Diabetes Hub

Researchers found an association between nonalcoholic fatty liver disease (NAFLD) and myocardial dysfunction and remodeling, according to a new study published in Hepatology.

“Both NAFLD and heart failure (particularly heart failure with preserved ejection fraction) are obesity-related conditions that have reached epidemic proportions. We know from epidemiologic studies that persons with NAFLD are more likely to die from cardiovascular disease than from liver-related death. This risk seems to be proportional to the amount of fat in the liver and is independent of the presence of nonalcoholic steatohepatitis (NASH). There have been numerous studies that have focused on the relationship between NAFLD and coronary artery disease, but very little work has been done to determine relationships with heart failure,” Dr. Lisa B. VanWagner of Northwestern University in Chicago noted. She continued, “There are several well-established major risk factors for the development of clinical heart failure, including coronary artery disease, diabetes, and hypertension, all of which are also closely associated with NAFLD. However, whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction that may lead to the development of clinical heart failure is unknown.”

Courtesy of Wikimedia /

NAFLD and heart failure are both associated with obesity. Likewise, there is evidence that NAFLD may also be related to endothelial dysfunction, coronary plaques, coronary artery calcifications, as well as being an independent risk factor for cardiovascular disease.

Dr. VanWagner and her colleagues conducted a cross-sectional study of 2,713 patients from the CARDIA (Coronary Artery Risk Development in Young Adults) study to understand any associations between NAFLD and abnormalities in left ventricular (LV) function and structure. Study participants completed CT quantification of liver fat and echocardiography with Doppler during the 25-year follow-up to the initial study (Hepatology 2015;62:773-83 [doi:10.1002/hep.27869]). Participants were excluded from analysis if they had missing or incomplete imaging, pregnancy, a history of MI or heart failure, cirrhosis, hepatitis, or chronic liver disease risk factors, or if they weighed more than 450 pounds,

Of the 2,713 subjects included in analysis, 48% were black and 58.8% were female. NAFLD was detected in 10% (n = 271) of participants. Those with NAFLD were more likely to be white males with metabolic syndrome and who were obese and had higher CT-measured levels of visceral adipose tissue, and an increased waist circumference and waist-to-hip ratio. Insulin resistance markers such as elevated fasting glucose, elevated C-reactive protein, and hypertriglyceridemia were more common in the participants with NAFLD.

Study participants with NAFLD had signs of myocardial remodeling such as more left ventricular wall thickness, LV end-diastolic volume, left aortic volume index, and LV mass index. Likewise, NAFLD was associated with more circumferential strain and global longitudinal strain but no differences in ejection fraction.

Subclinical systolic dysfunction (P less than .001 for the trend), subclinical diastolic dysfunction with impaired left ventricular relaxation (34.6% vs. 23.6%; P less than .0001), and elevated LV filling pressures (33.3% vs. 23.7%; P less than .001) was more common in NAFLD participants, compared with non-NAFLD subjects.

After researchers adjusted for health behaviors and demographic factors, evidence of NAFLD was associated with worse GLS (P less than .0001). Finally, NAFLD was associated with subclinical cardiac remodeling and dysfunction even after adjustment for body mass index and heart failure risk factors (P less than .01).

Dr. VanWagner summarized, “NAFLD may not necessarily be a ‘benign condition’ as previously thought. In our study, we determined liver fat by CT scan, which admittedly detects fat at a higher level (typically greater than 30%) than for example on MRI, which can detect fat as low as 5%. A fatty liver detected on CT or even on [ultrasound], which has similar sensitivity as CT for detecting liver fat should prompt evaluation for additional cardiovascular risk factors and treatment of identified abnormalities to reduce [atherosclerotic cardiovascular disease] and [heart failure] risk. Currently, our study only shows associations between liver fat and subclinical changes in the myocardium and causality cannot be determined. [On the basis] of our data, we cannot recommend screening for HF [heart failure] in this population, but future studies are needed to determine if NAFLD in fact lies in the casual pathway for the development of clinical HF.”

The investigators reported multiple supporting sources, including the National Institutes of Health, American Association for the Study of Liver Disease Foundation, and the American Heart Association. Dr. Lewis reported receiving grants from Novo Nordisk.

Researchers found an association between nonalcoholic fatty liver disease (NAFLD) and myocardial dysfunction and remodeling, according to a new study published in Hepatology.

“Both NAFLD and heart failure (particularly heart failure with preserved ejection fraction) are obesity-related conditions that have reached epidemic proportions. We know from epidemiologic studies that persons with NAFLD are more likely to die from cardiovascular disease than from liver-related death. This risk seems to be proportional to the amount of fat in the liver and is independent of the presence of nonalcoholic steatohepatitis (NASH). There have been numerous studies that have focused on the relationship between NAFLD and coronary artery disease, but very little work has been done to determine relationships with heart failure,” Dr. Lisa B. VanWagner of Northwestern University in Chicago noted. She continued, “There are several well-established major risk factors for the development of clinical heart failure, including coronary artery disease, diabetes, and hypertension, all of which are also closely associated with NAFLD. However, whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction that may lead to the development of clinical heart failure is unknown.”

Courtesy of Wikimedia /

NAFLD and heart failure are both associated with obesity. Likewise, there is evidence that NAFLD may also be related to endothelial dysfunction, coronary plaques, coronary artery calcifications, as well as being an independent risk factor for cardiovascular disease.

Dr. VanWagner and her colleagues conducted a cross-sectional study of 2,713 patients from the CARDIA (Coronary Artery Risk Development in Young Adults) study to understand any associations between NAFLD and abnormalities in left ventricular (LV) function and structure. Study participants completed CT quantification of liver fat and echocardiography with Doppler during the 25-year follow-up to the initial study (Hepatology 2015;62:773-83 [doi:10.1002/hep.27869]). Participants were excluded from analysis if they had missing or incomplete imaging, pregnancy, a history of MI or heart failure, cirrhosis, hepatitis, or chronic liver disease risk factors, or if they weighed more than 450 pounds,

Of the 2,713 subjects included in analysis, 48% were black and 58.8% were female. NAFLD was detected in 10% (n = 271) of participants. Those with NAFLD were more likely to be white males with metabolic syndrome and who were obese and had higher CT-measured levels of visceral adipose tissue, and an increased waist circumference and waist-to-hip ratio. Insulin resistance markers such as elevated fasting glucose, elevated C-reactive protein, and hypertriglyceridemia were more common in the participants with NAFLD.

Study participants with NAFLD had signs of myocardial remodeling such as more left ventricular wall thickness, LV end-diastolic volume, left aortic volume index, and LV mass index. Likewise, NAFLD was associated with more circumferential strain and global longitudinal strain but no differences in ejection fraction.

