances of hyperkalemia as defined by a level above 5.8 mmol/L, even though virtually all patients were on background therapy with an ACE inhibitor or angiotensin receptor blocker, Dr. Brown reported.

He noted that the amiloride-HCTZ combination is the only diuretic that has demonstrated superiority in terms of morbidity and mortality in long-term clinical trials versus a calcium channel blocker in the INSIGHT trial (Lancet. 2000 Jul 29;356[9227]:366-72) and versus beta blocker therapy in the MRC-Elderly trial (BMJ. 1992 Feb 15;304:405-12).

PATHWAY-3 is part of an ongoing program developed by the British Heart Foundation to reexamine old, inexpensive drugs that have been pushed aside by newer and far costlier alternatives.

“The continuing famine of new small molecules makes reappraisal and repurposing of old drugs even more important,” Dr. Brown noted.

Discussant Dr. Antonio Coca found the PATHWAY-3 results compelling.

“On the basis of PATHWAY-3, the combination of amiloride and hydrochlorothiazide in equivalent doses becomes the preferred choice for diuretic treatment in patients with insulin resistance, such as obese hypertensives or those with elevated fasting plasma glucose. These findings together with previous morbidity and mortality data from INSIGHT and MRC-Elderly support its first-line use in patients requiring diuretic therapy for hypertension, alone or in combination with other antihypertensive drugs,” said Dr. Coca of the University of Barcelona.

In an interview, Dr. Elliott M. Antmann, immediate past president of the American Heart Association, said he found the PATHWAY-3 study “very impressive.”

“I personally am going to be prescribing more amiloride, which I haven’t prescribed in years,” said Dr. Antmann of Harvard Medical School, Boston.

Dr. Brown reported no financial conflicts regarding the PATHWAY-3 trial, funded by the British Heart Foundation and the National Institute for Health Research.

[email protected]

LONDON – The combination of two old diuretics – amiloride and hydrochlorothiazide – at half-doses provides synergistic blood pressure lowering beyond the full doses of either drug alone while neutralizing the thiazide diuretic’s blood glucose– and uric acid–raising side effects, according to the results of the PATHWAY-3 trial.

“We think this combination of amiloride and hydrochlorothiazide at equipotent doses is a ‘win win,’ ” Dr. Morris J. Brown said in presenting the study findings at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

“Since unlocking the data, we’ve scarcely been able to contain our excitement at the results. I believe these results will return potassium-sparing diuretics to prominence,” said Dr. Brown, professor of clinical pharmacology at the University of Cambridge (England).

The thiazide diuretics as a group have fallen out of favor because of their adverse metabolic effects, including increased risks of diabetes and gout. But the PATHWAY-3 trial demonstrates that, with the half-dose combination approach, amiloride cancels those side effects, while hydrochlorothiazide (HCTZ) neutralizes amiloride’s tendency to boost serum potassium, he explained.

PATHWAY-3 was a 13-center, 24-week randomized trial involving 399 hypertensive patients with at least one additional component of the metabolic syndrome. They were assigned to 12 weeks of amiloride at 10 mg/day, HCTZ at 25 mg/day, or the combination at half-doses, followed by another 12 weeks at twice the dose in all three groups.

The primary outcome was a safety endpoint: the change from baseline in 2-hour oral glucose tolerance tests conducted at 12 and 24 weeks. Blood glucose levels rose in patients on HCTZ and fell significantly in patients on amiloride or the combination. At 24 weeks, the 2-hour blood glucose level was 0.71 mmol/L lower in the amiloride group and 0.58 mmol/L lower in the combination group than in the HCTZ group.

A key secondary endpoint was change in home systolic blood pressure levels. Averaged over 24 weeks, systolic blood pressure was reduced from baseline by 14.7 mm Hg with amiloride monotherapy, by 14.0 mm Hg with HCTZ, and by 17.5 mm Hg with half-dose combination therapy.

Serum potassium levels rose over time with amiloride, fell with HCTZ, and remained unchanged with combination therapy. But full-dose amiloride monotherapy was well tolerated, with no instances of hyperkalemia as defined by a level above 5.8 mmol/L, even though virtually all patients were on background therapy with an ACE inhibitor or angiotensin receptor blocker, Dr. Brown reported.

He noted that the amiloride-HCTZ combination is the only diuretic that has demonstrated superiority in terms of morbidity and mortality in long-term clinical trials versus a calcium channel blocker in the INSIGHT trial (Lancet. 2000 Jul 29;356[9227]:366-72) and versus beta blocker therapy in the MRC-Elderly trial (BMJ. 1992 Feb 15;304:405-12).

PATHWAY-3 is part of an ongoing program developed by the British Heart Foundation to reexamine old, inexpensive drugs that have been pushed aside by newer and far costlier alternatives.

“The continuing famine of new small molecules makes reappraisal and repurposing of old drugs even more important,” Dr. Brown noted.

Discussant Dr. Antonio Coca found the PATHWAY-3 results compelling.

“On the basis of PATHWAY-3, the combination of amiloride and hydrochlorothiazide in equivalent doses becomes the preferred choice for diuretic treatment in patients with insulin resistance, such as obese hypertensives or those with elevated fasting plasma glucose. These findings together with previous morbidity and mortality data from INSIGHT and MRC-Elderly support its first-line use in patients requiring diuretic therapy for hypertension, alone or in combination with other antihypertensive drugs,” said Dr. Coca of the University of Barcelona.

In an interview, Dr. Elliott M. Antmann, immediate past president of the American Heart Association, said he found the PATHWAY-3 study “very impressive.”

“I personally am going to be prescribing more amiloride, which I haven’t prescribed in years,” said Dr. Antmann of Harvard Medical School, Boston.

Dr. Brown reported no financial conflicts regarding the PATHWAY-3 trial, funded by the British Heart Foundation and the National Institute for Health Research.

[email protected]

LONDON – The combination of two old diuretics – amiloride and hydrochlorothiazide – at half-doses provides synergistic blood pressure lowering beyond the full doses of either drug alone while neutralizing the thiazide diuretic’s blood glucose– and uric acid–raising side effects, according to the results of the PATHWAY-3 trial.

