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Thirteen percent of patients with type 2 diabetes have major ECG abnormalities
Major ECG abnormalities were found in 13% of more than 8,000 unselected patients with type 2 diabetes, including a 9% prevalence in the subgroup of these patients without identified cardiovascular disease (CVD) in a community-based Dutch cohort. Minor ECG abnormalities were even more prevalent.
These prevalence rates were consistent with prior findings from patients with type 2 diabetes, but the current report is notable because “it provides the most thorough description of the prevalence of ECG abnormalities in people with type 2 diabetes,” and used an “unselected and large population with comprehensive measurements,” including many without a history of CVD, said Peter P. Harms, MSc, and associates noted in a recent report in the Journal of Diabetes and Its Complications.
The analysis also identified several parameters that significantly linked with the presence of a major ECG abnormality including hypertension, male sex, older age, and higher levels of hemoglobin A1c.
“Resting ECG abnormalities might be a useful tool for CVD screening in people with type 2 diabetes,” concluded Mr. Harms, a researcher at the Amsterdam University Medical Center, and coauthors.
Findings “not unexpected”
Patients with diabetes have a higher prevalence of ECG abnormalities “because of their higher likelihood of having hypertension and other CVD risk factors,” as well as potentially having subclinical CVD, said Fred M. Kusumoto, MD, so these findings are “not unexpected. The more risk factors a patient has for structural heart disease, atrial fibrillation (AFib), or stroke from AFib, the more a physician must consider whether a baseline ECG and future surveillance is appropriate,” Dr. Kusumoto said in an interview.
But he cautioned against seeing these findings as a rationale to routinely run a resting ECG examination on every adult with diabetes.
“Patients with diabetes are very heterogeneous,” which makes it “difficult to come up with a ‘one size fits all’ recommendation” for ECG screening of patients with diabetes, he said.
While a task force of the European Society of Cardiology and the European Association for the Study of Diabetes set a class I level C guideline for resting ECG screening of patients with diabetes if they also have either hypertension or suspected CVD, the American Diabetes Association has no specific recommendations on which patients with diabetes should receive ECG screening.
“The current absence of U.S. recommendations is reasonable, as it allows patients and physicians to discuss the issues and decide on the utility of an ECG in their specific situation,” said Dr. Kusumoto, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla. But he also suggested that “the more risk factors that a patient with diabetes has for structural heart disease, AFib, or stroke from AFib the more a physician must consider whether a baseline ECG and future surveillance is appropriate.”
Data from a Dutch prospective cohort
The new study used data collected from 8,068 patients with type 2 diabetes and enrolled in the prospective Hoorn Diabetes Care System cohort, which enrolled patients newly diagnosed with type 2 diabetes in the West Friesland region of the Netherlands starting in 1996. The study includes most of these patients in the region who are under regular care of a general practitioner, and the study protocol calls for an annual resting ECG examination.
The investigators used standard, 12-lead ECG readings taken for each patient during 2018, and classified abnormalities by the Minnesota Code criteria. They divided the abnormalities into major or minor groups “in accordance with consensus between previous studies who categorised abnormalities according to perceived importance and/or severity.” The major subgroup included major QS pattern abnormalities, major ST-segment abnormalities, complete left bundle branch block or intraventricular block, or atrial fibrillation or flutter. Minor abnormalities included minor QS pattern abnormalities, minor ST-segment abnormalities, complete right bundle branch block, or premature atrial or ventricular contractions.
The prevalence of a major abnormality in the entire cohort examined was 13%, and another 16% had a minor abnormality. The most common types of abnormalities were ventricular conduction defects, in 14%; and arrhythmias, in 11%. In the subgroup of 6,494 of these patients with no history of CVD, 9% had a major abnormality and 15% a minor abnormality. Within this subgroup, 23% also had no hypertension, and their prevalence of a major abnormality was 4%, while 9% had a minor abnormality.
A multivariable analysis of potential risk factors among the entire study cohort showed that patients with hypertension had nearly triple the prevalence of a major ECG abnormality as those without hypertension, and men had double the prevalence of a major abnormality compared with women. Other markers that significantly linked with a higher rate of a major abnormality were older age, higher body mass index, higher A1c levels, and moderately depressed renal function.
“While the criteria the authors used for differentiating major and minor criteria are reasonable, in an asymptomatic patient even the presence of frequent premature atrial contractions on a baseline ECG has been associated with the development of AFib and a higher risk for stroke. The presence of left or right bundle branch block could spur additional evaluation with an echocardiogram,” said Dr. Kusumoto, president-elect of the Heart Rhythm Society.
“Generally an ECG abnormality is supplemental to clinical data in deciding the choice and timing of next therapeutic steps or additional testing. Physicians should have a fairly low threshold for obtaining ECG in patients with diabetes since it is inexpensive and can provide supplemental and potentially actionable information,” he said. “The presence of ECG abnormalities increases the possibility of underlying cardiovascular disease. When taking care of patients with diabetes at initial evaluation or without prior cardiac history or symptoms referable to the heart, two main issues are identifying the likelihood of coronary artery disease and atrial fibrillation.”
Mr. Harms and coauthors, and Dr. Kusumoto, had no disclosures.
Major ECG abnormalities were found in 13% of more than 8,000 unselected patients with type 2 diabetes, including a 9% prevalence in the subgroup of these patients without identified cardiovascular disease (CVD) in a community-based Dutch cohort. Minor ECG abnormalities were even more prevalent.
These prevalence rates were consistent with prior findings from patients with type 2 diabetes, but the current report is notable because “it provides the most thorough description of the prevalence of ECG abnormalities in people with type 2 diabetes,” and used an “unselected and large population with comprehensive measurements,” including many without a history of CVD, said Peter P. Harms, MSc, and associates noted in a recent report in the Journal of Diabetes and Its Complications.
The analysis also identified several parameters that significantly linked with the presence of a major ECG abnormality including hypertension, male sex, older age, and higher levels of hemoglobin A1c.
“Resting ECG abnormalities might be a useful tool for CVD screening in people with type 2 diabetes,” concluded Mr. Harms, a researcher at the Amsterdam University Medical Center, and coauthors.
Findings “not unexpected”
Patients with diabetes have a higher prevalence of ECG abnormalities “because of their higher likelihood of having hypertension and other CVD risk factors,” as well as potentially having subclinical CVD, said Fred M. Kusumoto, MD, so these findings are “not unexpected. The more risk factors a patient has for structural heart disease, atrial fibrillation (AFib), or stroke from AFib, the more a physician must consider whether a baseline ECG and future surveillance is appropriate,” Dr. Kusumoto said in an interview.
But he cautioned against seeing these findings as a rationale to routinely run a resting ECG examination on every adult with diabetes.
“Patients with diabetes are very heterogeneous,” which makes it “difficult to come up with a ‘one size fits all’ recommendation” for ECG screening of patients with diabetes, he said.
While a task force of the European Society of Cardiology and the European Association for the Study of Diabetes set a class I level C guideline for resting ECG screening of patients with diabetes if they also have either hypertension or suspected CVD, the American Diabetes Association has no specific recommendations on which patients with diabetes should receive ECG screening.
“The current absence of U.S. recommendations is reasonable, as it allows patients and physicians to discuss the issues and decide on the utility of an ECG in their specific situation,” said Dr. Kusumoto, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla. But he also suggested that “the more risk factors that a patient with diabetes has for structural heart disease, AFib, or stroke from AFib the more a physician must consider whether a baseline ECG and future surveillance is appropriate.”
Data from a Dutch prospective cohort
The new study used data collected from 8,068 patients with type 2 diabetes and enrolled in the prospective Hoorn Diabetes Care System cohort, which enrolled patients newly diagnosed with type 2 diabetes in the West Friesland region of the Netherlands starting in 1996. The study includes most of these patients in the region who are under regular care of a general practitioner, and the study protocol calls for an annual resting ECG examination.
The investigators used standard, 12-lead ECG readings taken for each patient during 2018, and classified abnormalities by the Minnesota Code criteria. They divided the abnormalities into major or minor groups “in accordance with consensus between previous studies who categorised abnormalities according to perceived importance and/or severity.” The major subgroup included major QS pattern abnormalities, major ST-segment abnormalities, complete left bundle branch block or intraventricular block, or atrial fibrillation or flutter. Minor abnormalities included minor QS pattern abnormalities, minor ST-segment abnormalities, complete right bundle branch block, or premature atrial or ventricular contractions.
The prevalence of a major abnormality in the entire cohort examined was 13%, and another 16% had a minor abnormality. The most common types of abnormalities were ventricular conduction defects, in 14%; and arrhythmias, in 11%. In the subgroup of 6,494 of these patients with no history of CVD, 9% had a major abnormality and 15% a minor abnormality. Within this subgroup, 23% also had no hypertension, and their prevalence of a major abnormality was 4%, while 9% had a minor abnormality.
A multivariable analysis of potential risk factors among the entire study cohort showed that patients with hypertension had nearly triple the prevalence of a major ECG abnormality as those without hypertension, and men had double the prevalence of a major abnormality compared with women. Other markers that significantly linked with a higher rate of a major abnormality were older age, higher body mass index, higher A1c levels, and moderately depressed renal function.