Subclinical systolic dysfunction (P less than .001 for the trend), subclinical diastolic dysfunction with impaired left ventricular relaxation (34.6% vs. 23.6%; P less than .0001), and elevated LV filling pressures (33.3% vs. 23.7%; P less than .001) was more common in NAFLD participants, compared with non-NAFLD subjects.

After researchers adjusted for health behaviors and demographic factors, evidence of NAFLD was associated with worse GLS (P less than .0001). Finally, NAFLD was associated with subclinical cardiac remodeling and dysfunction even after adjustment for body mass index and heart failure risk factors (P less than .01).

Dr. VanWagner summarized, “NAFLD may not necessarily be a ‘benign condition’ as previously thought. In our study, we determined liver fat by CT scan, which admittedly detects fat at a higher level (typically greater than 30%) than for example on MRI, which can detect fat as low as 5%. A fatty liver detected on CT or even on [ultrasound], which has similar sensitivity as CT for detecting liver fat should prompt evaluation for additional cardiovascular risk factors and treatment of identified abnormalities to reduce [atherosclerotic cardiovascular disease] and [heart failure] risk. Currently, our study only shows associations between liver fat and subclinical changes in the myocardium and causality cannot be determined. [On the basis] of our data, we cannot recommend screening for HF [heart failure] in this population, but future studies are needed to determine if NAFLD in fact lies in the casual pathway for the development of clinical HF.”

The investigators reported multiple supporting sources, including the National Institutes of Health, American Association for the Study of Liver Disease Foundation, and the American Heart Association. Dr. Lewis reported receiving grants from Novo Nordisk.

Researchers found an association between nonalcoholic fatty liver disease (NAFLD) and myocardial dysfunction and remodeling, according to a new study published in Hepatology.

“Both NAFLD and heart failure (particularly heart failure with preserved ejection fraction) are obesity-related conditions that have reached epidemic proportions. We know from epidemiologic studies that persons with NAFLD are more likely to die from cardiovascular disease than from liver-related death. This risk seems to be proportional to the amount of fat in the liver and is independent of the presence of nonalcoholic steatohepatitis (NASH). There have been numerous studies that have focused on the relationship between NAFLD and coronary artery disease, but very little work has been done to determine relationships with heart failure,” Dr. Lisa B. VanWagner of Northwestern University in Chicago noted. She continued, “There are several well-established major risk factors for the development of clinical heart failure, including coronary artery disease, diabetes, and hypertension, all of which are also closely associated with NAFLD. However, whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction that may lead to the development of clinical heart failure is unknown.”

Courtesy of Wikimedia /

NAFLD and heart failure are both associated with obesity. Likewise, there is evidence that NAFLD may also be related to endothelial dysfunction, coronary plaques, coronary artery calcifications, as well as being an independent risk factor for cardiovascular disease.

Dr. VanWagner and her colleagues conducted a cross-sectional study of 2,713 patients from the CARDIA (Coronary Artery Risk Development in Young Adults) study to understand any associations between NAFLD and abnormalities in left ventricular (LV) function and structure. Study participants completed CT quantification of liver fat and echocardiography with Doppler during the 25-year follow-up to the initial study (Hepatology 2015;62:773-83 [doi:10.1002/hep.27869]). Participants were excluded from analysis if they had missing or incomplete imaging, pregnancy, a history of MI or heart failure, cirrhosis, hepatitis, or chronic liver disease risk factors, or if they weighed more than 450 pounds,

Of the 2,713 subjects included in analysis, 48% were black and 58.8% were female. NAFLD was detected in 10% (n = 271) of participants. Those with NAFLD were more likely to be white males with metabolic syndrome and who were obese and had higher CT-measured levels of visceral adipose tissue, and an increased waist circumference and waist-to-hip ratio. Insulin resistance markers such as elevated fasting glucose, elevated C-reactive protein, and hypertriglyceridemia were more common in the participants with NAFLD.

Study participants with NAFLD had signs of myocardial remodeling such as more left ventricular wall thickness, LV end-diastolic volume, left aortic volume index, and LV mass index. Likewise, NAFLD was associated with more circumferential strain and global longitudinal strain but no differences in ejection fraction.

Subclinical systolic dysfunction (P less than .001 for the trend), subclinical diastolic dysfunction with impaired left ventricular relaxation (34.6% vs. 23.6%; P less than .0001), and elevated LV filling pressures (33.3% vs. 23.7%; P less than .001) was more common in NAFLD participants, compared with non-NAFLD subjects.

After researchers adjusted for health behaviors and demographic factors, evidence of NAFLD was associated with worse GLS (P less than .0001). Finally, NAFLD was associated with subclinical cardiac remodeling and dysfunction even after adjustment for body mass index and heart failure risk factors (P less than .01).

Dr. VanWagner summarized, “NAFLD may not necessarily be a ‘benign condition’ as previously thought. In our study, we determined liver fat by CT scan, which admittedly detects fat at a higher level (typically greater than 30%) than for example on MRI, which can detect fat as low as 5%. A fatty liver detected on CT or even on [ultrasound], which has similar sensitivity as CT for detecting liver fat should prompt evaluation for additional cardiovascular risk factors and treatment of identified abnormalities to reduce [atherosclerotic cardiovascular disease] and [heart failure] risk. Currently, our study only shows associations between liver fat and subclinical changes in the myocardium and causality cannot be determined. [On the basis] of our data, we cannot recommend screening for HF [heart failure] in this population, but future studies are needed to determine if NAFLD in fact lies in the casual pathway for the development of clinical HF.”

The investigators reported multiple supporting sources, including the National Institutes of Health, American Association for the Study of Liver Disease Foundation, and the American Heart Association. Dr. Lewis reported receiving grants from Novo Nordisk.

LONDON – Neither the GLP-1 receptor agonist lixisenatide nor the DPP-4 inhibitor sitagliptin significantly increased the risk of heart failure or associated hospitalizations in patients with type 2 diabetes, according to data from two large cardiovascular safety trials.

Further analysis from ELIXA (Evaluation of Lixisenatide [Lyxumia] in Acute Coronary Syndrome) showed that the hazard ratios for several secondary heart failure endpoints were 1.00 or below. Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure than in those who did not, there was there was no difference between treatment with the GLP-1 (glucagon-like peptide 1) agonist or placebo.

The findings add to those already presented in June at the annual scientific sessions of the American Diabetes Association from the 6,068-patient trial, which enrolled patients with type 2 diabetes who had experienced an acute coronary syndrome within the past 6 months.

Other reassuring data on the safety of newer diabetes medicines came from an updated analysis of TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin [Januvia]). The time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms, and there were no differences between the treatments in terms of hospitalization for heart failure or cardiovascular death or hospitalization for heart failure or all-cause death with the DPP-4 (dipeptyl peptidase 4) inhibitor. TECOS enrolled nearly 15,000 patients with type 2 diabetes and concurrent cardiovascular disease who were aged 50 years or older and the primary findings have been published (N Engl J Med. 2015 July 15;373:232-42).