“We think this combination of amiloride and hydrochlorothiazide at equipotent doses is a ‘win win,’ ” Dr. Morris J. Brown said in presenting the study findings at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

“Since unlocking the data, we’ve scarcely been able to contain our excitement at the results. I believe these results will return potassium-sparing diuretics to prominence,” said Dr. Brown, professor of clinical pharmacology at the University of Cambridge (England).

The thiazide diuretics as a group have fallen out of favor because of their adverse metabolic effects, including increased risks of diabetes and gout. But the PATHWAY-3 trial demonstrates that, with the half-dose combination approach, amiloride cancels those side effects, while hydrochlorothiazide (HCTZ) neutralizes amiloride’s tendency to boost serum potassium, he explained.

PATHWAY-3 was a 13-center, 24-week randomized trial involving 399 hypertensive patients with at least one additional component of the metabolic syndrome. They were assigned to 12 weeks of amiloride at 10 mg/day, HCTZ at 25 mg/day, or the combination at half-doses, followed by another 12 weeks at twice the dose in all three groups.

The primary outcome was a safety endpoint: the change from baseline in 2-hour oral glucose tolerance tests conducted at 12 and 24 weeks. Blood glucose levels rose in patients on HCTZ and fell significantly in patients on amiloride or the combination. At 24 weeks, the 2-hour blood glucose level was 0.71 mmol/L lower in the amiloride group and 0.58 mmol/L lower in the combination group than in the HCTZ group.

A key secondary endpoint was change in home systolic blood pressure levels. Averaged over 24 weeks, systolic blood pressure was reduced from baseline by 14.7 mm Hg with amiloride monotherapy, by 14.0 mm Hg with HCTZ, and by 17.5 mm Hg with half-dose combination therapy.

Serum potassium levels rose over time with amiloride, fell with HCTZ, and remained unchanged with combination therapy. But full-dose amiloride monotherapy was well tolerated, with no instances of hyperkalemia as defined by a level above 5.8 mmol/L, even though virtually all patients were on background therapy with an ACE inhibitor or angiotensin receptor blocker, Dr. Brown reported.

He noted that the amiloride-HCTZ combination is the only diuretic that has demonstrated superiority in terms of morbidity and mortality in long-term clinical trials versus a calcium channel blocker in the INSIGHT trial (Lancet. 2000 Jul 29;356[9227]:366-72) and versus beta blocker therapy in the MRC-Elderly trial (BMJ. 1992 Feb 15;304:405-12).

PATHWAY-3 is part of an ongoing program developed by the British Heart Foundation to reexamine old, inexpensive drugs that have been pushed aside by newer and far costlier alternatives.

“The continuing famine of new small molecules makes reappraisal and repurposing of old drugs even more important,” Dr. Brown noted.

Discussant Dr. Antonio Coca found the PATHWAY-3 results compelling.

“On the basis of PATHWAY-3, the combination of amiloride and hydrochlorothiazide in equivalent doses becomes the preferred choice for diuretic treatment in patients with insulin resistance, such as obese hypertensives or those with elevated fasting plasma glucose. These findings together with previous morbidity and mortality data from INSIGHT and MRC-Elderly support its first-line use in patients requiring diuretic therapy for hypertension, alone or in combination with other antihypertensive drugs,” said Dr. Coca of the University of Barcelona.

In an interview, Dr. Elliott M. Antmann, immediate past president of the American Heart Association, said he found the PATHWAY-3 study “very impressive.”

“I personally am going to be prescribing more amiloride, which I haven’t prescribed in years,” said Dr. Antmann of Harvard Medical School, Boston.

Dr. Brown reported no financial conflicts regarding the PATHWAY-3 trial, funded by the British Heart Foundation and the National Institute for Health Research.

[email protected]

STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A_1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.

Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA_1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA_1c at baseline in both groups was around 7.5%.

Patients with higher HbA_1c values at baseline achieved greater reductions in HbA_1c than those with lower starting HbA_1c values, although there was no significant difference between the two treatments.

A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA_1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.

“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.

“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.

While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.

“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.

The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.

Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.

No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.

Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.

Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”

The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.

STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A_1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.

Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA_1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA_1c at baseline in both groups was around 7.5%.

Patients with higher HbA_1c values at baseline achieved greater reductions in HbA_1c than those with lower starting HbA_1c values, although there was no significant difference between the two treatments.

A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA_1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.

“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.

“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.

While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.

“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.

The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.

Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.

No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.

Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.

Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”

The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.

STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A_1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.

Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA_1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA_1c at baseline in both groups was around 7.5%.

Patients with higher HbA_1c values at baseline achieved greater reductions in HbA_1c than those with lower starting HbA_1c values, although there was no significant difference between the two treatments.

A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA_1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.

“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.

“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.

While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.

“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.

The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.

Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.

No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.

Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.

Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”

The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.

STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A_1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.

Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA_1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA_1c at baseline in both groups was around 7.5%.

Patients with higher HbA_1c values at baseline achieved greater reductions in HbA_1c than those with lower starting HbA_1c values, although there was no significant difference between the two treatments.

A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA_1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.

“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.

“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.

While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.

“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.

The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.

Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.

No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.

Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.

Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”

The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.

STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A_1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.

Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA_1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA_1c at baseline in both groups was around 7.5%.

Patients with higher HbA_1c values at baseline achieved greater reductions in HbA_1c than those with lower starting HbA_1c values, although there was no significant difference between the two treatments.

A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA_1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.

“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.

“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.

While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.

“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.

The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.

Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.

No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.

Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.

Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”

The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.

STOCKHOLM – Once-weekly treatment with the investigational, oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin lowered hemoglobin A_1c as effectively as daily sitagliptin in a large, head-to-head, phase III trial of patients with type 2 diabetes.

Results of the O-QWEST noninferiority to sitagliptin study showed similar reductions in HbA_1c from baseline to week 24 of treatment comparing omarigliptin (–0.47%) and sitagliptin (–0.43%) with an overall difference of just –0.03% (P = 0.561). The mean HbA_1c at baseline in both groups was around 7.5%.

Patients with higher HbA_1c values at baseline achieved greater reductions in HbA_1c than those with lower starting HbA_1c values, although there was no significant difference between the two treatments.