“While the criteria the authors used for differentiating major and minor criteria are reasonable, in an asymptomatic patient even the presence of frequent premature atrial contractions on a baseline ECG has been associated with the development of AFib and a higher risk for stroke. The presence of left or right bundle branch block could spur additional evaluation with an echocardiogram,” said Dr. Kusumoto, president-elect of the Heart Rhythm Society.
“Generally an ECG abnormality is supplemental to clinical data in deciding the choice and timing of next therapeutic steps or additional testing. Physicians should have a fairly low threshold for obtaining ECG in patients with diabetes since it is inexpensive and can provide supplemental and potentially actionable information,” he said. “The presence of ECG abnormalities increases the possibility of underlying cardiovascular disease. When taking care of patients with diabetes at initial evaluation or without prior cardiac history or symptoms referable to the heart, two main issues are identifying the likelihood of coronary artery disease and atrial fibrillation.”
Mr. Harms and coauthors, and Dr. Kusumoto, had no disclosures.
Major ECG abnormalities were found in 13% of more than 8,000 unselected patients with type 2 diabetes, including a 9% prevalence in the subgroup of these patients without identified cardiovascular disease (CVD) in a community-based Dutch cohort. Minor ECG abnormalities were even more prevalent.
These prevalence rates were consistent with prior findings from patients with type 2 diabetes, but the current report is notable because “it provides the most thorough description of the prevalence of ECG abnormalities in people with type 2 diabetes,” and used an “unselected and large population with comprehensive measurements,” including many without a history of CVD, said Peter P. Harms, MSc, and associates noted in a recent report in the Journal of Diabetes and Its Complications.
The analysis also identified several parameters that significantly linked with the presence of a major ECG abnormality including hypertension, male sex, older age, and higher levels of hemoglobin A1c.
“Resting ECG abnormalities might be a useful tool for CVD screening in people with type 2 diabetes,” concluded Mr. Harms, a researcher at the Amsterdam University Medical Center, and coauthors.
Findings “not unexpected”
Patients with diabetes have a higher prevalence of ECG abnormalities “because of their higher likelihood of having hypertension and other CVD risk factors,” as well as potentially having subclinical CVD, said Fred M. Kusumoto, MD, so these findings are “not unexpected. The more risk factors a patient has for structural heart disease, atrial fibrillation (AFib), or stroke from AFib, the more a physician must consider whether a baseline ECG and future surveillance is appropriate,” Dr. Kusumoto said in an interview.
But he cautioned against seeing these findings as a rationale to routinely run a resting ECG examination on every adult with diabetes.
“Patients with diabetes are very heterogeneous,” which makes it “difficult to come up with a ‘one size fits all’ recommendation” for ECG screening of patients with diabetes, he said.
While a task force of the European Society of Cardiology and the European Association for the Study of Diabetes set a class I level C guideline for resting ECG screening of patients with diabetes if they also have either hypertension or suspected CVD, the American Diabetes Association has no specific recommendations on which patients with diabetes should receive ECG screening.
“The current absence of U.S. recommendations is reasonable, as it allows patients and physicians to discuss the issues and decide on the utility of an ECG in their specific situation,” said Dr. Kusumoto, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla. But he also suggested that “the more risk factors that a patient with diabetes has for structural heart disease, AFib, or stroke from AFib the more a physician must consider whether a baseline ECG and future surveillance is appropriate.”
Data from a Dutch prospective cohort
The new study used data collected from 8,068 patients with type 2 diabetes and enrolled in the prospective Hoorn Diabetes Care System cohort, which enrolled patients newly diagnosed with type 2 diabetes in the West Friesland region of the Netherlands starting in 1996. The study includes most of these patients in the region who are under regular care of a general practitioner, and the study protocol calls for an annual resting ECG examination.
The investigators used standard, 12-lead ECG readings taken for each patient during 2018, and classified abnormalities by the Minnesota Code criteria. They divided the abnormalities into major or minor groups “in accordance with consensus between previous studies who categorised abnormalities according to perceived importance and/or severity.” The major subgroup included major QS pattern abnormalities, major ST-segment abnormalities, complete left bundle branch block or intraventricular block, or atrial fibrillation or flutter. Minor abnormalities included minor QS pattern abnormalities, minor ST-segment abnormalities, complete right bundle branch block, or premature atrial or ventricular contractions.
The prevalence of a major abnormality in the entire cohort examined was 13%, and another 16% had a minor abnormality. The most common types of abnormalities were ventricular conduction defects, in 14%; and arrhythmias, in 11%. In the subgroup of 6,494 of these patients with no history of CVD, 9% had a major abnormality and 15% a minor abnormality. Within this subgroup, 23% also had no hypertension, and their prevalence of a major abnormality was 4%, while 9% had a minor abnormality.
A multivariable analysis of potential risk factors among the entire study cohort showed that patients with hypertension had nearly triple the prevalence of a major ECG abnormality as those without hypertension, and men had double the prevalence of a major abnormality compared with women. Other markers that significantly linked with a higher rate of a major abnormality were older age, higher body mass index, higher A1c levels, and moderately depressed renal function.
“While the criteria the authors used for differentiating major and minor criteria are reasonable, in an asymptomatic patient even the presence of frequent premature atrial contractions on a baseline ECG has been associated with the development of AFib and a higher risk for stroke. The presence of left or right bundle branch block could spur additional evaluation with an echocardiogram,” said Dr. Kusumoto, president-elect of the Heart Rhythm Society.
“Generally an ECG abnormality is supplemental to clinical data in deciding the choice and timing of next therapeutic steps or additional testing. Physicians should have a fairly low threshold for obtaining ECG in patients with diabetes since it is inexpensive and can provide supplemental and potentially actionable information,” he said. “The presence of ECG abnormalities increases the possibility of underlying cardiovascular disease. When taking care of patients with diabetes at initial evaluation or without prior cardiac history or symptoms referable to the heart, two main issues are identifying the likelihood of coronary artery disease and atrial fibrillation.”
Mr. Harms and coauthors, and Dr. Kusumoto, had no disclosures.
FROM THE JOURNAL OF DIABETES AND ITS COMPLICATIONS
Obesity pegged as diabetes cause in almost half of U.S. cases
Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.
Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.
They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.
Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.
This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
Potential for “meaningful impact” by reducing obesity
“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.
“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.
MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.
For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m2.
During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.
The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.
During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.
To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.
The study received no commercial funding, and none of the authors had disclosures.
A version of this article first appeared on Medscape.com.
Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.
Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.
They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.
Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.
This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
Potential for “meaningful impact” by reducing obesity
“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.
“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.
MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.
For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m2.
During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.
The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.
During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.
To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.
The study received no commercial funding, and none of the authors had disclosures.
A version of this article first appeared on Medscape.com.
Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.
Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.
They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.
Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.
This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
Potential for “meaningful impact” by reducing obesity
“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.
“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.
MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.
For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m2.
During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.
The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.
During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.
To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.
The study received no commercial funding, and none of the authors had disclosures.
A version of this article first appeared on Medscape.com.
More from DAPA-HF: Dapagliflozin quickly reduces heart failure events
Dapagliflozin’s benefits in patients with heart failure with reduced ejection fraction appeared quickly after treatment began, and patients who had been hospitalized for heart failure within the prior year got the biggest boost from the drug, according to secondary analyses of the more than 4,700-patient DAPA-HF trial.
Dapagliflozin’s significant reduction of the incidence of cardiovascular death or worsening heart failure became apparent in DAPA-HF within 28 days after patients started treatment, by which time those on the study drug had a 49% cut in this combined endpoint, compared with patients on placebo, David D. Berg, MD, and associates said in a recent report published in JAMA Cardiology.
Their analyses also showed that the absolute reduction linked with dapagliflozin treatment for this primary endpoint of the study (which classified worsening heart failure as either hospitalization for heart failure or an urgent visit because of heart failure that required intravenous therapy) was greatest, 10% during 2 years of follow-up, among the roughly one-quarter of enrolled patients who had been hospitalized for heart failure within 12 months of entering the study. Patients previously hospitalized for heart failure more than 12 months before they entered DAPA-HF had a 4% absolute cut in their primary-outcome events during the trial, and those who had never been hospitalized for heart failure had a 2% absolute benefit, compared with placebo, during 2 years of follow-up.
These findings were consistent with the timing of benefits for patients with heart failure with reduced ejection fraction (HFrEF) in recent studies of two other drugs from the same class, the sodium-glucose cotransporter (SGLT) inhibitors, including empagliflozin (Jardiance, which inhibits SGLT-2) in the EMPEROR-Reduced trial, and sotagliflozin (Zynquista, which inhibits both SGLT1 and -2) in the SOLOIST-WHF trial, noted Gregg C. Fonarow, MD, and Clyde W. Yancy, MD, in an editor’s note that accompanied the new report.