These trials provide accumulating evidence that there is no heart failure risk with these particular diabetes medications, Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm, commented in an interview at the annual congress of the European Society of Cardiology. Dr. Rydén added that the trial results everyone is waiting to hear about concern the cardiovascular safety of the selective sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance).

Advance information issued by manufacturer Boehringer-Ingelheim suggests that this drug actually may lower cardiovascular risk in patients at high risk for cardiovascular events, Dr. Rydén observed. “Now, if that is true, it is the only modern glucose-lowering drug to have shown such a capacity.” Results of the EMPA-REG OUTCOME study will be presented in September at the annual meeting of the European Association for the Study of Diabetes in Stockholm.

LONDON – Neither the GLP-1 receptor agonist lixisenatide nor the DPP-4 inhibitor sitagliptin significantly increased the risk of heart failure or associated hospitalizations in patients with type 2 diabetes, according to data from two large cardiovascular safety trials.

Further analysis from ELIXA (Evaluation of Lixisenatide [Lyxumia] in Acute Coronary Syndrome) showed that the hazard ratios for several secondary heart failure endpoints were 1.00 or below. Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure than in those who did not, there was there was no difference between treatment with the GLP-1 (glucagon-like peptide 1) agonist or placebo.

The findings add to those already presented in June at the annual scientific sessions of the American Diabetes Association from the 6,068-patient trial, which enrolled patients with type 2 diabetes who had experienced an acute coronary syndrome within the past 6 months.

Other reassuring data on the safety of newer diabetes medicines came from an updated analysis of TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin [Januvia]). The time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms, and there were no differences between the treatments in terms of hospitalization for heart failure or cardiovascular death or hospitalization for heart failure or all-cause death with the DPP-4 (dipeptyl peptidase 4) inhibitor. TECOS enrolled nearly 15,000 patients with type 2 diabetes and concurrent cardiovascular disease who were aged 50 years or older and the primary findings have been published (N Engl J Med. 2015 July 15;373:232-42).

These trials provide accumulating evidence that there is no heart failure risk with these particular diabetes medications, Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm, commented in an interview at the annual congress of the European Society of Cardiology. Dr. Rydén added that the trial results everyone is waiting to hear about concern the cardiovascular safety of the selective sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance).

Advance information issued by manufacturer Boehringer-Ingelheim suggests that this drug actually may lower cardiovascular risk in patients at high risk for cardiovascular events, Dr. Rydén observed. “Now, if that is true, it is the only modern glucose-lowering drug to have shown such a capacity.” Results of the EMPA-REG OUTCOME study will be presented in September at the annual meeting of the European Association for the Study of Diabetes in Stockholm.

LONDON – Neither the GLP-1 receptor agonist lixisenatide nor the DPP-4 inhibitor sitagliptin significantly increased the risk of heart failure or associated hospitalizations in patients with type 2 diabetes, according to data from two large cardiovascular safety trials.

Further analysis from ELIXA (Evaluation of Lixisenatide [Lyxumia] in Acute Coronary Syndrome) showed that the hazard ratios for several secondary heart failure endpoints were 1.00 or below. Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure than in those who did not, there was there was no difference between treatment with the GLP-1 (glucagon-like peptide 1) agonist or placebo.

The findings add to those already presented in June at the annual scientific sessions of the American Diabetes Association from the 6,068-patient trial, which enrolled patients with type 2 diabetes who had experienced an acute coronary syndrome within the past 6 months.

Other reassuring data on the safety of newer diabetes medicines came from an updated analysis of TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin [Januvia]). The time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms, and there were no differences between the treatments in terms of hospitalization for heart failure or cardiovascular death or hospitalization for heart failure or all-cause death with the DPP-4 (dipeptyl peptidase 4) inhibitor. TECOS enrolled nearly 15,000 patients with type 2 diabetes and concurrent cardiovascular disease who were aged 50 years or older and the primary findings have been published (N Engl J Med. 2015 July 15;373:232-42).

These trials provide accumulating evidence that there is no heart failure risk with these particular diabetes medications, Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm, commented in an interview at the annual congress of the European Society of Cardiology. Dr. Rydén added that the trial results everyone is waiting to hear about concern the cardiovascular safety of the selective sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance).

Advance information issued by manufacturer Boehringer-Ingelheim suggests that this drug actually may lower cardiovascular risk in patients at high risk for cardiovascular events, Dr. Rydén observed. “Now, if that is true, it is the only modern glucose-lowering drug to have shown such a capacity.” Results of the EMPA-REG OUTCOME study will be presented in September at the annual meeting of the European Association for the Study of Diabetes in Stockholm.

LONDON – Drinking more than three cups of coffee daily increased the risk of a cardiovascular event by 50% in a study of more than 1,000 adults aged 45 years or younger with mild, untreated hypertension.

The results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) also showed that even moderate coffee intake, defined as between one and three cups per day, could up the risk of a cardiovascular event when compared with non–coffee drinkers.

“Don’t drink a lot of coffee; reduce your intake,” Dr. Lucio Mos advised young to middle-aged hypertensive adults in a video interview at the annual congress of the European Society of Cardiology.

Heavy coffee drinking is a strong predictor of increasing blood pressure and rising blood glucose, said Dr. Mos of Hospital San Daniele del Friuli in Udine, Italy. In this study, which had a mean of 12.5 years of follow-up, there was a linear relationship between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake.

LONDON – Drinking more than three cups of coffee daily increased the risk of a cardiovascular event by 50% in a study of more than 1,000 adults aged 45 years or younger with mild, untreated hypertension.

The results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) also showed that even moderate coffee intake, defined as between one and three cups per day, could up the risk of a cardiovascular event when compared with non–coffee drinkers.

“Don’t drink a lot of coffee; reduce your intake,” Dr. Lucio Mos advised young to middle-aged hypertensive adults in a video interview at the annual congress of the European Society of Cardiology.

Heavy coffee drinking is a strong predictor of increasing blood pressure and rising blood glucose, said Dr. Mos of Hospital San Daniele del Friuli in Udine, Italy. In this study, which had a mean of 12.5 years of follow-up, there was a linear relationship between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake.

LONDON – Drinking more than three cups of coffee daily increased the risk of a cardiovascular event by 50% in a study of more than 1,000 adults aged 45 years or younger with mild, untreated hypertension.

The results of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) also showed that even moderate coffee intake, defined as between one and three cups per day, could up the risk of a cardiovascular event when compared with non–coffee drinkers.

“Don’t drink a lot of coffee; reduce your intake,” Dr. Lucio Mos advised young to middle-aged hypertensive adults in a video interview at the annual congress of the European Society of Cardiology.