A similar percentage of patients in the omarigliptin and sitagliptin groups achieved target HbA_1c values of less than 7% (54.4% vs. 52.4%; P = .619) and less than 6.5% (28.8% vs. 24.4%; P = .212), and there was no significant difference in fasting plasma glucose levels, with a mean difference overall of –0.2 mmol/L.

“According to a relatively recent joint position statement by the ADA and EASD (Diabetes Care. 2012;35:1364-1379) providing care that is responsive to individual patient preferences and needs is a recommended approach to health care in chronic diseases such as type 2 diabetes,” said Dr. Ira Gantz, who presented the study findings.

“Providing patients with medications tailored to their individual preferences and needs is consistent with this patient-centered approach, and the convenience of an effective, well-tolerated, weekly, oral, DPP-4 inhibitor may be an attractive option for some patients,” added Dr. Gantz, who is an employee of Merck & Co.

While an oral drug that is delivered weekly might prove more convenient and potentially improve patients’ adherence and quality of life, this was not possible to measure in the present study, Dr. Gantz noted during the discussion that followed his presentation of the results at the annual meeting of the European Association for the Study of Diabetes.

“The design of the study and of our other phase III programs makes that difficult because they’re double dummy, and the patients in this study who were taking omarigliptin also took daily sitagliptin [or placebo pill] and vice versa – those taking sitagliptin took a weekly placebo pill,” Dr. Gantz explained.

The global study compared the efficacy and safety of omarigliptin given at a once-weekly dose of 25 mg with that of sitagliptin (Januvia) at a daily dose of 100 mg in 642 patients with type 2 diabetes who were not achieving adequate glucose control despite being on metformin. The mean age of patients enrolled was around 57 years in both groups, with around half being male; the average duration of type 2 diabetes was 7 years.

Very small reductions in body weight were seen with both drugs but “no meaningful differences” in specific adverse events were seen, Dr. Gantz reported. Hypoglycemia developed in 3.7% of patients on the weekly regimen versus 4.7% in the subjects taking the daily DPP-4 inhibitor.

No confirmed cases of pancreatitis were reported in either treatment group. Two instances of angioedema, which was a prespecified hypersensitivity adverse event, of the tongue were noted in one subject in the omarigliptin group. There were some small increases in serum amylase and lipase in both groups although these were within normal laboratory limits and did not result in any treatment discontinuations.

Asked if there was any advantage of weekly over daily administration of a DPP-4 inhibitor in terms of renal function, Dr. Gantz replied that it might allow for “broader dose adjustment.” Patents with mild to moderate renal insufficiency would probably not need dose adjustment of omarigliptin, but for those with severe impairment and those on dialysis there would be a recommendation to halve the dose to 12.5 mg/week.

Dr. Gantz observed: “I think the major selling point is that it provides options for patients, as far as a weekly administration it’s a patient-centric approach.”

The study was funded by Merck & Co. Dr. Gantz and his coinvestigators are all employees of the company.

STOCKHOLM – The ultra-long-acting GLP-1 receptor agonist efpeglenatide was efficacious when given once a month and improved glycemic control versus placebo, according to interim data from a 16-week, phase II study involving just over 200 patients with type 2 diabetes.

However, “tolerability and safety seem critical for final dose selection of a monthly regimen,” said Dr. Stefano Del Prato of the University of Pisa in Italy. He presented the findings at the annual meeting of the European Association for the Study of Diabetes.

Efpeglenatide is a new incretin-based therapy being developed by the South Korea–based company Hanmi Pharmaceutical. It has been created via the company’s LAPSCOVERY (Long Acting Protein/Peptide Discovery Platform) Technology whereby the therapeutic agent (GLP-1) is conjugated with a human immunoglobulin G Fc fragment via a linking molecule. This makes a larger molecule that extends the half-life to make it suitable for less frequent (weekly or monthly) dosing.

Dr. Del Prato noted that in a previous study reported at the American Diabetes Association annual scientific sessions in June (Diabetes. 2015;64:A73), efpeglenatide administered once weekly had been shown to be noninferior to once-daily liraglutide in terms of improved hemoglobin A1c from baseline. The aim of the present study was to see whether the interval between doses could be extended further and what might be the optimal dose for monthly administration.

Data were presented on 209 patients enrolled in the trial. The mean age was 56 years and mean diabetes duration, 7 years. Patients had been treated with metformin for an average of 4 years but had unsatisfactory glycemic control despite being on stable doses for at least 3 months.

Patients were randomized to treatment with one of three monthly doses of efpeglenatide (8 mg, 12 mg, or 16 mg) or to placebo. Initially all patients randomized to the active treatment received a 4-mg weekly dose for 4 weeks before the dose was increased to a monthly 8-mg dose for 4 weeks, then either continued (n = 51) or raised again to 12 mg (n = 52) or 16 mg (n = 53) for the remainder of the study.

Overall, 158 patients completed the 16-week trial and a 6-week follow-up phase. The main reasons for treatment discontinuation was patient decision (n = 11), nausea (n = 5), or vomiting (n = 7) in the active treatment groups, or serious adverse event (n = 4).

The mean change in HbA1c over time was the primary endpoint and all three doses of efpeglenatide significantly reduced HbA1c to a greater extent than did placebo, with final recorded values of 6.92%, 6.64%, and 6.74% for the 8-mg, 12-mg, and 16-mg doses, respectively, and 7.56% for placebo. There was no significant difference seen between the three efpeglenatide doses. The respective mean changes in HbA1c from baseline to week 17 were –0.66%, –0.67%, –0.79%, and –0.32%.

The percentage of patients achieving an HbA1c of less than 7% or 6.5% or lower were 57.7% and 34.6% for the 8-mg dose, 63.5% and 50% for the 12-mg dose, 57.7% and 36.5% for the 16-mg dose, and 30.6% and 12.2% for placebo. The differences between the doses were not significant, but all values were significant versus placebo.

Greater reductions in fasting plasma glucose were seen comparing active treatment (–0.78, –0.45, –0.79 mmol/L) versus placebo (–0.07 mmol/L). Body weight was lowered to a greater extent by all doses of efpeglenatide when compared to placebo (–1.78, –3.05, –2.20 kg vs. –0.34 kg).