The new findings show “the opportunity to expeditiously implement this remarkable class of therapy for HFrEF is now compelling and deserves disruptive efforts to ensure comprehensive treatment and the best patient outcomes,” wrote Dr. Fonarow, a professor of medicine at the University of California, Los Angeles, and Dr. Yancy, a professor of medicine at Northwestern University, Chicago.
But despite these new findings, their exact meaning remains unclear in terms of when to start dapagliflozin (or a different drug from the same class), compared with the other drug classes that have proven highly effective in patients with HFrEF, and exactly how long after hospitalization for heart failure dapagliflozin can safely and effectively begin.
Data needed on starting an SGLT inhibitor soon after hospitalization in patients without diabetes
“DAPA-HF showed that, in patients with or without diabetes, an SGLT2 inhibitor reduced the risk of cardiovascular death or worsening heart failure in patients with stable HFrEF. SOLOIST-WHF looked strictly at patients with diabetes, and showed that a combined SGLT1 and SGLT2 inhibitor could reduce the risk of cardiovascular death or worsening heart failure in patients with recently decompensated heart failure,” Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston, noted in an interview. “What we don’t have is a trial focused exclusively on enrolling patients while hospitalized with acute heart failure, irrespective of whether they have diabetes, and testing the immediate clinical efficacy and safety of starting an SGLT2 inhibitor. That is what we are testing with the ongoing DAPA ACT HF-TIMI 68 trial.”
In addition, updated recommendations from the American College of Cardiology on initiating drug therapy in patients newly diagnosed with HFrEF that appeared in early 2021 promoted a sequence that starts most patients on sacubitril/valsartan (Entresto) and a beta-blocker, followed by a diuretic (when needed), a mineralocorticoid receptor agonist, and then an SGLT inhibitor. The recommendations note that starting a patient on all these drug classes could take 3-6 months.
“There are intense debates about the optimal sequence for introducing these therapies, and I don’t think we have solid data to suggest that one sequence is clearly better than another,” noted Dr. Berg. “A one-size-fits-all approach probably doesn’t make sense. For example, each of these therapies has a different set of effects on heart rate and blood pressure, and each has a unique side effect profile, so clinicians will often need to tailor the treatment approach to the patient. And, of course, cost is an important consideration. Although the optimal time to start an SGLT2 inhibitor remains uncertain, the results of our analysis suggest that waiting may result in preventable adverse heart failure events.”
DAPA-HF randomized 4,744 patients with HFrEF and in New York Heart Association functional class II-IV at 410 sites in 20 countries. The incidence of the primary, combined endpoint fell by 26% with dapagliflozin treatment, compared with placebo, during a median 18-month follow-up. Among the study cohort 27% of patients had been hospitalized for heart failure within a year of their entry, 20% had been hospitalized for heart failure more than 1 year before entry, and 53% had no history of a hospitalization for heart failure.
DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Berg has received research support through his institution from AstraZeneca. Dr. Fonarow has received personal fees from AstraZeneca and from numerous other companies. Dr. Yancy’s spouse works for Abbott Laboratories.
Dapagliflozin’s benefits in patients with heart failure with reduced ejection fraction appeared quickly after treatment began, and patients who had been hospitalized for heart failure within the prior year got the biggest boost from the drug, according to secondary analyses of the more than 4,700-patient DAPA-HF trial.
Dapagliflozin’s significant reduction of the incidence of cardiovascular death or worsening heart failure became apparent in DAPA-HF within 28 days after patients started treatment, by which time those on the study drug had a 49% cut in this combined endpoint, compared with patients on placebo, David D. Berg, MD, and associates said in a recent report published in JAMA Cardiology.
Their analyses also showed that the absolute reduction linked with dapagliflozin treatment for this primary endpoint of the study (which classified worsening heart failure as either hospitalization for heart failure or an urgent visit because of heart failure that required intravenous therapy) was greatest, 10% during 2 years of follow-up, among the roughly one-quarter of enrolled patients who had been hospitalized for heart failure within 12 months of entering the study. Patients previously hospitalized for heart failure more than 12 months before they entered DAPA-HF had a 4% absolute cut in their primary-outcome events during the trial, and those who had never been hospitalized for heart failure had a 2% absolute benefit, compared with placebo, during 2 years of follow-up.
These findings were consistent with the timing of benefits for patients with heart failure with reduced ejection fraction (HFrEF) in recent studies of two other drugs from the same class, the sodium-glucose cotransporter (SGLT) inhibitors, including empagliflozin (Jardiance, which inhibits SGLT-2) in the EMPEROR-Reduced trial, and sotagliflozin (Zynquista, which inhibits both SGLT1 and -2) in the SOLOIST-WHF trial, noted Gregg C. Fonarow, MD, and Clyde W. Yancy, MD, in an editor’s note that accompanied the new report.
The new findings show “the opportunity to expeditiously implement this remarkable class of therapy for HFrEF is now compelling and deserves disruptive efforts to ensure comprehensive treatment and the best patient outcomes,” wrote Dr. Fonarow, a professor of medicine at the University of California, Los Angeles, and Dr. Yancy, a professor of medicine at Northwestern University, Chicago.
But despite these new findings, their exact meaning remains unclear in terms of when to start dapagliflozin (or a different drug from the same class), compared with the other drug classes that have proven highly effective in patients with HFrEF, and exactly how long after hospitalization for heart failure dapagliflozin can safely and effectively begin.
Data needed on starting an SGLT inhibitor soon after hospitalization in patients without diabetes
“DAPA-HF showed that, in patients with or without diabetes, an SGLT2 inhibitor reduced the risk of cardiovascular death or worsening heart failure in patients with stable HFrEF. SOLOIST-WHF looked strictly at patients with diabetes, and showed that a combined SGLT1 and SGLT2 inhibitor could reduce the risk of cardiovascular death or worsening heart failure in patients with recently decompensated heart failure,” Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston, noted in an interview. “What we don’t have is a trial focused exclusively on enrolling patients while hospitalized with acute heart failure, irrespective of whether they have diabetes, and testing the immediate clinical efficacy and safety of starting an SGLT2 inhibitor. That is what we are testing with the ongoing DAPA ACT HF-TIMI 68 trial.”
In addition, updated recommendations from the American College of Cardiology on initiating drug therapy in patients newly diagnosed with HFrEF that appeared in early 2021 promoted a sequence that starts most patients on sacubitril/valsartan (Entresto) and a beta-blocker, followed by a diuretic (when needed), a mineralocorticoid receptor agonist, and then an SGLT inhibitor. The recommendations note that starting a patient on all these drug classes could take 3-6 months.
“There are intense debates about the optimal sequence for introducing these therapies, and I don’t think we have solid data to suggest that one sequence is clearly better than another,” noted Dr. Berg. “A one-size-fits-all approach probably doesn’t make sense. For example, each of these therapies has a different set of effects on heart rate and blood pressure, and each has a unique side effect profile, so clinicians will often need to tailor the treatment approach to the patient. And, of course, cost is an important consideration. Although the optimal time to start an SGLT2 inhibitor remains uncertain, the results of our analysis suggest that waiting may result in preventable adverse heart failure events.”
DAPA-HF randomized 4,744 patients with HFrEF and in New York Heart Association functional class II-IV at 410 sites in 20 countries. The incidence of the primary, combined endpoint fell by 26% with dapagliflozin treatment, compared with placebo, during a median 18-month follow-up. Among the study cohort 27% of patients had been hospitalized for heart failure within a year of their entry, 20% had been hospitalized for heart failure more than 1 year before entry, and 53% had no history of a hospitalization for heart failure.
DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Berg has received research support through his institution from AstraZeneca. Dr. Fonarow has received personal fees from AstraZeneca and from numerous other companies. Dr. Yancy’s spouse works for Abbott Laboratories.
Dapagliflozin’s benefits in patients with heart failure with reduced ejection fraction appeared quickly after treatment began, and patients who had been hospitalized for heart failure within the prior year got the biggest boost from the drug, according to secondary analyses of the more than 4,700-patient DAPA-HF trial.
Dapagliflozin’s significant reduction of the incidence of cardiovascular death or worsening heart failure became apparent in DAPA-HF within 28 days after patients started treatment, by which time those on the study drug had a 49% cut in this combined endpoint, compared with patients on placebo, David D. Berg, MD, and associates said in a recent report published in JAMA Cardiology.
Their analyses also showed that the absolute reduction linked with dapagliflozin treatment for this primary endpoint of the study (which classified worsening heart failure as either hospitalization for heart failure or an urgent visit because of heart failure that required intravenous therapy) was greatest, 10% during 2 years of follow-up, among the roughly one-quarter of enrolled patients who had been hospitalized for heart failure within 12 months of entering the study. Patients previously hospitalized for heart failure more than 12 months before they entered DAPA-HF had a 4% absolute cut in their primary-outcome events during the trial, and those who had never been hospitalized for heart failure had a 2% absolute benefit, compared with placebo, during 2 years of follow-up.
These findings were consistent with the timing of benefits for patients with heart failure with reduced ejection fraction (HFrEF) in recent studies of two other drugs from the same class, the sodium-glucose cotransporter (SGLT) inhibitors, including empagliflozin (Jardiance, which inhibits SGLT-2) in the EMPEROR-Reduced trial, and sotagliflozin (Zynquista, which inhibits both SGLT1 and -2) in the SOLOIST-WHF trial, noted Gregg C. Fonarow, MD, and Clyde W. Yancy, MD, in an editor’s note that accompanied the new report.