Heavy coffee drinking is a strong predictor of increasing blood pressure and rising blood glucose, said Dr. Mos of Hospital San Daniele del Friuli in Udine, Italy. In this study, which had a mean of 12.5 years of follow-up, there was a linear relationship between coffee intake and cardiovascular events such as heart attacks, with the risk increasing with higher coffee intake.

LONDON – A regular midday nap is associated with clinically meaningful reductions in blood pressure in hypertensive patients, according to a prospective observational study presented at the annual congress of the European Society of Cardiology.

The midday nappers in the 386-patient study averaged 5 mm Hg lower daytime and 8 mm Hg lower nighttime systolic blood pressure, compared with non-nappers, Dr. Manolis Kallistratos said in a video interview.

Sleep during nap time was associated with bigger blood pressure reductions than simply resting. Sawing logs for 60 minutes or more brought the most benefits, according to Dr. Kallistratos, head of the hypertension division at Asklepieion Voula General Hospital in Athens.

Nappers also had significantly less arterial stiffness as reflected in a lower pulse wave velocity, as well as a smaller average left atrial diameter indicative of less structural heart damage, the cardiologist noted.

[email protected]

LONDON – A regular midday nap is associated with clinically meaningful reductions in blood pressure in hypertensive patients, according to a prospective observational study presented at the annual congress of the European Society of Cardiology.

The midday nappers in the 386-patient study averaged 5 mm Hg lower daytime and 8 mm Hg lower nighttime systolic blood pressure, compared with non-nappers, Dr. Manolis Kallistratos said in a video interview.

Sleep during nap time was associated with bigger blood pressure reductions than simply resting. Sawing logs for 60 minutes or more brought the most benefits, according to Dr. Kallistratos, head of the hypertension division at Asklepieion Voula General Hospital in Athens.

Nappers also had significantly less arterial stiffness as reflected in a lower pulse wave velocity, as well as a smaller average left atrial diameter indicative of less structural heart damage, the cardiologist noted.

[email protected]

LONDON – A regular midday nap is associated with clinically meaningful reductions in blood pressure in hypertensive patients, according to a prospective observational study presented at the annual congress of the European Society of Cardiology.

The midday nappers in the 386-patient study averaged 5 mm Hg lower daytime and 8 mm Hg lower nighttime systolic blood pressure, compared with non-nappers, Dr. Manolis Kallistratos said in a video interview.

Sleep during nap time was associated with bigger blood pressure reductions than simply resting. Sawing logs for 60 minutes or more brought the most benefits, according to Dr. Kallistratos, head of the hypertension division at Asklepieion Voula General Hospital in Athens.

Nappers also had significantly less arterial stiffness as reflected in a lower pulse wave velocity, as well as a smaller average left atrial diameter indicative of less structural heart damage, the cardiologist noted.

[email protected]

The FDA has approved Synjardy (empagliflozin/metformin hydrochloride) to help control blood glucose in adults with type 2 diabetes, the drug’s manufacturers announced Aug. 27.

Synjardy, which contains the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, is indicated as an adjunct to diet and exercise in patients unable to achieve sufficient glycemic control on empagliflozin or metformin, or in patients already being treated with both drugs.

When combined, empagliflozin and metformin offer “complementary mechanisms of action” to help control blood glucose, according to a statement by the manufacturers, Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Co.

“Empagliflozin ... removes excess glucose through the urine by blocking glucose reabsorption in the kidney,” the statement said. Metformin, frequently prescribed as a first-line treatment, lowers glucose production by the liver and its absorption in the intestine.

Synjardy contains a boxed warning for lactic acidosis and should not be used by adults with severe kidney problems or allergies to empagliflozin, metformin, or any other ingredients in the medication. It also should not be used to treat type 1 diabetes or diabetic ketoacidosis.

Common side effects from Synjardy include runny nose, sore throat, urinary tract infections, female genital infections, diarrhea, headache, nausea, and vomiting.

Visit the Boehringer Ingelheim website for full prescribing information. Adverse effects may be reported to the FDA at http://www.fda.gov/medwatch.com.

[email protected]

The FDA has approved Synjardy (empagliflozin/metformin hydrochloride) to help control blood glucose in adults with type 2 diabetes, the drug’s manufacturers announced Aug. 27.

Synjardy, which contains the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, is indicated as an adjunct to diet and exercise in patients unable to achieve sufficient glycemic control on empagliflozin or metformin, or in patients already being treated with both drugs.

When combined, empagliflozin and metformin offer “complementary mechanisms of action” to help control blood glucose, according to a statement by the manufacturers, Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Co.

“Empagliflozin ... removes excess glucose through the urine by blocking glucose reabsorption in the kidney,” the statement said. Metformin, frequently prescribed as a first-line treatment, lowers glucose production by the liver and its absorption in the intestine.

Synjardy contains a boxed warning for lactic acidosis and should not be used by adults with severe kidney problems or allergies to empagliflozin, metformin, or any other ingredients in the medication. It also should not be used to treat type 1 diabetes or diabetic ketoacidosis.

Common side effects from Synjardy include runny nose, sore throat, urinary tract infections, female genital infections, diarrhea, headache, nausea, and vomiting.

Visit the Boehringer Ingelheim website for full prescribing information. Adverse effects may be reported to the FDA at http://www.fda.gov/medwatch.com.

[email protected]

The FDA has approved Synjardy (empagliflozin/metformin hydrochloride) to help control blood glucose in adults with type 2 diabetes, the drug’s manufacturers announced Aug. 27.

Synjardy, which contains the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, is indicated as an adjunct to diet and exercise in patients unable to achieve sufficient glycemic control on empagliflozin or metformin, or in patients already being treated with both drugs.

When combined, empagliflozin and metformin offer “complementary mechanisms of action” to help control blood glucose, according to a statement by the manufacturers, Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Co.

“Empagliflozin ... removes excess glucose through the urine by blocking glucose reabsorption in the kidney,” the statement said. Metformin, frequently prescribed as a first-line treatment, lowers glucose production by the liver and its absorption in the intestine.

Synjardy contains a boxed warning for lactic acidosis and should not be used by adults with severe kidney problems or allergies to empagliflozin, metformin, or any other ingredients in the medication. It also should not be used to treat type 1 diabetes or diabetic ketoacidosis.

Common side effects from Synjardy include runny nose, sore throat, urinary tract infections, female genital infections, diarrhea, headache, nausea, and vomiting.

Visit the Boehringer Ingelheim website for full prescribing information. Adverse effects may be reported to the FDA at http://www.fda.gov/medwatch.com.

[email protected]

VANCOUVER – When diabetic foot ulcer healing has stalled despite 4 weeks of optimal standard therapy, it’s time to seriously consider resorting to advanced therapies, according to Dr. Afsaneh Alavi of the University of Toronto.

Advanced therapy options include negative pressure wound therapy, hyperbaric oxygen, artificial skin substitutes, growth factors, collagen-based dressings, and electromagnetic therapy.