Dr. Del Prato noted that all three doses seemed effective and were likely to be within the maximal dosage range. There might be some differences in tolerability, however, with patient-reported hypoglycemia occurring more frequently with the highest dose use (17% vs. 2% for placebo and 11.5% for the 8-mg and 13.5% for the 12-mg doses). Nausea and vomiting, which subsided over the course of treatment, tended to recur after the second monthly dose and thereafter with the highest doses of efpeglenatide.

A slight increase of five to eight or nine beats per minute was observed in the patients who received efpeglenatide versus placebo, and there was a slight drop in systolic blood pressure over time.

“The use of GLP-1 receptor agonists, in particular long-acting GLP-1 receptor agonists, is becoming more common, because of their well-known effects on glucose-dependent insulin secretion and glucose-dependent inhibitor of glucagon release,” Dr. Del Prato observed. “These effects, together with the reduction in body weight and effect on gastric emptying results in very appealing possibilities or opportunities for treatment in type 2 diabetes.”

He concluded: “Once-monthly efpeglenatide therapy is efficacious in type 2 diabetic patients inadequately controlled with metformin.”

STOCKHOLM – The ultra-long-acting GLP-1 receptor agonist efpeglenatide was efficacious when given once a month and improved glycemic control versus placebo, according to interim data from a 16-week, phase II study involving just over 200 patients with type 2 diabetes.

However, “tolerability and safety seem critical for final dose selection of a monthly regimen,” said Dr. Stefano Del Prato of the University of Pisa in Italy. He presented the findings at the annual meeting of the European Association for the Study of Diabetes.

Efpeglenatide is a new incretin-based therapy being developed by the South Korea–based company Hanmi Pharmaceutical. It has been created via the company’s LAPSCOVERY (Long Acting Protein/Peptide Discovery Platform) Technology whereby the therapeutic agent (GLP-1) is conjugated with a human immunoglobulin G Fc fragment via a linking molecule. This makes a larger molecule that extends the half-life to make it suitable for less frequent (weekly or monthly) dosing.

Dr. Del Prato noted that in a previous study reported at the American Diabetes Association annual scientific sessions in June (Diabetes. 2015;64:A73), efpeglenatide administered once weekly had been shown to be noninferior to once-daily liraglutide in terms of improved hemoglobin A1c from baseline. The aim of the present study was to see whether the interval between doses could be extended further and what might be the optimal dose for monthly administration.

Data were presented on 209 patients enrolled in the trial. The mean age was 56 years and mean diabetes duration, 7 years. Patients had been treated with metformin for an average of 4 years but had unsatisfactory glycemic control despite being on stable doses for at least 3 months.

Patients were randomized to treatment with one of three monthly doses of efpeglenatide (8 mg, 12 mg, or 16 mg) or to placebo. Initially all patients randomized to the active treatment received a 4-mg weekly dose for 4 weeks before the dose was increased to a monthly 8-mg dose for 4 weeks, then either continued (n = 51) or raised again to 12 mg (n = 52) or 16 mg (n = 53) for the remainder of the study.

Overall, 158 patients completed the 16-week trial and a 6-week follow-up phase. The main reasons for treatment discontinuation was patient decision (n = 11), nausea (n = 5), or vomiting (n = 7) in the active treatment groups, or serious adverse event (n = 4).

The mean change in HbA1c over time was the primary endpoint and all three doses of efpeglenatide significantly reduced HbA1c to a greater extent than did placebo, with final recorded values of 6.92%, 6.64%, and 6.74% for the 8-mg, 12-mg, and 16-mg doses, respectively, and 7.56% for placebo. There was no significant difference seen between the three efpeglenatide doses. The respective mean changes in HbA1c from baseline to week 17 were –0.66%, –0.67%, –0.79%, and –0.32%.

The percentage of patients achieving an HbA1c of less than 7% or 6.5% or lower were 57.7% and 34.6% for the 8-mg dose, 63.5% and 50% for the 12-mg dose, 57.7% and 36.5% for the 16-mg dose, and 30.6% and 12.2% for placebo. The differences between the doses were not significant, but all values were significant versus placebo.

Greater reductions in fasting plasma glucose were seen comparing active treatment (–0.78, –0.45, –0.79 mmol/L) versus placebo (–0.07 mmol/L). Body weight was lowered to a greater extent by all doses of efpeglenatide when compared to placebo (–1.78, –3.05, –2.20 kg vs. –0.34 kg).

Dr. Del Prato noted that all three doses seemed effective and were likely to be within the maximal dosage range. There might be some differences in tolerability, however, with patient-reported hypoglycemia occurring more frequently with the highest dose use (17% vs. 2% for placebo and 11.5% for the 8-mg and 13.5% for the 12-mg doses). Nausea and vomiting, which subsided over the course of treatment, tended to recur after the second monthly dose and thereafter with the highest doses of efpeglenatide.

A slight increase of five to eight or nine beats per minute was observed in the patients who received efpeglenatide versus placebo, and there was a slight drop in systolic blood pressure over time.

“The use of GLP-1 receptor agonists, in particular long-acting GLP-1 receptor agonists, is becoming more common, because of their well-known effects on glucose-dependent insulin secretion and glucose-dependent inhibitor of glucagon release,” Dr. Del Prato observed. “These effects, together with the reduction in body weight and effect on gastric emptying results in very appealing possibilities or opportunities for treatment in type 2 diabetes.”

He concluded: “Once-monthly efpeglenatide therapy is efficacious in type 2 diabetic patients inadequately controlled with metformin.”

STOCKHOLM – The ultra-long-acting GLP-1 receptor agonist efpeglenatide was efficacious when given once a month and improved glycemic control versus placebo, according to interim data from a 16-week, phase II study involving just over 200 patients with type 2 diabetes.

However, “tolerability and safety seem critical for final dose selection of a monthly regimen,” said Dr. Stefano Del Prato of the University of Pisa in Italy. He presented the findings at the annual meeting of the European Association for the Study of Diabetes.