The new findings show “the opportunity to expeditiously implement this remarkable class of therapy for HFrEF is now compelling and deserves disruptive efforts to ensure comprehensive treatment and the best patient outcomes,” wrote Dr. Fonarow, a professor of medicine at the University of California, Los Angeles, and Dr. Yancy, a professor of medicine at Northwestern University, Chicago.
But despite these new findings, their exact meaning remains unclear in terms of when to start dapagliflozin (or a different drug from the same class), compared with the other drug classes that have proven highly effective in patients with HFrEF, and exactly how long after hospitalization for heart failure dapagliflozin can safely and effectively begin.
Data needed on starting an SGLT inhibitor soon after hospitalization in patients without diabetes
“DAPA-HF showed that, in patients with or without diabetes, an SGLT2 inhibitor reduced the risk of cardiovascular death or worsening heart failure in patients with stable HFrEF. SOLOIST-WHF looked strictly at patients with diabetes, and showed that a combined SGLT1 and SGLT2 inhibitor could reduce the risk of cardiovascular death or worsening heart failure in patients with recently decompensated heart failure,” Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston, noted in an interview. “What we don’t have is a trial focused exclusively on enrolling patients while hospitalized with acute heart failure, irrespective of whether they have diabetes, and testing the immediate clinical efficacy and safety of starting an SGLT2 inhibitor. That is what we are testing with the ongoing DAPA ACT HF-TIMI 68 trial.”
In addition, updated recommendations from the American College of Cardiology on initiating drug therapy in patients newly diagnosed with HFrEF that appeared in early 2021 promoted a sequence that starts most patients on sacubitril/valsartan (Entresto) and a beta-blocker, followed by a diuretic (when needed), a mineralocorticoid receptor agonist, and then an SGLT inhibitor. The recommendations note that starting a patient on all these drug classes could take 3-6 months.
“There are intense debates about the optimal sequence for introducing these therapies, and I don’t think we have solid data to suggest that one sequence is clearly better than another,” noted Dr. Berg. “A one-size-fits-all approach probably doesn’t make sense. For example, each of these therapies has a different set of effects on heart rate and blood pressure, and each has a unique side effect profile, so clinicians will often need to tailor the treatment approach to the patient. And, of course, cost is an important consideration. Although the optimal time to start an SGLT2 inhibitor remains uncertain, the results of our analysis suggest that waiting may result in preventable adverse heart failure events.”
DAPA-HF randomized 4,744 patients with HFrEF and in New York Heart Association functional class II-IV at 410 sites in 20 countries. The incidence of the primary, combined endpoint fell by 26% with dapagliflozin treatment, compared with placebo, during a median 18-month follow-up. Among the study cohort 27% of patients had been hospitalized for heart failure within a year of their entry, 20% had been hospitalized for heart failure more than 1 year before entry, and 53% had no history of a hospitalization for heart failure.
DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Berg has received research support through his institution from AstraZeneca. Dr. Fonarow has received personal fees from AstraZeneca and from numerous other companies. Dr. Yancy’s spouse works for Abbott Laboratories.
FROM JAMA CARDIOLOGY
ASDSA warns of rogue insulin pen use for DIY fillers
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In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.
The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.
“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.
“TikTok is proving to be an extremely powerful platform to communicate, entertain, and even educate, which is why many physicians are getting involved and finding success there. Unfortunately, just like the World Wide Web, there is misinformation there and even dangerous lies,” Sandra Lee, MD, who practices in Upland, Calif. (and is also known as “Dr. Pimple Popper”), said in the statement.
“It’s very concerning to see young people posting a How To on injecting their own lips with hyaluronic acid serum using an ‘airgun’ pen, which acts much like a BB gun to push with force the product under the skin,” she added. “So many things can go wrong.”
The ASDSA has contacted the Food and Drug Administration to report these safety concerns. “In addition, the ASDSA is alerting state medical and estheticians’ boards regarding these patient safety concerns and alerting consumers directly about the risks through social media and other education materials,” according to the statement.
.
In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.
The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.
“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.
“TikTok is proving to be an extremely powerful platform to communicate, entertain, and even educate, which is why many physicians are getting involved and finding success there. Unfortunately, just like the World Wide Web, there is misinformation there and even dangerous lies,” Sandra Lee, MD, who practices in Upland, Calif. (and is also known as “Dr. Pimple Popper”), said in the statement.
“It’s very concerning to see young people posting a How To on injecting their own lips with hyaluronic acid serum using an ‘airgun’ pen, which acts much like a BB gun to push with force the product under the skin,” she added. “So many things can go wrong.”
The ASDSA has contacted the Food and Drug Administration to report these safety concerns. “In addition, the ASDSA is alerting state medical and estheticians’ boards regarding these patient safety concerns and alerting consumers directly about the risks through social media and other education materials,” according to the statement.
.
In the safety warning, issued on Feb. 18, the ASDSA reported that ASDSA members, all board-certified dermatologists, have seen evidence online of young people using so-called “hyaluron pens” to inject hyaluronic acid filler in the epidermal and upper dermal skin.
The pens being used and promoted in social media for do-it-yourself filler injections are medical devices originally developed for insulin injections. “The use of air pressure technology causes these pens to deliver the hyaluronic acid to insert nanoscale molecules of the filler through the skin,” according to the ASDSA statement. Marketing materials state that the pens can be used to create volume and shape in the lips, and to improve the appearance of nasolabial lines, marionette lines, brow lines known as “elevens,” and forehead wrinkles. Claims that the hyaluronic acid only reaches the papillary layer of the dermis, and is therefore safe, do not alleviate the risk of injury in inexperienced hands, the ASDSA statement points out.
“We are concerned about California children falling prey to products that are not appropriate and safe for them to use,” Elan Newland, MD, member of the ASDSA and the California Society for Dermatology and Dermatological Surgery (CalDerm), said in the statement. “The power of social media is very strong, especially for impressionable teenagers. CalDerm supports alerting consumers and regulators of the dangers of these pens,” he said.
“TikTok is proving to be an extremely powerful platform to communicate, entertain, and even educate, which is why many physicians are getting involved and finding success there. Unfortunately, just like the World Wide Web, there is misinformation there and even dangerous lies,” Sandra Lee, MD, who practices in Upland, Calif. (and is also known as “Dr. Pimple Popper”), said in the statement.
“It’s very concerning to see young people posting a How To on injecting their own lips with hyaluronic acid serum using an ‘airgun’ pen, which acts much like a BB gun to push with force the product under the skin,” she added. “So many things can go wrong.”
The ASDSA has contacted the Food and Drug Administration to report these safety concerns. “In addition, the ASDSA is alerting state medical and estheticians’ boards regarding these patient safety concerns and alerting consumers directly about the risks through social media and other education materials,” according to the statement.
Quick byte: Curing diabetes
Harvard biologist Doug Melton, PhD, is exploring the use of stem cells to create replacement beta cells that produce insulin, according to Time magazine.
In 2014, he co-founded Semma Therapeutics to develop the technology, which was acquired by Vertex Pharmaceuticals.
“The company has created a small, implantable device that holds millions of replacement beta cells, letting glucose and insulin through but keeping immune cells out. ‘If it works in people as well as it does in animals, it’s possible that people will not be diabetic,’ said Dr. Melton, co-director of the Harvard Stem Cell Institute and an investigator of the Howard Hughes Medical Institute. ‘They will eat and drink and play like those of us who are not.’”
Reference
Steinberg D. 12 innovations that will change health care and medicine in the 2020s. Time. 2019 Oct 25. https://time.com/5710295/top-health-innovations/ Accessed Dec 5, 2019.
Harvard biologist Doug Melton, PhD, is exploring the use of stem cells to create replacement beta cells that produce insulin, according to Time magazine.
In 2014, he co-founded Semma Therapeutics to develop the technology, which was acquired by Vertex Pharmaceuticals.
“The company has created a small, implantable device that holds millions of replacement beta cells, letting glucose and insulin through but keeping immune cells out. ‘If it works in people as well as it does in animals, it’s possible that people will not be diabetic,’ said Dr. Melton, co-director of the Harvard Stem Cell Institute and an investigator of the Howard Hughes Medical Institute. ‘They will eat and drink and play like those of us who are not.’”
Reference
Steinberg D. 12 innovations that will change health care and medicine in the 2020s. Time. 2019 Oct 25. https://time.com/5710295/top-health-innovations/ Accessed Dec 5, 2019.
Harvard biologist Doug Melton, PhD, is exploring the use of stem cells to create replacement beta cells that produce insulin, according to Time magazine.
In 2014, he co-founded Semma Therapeutics to develop the technology, which was acquired by Vertex Pharmaceuticals.