“You hear a lot about advanced therapy for diabetic foot ulcers. It’s expensive. But it can be cost-effective if used properly. It’s our duty to see who is the best person to receive this therapy,” she said at the World Congress of Dermatology.

A useful rule of thumb, the dermatologist added, is that if a healable ulcer isn’t 50% smaller at week 4 despite optimal care, it’s time to consider moving on to advanced therapies. As was shown in a well-conducted, 203-patient, randomized, prospective controlled clinical trial, a wound that hasn’t met that threshold is unlikely to be healed at 12 weeks (Diabetes Care. 2003 Jun;26(6):1879-82).

Two caveats: advanced therapy is appropriate only for healable diabetic foot ulcers, meaning those in patients with adequate peripheral circulation as defined by measurements of transcutaneous oxygen pressure, toe pressure brachial index, and Doppler studies.

“Eighty percent of diabetic patients have noncompressible arteries and therefore the ankle brachial index is not an accurate test to evaluate their circulation,” according to Dr. Avali.

The other caveat regarding advanced therapy is that appropriate candidates should have a wound edge that’s sharp, not migrating, she continued.

The 4-week cutoff for seeing substantial progress in wound healing with standard therapy before turning to advanced therapies is based in part upon an influential study of 2,517 patients with diabetic neuropathic foot ulcers who received one of three advanced biological therapies. On average, patients started advanced biological therapy within 28 days following their first visit to a specialized wound clinic. Prolonged time to initiation of advanced treatment was associated with significantly longer time to healing (Arch Dermatol. 2010 Aug;146(8):857-62).

While thinking about local wound care in a patient with a diabetic foot ulcer, Dr. Avali said it’s also important to take a step back and make sure hypertension and other conventional cardiovascular risk factors are well controlled and also to take a close look at the HbA1c. In a study of 183 patients with diabetic wounds treated at a specialized academic wound center, for every 1.0% increase in HbA1c above the mean level of 8.0%, the wound-area healing rate was reduced by 0.028 cm² per day. The implication is that HbA1c may be a key biomarker that’s useful in predicting wound-healing rate in patients with diabetic ulcers (J. Invest Dermatol. 2011 Oct;131(10):2121-7).

She reported serving as a consultant to Acelity and Smith & Nephew.

[email protected]

VANCOUVER – When diabetic foot ulcer healing has stalled despite 4 weeks of optimal standard therapy, it’s time to seriously consider resorting to advanced therapies, according to Dr. Afsaneh Alavi of the University of Toronto.

Advanced therapy options include negative pressure wound therapy, hyperbaric oxygen, artificial skin substitutes, growth factors, collagen-based dressings, and electromagnetic therapy.

“You hear a lot about advanced therapy for diabetic foot ulcers. It’s expensive. But it can be cost-effective if used properly. It’s our duty to see who is the best person to receive this therapy,” she said at the World Congress of Dermatology.

A useful rule of thumb, the dermatologist added, is that if a healable ulcer isn’t 50% smaller at week 4 despite optimal care, it’s time to consider moving on to advanced therapies. As was shown in a well-conducted, 203-patient, randomized, prospective controlled clinical trial, a wound that hasn’t met that threshold is unlikely to be healed at 12 weeks (Diabetes Care. 2003 Jun;26(6):1879-82).

Two caveats: advanced therapy is appropriate only for healable diabetic foot ulcers, meaning those in patients with adequate peripheral circulation as defined by measurements of transcutaneous oxygen pressure, toe pressure brachial index, and Doppler studies.

“Eighty percent of diabetic patients have noncompressible arteries and therefore the ankle brachial index is not an accurate test to evaluate their circulation,” according to Dr. Avali.

The other caveat regarding advanced therapy is that appropriate candidates should have a wound edge that’s sharp, not migrating, she continued.

The 4-week cutoff for seeing substantial progress in wound healing with standard therapy before turning to advanced therapies is based in part upon an influential study of 2,517 patients with diabetic neuropathic foot ulcers who received one of three advanced biological therapies. On average, patients started advanced biological therapy within 28 days following their first visit to a specialized wound clinic. Prolonged time to initiation of advanced treatment was associated with significantly longer time to healing (Arch Dermatol. 2010 Aug;146(8):857-62).

While thinking about local wound care in a patient with a diabetic foot ulcer, Dr. Avali said it’s also important to take a step back and make sure hypertension and other conventional cardiovascular risk factors are well controlled and also to take a close look at the HbA1c. In a study of 183 patients with diabetic wounds treated at a specialized academic wound center, for every 1.0% increase in HbA1c above the mean level of 8.0%, the wound-area healing rate was reduced by 0.028 cm² per day. The implication is that HbA1c may be a key biomarker that’s useful in predicting wound-healing rate in patients with diabetic ulcers (J. Invest Dermatol. 2011 Oct;131(10):2121-7).

She reported serving as a consultant to Acelity and Smith & Nephew.

[email protected]

VANCOUVER – When diabetic foot ulcer healing has stalled despite 4 weeks of optimal standard therapy, it’s time to seriously consider resorting to advanced therapies, according to Dr. Afsaneh Alavi of the University of Toronto.

Advanced therapy options include negative pressure wound therapy, hyperbaric oxygen, artificial skin substitutes, growth factors, collagen-based dressings, and electromagnetic therapy.

“You hear a lot about advanced therapy for diabetic foot ulcers. It’s expensive. But it can be cost-effective if used properly. It’s our duty to see who is the best person to receive this therapy,” she said at the World Congress of Dermatology.

A useful rule of thumb, the dermatologist added, is that if a healable ulcer isn’t 50% smaller at week 4 despite optimal care, it’s time to consider moving on to advanced therapies. As was shown in a well-conducted, 203-patient, randomized, prospective controlled clinical trial, a wound that hasn’t met that threshold is unlikely to be healed at 12 weeks (Diabetes Care. 2003 Jun;26(6):1879-82).

Two caveats: advanced therapy is appropriate only for healable diabetic foot ulcers, meaning those in patients with adequate peripheral circulation as defined by measurements of transcutaneous oxygen pressure, toe pressure brachial index, and Doppler studies.

“Eighty percent of diabetic patients have noncompressible arteries and therefore the ankle brachial index is not an accurate test to evaluate their circulation,” according to Dr. Avali.

The other caveat regarding advanced therapy is that appropriate candidates should have a wound edge that’s sharp, not migrating, she continued.

The 4-week cutoff for seeing substantial progress in wound healing with standard therapy before turning to advanced therapies is based in part upon an influential study of 2,517 patients with diabetic neuropathic foot ulcers who received one of three advanced biological therapies. On average, patients started advanced biological therapy within 28 days following their first visit to a specialized wound clinic. Prolonged time to initiation of advanced treatment was associated with significantly longer time to healing (Arch Dermatol. 2010 Aug;146(8):857-62).