Efpeglenatide is a new incretin-based therapy being developed by the South Korea–based company Hanmi Pharmaceutical. It has been created via the company’s LAPSCOVERY (Long Acting Protein/Peptide Discovery Platform) Technology whereby the therapeutic agent (GLP-1) is conjugated with a human immunoglobulin G Fc fragment via a linking molecule. This makes a larger molecule that extends the half-life to make it suitable for less frequent (weekly or monthly) dosing.

Dr. Del Prato noted that in a previous study reported at the American Diabetes Association annual scientific sessions in June (Diabetes. 2015;64:A73), efpeglenatide administered once weekly had been shown to be noninferior to once-daily liraglutide in terms of improved hemoglobin A1c from baseline. The aim of the present study was to see whether the interval between doses could be extended further and what might be the optimal dose for monthly administration.

Data were presented on 209 patients enrolled in the trial. The mean age was 56 years and mean diabetes duration, 7 years. Patients had been treated with metformin for an average of 4 years but had unsatisfactory glycemic control despite being on stable doses for at least 3 months.

Patients were randomized to treatment with one of three monthly doses of efpeglenatide (8 mg, 12 mg, or 16 mg) or to placebo. Initially all patients randomized to the active treatment received a 4-mg weekly dose for 4 weeks before the dose was increased to a monthly 8-mg dose for 4 weeks, then either continued (n = 51) or raised again to 12 mg (n = 52) or 16 mg (n = 53) for the remainder of the study.

Overall, 158 patients completed the 16-week trial and a 6-week follow-up phase. The main reasons for treatment discontinuation was patient decision (n = 11), nausea (n = 5), or vomiting (n = 7) in the active treatment groups, or serious adverse event (n = 4).

The mean change in HbA1c over time was the primary endpoint and all three doses of efpeglenatide significantly reduced HbA1c to a greater extent than did placebo, with final recorded values of 6.92%, 6.64%, and 6.74% for the 8-mg, 12-mg, and 16-mg doses, respectively, and 7.56% for placebo. There was no significant difference seen between the three efpeglenatide doses. The respective mean changes in HbA1c from baseline to week 17 were –0.66%, –0.67%, –0.79%, and –0.32%.

The percentage of patients achieving an HbA1c of less than 7% or 6.5% or lower were 57.7% and 34.6% for the 8-mg dose, 63.5% and 50% for the 12-mg dose, 57.7% and 36.5% for the 16-mg dose, and 30.6% and 12.2% for placebo. The differences between the doses were not significant, but all values were significant versus placebo.

Greater reductions in fasting plasma glucose were seen comparing active treatment (–0.78, –0.45, –0.79 mmol/L) versus placebo (–0.07 mmol/L). Body weight was lowered to a greater extent by all doses of efpeglenatide when compared to placebo (–1.78, –3.05, –2.20 kg vs. –0.34 kg).

Dr. Del Prato noted that all three doses seemed effective and were likely to be within the maximal dosage range. There might be some differences in tolerability, however, with patient-reported hypoglycemia occurring more frequently with the highest dose use (17% vs. 2% for placebo and 11.5% for the 8-mg and 13.5% for the 12-mg doses). Nausea and vomiting, which subsided over the course of treatment, tended to recur after the second monthly dose and thereafter with the highest doses of efpeglenatide.

A slight increase of five to eight or nine beats per minute was observed in the patients who received efpeglenatide versus placebo, and there was a slight drop in systolic blood pressure over time.

“The use of GLP-1 receptor agonists, in particular long-acting GLP-1 receptor agonists, is becoming more common, because of their well-known effects on glucose-dependent insulin secretion and glucose-dependent inhibitor of glucagon release,” Dr. Del Prato observed. “These effects, together with the reduction in body weight and effect on gastric emptying results in very appealing possibilities or opportunities for treatment in type 2 diabetes.”

He concluded: “Once-monthly efpeglenatide therapy is efficacious in type 2 diabetic patients inadequately controlled with metformin.”

STOCKHOLM – The lipid-lowering drug alirocumab significantly lowered low-density lipoprotein cholesterol level to a similar extent in people with diabetes mellitus as in those without diabetes, based on a subanalysis of data from the ODYSSEY Long-Term study.

The calculated change in low-density lipoprotein cholesterol from baseline to 24 weeks was –60.1% with alirocumab vs. –0.9% with placebo, for an overall difference of –59.2% in those with diabetes. By comparison, the corresponding mean changes in LDL cholesterol were –61.5% and –1.8% (a difference of –59.7%) in nondiabetic individuals.

Improvements in other parameters – including triglycerides, high-density lipoprotein cholesterol, and lipoprotein(a) (Lp[a]) – were also similar in individuals with and without diabetes.

“The ODYSSEY Long-Term study is the longest study in the ODYSSEY phase III program,” said study investigator Dr. Helen Colhoun of the University of Dundee (Scotland). The primary endpoint was assessed at 24 weeks, but the trial ran for a further 54 weeks to gather as much lipid and general safety data as possible, she explained at the annual meeting of the European Association for the Study of Diabetes.

Alirocumab (Praulent) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) that was recently approved by the Food and Drug Administration for use as an adjunct to diet and maximally tolerated statin therapy in people with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who need additional LDL-cholesterol lowering.

The main results of the ODYSSEY Long-Term study were published in the New England Journal of Medicine in April (2015;372:1489-99 doi: 10.1056/NEJMoa1501031) and showed a –62% difference (P less than .001) in the mean percentage change from baseline in calculated LDL cholesterol between the alirocumab and placebo groups at 24 weeks. The difference remained consistent over the 78 weeks of follow-up.

Overall, the study included 2,341 individuals at high risk for cardiovascular disease with an LDL cholesterol level of more than 70 mg/dL despite being treated with maximally tolerated doses of statins with or without additional lipid-lowering therapy. Of these, just over one third of the population (35.7%, n = 838) had diabetes. Patients in the trial were randomized 2:1 to receive either alirocumab 150 mg or matching placebo as a 1-mL injection once every 2 weeks.

The present analysis looked at the long-term efficacy and safety of alirocumab in the diabetic subpopulation. Baseline demographic and lipid characteristics of the 838 patients with diabetes were broadly similar to the 1,503 patients in the trial who did not have diabetes, with mean ages of 61 and 60 years. Dr. Colhoun pointed out that virtually all patients (999; 100%) were taking a background statin, and well over one-third of those with diabetes and half of those without were taking a high-dose statin. Approximately 26% of the diabetic population were receiving insulin. Diabetic patients had slightly lower LDL cholesterol and higher triglycerides than their nondiabetic counterparts at baseline, as would be expected, she added.