“The company has created a small, implantable device that holds millions of replacement beta cells, letting glucose and insulin through but keeping immune cells out. ‘If it works in people as well as it does in animals, it’s possible that people will not be diabetic,’ said Dr. Melton, co-director of the Harvard Stem Cell Institute and an investigator of the Howard Hughes Medical Institute. ‘They will eat and drink and play like those of us who are not.’”
Reference
Steinberg D. 12 innovations that will change health care and medicine in the 2020s. Time. 2019 Oct 25. https://time.com/5710295/top-health-innovations/ Accessed Dec 5, 2019.
Goldenseal may interfere with metformin absorption, jeopardizing glucose control
Goldenseal, a natural botanical product, may interfere with intestinal absorption of metformin, potentially compromising blood glucose control in patients with type 2 diabetes, according to investigators.
The study, which tested for interactions between goldenseal and several drugs in healthy volunteers, reveals that current models for predicting transporter-mediated drug-drug interactions may be insufficient to screen commonly used dietary supplements, reported lead investigator James T. Nguyen, PharmD, a PhD candidate at Washington State University, Spokane, and colleagues.
“Supplements containing goldenseal ... a perennial herb native to North America, have consistently ranked among the top 20 highest selling natural products during the last decade,” the investigators wrote in Clinical Pharmacology & Therapeutics . “As more patients continue to seek goldenseal and other natural products to self-treat their medical conditions, there is an increasing need to characterize their safety profiles, especially when co-consumed with prescribed medications, which can lead to adverse natural product-drug interactions.”
Previous clinical studies have shown that goldenseal inhibits cytochrome P450, with one study showing a roughly 40% increase in systemic midazolam exposure via CYP3A inhibition, “suggesting goldenseal could have prolonged inhibitory effects in vivo similar to grapefruit juice,” the investigators wrote.
Clinical and in vitro results for goldenseal-transporter interactions have been mixed, the investigators noted, specifically for P-glycoprotein, while other transporters remain clinically untested.
“Likewise, the effects of [goldenseal alkaloids], all of which are time-dependent inhibitors of CYP3A and/or CYP2D6, have not been tested on transporter function,” the investigators wrote.
To address this knowledge gap, the investigators first performed in vitro transporter inhibition assays and in vitro–in vivo predictions involving goldenseal, plus the alkaloids berberine, (−)-beta-hydrastine, and hydrastinine.
This analysis revealed that a number of transporters were sensitive to inhibition by goldenseal and its alkaloids.
“Using current [Food and Drug Administration]–recommended basic models, the goldenseal product was predicted to inhibit the intestinal efflux transporter BCRP [breast cancer resistance protein] and the hepatic uptake transporters OATP1B1 and OATP1B3,” the investigators wrote, which suggested that goldenseal would increase the area under the plasma concentration-time curve (AUC) of rosuvastatin acid and lactone.
This prediction was clinically tested in 16 healthy volunteers: 8 men and 8 nonpregnant women.
In the baseline portion of the study, each participant received an oral transporter probe cocktail consisting of 10 mg rosuvastatin (OATP1B1/3 and BCRP), 50 mg metformin (OCT1/2 and MATE1/2-K), 1 mg furosemide (OAT1/3), and 2.5 mg midazolam (CYP3A; positive control). Plasma and urine samples were collected before and after the cocktail, with urine collected up to 24 hours later, and plasma collected up to 96 hours later.
Following a minimum 9-day washout period, the same cohort received 1 gram of goldenseal every 8 hours for 5 days. On the day 6, the drug cocktail was given again, followed by two additional doses of goldenseal at 4-hour intervals. At the same time points used in the baseline protocol, urine and plasma samples were collected.
Plasma concentration vs. time profiles revealed that the model-based prediction was false, in that the presence of goldenseal did not alter the pharmacokinetics of rosuvastatin acid and lactone. The investigators suggested that this could be due to incomplete dissolution of goldenseal in the intestinal lumen, and/or low enterocyte concentrations of goldenseal stemming from “low permeability or extensive enterocyte metabolism or efflux.”
In contrast, and unpredicted by the basic model, goldenseal had a significant impact on apical efflux transporters MATE1 and MATE2-K, which mediate renal excretion of metformin. In consequence, AUC from zero to infinity and maximum plasma concentration of metformin were reduced by 23% and 27%, respectively.
“These observations, coupled with no change in half-life, suggested that goldenseal decreased metformin oral bioavailability by altering intestinal permeability, transport, and/or other processes involved in metformin absorption,” the investigators wrote.
According to principal author Mary Paine, PhD, of Washington State University, Spokane, this finding may have clinically significant implications for patients currently taking metformin for type 2 diabetes.
“Our study showed that goldenseal has an effect on the intestinal absorption of metformin, suggesting that the co-use of metformin and goldenseal may compromise blood glucose control in patients with type 2 diabetes and increase their risk of negative health outcomes,” Dr. Paine said. “While this finding warrants a degree of caution to be exercised among patients and their treating physicians, we have more work to do to confirm whether these findings in healthy volunteers in fact have clinical relevance in the management of diabetes. We are in the process of starting a follow-up study that should ultimately answer that question.”
The study was supported by the National Institutes of Health. The investigators reported no conflicts of interest.
Goldenseal, a natural botanical product, may interfere with intestinal absorption of metformin, potentially compromising blood glucose control in patients with type 2 diabetes, according to investigators.
The study, which tested for interactions between goldenseal and several drugs in healthy volunteers, reveals that current models for predicting transporter-mediated drug-drug interactions may be insufficient to screen commonly used dietary supplements, reported lead investigator James T. Nguyen, PharmD, a PhD candidate at Washington State University, Spokane, and colleagues.
“Supplements containing goldenseal ... a perennial herb native to North America, have consistently ranked among the top 20 highest selling natural products during the last decade,” the investigators wrote in Clinical Pharmacology & Therapeutics . “As more patients continue to seek goldenseal and other natural products to self-treat their medical conditions, there is an increasing need to characterize their safety profiles, especially when co-consumed with prescribed medications, which can lead to adverse natural product-drug interactions.”
Previous clinical studies have shown that goldenseal inhibits cytochrome P450, with one study showing a roughly 40% increase in systemic midazolam exposure via CYP3A inhibition, “suggesting goldenseal could have prolonged inhibitory effects in vivo similar to grapefruit juice,” the investigators wrote.
Clinical and in vitro results for goldenseal-transporter interactions have been mixed, the investigators noted, specifically for P-glycoprotein, while other transporters remain clinically untested.
“Likewise, the effects of [goldenseal alkaloids], all of which are time-dependent inhibitors of CYP3A and/or CYP2D6, have not been tested on transporter function,” the investigators wrote.
To address this knowledge gap, the investigators first performed in vitro transporter inhibition assays and in vitro–in vivo predictions involving goldenseal, plus the alkaloids berberine, (−)-beta-hydrastine, and hydrastinine.
This analysis revealed that a number of transporters were sensitive to inhibition by goldenseal and its alkaloids.
“Using current [Food and Drug Administration]–recommended basic models, the goldenseal product was predicted to inhibit the intestinal efflux transporter BCRP [breast cancer resistance protein] and the hepatic uptake transporters OATP1B1 and OATP1B3,” the investigators wrote, which suggested that goldenseal would increase the area under the plasma concentration-time curve (AUC) of rosuvastatin acid and lactone.
This prediction was clinically tested in 16 healthy volunteers: 8 men and 8 nonpregnant women.
In the baseline portion of the study, each participant received an oral transporter probe cocktail consisting of 10 mg rosuvastatin (OATP1B1/3 and BCRP), 50 mg metformin (OCT1/2 and MATE1/2-K), 1 mg furosemide (OAT1/3), and 2.5 mg midazolam (CYP3A; positive control). Plasma and urine samples were collected before and after the cocktail, with urine collected up to 24 hours later, and plasma collected up to 96 hours later.
Following a minimum 9-day washout period, the same cohort received 1 gram of goldenseal every 8 hours for 5 days. On the day 6, the drug cocktail was given again, followed by two additional doses of goldenseal at 4-hour intervals. At the same time points used in the baseline protocol, urine and plasma samples were collected.
Plasma concentration vs. time profiles revealed that the model-based prediction was false, in that the presence of goldenseal did not alter the pharmacokinetics of rosuvastatin acid and lactone. The investigators suggested that this could be due to incomplete dissolution of goldenseal in the intestinal lumen, and/or low enterocyte concentrations of goldenseal stemming from “low permeability or extensive enterocyte metabolism or efflux.”
In contrast, and unpredicted by the basic model, goldenseal had a significant impact on apical efflux transporters MATE1 and MATE2-K, which mediate renal excretion of metformin. In consequence, AUC from zero to infinity and maximum plasma concentration of metformin were reduced by 23% and 27%, respectively.
“These observations, coupled with no change in half-life, suggested that goldenseal decreased metformin oral bioavailability by altering intestinal permeability, transport, and/or other processes involved in metformin absorption,” the investigators wrote.
According to principal author Mary Paine, PhD, of Washington State University, Spokane, this finding may have clinically significant implications for patients currently taking metformin for type 2 diabetes.