While thinking about local wound care in a patient with a diabetic foot ulcer, Dr. Avali said it’s also important to take a step back and make sure hypertension and other conventional cardiovascular risk factors are well controlled and also to take a close look at the HbA1c. In a study of 183 patients with diabetic wounds treated at a specialized academic wound center, for every 1.0% increase in HbA1c above the mean level of 8.0%, the wound-area healing rate was reduced by 0.028 cm² per day. The implication is that HbA1c may be a key biomarker that’s useful in predicting wound-healing rate in patients with diabetic ulcers (J. Invest Dermatol. 2011 Oct;131(10):2121-7).

She reported serving as a consultant to Acelity and Smith & Nephew.

[email protected]

VANCOUVER – Offloading of plantar pressures is the key component of successful management of plantar diabetic foot ulcers, Dr. Afsaneh Alavi asserted at the World Congress of Dermatology.

“Debridement to remove the callous is the most important part of local wound care, but debridement without offloading afterwards will rebuild callous,” explained Dr. Alavi, a University of Toronto dermatologist.

Many options exist in terms of offloading devices. The total contact cast is recognized as the gold standard. It reduces pressures by 90%. Yet a national survey of more than 900 foot clinics found that less than 2% of centers utilized total contact casts for the majority of their patients with plantar diabetic foot ulcers. Only 15% of centers utilized another highly effective option, the removable cast walker, in the majority of patients (Diabetes Care. 2008 Nov; 31(11): 2118–2119). Cost is believed to be a major issue. Other options include custom orthotic inserts and forefoot and heel relief shoes.

The diabetic foot ulcer recurrence rate is extremely high: up to 83% within the first year.

“Counsel patients to use therapeutic shoes and insoles, engage in self-inspection, and get professional foot care. Shoes should be worn at all times, even in the house. Patients typically spend 30%-40% of their time at home,” Dr. Alavi continued.

The pathophysiology of diabetic foot ulcers is a vicious circle of immunopathy, neuropathy, and angiopathy. Callous formation secondary to sensory and motor neuropathy leads to subcutaneous bleeding, ulcer formation, and deeper infection, sometimes with life- or limb-threatening osteomyelitis.

“Detection of this chain of events at the stage of callous formation would make a huge difference,” according to the dermatologist. She pointed out that “Most of our health care system is focused more on management than prevention. We spend more on amputations due to diabetic foot ulcers than for prevention.”

Although many methods of callous removal are available, including autolytic therapy with hydrogels, whirlpools, and wet-to-dry dressings, Dr. Alavi said the best method is sharp surgical debridement. She highlighted a retrospective 12-week study of topical wound treatments in 310 diabetic foot ulcers and 366 chronic venous leg ulcers which found that venous leg ulcers showed a 34% greater median wound surface area reduction following office visits with surgical debridement compared with no surgical debridement. Serial surgical debridement in patients with diabetic foot ulcers was also associated with a 2.35-fold increased likelihood of wound closure (Wound Repair Regen. 2009 May-June;17(3):306-11).

She noted that it has been estimated that by 2030, at least 10% of the world’s adult population -- some 550 million people -- will have diabetes. And a diabetic individual’s lifetime risk of developing diabetic foot ulcers is up to 25%. The 5-year mortality rate following amputation related to a diabetic foot ulcer is nearly 50%, about the same as following diagnosis of colon cancer.

Dr. Alavi reported serving as a consultant to Acelity and Smith & Nephew.

[email protected]

VANCOUVER – Offloading of plantar pressures is the key component of successful management of plantar diabetic foot ulcers, Dr. Afsaneh Alavi asserted at the World Congress of Dermatology.

“Debridement to remove the callous is the most important part of local wound care, but debridement without offloading afterwards will rebuild callous,” explained Dr. Alavi, a University of Toronto dermatologist.

Many options exist in terms of offloading devices. The total contact cast is recognized as the gold standard. It reduces pressures by 90%. Yet a national survey of more than 900 foot clinics found that less than 2% of centers utilized total contact casts for the majority of their patients with plantar diabetic foot ulcers. Only 15% of centers utilized another highly effective option, the removable cast walker, in the majority of patients (Diabetes Care. 2008 Nov; 31(11): 2118–2119). Cost is believed to be a major issue. Other options include custom orthotic inserts and forefoot and heel relief shoes.

The diabetic foot ulcer recurrence rate is extremely high: up to 83% within the first year.

“Counsel patients to use therapeutic shoes and insoles, engage in self-inspection, and get professional foot care. Shoes should be worn at all times, even in the house. Patients typically spend 30%-40% of their time at home,” Dr. Alavi continued.

The pathophysiology of diabetic foot ulcers is a vicious circle of immunopathy, neuropathy, and angiopathy. Callous formation secondary to sensory and motor neuropathy leads to subcutaneous bleeding, ulcer formation, and deeper infection, sometimes with life- or limb-threatening osteomyelitis.

“Detection of this chain of events at the stage of callous formation would make a huge difference,” according to the dermatologist. She pointed out that “Most of our health care system is focused more on management than prevention. We spend more on amputations due to diabetic foot ulcers than for prevention.”

Although many methods of callous removal are available, including autolytic therapy with hydrogels, whirlpools, and wet-to-dry dressings, Dr. Alavi said the best method is sharp surgical debridement. She highlighted a retrospective 12-week study of topical wound treatments in 310 diabetic foot ulcers and 366 chronic venous leg ulcers which found that venous leg ulcers showed a 34% greater median wound surface area reduction following office visits with surgical debridement compared with no surgical debridement. Serial surgical debridement in patients with diabetic foot ulcers was also associated with a 2.35-fold increased likelihood of wound closure (Wound Repair Regen. 2009 May-June;17(3):306-11).

She noted that it has been estimated that by 2030, at least 10% of the world’s adult population -- some 550 million people -- will have diabetes. And a diabetic individual’s lifetime risk of developing diabetic foot ulcers is up to 25%. The 5-year mortality rate following amputation related to a diabetic foot ulcer is nearly 50%, about the same as following diagnosis of colon cancer.

Dr. Alavi reported serving as a consultant to Acelity and Smith & Nephew.

[email protected]

VANCOUVER – Offloading of plantar pressures is the key component of successful management of plantar diabetic foot ulcers, Dr. Afsaneh Alavi asserted at the World Congress of Dermatology.

“Debridement to remove the callous is the most important part of local wound care, but debridement without offloading afterwards will rebuild callous,” explained Dr. Alavi, a University of Toronto dermatologist.