Similarly high proportions of patients with (78.4% vs. 10.6%, P less than .0001) and without (79.7% vs. 6.6%, P less than .0001) diabetes who were treated with alirocumab vs. placebo achieved a target LDL cholesterol level of less than 70 mg/dL at 24 weeks.

Alirocumab treatment was associated with a 3.5% increase in HDL cholesterol in patients with diabetes and a 5.6% increase in those without, and triglycerides were reduced by a respective –18.5% and –16.7%. The adjusted mean differences in Lp(a) were –27.2% and –24.9%, an effect not seen with statins, Dr. Colhoun said.

“Overall the safety profile was excellent with this new class of drug, and there weren’t any major surprises or differences in safety profile between those with diabetes receiving alirocumab and those without diabetes,” she noted. Less than 10% of adverse events led to treatment discontinuation, at 8.3% vs. 5.0% for active and placebo treatment in the diabetic group and 6.5% vs. 6.3% in those without diabetes.

Data on the risk for new-onset or worsening diabetes in the ODYSSEY program will be presented at the scientific sessions of the American Heart Association in November, Dr. Colhoun said, giving a sneak peak of the findings from the ODYSSEY Long-Term study that indicated that there was no increased risk for either. Rates of new-onset diabetes were 1.8% in the alirocumab-treated group and 2% in the placebo group and of worsening diabetes, were 12.9% and 13.6%, respectively.

Treatment-emergent major cardiovascular events (MACE) were evaluated as a safety parameter in a post hoc analysis. Although not a main endpoint of the study, the results showed a lower rate of MACE in the overall population with alirocumab than placebo treatment (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31-0.90) and in both diabetic (2.5% vs. 4.3%; HR, 0.58; 95% CI, 0.27-1.25) and nondiabetic subjects (1.3% vs. 2.8%; HR, 0.47; 95% CI, 0.22-1.0). “This is reassuring, but it is not by any means definitive evidence of a [cardiovascular disease] benefit,” Dr. Colhoun stressed.

The potential for alirocumab to reduce cardiovascular events will be investigated in the large, phase III ODYSSEY Outcomes study. This trial is currently recruiting and aims to accrue around 18,000 high-risk patients including those with diabetes. The study is projected to complete by the end of 2017.

STOCKHOLM – The lipid-lowering drug alirocumab significantly lowered low-density lipoprotein cholesterol level to a similar extent in people with diabetes mellitus as in those without diabetes, based on a subanalysis of data from the ODYSSEY Long-Term study.

The calculated change in low-density lipoprotein cholesterol from baseline to 24 weeks was –60.1% with alirocumab vs. –0.9% with placebo, for an overall difference of –59.2% in those with diabetes. By comparison, the corresponding mean changes in LDL cholesterol were –61.5% and –1.8% (a difference of –59.7%) in nondiabetic individuals.

Improvements in other parameters – including triglycerides, high-density lipoprotein cholesterol, and lipoprotein(a) (Lp[a]) – were also similar in individuals with and without diabetes.

“The ODYSSEY Long-Term study is the longest study in the ODYSSEY phase III program,” said study investigator Dr. Helen Colhoun of the University of Dundee (Scotland). The primary endpoint was assessed at 24 weeks, but the trial ran for a further 54 weeks to gather as much lipid and general safety data as possible, she explained at the annual meeting of the European Association for the Study of Diabetes.

Alirocumab (Praulent) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) that was recently approved by the Food and Drug Administration for use as an adjunct to diet and maximally tolerated statin therapy in people with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who need additional LDL-cholesterol lowering.

The main results of the ODYSSEY Long-Term study were published in the New England Journal of Medicine in April (2015;372:1489-99 doi: 10.1056/NEJMoa1501031) and showed a –62% difference (P less than .001) in the mean percentage change from baseline in calculated LDL cholesterol between the alirocumab and placebo groups at 24 weeks. The difference remained consistent over the 78 weeks of follow-up.

Overall, the study included 2,341 individuals at high risk for cardiovascular disease with an LDL cholesterol level of more than 70 mg/dL despite being treated with maximally tolerated doses of statins with or without additional lipid-lowering therapy. Of these, just over one third of the population (35.7%, n = 838) had diabetes. Patients in the trial were randomized 2:1 to receive either alirocumab 150 mg or matching placebo as a 1-mL injection once every 2 weeks.

The present analysis looked at the long-term efficacy and safety of alirocumab in the diabetic subpopulation. Baseline demographic and lipid characteristics of the 838 patients with diabetes were broadly similar to the 1,503 patients in the trial who did not have diabetes, with mean ages of 61 and 60 years. Dr. Colhoun pointed out that virtually all patients (999; 100%) were taking a background statin, and well over one-third of those with diabetes and half of those without were taking a high-dose statin. Approximately 26% of the diabetic population were receiving insulin. Diabetic patients had slightly lower LDL cholesterol and higher triglycerides than their nondiabetic counterparts at baseline, as would be expected, she added.

Similarly high proportions of patients with (78.4% vs. 10.6%, P less than .0001) and without (79.7% vs. 6.6%, P less than .0001) diabetes who were treated with alirocumab vs. placebo achieved a target LDL cholesterol level of less than 70 mg/dL at 24 weeks.

Alirocumab treatment was associated with a 3.5% increase in HDL cholesterol in patients with diabetes and a 5.6% increase in those without, and triglycerides were reduced by a respective –18.5% and –16.7%. The adjusted mean differences in Lp(a) were –27.2% and –24.9%, an effect not seen with statins, Dr. Colhoun said.

“Overall the safety profile was excellent with this new class of drug, and there weren’t any major surprises or differences in safety profile between those with diabetes receiving alirocumab and those without diabetes,” she noted. Less than 10% of adverse events led to treatment discontinuation, at 8.3% vs. 5.0% for active and placebo treatment in the diabetic group and 6.5% vs. 6.3% in those without diabetes.