“Our study showed that goldenseal has an effect on the intestinal absorption of metformin, suggesting that the co-use of metformin and goldenseal may compromise blood glucose control in patients with type 2 diabetes and increase their risk of negative health outcomes,” Dr. Paine said. “While this finding warrants a degree of caution to be exercised among patients and their treating physicians, we have more work to do to confirm whether these findings in healthy volunteers in fact have clinical relevance in the management of diabetes. We are in the process of starting a follow-up study that should ultimately answer that question.”
The study was supported by the National Institutes of Health. The investigators reported no conflicts of interest.
Goldenseal, a natural botanical product, may interfere with intestinal absorption of metformin, potentially compromising blood glucose control in patients with type 2 diabetes, according to investigators.
The study, which tested for interactions between goldenseal and several drugs in healthy volunteers, reveals that current models for predicting transporter-mediated drug-drug interactions may be insufficient to screen commonly used dietary supplements, reported lead investigator James T. Nguyen, PharmD, a PhD candidate at Washington State University, Spokane, and colleagues.
“Supplements containing goldenseal ... a perennial herb native to North America, have consistently ranked among the top 20 highest selling natural products during the last decade,” the investigators wrote in Clinical Pharmacology & Therapeutics . “As more patients continue to seek goldenseal and other natural products to self-treat their medical conditions, there is an increasing need to characterize their safety profiles, especially when co-consumed with prescribed medications, which can lead to adverse natural product-drug interactions.”
Previous clinical studies have shown that goldenseal inhibits cytochrome P450, with one study showing a roughly 40% increase in systemic midazolam exposure via CYP3A inhibition, “suggesting goldenseal could have prolonged inhibitory effects in vivo similar to grapefruit juice,” the investigators wrote.
Clinical and in vitro results for goldenseal-transporter interactions have been mixed, the investigators noted, specifically for P-glycoprotein, while other transporters remain clinically untested.
“Likewise, the effects of [goldenseal alkaloids], all of which are time-dependent inhibitors of CYP3A and/or CYP2D6, have not been tested on transporter function,” the investigators wrote.
To address this knowledge gap, the investigators first performed in vitro transporter inhibition assays and in vitro–in vivo predictions involving goldenseal, plus the alkaloids berberine, (−)-beta-hydrastine, and hydrastinine.
This analysis revealed that a number of transporters were sensitive to inhibition by goldenseal and its alkaloids.
“Using current [Food and Drug Administration]–recommended basic models, the goldenseal product was predicted to inhibit the intestinal efflux transporter BCRP [breast cancer resistance protein] and the hepatic uptake transporters OATP1B1 and OATP1B3,” the investigators wrote, which suggested that goldenseal would increase the area under the plasma concentration-time curve (AUC) of rosuvastatin acid and lactone.
This prediction was clinically tested in 16 healthy volunteers: 8 men and 8 nonpregnant women.
In the baseline portion of the study, each participant received an oral transporter probe cocktail consisting of 10 mg rosuvastatin (OATP1B1/3 and BCRP), 50 mg metformin (OCT1/2 and MATE1/2-K), 1 mg furosemide (OAT1/3), and 2.5 mg midazolam (CYP3A; positive control). Plasma and urine samples were collected before and after the cocktail, with urine collected up to 24 hours later, and plasma collected up to 96 hours later.
Following a minimum 9-day washout period, the same cohort received 1 gram of goldenseal every 8 hours for 5 days. On the day 6, the drug cocktail was given again, followed by two additional doses of goldenseal at 4-hour intervals. At the same time points used in the baseline protocol, urine and plasma samples were collected.
Plasma concentration vs. time profiles revealed that the model-based prediction was false, in that the presence of goldenseal did not alter the pharmacokinetics of rosuvastatin acid and lactone. The investigators suggested that this could be due to incomplete dissolution of goldenseal in the intestinal lumen, and/or low enterocyte concentrations of goldenseal stemming from “low permeability or extensive enterocyte metabolism or efflux.”
In contrast, and unpredicted by the basic model, goldenseal had a significant impact on apical efflux transporters MATE1 and MATE2-K, which mediate renal excretion of metformin. In consequence, AUC from zero to infinity and maximum plasma concentration of metformin were reduced by 23% and 27%, respectively.
“These observations, coupled with no change in half-life, suggested that goldenseal decreased metformin oral bioavailability by altering intestinal permeability, transport, and/or other processes involved in metformin absorption,” the investigators wrote.
According to principal author Mary Paine, PhD, of Washington State University, Spokane, this finding may have clinically significant implications for patients currently taking metformin for type 2 diabetes.
“Our study showed that goldenseal has an effect on the intestinal absorption of metformin, suggesting that the co-use of metformin and goldenseal may compromise blood glucose control in patients with type 2 diabetes and increase their risk of negative health outcomes,” Dr. Paine said. “While this finding warrants a degree of caution to be exercised among patients and their treating physicians, we have more work to do to confirm whether these findings in healthy volunteers in fact have clinical relevance in the management of diabetes. We are in the process of starting a follow-up study that should ultimately answer that question.”
The study was supported by the National Institutes of Health. The investigators reported no conflicts of interest.
FROM CLINICAL PHARMACOLOGY & THERAPEUTICS
Opioids prescribed for diabetic neuropathy pain, against advice
Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.
“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general, and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minn., told this news organization.
That’s true even for severe DPN pain or painful exacerbations, she added.
“There’s a myth that opioids are the strongest pain meds possible ... For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained. “But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”
What’s more, she noted, “evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”
The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.
The new findings, from a retrospective study of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.
Are fewer patients with DPN receiving any treatment now?
The data also reveal that, while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, Dr. McCoy explained.)
“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” Dr. McCoy noted.
“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” Dr. McCoy said, including nonpharmacologic approaches.
Opioids dominated in new-onset DPN prescribing during 2014-2018
The study involved 3,495 adults with newly diagnosed DPN from all three Mayo Clinic locations in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla. during the period 2014-2018. Of those, 40.2% (1,406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.
The odds of initiating any treatment were significantly greater among patients with depression (odds ratio, 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.
Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.
Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.
Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).
Use of opioids was 29% less likely in 2018, compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018, compared with 2014, also not a significant difference.
Dr. McCoy offers clinical pearls for treating pain in DPN
Clinically, Dr. McCoy said that she individualizes treatment for painful DPN.
“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low-back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”
All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.
“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”
Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”
Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.
Supplements such as vitamin B12 – which can also help with metformin-induced B12 deficiency – or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.
Dr. McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo ... I think it affects all practices,” she said.
Since the study, “we [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain ... so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.
A version of this article first appeared on Medscape.com.
Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.
“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general, and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minn., told this news organization.
That’s true even for severe DPN pain or painful exacerbations, she added.
“There’s a myth that opioids are the strongest pain meds possible ... For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained. “But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”
What’s more, she noted, “evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”
The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.
The new findings, from a retrospective study of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.
Are fewer patients with DPN receiving any treatment now?
The data also reveal that, while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, Dr. McCoy explained.)
“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” Dr. McCoy noted.
“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” Dr. McCoy said, including nonpharmacologic approaches.
Opioids dominated in new-onset DPN prescribing during 2014-2018
The study involved 3,495 adults with newly diagnosed DPN from all three Mayo Clinic locations in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla. during the period 2014-2018. Of those, 40.2% (1,406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.
The odds of initiating any treatment were significantly greater among patients with depression (odds ratio, 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.
Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.
Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.
Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).
Use of opioids was 29% less likely in 2018, compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018, compared with 2014, also not a significant difference.
Dr. McCoy offers clinical pearls for treating pain in DPN
Clinically, Dr. McCoy said that she individualizes treatment for painful DPN.
“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low-back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”
All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.
“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”
Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”
Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.
Supplements such as vitamin B12 – which can also help with metformin-induced B12 deficiency – or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.
Dr. McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo ... I think it affects all practices,” she said.
Since the study, “we [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain ... so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.
A version of this article first appeared on Medscape.com.
Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.
“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general, and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minn., told this news organization.
That’s true even for severe DPN pain or painful exacerbations, she added.
“There’s a myth that opioids are the strongest pain meds possible ... For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained. “But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”
What’s more, she noted, “evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”
The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.
The new findings, from a retrospective study of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.
Are fewer patients with DPN receiving any treatment now?
The data also reveal that, while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, Dr. McCoy explained.)
“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” Dr. McCoy noted.
“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” Dr. McCoy said, including nonpharmacologic approaches.
Opioids dominated in new-onset DPN prescribing during 2014-2018
The study involved 3,495 adults with newly diagnosed DPN from all three Mayo Clinic locations in Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla. during the period 2014-2018. Of those, 40.2% (1,406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.
The odds of initiating any treatment were significantly greater among patients with depression (odds ratio, 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.
Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.
Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.
Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).
Use of opioids was 29% less likely in 2018, compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018, compared with 2014, also not a significant difference.
Dr. McCoy offers clinical pearls for treating pain in DPN
Clinically, Dr. McCoy said that she individualizes treatment for painful DPN.
“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low-back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”
All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.
“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”
Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”
Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.
Supplements such as vitamin B12 – which can also help with metformin-induced B12 deficiency – or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.