Many options exist in terms of offloading devices. The total contact cast is recognized as the gold standard. It reduces pressures by 90%. Yet a national survey of more than 900 foot clinics found that less than 2% of centers utilized total contact casts for the majority of their patients with plantar diabetic foot ulcers. Only 15% of centers utilized another highly effective option, the removable cast walker, in the majority of patients (Diabetes Care. 2008 Nov; 31(11): 2118–2119). Cost is believed to be a major issue. Other options include custom orthotic inserts and forefoot and heel relief shoes.

The diabetic foot ulcer recurrence rate is extremely high: up to 83% within the first year.

“Counsel patients to use therapeutic shoes and insoles, engage in self-inspection, and get professional foot care. Shoes should be worn at all times, even in the house. Patients typically spend 30%-40% of their time at home,” Dr. Alavi continued.

The pathophysiology of diabetic foot ulcers is a vicious circle of immunopathy, neuropathy, and angiopathy. Callous formation secondary to sensory and motor neuropathy leads to subcutaneous bleeding, ulcer formation, and deeper infection, sometimes with life- or limb-threatening osteomyelitis.

“Detection of this chain of events at the stage of callous formation would make a huge difference,” according to the dermatologist. She pointed out that “Most of our health care system is focused more on management than prevention. We spend more on amputations due to diabetic foot ulcers than for prevention.”

Although many methods of callous removal are available, including autolytic therapy with hydrogels, whirlpools, and wet-to-dry dressings, Dr. Alavi said the best method is sharp surgical debridement. She highlighted a retrospective 12-week study of topical wound treatments in 310 diabetic foot ulcers and 366 chronic venous leg ulcers which found that venous leg ulcers showed a 34% greater median wound surface area reduction following office visits with surgical debridement compared with no surgical debridement. Serial surgical debridement in patients with diabetic foot ulcers was also associated with a 2.35-fold increased likelihood of wound closure (Wound Repair Regen. 2009 May-June;17(3):306-11).

She noted that it has been estimated that by 2030, at least 10% of the world’s adult population -- some 550 million people -- will have diabetes. And a diabetic individual’s lifetime risk of developing diabetic foot ulcers is up to 25%. The 5-year mortality rate following amputation related to a diabetic foot ulcer is nearly 50%, about the same as following diagnosis of colon cancer.

Dr. Alavi reported serving as a consultant to Acelity and Smith & Nephew.

[email protected]

Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.

The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.

This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.

The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.

Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said (JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676]).

In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A_1c level; in the proportion of patients achieving HbA_1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.

Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.

Liraglutide 3 mg (Saxenda*, Novo Nordisk) was approved by the Food and Drug Administration in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m² or greater and in overweight adults with a BMI of 27 kg/m² or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Liraglutide up to 1.8 mg (Victoza) was approved by the FDA in 2010 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is recommended as second-line therapy.”

SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.

*Correction, 8/21/2015: The 3.0-mg dosage of liraglutide was incorrectly identified. The trade name is Saxenda.

Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.

The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.

This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.

The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.

Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said (JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676]).

In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A_1c level; in the proportion of patients achieving HbA_1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.

Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.

Liraglutide 3 mg (Saxenda*, Novo Nordisk) was approved by the Food and Drug Administration in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m² or greater and in overweight adults with a BMI of 27 kg/m² or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Liraglutide up to 1.8 mg (Victoza) was approved by the FDA in 2010 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is recommended as second-line therapy.”

SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.

*Correction, 8/21/2015: The 3.0-mg dosage of liraglutide was incorrectly identified. The trade name is Saxenda.

Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.

The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.

This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.

The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.

Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said (JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676]).

In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A_1c level; in the proportion of patients achieving HbA_1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.

Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.

Liraglutide 3 mg (Saxenda*, Novo Nordisk) was approved by the Food and Drug Administration in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m² or greater and in overweight adults with a BMI of 27 kg/m² or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Liraglutide up to 1.8 mg (Victoza) was approved by the FDA in 2010 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is recommended as second-line therapy.”

SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.

*Correction, 8/21/2015: The 3.0-mg dosage of liraglutide was incorrectly identified. The trade name is Saxenda.

The incidence of gestational diabetes can be reduced in high-risk women with individualized lifestyle intervention focused on diet and physical activity, new research suggests.

A randomized, controlled trial of 269 women with a history of gestational diabetes or a prepregnancy body mass index of at least 30 kg/m² showed the intervention was associated with a 36% reduction in the incidence of gestational diabetes, compared with usual care (13.9% vs. 21.6%, P = .044).

©dblight/iStockphoto.com

This was after adjustment for age, prepregnancy BMI, previous gestational diabetes status, and number of weeks’ gestation at the time of the oral glucose tolerance test, according to a paper published online July 29 in Diabetes Care.

From baseline to the second trimester oral glucose tolerance test – when the gestational diabetes diagnosis was made – women in the intervention group gained slightly less weight than did those in the control group (2.5 kg vs. 3.1 kg).

The intervention was associated with a significantly greater reduction in fasting plasma glucose concentration from baseline to third trimester, but there were no impacts on other pregnancy or birth outcomes such as preeclampsia, birth weight, or gestational age at birth.

“This is, to our knowledge, the first randomized controlled lifestyle intervention trial that has succeeded in reducing the overall incidence of GDM [gestational diabetes mellitus] among high-risk pregnant women,” wrote Dr. Saila B. Koivusalo of University of Helsinki and Helsinki University Hospital.

Women in the intervention arm were counseled by study nurses and dietitians three times during their pregnancy. Counseling was tailored to their risk and stage of pregnancy. The women continued their normal antenatal clinic visits (Diabetes Care 2015, Jul 29 [doi:10.2337/dc15-0511]).

Women with a prepregnancy BMI of 30 kg/m² were advised not to gain any weight during the first two trimesters, and were given dietary counseling to optimize their consumption of healthy foods and reduce their intake of sugar-rich foods.

They also were counseled to aim for a minimum of 150 minutes of moderate-intensity physical activity per week, as part of an active lifestyle.

Participants in the control group received leaflets on diet and physical activity, which were usually provide by the local antenatal clinics.

Women who undertook the intervention showed significantly greater improvements in their dietary index scores than did those in the control arm, and they increased their median weekly physical activity by 15 minutes while the control group showed no increases.

However, there was no significant difference between the two groups in the number of women who met the physical activity goal of 150 minutes/week in their second trimester (26% of intervention group vs. 23% of the control group).

“Despite the fact that only a small proportion of the women in the intervention group reached the physical activity goals, and the difference in weight gain was modest between the groups, it is obvious that the individual changes in lifestyle do not need to be large but together they have a beneficial effect on the reduction of the incidence of GDM,” the authors wrote.

They pointed out that as the women participating in the trial were all known to be at high risk for gestational diabetes, even the women in the control group would have received advice on weight control as part of their antenatal care and were therefore more of a “mini-intervention” group than pure control.

“We believe that in an unselected high-risk population the impact of this kind of lifestyle intervention could be even more pronounced.”