Data on the risk for new-onset or worsening diabetes in the ODYSSEY program will be presented at the scientific sessions of the American Heart Association in November, Dr. Colhoun said, giving a sneak peak of the findings from the ODYSSEY Long-Term study that indicated that there was no increased risk for either. Rates of new-onset diabetes were 1.8% in the alirocumab-treated group and 2% in the placebo group and of worsening diabetes, were 12.9% and 13.6%, respectively.

Treatment-emergent major cardiovascular events (MACE) were evaluated as a safety parameter in a post hoc analysis. Although not a main endpoint of the study, the results showed a lower rate of MACE in the overall population with alirocumab than placebo treatment (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31-0.90) and in both diabetic (2.5% vs. 4.3%; HR, 0.58; 95% CI, 0.27-1.25) and nondiabetic subjects (1.3% vs. 2.8%; HR, 0.47; 95% CI, 0.22-1.0). “This is reassuring, but it is not by any means definitive evidence of a [cardiovascular disease] benefit,” Dr. Colhoun stressed.

The potential for alirocumab to reduce cardiovascular events will be investigated in the large, phase III ODYSSEY Outcomes study. This trial is currently recruiting and aims to accrue around 18,000 high-risk patients including those with diabetes. The study is projected to complete by the end of 2017.

STOCKHOLM – The lipid-lowering drug alirocumab significantly lowered low-density lipoprotein cholesterol level to a similar extent in people with diabetes mellitus as in those without diabetes, based on a subanalysis of data from the ODYSSEY Long-Term study.

The calculated change in low-density lipoprotein cholesterol from baseline to 24 weeks was –60.1% with alirocumab vs. –0.9% with placebo, for an overall difference of –59.2% in those with diabetes. By comparison, the corresponding mean changes in LDL cholesterol were –61.5% and –1.8% (a difference of –59.7%) in nondiabetic individuals.

Improvements in other parameters – including triglycerides, high-density lipoprotein cholesterol, and lipoprotein(a) (Lp[a]) – were also similar in individuals with and without diabetes.

“The ODYSSEY Long-Term study is the longest study in the ODYSSEY phase III program,” said study investigator Dr. Helen Colhoun of the University of Dundee (Scotland). The primary endpoint was assessed at 24 weeks, but the trial ran for a further 54 weeks to gather as much lipid and general safety data as possible, she explained at the annual meeting of the European Association for the Study of Diabetes.

Alirocumab (Praulent) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) that was recently approved by the Food and Drug Administration for use as an adjunct to diet and maximally tolerated statin therapy in people with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who need additional LDL-cholesterol lowering.

The main results of the ODYSSEY Long-Term study were published in the New England Journal of Medicine in April (2015;372:1489-99 doi: 10.1056/NEJMoa1501031) and showed a –62% difference (P less than .001) in the mean percentage change from baseline in calculated LDL cholesterol between the alirocumab and placebo groups at 24 weeks. The difference remained consistent over the 78 weeks of follow-up.

Overall, the study included 2,341 individuals at high risk for cardiovascular disease with an LDL cholesterol level of more than 70 mg/dL despite being treated with maximally tolerated doses of statins with or without additional lipid-lowering therapy. Of these, just over one third of the population (35.7%, n = 838) had diabetes. Patients in the trial were randomized 2:1 to receive either alirocumab 150 mg or matching placebo as a 1-mL injection once every 2 weeks.

The present analysis looked at the long-term efficacy and safety of alirocumab in the diabetic subpopulation. Baseline demographic and lipid characteristics of the 838 patients with diabetes were broadly similar to the 1,503 patients in the trial who did not have diabetes, with mean ages of 61 and 60 years. Dr. Colhoun pointed out that virtually all patients (999; 100%) were taking a background statin, and well over one-third of those with diabetes and half of those without were taking a high-dose statin. Approximately 26% of the diabetic population were receiving insulin. Diabetic patients had slightly lower LDL cholesterol and higher triglycerides than their nondiabetic counterparts at baseline, as would be expected, she added.

Similarly high proportions of patients with (78.4% vs. 10.6%, P less than .0001) and without (79.7% vs. 6.6%, P less than .0001) diabetes who were treated with alirocumab vs. placebo achieved a target LDL cholesterol level of less than 70 mg/dL at 24 weeks.

Alirocumab treatment was associated with a 3.5% increase in HDL cholesterol in patients with diabetes and a 5.6% increase in those without, and triglycerides were reduced by a respective –18.5% and –16.7%. The adjusted mean differences in Lp(a) were –27.2% and –24.9%, an effect not seen with statins, Dr. Colhoun said.

“Overall the safety profile was excellent with this new class of drug, and there weren’t any major surprises or differences in safety profile between those with diabetes receiving alirocumab and those without diabetes,” she noted. Less than 10% of adverse events led to treatment discontinuation, at 8.3% vs. 5.0% for active and placebo treatment in the diabetic group and 6.5% vs. 6.3% in those without diabetes.

Data on the risk for new-onset or worsening diabetes in the ODYSSEY program will be presented at the scientific sessions of the American Heart Association in November, Dr. Colhoun said, giving a sneak peak of the findings from the ODYSSEY Long-Term study that indicated that there was no increased risk for either. Rates of new-onset diabetes were 1.8% in the alirocumab-treated group and 2% in the placebo group and of worsening diabetes, were 12.9% and 13.6%, respectively.

Treatment-emergent major cardiovascular events (MACE) were evaluated as a safety parameter in a post hoc analysis. Although not a main endpoint of the study, the results showed a lower rate of MACE in the overall population with alirocumab than placebo treatment (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31-0.90) and in both diabetic (2.5% vs. 4.3%; HR, 0.58; 95% CI, 0.27-1.25) and nondiabetic subjects (1.3% vs. 2.8%; HR, 0.47; 95% CI, 0.22-1.0). “This is reassuring, but it is not by any means definitive evidence of a [cardiovascular disease] benefit,” Dr. Colhoun stressed.

The potential for alirocumab to reduce cardiovascular events will be investigated in the large, phase III ODYSSEY Outcomes study. This trial is currently recruiting and aims to accrue around 18,000 high-risk patients including those with diabetes. The study is projected to complete by the end of 2017.