Dr. McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo ... I think it affects all practices,” she said.
Since the study, “we [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain ... so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.
A version of this article first appeared on Medscape.com.
Super Bowl ad for diabetes device prompts debate
A commercial for the continuous glucose monitor (CGM) Dexcom G6 shown during the Super Bowl has provoked strong reactions in the diabetes community, both positive and negative.
The 30-second ad, which aired between the first two quarters of the American football game yesterday, features singer-songwriter-actor Nick Jonas, who has type 1 diabetes. During the ad, Mr. Jonas asks – with so much technology available today, including drones that deliver packages and self-driving cars – why are people with diabetes still pricking their fingers to test their blood sugar?
Mr. Jonas goes on to demonstrate the Dexcom G6 smartphone glucose app as it displays three different glucose levels including two trending upward, explaining: “It shows your glucose right in your phone, and where it’s heading, without fingersticks. Finally, technology that makes it easier to manage our diabetes.”
Diabetes type or insulin treatment are not mentioned in the ad, despite the fact that most insurance plans typically only cover CGMs for people with type 1 diabetes and sometimes for those with type 2 diabetes who take multiple daily insulin doses (given the risk for hypoglycemia).
Ad prompts mixed reaction on social media
Reactions rolled in on Twitter after the ad debuted Feb. 2, and then again after it aired during the game.
Some people who have type 1 diabetes themselves or have children with the disease who use the product were thrilled.
“Thanks to @NickJonas for his advocacy on T1. My 11-year old has been on the Dexcom for 3 weeks. For a newly diagnosed kid, it removes a lot of anxiety (and for his parents, too!) Plus, he is thrilled his meter has a Super Bowl commercial!” tweeted @KatisJewell.
Another positive tweet, from @rturnerroy, read: “@nickjonas Thank you for bringing representation to #type1diabetes. And hey #Dexcom, you’re the best.”
But many others were critical, both of Jonas and Dexcom. @hb_herrick tweeted: “Diabetes awareness is fantastic. Dexcom being able to afford Nick Jonas for a #SuperBowl commercial is not. This is a health care product. Make it more affordable for those who need it.”
Another Twitter user, @universeofdust, tweeted: “Feeling ambivalent about the #Dexcom ad tbh. I love the awareness & representation. But also not a big fan of dexcom spending $5.5 mill+ to make the CGM seem like this ~cool & trendy~ thing when many type 1s can’t afford their insulin, let alone a CGM.”
And @andricheli wrote: “Only people lucky enough to have excellent insurance and be able to afford the out-of-pocket costs have access. Many others do not.”
And in another tweet the same user said, “The #Dexcom is an amazing device. It’s literally lifesaving and life extending. But it’s also very expensive and not available to everyone. Maybe instead of spending $5 mil on a Super Bowl ad, @dexcom should spend that on getting Dex into the handle of people who need it.”
Others, including @1hitwonderdate, criticized Mr. Jonas directly, asking him: “As someone who has struggled with diabetes and is trying to support themselves along with millions of others, why not use this platform to help those who can’t afford their supplies or are rationing them?!”
Dexcom and Jonas’ organization respond
This news organization reached out to both Dexcom and to Beyond Type 1, a nonprofit organization cofounded by Mr. Jonas, for comment. Both emailed responses.
Regarding the intended audience for the ad, Dexcom acknowledged that it hoped to reach a much wider group than just people with type 1 diabetes or even just insulin users.
“We believe our CGM technology has the ability to empower any person with diabetes and significantly improve their treatment and quality of life, whether they are using insulin or not,” the company said, adding that the ad was also aimed at “loved ones, caregivers, and even health care professionals who need to know about this technology.”
According to Dexcom, the G6 is covered by 99% of commercial insurance in the United States, in addition to Medicare, and by Medicaid in more than 40 states. Over 70% of Dexcom patients with pharmacy coverage in the United States pay under $60 per month for CGM, and a third pay $0 out-of-pocket.
“That said, we know there’s more to be done to improve access, and we are working with several partners to broaden access to Dexcom CGM, especially for people with type 2 diabetes not on mealtime insulin,” the company noted.
Beyond Type 1 responded to the criticisms about Mr. Jonas personally, noting that the celebrity is, in fact, heavily involved in advocacy.
“Nick was involved in the launch of GetInsulin.org this past October,” they said. “GetInsulin.org is a tool created by Beyond Type 1 to connect people with diabetes in the United States to the insulin access and affordability options that match their unique circumstances. ... Beyond Type 1 will continue driving awareness of short-term solutions related to insulin access and affordability while fighting for systemic change.”
The organization “is also advocating for systemic payment policies that will make devices less expensive and avoid the same pitfalls (and rising prices) as the drug pricing system in the U.S.”
Mr. Jonas himself appears aware of the concerns.
Is 2021’s most expensive Super Bowl ad justified?
Meanwhile, in a piece in Esquire, Dave Holmes, who has type 1 diabetes, weighs up the pros and cons of the ad.
He writes: “While Jonas makes it look fun and easy to use a Dexcom G6 – a program to just get with like you would a drone or LED eyelashes – the process of acquiring one is complicated and often very expensive, even for people with good insurance. Which makes the year’s most expensive ad buy, for a product that only a small percentage of the U.S. population needs, confusing to me and others.”
Mr. Holmes also spoke with Craig Stubing, founder of the Beta Cell Foundation, a nonprofit that aims to educate and empower those with type 1 diabetes.
“Spending all this money on an ad, when people’s lives are at stake. I don’t know if offensive is the right word, but it seems out of touch with the reality that their patients are facing,” Mr. Stubing told Mr. Holmes.
A version of this article first appeared on Medscape.com.
A commercial for the continuous glucose monitor (CGM) Dexcom G6 shown during the Super Bowl has provoked strong reactions in the diabetes community, both positive and negative.
The 30-second ad, which aired between the first two quarters of the American football game yesterday, features singer-songwriter-actor Nick Jonas, who has type 1 diabetes. During the ad, Mr. Jonas asks – with so much technology available today, including drones that deliver packages and self-driving cars – why are people with diabetes still pricking their fingers to test their blood sugar?
Mr. Jonas goes on to demonstrate the Dexcom G6 smartphone glucose app as it displays three different glucose levels including two trending upward, explaining: “It shows your glucose right in your phone, and where it’s heading, without fingersticks. Finally, technology that makes it easier to manage our diabetes.”
Diabetes type or insulin treatment are not mentioned in the ad, despite the fact that most insurance plans typically only cover CGMs for people with type 1 diabetes and sometimes for those with type 2 diabetes who take multiple daily insulin doses (given the risk for hypoglycemia).
Ad prompts mixed reaction on social media
Reactions rolled in on Twitter after the ad debuted Feb. 2, and then again after it aired during the game.
Some people who have type 1 diabetes themselves or have children with the disease who use the product were thrilled.
“Thanks to @NickJonas for his advocacy on T1. My 11-year old has been on the Dexcom for 3 weeks. For a newly diagnosed kid, it removes a lot of anxiety (and for his parents, too!) Plus, he is thrilled his meter has a Super Bowl commercial!” tweeted @KatisJewell.
Another positive tweet, from @rturnerroy, read: “@nickjonas Thank you for bringing representation to #type1diabetes. And hey #Dexcom, you’re the best.”
But many others were critical, both of Jonas and Dexcom. @hb_herrick tweeted: “Diabetes awareness is fantastic. Dexcom being able to afford Nick Jonas for a #SuperBowl commercial is not. This is a health care product. Make it more affordable for those who need it.”
Another Twitter user, @universeofdust, tweeted: “Feeling ambivalent about the #Dexcom ad tbh. I love the awareness & representation. But also not a big fan of dexcom spending $5.5 mill+ to make the CGM seem like this ~cool & trendy~ thing when many type 1s can’t afford their insulin, let alone a CGM.”
And @andricheli wrote: “Only people lucky enough to have excellent insurance and be able to afford the out-of-pocket costs have access. Many others do not.”
And in another tweet the same user said, “The #Dexcom is an amazing device. It’s literally lifesaving and life extending. But it’s also very expensive and not available to everyone. Maybe instead of spending $5 mil on a Super Bowl ad, @dexcom should spend that on getting Dex into the handle of people who need it.”
Others, including @1hitwonderdate, criticized Mr. Jonas directly, asking him: “As someone who has struggled with diabetes and is trying to support themselves along with millions of others, why not use this platform to help those who can’t afford their supplies or are rationing them?!”
Dexcom and Jonas’ organization respond
This news organization reached out to both Dexcom and to Beyond Type 1, a nonprofit organization cofounded by Mr. Jonas, for comment. Both emailed responses.
Regarding the intended audience for the ad, Dexcom acknowledged that it hoped to reach a much wider group than just people with type 1 diabetes or even just insulin users.
“We believe our CGM technology has the ability to empower any person with diabetes and significantly improve their treatment and quality of life, whether they are using insulin or not,” the company said, adding that the ad was also aimed at “loved ones, caregivers, and even health care professionals who need to know about this technology.”