The Ahokas Foundation, Finnish Foundation for Cardiovascular Disease, Special State Subsidy for Health Science Research of Helsinki University Central Hospital, Samfundet Folkhälsan, Finnish Diabetes Research Foundation, State Provincial Office of Southern Finland, and Social Insurance Institution of Finland funded the study. There were no conflicts of interest declared.

The incidence of gestational diabetes can be reduced in high-risk women with individualized lifestyle intervention focused on diet and physical activity, new research suggests.

A randomized, controlled trial of 269 women with a history of gestational diabetes or a prepregnancy body mass index of at least 30 kg/m² showed the intervention was associated with a 36% reduction in the incidence of gestational diabetes, compared with usual care (13.9% vs. 21.6%, P = .044).

©dblight/iStockphoto.com

This was after adjustment for age, prepregnancy BMI, previous gestational diabetes status, and number of weeks’ gestation at the time of the oral glucose tolerance test, according to a paper published online July 29 in Diabetes Care.

From baseline to the second trimester oral glucose tolerance test – when the gestational diabetes diagnosis was made – women in the intervention group gained slightly less weight than did those in the control group (2.5 kg vs. 3.1 kg).

The intervention was associated with a significantly greater reduction in fasting plasma glucose concentration from baseline to third trimester, but there were no impacts on other pregnancy or birth outcomes such as preeclampsia, birth weight, or gestational age at birth.

“This is, to our knowledge, the first randomized controlled lifestyle intervention trial that has succeeded in reducing the overall incidence of GDM [gestational diabetes mellitus] among high-risk pregnant women,” wrote Dr. Saila B. Koivusalo of University of Helsinki and Helsinki University Hospital.

Women in the intervention arm were counseled by study nurses and dietitians three times during their pregnancy. Counseling was tailored to their risk and stage of pregnancy. The women continued their normal antenatal clinic visits (Diabetes Care 2015, Jul 29 [doi:10.2337/dc15-0511]).

Women with a prepregnancy BMI of 30 kg/m² were advised not to gain any weight during the first two trimesters, and were given dietary counseling to optimize their consumption of healthy foods and reduce their intake of sugar-rich foods.

They also were counseled to aim for a minimum of 150 minutes of moderate-intensity physical activity per week, as part of an active lifestyle.

Participants in the control group received leaflets on diet and physical activity, which were usually provide by the local antenatal clinics.

Women who undertook the intervention showed significantly greater improvements in their dietary index scores than did those in the control arm, and they increased their median weekly physical activity by 15 minutes while the control group showed no increases.

However, there was no significant difference between the two groups in the number of women who met the physical activity goal of 150 minutes/week in their second trimester (26% of intervention group vs. 23% of the control group).

“Despite the fact that only a small proportion of the women in the intervention group reached the physical activity goals, and the difference in weight gain was modest between the groups, it is obvious that the individual changes in lifestyle do not need to be large but together they have a beneficial effect on the reduction of the incidence of GDM,” the authors wrote.

They pointed out that as the women participating in the trial were all known to be at high risk for gestational diabetes, even the women in the control group would have received advice on weight control as part of their antenatal care and were therefore more of a “mini-intervention” group than pure control.

“We believe that in an unselected high-risk population the impact of this kind of lifestyle intervention could be even more pronounced.”

The Ahokas Foundation, Finnish Foundation for Cardiovascular Disease, Special State Subsidy for Health Science Research of Helsinki University Central Hospital, Samfundet Folkhälsan, Finnish Diabetes Research Foundation, State Provincial Office of Southern Finland, and Social Insurance Institution of Finland funded the study. There were no conflicts of interest declared.

The incidence of gestational diabetes can be reduced in high-risk women with individualized lifestyle intervention focused on diet and physical activity, new research suggests.

A randomized, controlled trial of 269 women with a history of gestational diabetes or a prepregnancy body mass index of at least 30 kg/m² showed the intervention was associated with a 36% reduction in the incidence of gestational diabetes, compared with usual care (13.9% vs. 21.6%, P = .044).

©dblight/iStockphoto.com

This was after adjustment for age, prepregnancy BMI, previous gestational diabetes status, and number of weeks’ gestation at the time of the oral glucose tolerance test, according to a paper published online July 29 in Diabetes Care.

From baseline to the second trimester oral glucose tolerance test – when the gestational diabetes diagnosis was made – women in the intervention group gained slightly less weight than did those in the control group (2.5 kg vs. 3.1 kg).

The intervention was associated with a significantly greater reduction in fasting plasma glucose concentration from baseline to third trimester, but there were no impacts on other pregnancy or birth outcomes such as preeclampsia, birth weight, or gestational age at birth.

“This is, to our knowledge, the first randomized controlled lifestyle intervention trial that has succeeded in reducing the overall incidence of GDM [gestational diabetes mellitus] among high-risk pregnant women,” wrote Dr. Saila B. Koivusalo of University of Helsinki and Helsinki University Hospital.

Women in the intervention arm were counseled by study nurses and dietitians three times during their pregnancy. Counseling was tailored to their risk and stage of pregnancy. The women continued their normal antenatal clinic visits (Diabetes Care 2015, Jul 29 [doi:10.2337/dc15-0511]).

Women with a prepregnancy BMI of 30 kg/m² were advised not to gain any weight during the first two trimesters, and were given dietary counseling to optimize their consumption of healthy foods and reduce their intake of sugar-rich foods.

They also were counseled to aim for a minimum of 150 minutes of moderate-intensity physical activity per week, as part of an active lifestyle.

Participants in the control group received leaflets on diet and physical activity, which were usually provide by the local antenatal clinics.

Women who undertook the intervention showed significantly greater improvements in their dietary index scores than did those in the control arm, and they increased their median weekly physical activity by 15 minutes while the control group showed no increases.

However, there was no significant difference between the two groups in the number of women who met the physical activity goal of 150 minutes/week in their second trimester (26% of intervention group vs. 23% of the control group).

“Despite the fact that only a small proportion of the women in the intervention group reached the physical activity goals, and the difference in weight gain was modest between the groups, it is obvious that the individual changes in lifestyle do not need to be large but together they have a beneficial effect on the reduction of the incidence of GDM,” the authors wrote.

They pointed out that as the women participating in the trial were all known to be at high risk for gestational diabetes, even the women in the control group would have received advice on weight control as part of their antenatal care and were therefore more of a “mini-intervention” group than pure control.

“We believe that in an unselected high-risk population the impact of this kind of lifestyle intervention could be even more pronounced.”

The Ahokas Foundation, Finnish Foundation for Cardiovascular Disease, Special State Subsidy for Health Science Research of Helsinki University Central Hospital, Samfundet Folkhälsan, Finnish Diabetes Research Foundation, State Provincial Office of Southern Finland, and Social Insurance Institution of Finland funded the study. There were no conflicts of interest declared.