Children and adolescents with more severe obesity show a higher prevalence of cardiometabolic abnormalities than those with less severe obesity, so differentiating among levels of obesity is important in the pediatric population, according to a report published online Oct. 1 in New England Journal of Medicine.

Current screening guidelines for pediatric patients use only a single category for obesity, which doesn’t take into account their varying levels of risk for obesity-related disorders. To assess the distribution of cardiometabolic risk factors in obese children and adolescents, researchers performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey for 2011-2012.

©moodboard/thinkstockphotos.com

They assessed a nationally representative sample of 8,579 participants aged 3-19 years, categorizing them by age- and gender-specific body mass index percentiles: overweight (85th-94th percentile), class I obesity (95th percentile to 119% of the 95th percentile), class II obesity (120% to 139% of the 95th percentile, or BMI of 35-39, whichever was lower), or class III obesity (140% of the 95th percentile, or BMI of 40 or greater, whichever was lower).

A total of 47% of the study participants were overweight, 36% had class I obesity, 12% had class II obesity, and 5% had class III obesity. The prevalence of abnormal values for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, systolic BP, diastolic BP, glycated hemoglobin, and fasting glucose all increased with increasing severity of obesity, at most ages and across both genders. The correlations were more pronounced in boys than in girls, said Asheley C. Skinner, Ph.D., of the department of pediatrics and the department of health policy and management, University of North Carolina at Chapel Hill, and her associates.

The findings indicate that distinguishing among at least three levels of obesity severity “provides a more fine-tuned approach to identifying patients with the greatest risk of potential complications and death,” allowing targeted interventions to those at greatest risk. This is especially important because resources are too limited to provide services for every child with obesity, the investigators said (N Engl J Med. 2015 Oct 1. doi:10.1056/NEJMoa1502821). “As older adolescents transition to young adulthood, the recognition that teens with obesity have increased cardiometabolic risk will be important,” they added.

This study did not specify a source of funding. Dr. Skinner reported having no relevant financial disclosures; one of her associates reported receiving personal fees from Nestle unrelated to this work.

Children and adolescents with more severe obesity show a higher prevalence of cardiometabolic abnormalities than those with less severe obesity, so differentiating among levels of obesity is important in the pediatric population, according to a report published online Oct. 1 in New England Journal of Medicine.

Current screening guidelines for pediatric patients use only a single category for obesity, which doesn’t take into account their varying levels of risk for obesity-related disorders. To assess the distribution of cardiometabolic risk factors in obese children and adolescents, researchers performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey for 2011-2012.

©moodboard/thinkstockphotos.com

They assessed a nationally representative sample of 8,579 participants aged 3-19 years, categorizing them by age- and gender-specific body mass index percentiles: overweight (85th-94th percentile), class I obesity (95th percentile to 119% of the 95th percentile), class II obesity (120% to 139% of the 95th percentile, or BMI of 35-39, whichever was lower), or class III obesity (140% of the 95th percentile, or BMI of 40 or greater, whichever was lower).

A total of 47% of the study participants were overweight, 36% had class I obesity, 12% had class II obesity, and 5% had class III obesity. The prevalence of abnormal values for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, systolic BP, diastolic BP, glycated hemoglobin, and fasting glucose all increased with increasing severity of obesity, at most ages and across both genders. The correlations were more pronounced in boys than in girls, said Asheley C. Skinner, Ph.D., of the department of pediatrics and the department of health policy and management, University of North Carolina at Chapel Hill, and her associates.

The findings indicate that distinguishing among at least three levels of obesity severity “provides a more fine-tuned approach to identifying patients with the greatest risk of potential complications and death,” allowing targeted interventions to those at greatest risk. This is especially important because resources are too limited to provide services for every child with obesity, the investigators said (N Engl J Med. 2015 Oct 1. doi:10.1056/NEJMoa1502821). “As older adolescents transition to young adulthood, the recognition that teens with obesity have increased cardiometabolic risk will be important,” they added.

This study did not specify a source of funding. Dr. Skinner reported having no relevant financial disclosures; one of her associates reported receiving personal fees from Nestle unrelated to this work.

Children and adolescents with more severe obesity show a higher prevalence of cardiometabolic abnormalities than those with less severe obesity, so differentiating among levels of obesity is important in the pediatric population, according to a report published online Oct. 1 in New England Journal of Medicine.

Current screening guidelines for pediatric patients use only a single category for obesity, which doesn’t take into account their varying levels of risk for obesity-related disorders. To assess the distribution of cardiometabolic risk factors in obese children and adolescents, researchers performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey for 2011-2012.

©moodboard/thinkstockphotos.com

They assessed a nationally representative sample of 8,579 participants aged 3-19 years, categorizing them by age- and gender-specific body mass index percentiles: overweight (85th-94th percentile), class I obesity (95th percentile to 119% of the 95th percentile), class II obesity (120% to 139% of the 95th percentile, or BMI of 35-39, whichever was lower), or class III obesity (140% of the 95th percentile, or BMI of 40 or greater, whichever was lower).

A total of 47% of the study participants were overweight, 36% had class I obesity, 12% had class II obesity, and 5% had class III obesity. The prevalence of abnormal values for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, systolic BP, diastolic BP, glycated hemoglobin, and fasting glucose all increased with increasing severity of obesity, at most ages and across both genders. The correlations were more pronounced in boys than in girls, said Asheley C. Skinner, Ph.D., of the department of pediatrics and the department of health policy and management, University of North Carolina at Chapel Hill, and her associates.

The findings indicate that distinguishing among at least three levels of obesity severity “provides a more fine-tuned approach to identifying patients with the greatest risk of potential complications and death,” allowing targeted interventions to those at greatest risk. This is especially important because resources are too limited to provide services for every child with obesity, the investigators said (N Engl J Med. 2015 Oct 1. doi:10.1056/NEJMoa1502821). “As older adolescents transition to young adulthood, the recognition that teens with obesity have increased cardiometabolic risk will be important,” they added.

This study did not specify a source of funding. Dr. Skinner reported having no relevant financial disclosures; one of her associates reported receiving personal fees from Nestle unrelated to this work.