According to Dexcom, the G6 is covered by 99% of commercial insurance in the United States, in addition to Medicare, and by Medicaid in more than 40 states. Over 70% of Dexcom patients with pharmacy coverage in the United States pay under $60 per month for CGM, and a third pay $0 out-of-pocket.
“That said, we know there’s more to be done to improve access, and we are working with several partners to broaden access to Dexcom CGM, especially for people with type 2 diabetes not on mealtime insulin,” the company noted.
Beyond Type 1 responded to the criticisms about Mr. Jonas personally, noting that the celebrity is, in fact, heavily involved in advocacy.
“Nick was involved in the launch of GetInsulin.org this past October,” they said. “GetInsulin.org is a tool created by Beyond Type 1 to connect people with diabetes in the United States to the insulin access and affordability options that match their unique circumstances. ... Beyond Type 1 will continue driving awareness of short-term solutions related to insulin access and affordability while fighting for systemic change.”
The organization “is also advocating for systemic payment policies that will make devices less expensive and avoid the same pitfalls (and rising prices) as the drug pricing system in the U.S.”
Mr. Jonas himself appears aware of the concerns.
Is 2021’s most expensive Super Bowl ad justified?
Meanwhile, in a piece in Esquire, Dave Holmes, who has type 1 diabetes, weighs up the pros and cons of the ad.
He writes: “While Jonas makes it look fun and easy to use a Dexcom G6 – a program to just get with like you would a drone or LED eyelashes – the process of acquiring one is complicated and often very expensive, even for people with good insurance. Which makes the year’s most expensive ad buy, for a product that only a small percentage of the U.S. population needs, confusing to me and others.”
Mr. Holmes also spoke with Craig Stubing, founder of the Beta Cell Foundation, a nonprofit that aims to educate and empower those with type 1 diabetes.
“Spending all this money on an ad, when people’s lives are at stake. I don’t know if offensive is the right word, but it seems out of touch with the reality that their patients are facing,” Mr. Stubing told Mr. Holmes.
A version of this article first appeared on Medscape.com.
A commercial for the continuous glucose monitor (CGM) Dexcom G6 shown during the Super Bowl has provoked strong reactions in the diabetes community, both positive and negative.
The 30-second ad, which aired between the first two quarters of the American football game yesterday, features singer-songwriter-actor Nick Jonas, who has type 1 diabetes. During the ad, Mr. Jonas asks – with so much technology available today, including drones that deliver packages and self-driving cars – why are people with diabetes still pricking their fingers to test their blood sugar?
Mr. Jonas goes on to demonstrate the Dexcom G6 smartphone glucose app as it displays three different glucose levels including two trending upward, explaining: “It shows your glucose right in your phone, and where it’s heading, without fingersticks. Finally, technology that makes it easier to manage our diabetes.”
Diabetes type or insulin treatment are not mentioned in the ad, despite the fact that most insurance plans typically only cover CGMs for people with type 1 diabetes and sometimes for those with type 2 diabetes who take multiple daily insulin doses (given the risk for hypoglycemia).
Ad prompts mixed reaction on social media
Reactions rolled in on Twitter after the ad debuted Feb. 2, and then again after it aired during the game.
Some people who have type 1 diabetes themselves or have children with the disease who use the product were thrilled.
“Thanks to @NickJonas for his advocacy on T1. My 11-year old has been on the Dexcom for 3 weeks. For a newly diagnosed kid, it removes a lot of anxiety (and for his parents, too!) Plus, he is thrilled his meter has a Super Bowl commercial!” tweeted @KatisJewell.
Another positive tweet, from @rturnerroy, read: “@nickjonas Thank you for bringing representation to #type1diabetes. And hey #Dexcom, you’re the best.”
But many others were critical, both of Jonas and Dexcom. @hb_herrick tweeted: “Diabetes awareness is fantastic. Dexcom being able to afford Nick Jonas for a #SuperBowl commercial is not. This is a health care product. Make it more affordable for those who need it.”
Another Twitter user, @universeofdust, tweeted: “Feeling ambivalent about the #Dexcom ad tbh. I love the awareness & representation. But also not a big fan of dexcom spending $5.5 mill+ to make the CGM seem like this ~cool & trendy~ thing when many type 1s can’t afford their insulin, let alone a CGM.”
And @andricheli wrote: “Only people lucky enough to have excellent insurance and be able to afford the out-of-pocket costs have access. Many others do not.”
And in another tweet the same user said, “The #Dexcom is an amazing device. It’s literally lifesaving and life extending. But it’s also very expensive and not available to everyone. Maybe instead of spending $5 mil on a Super Bowl ad, @dexcom should spend that on getting Dex into the handle of people who need it.”
Others, including @1hitwonderdate, criticized Mr. Jonas directly, asking him: “As someone who has struggled with diabetes and is trying to support themselves along with millions of others, why not use this platform to help those who can’t afford their supplies or are rationing them?!”
Dexcom and Jonas’ organization respond
This news organization reached out to both Dexcom and to Beyond Type 1, a nonprofit organization cofounded by Mr. Jonas, for comment. Both emailed responses.
Regarding the intended audience for the ad, Dexcom acknowledged that it hoped to reach a much wider group than just people with type 1 diabetes or even just insulin users.
“We believe our CGM technology has the ability to empower any person with diabetes and significantly improve their treatment and quality of life, whether they are using insulin or not,” the company said, adding that the ad was also aimed at “loved ones, caregivers, and even health care professionals who need to know about this technology.”
According to Dexcom, the G6 is covered by 99% of commercial insurance in the United States, in addition to Medicare, and by Medicaid in more than 40 states. Over 70% of Dexcom patients with pharmacy coverage in the United States pay under $60 per month for CGM, and a third pay $0 out-of-pocket.
“That said, we know there’s more to be done to improve access, and we are working with several partners to broaden access to Dexcom CGM, especially for people with type 2 diabetes not on mealtime insulin,” the company noted.
Beyond Type 1 responded to the criticisms about Mr. Jonas personally, noting that the celebrity is, in fact, heavily involved in advocacy.
“Nick was involved in the launch of GetInsulin.org this past October,” they said. “GetInsulin.org is a tool created by Beyond Type 1 to connect people with diabetes in the United States to the insulin access and affordability options that match their unique circumstances. ... Beyond Type 1 will continue driving awareness of short-term solutions related to insulin access and affordability while fighting for systemic change.”
The organization “is also advocating for systemic payment policies that will make devices less expensive and avoid the same pitfalls (and rising prices) as the drug pricing system in the U.S.”
Mr. Jonas himself appears aware of the concerns.
Is 2021’s most expensive Super Bowl ad justified?
Meanwhile, in a piece in Esquire, Dave Holmes, who has type 1 diabetes, weighs up the pros and cons of the ad.
He writes: “While Jonas makes it look fun and easy to use a Dexcom G6 – a program to just get with like you would a drone or LED eyelashes – the process of acquiring one is complicated and often very expensive, even for people with good insurance. Which makes the year’s most expensive ad buy, for a product that only a small percentage of the U.S. population needs, confusing to me and others.”
Mr. Holmes also spoke with Craig Stubing, founder of the Beta Cell Foundation, a nonprofit that aims to educate and empower those with type 1 diabetes.
“Spending all this money on an ad, when people’s lives are at stake. I don’t know if offensive is the right word, but it seems out of touch with the reality that their patients are facing,” Mr. Stubing told Mr. Holmes.
A version of this article first appeared on Medscape.com.
Semaglutide for weight loss? A good first STEP, with caveats
The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.
“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.
The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.
“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.
However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”
Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.
“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.
However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”
Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.
Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.
And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.
In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
‘Pressing need’ to address obesity; semaglutide filed for obesity
There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.
Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.
In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”
Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Topline results from STEP 1 were presented June 4, 2020.
And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.
The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
Most patients had 5% weight loss with semaglutide
The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m2 or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.
Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).
On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.
Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.
Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).
Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).
At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).
About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.
Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.
In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
GI disorders and ‘important limitations’
More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).
More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.
Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.
The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.
A version of this article first appeared on Medscape.com.
The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.
“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.
The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.
“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.
However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”
Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.
“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.
However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”
Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.
Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.
And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.
In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
‘Pressing need’ to address obesity; semaglutide filed for obesity
There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.
Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.
In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”
Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Topline results from STEP 1 were presented June 4, 2020.
And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.
The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
Most patients had 5% weight loss with semaglutide
The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m2 or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.
Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).
On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.
Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.
Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).
Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).
At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).
About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.
Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.
In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
GI disorders and ‘important limitations’
More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).
More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.
Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.
The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.
A version of this article first appeared on Medscape.com.
The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.
“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.
The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.
“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.
However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”
Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.
“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.
However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”
Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.
Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.
And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.
In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
‘Pressing need’ to address obesity; semaglutide filed for obesity
There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.
Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.
In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”
Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Topline results from STEP 1 were presented June 4, 2020.
And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.
The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
Most patients had 5% weight loss with semaglutide
The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m2 or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.
Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).
On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.
Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.
Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).
Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).
At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).
About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.
Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.
In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
GI disorders and ‘important limitations’
More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).
More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.
Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.
The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.
A version of this article first appeared on Medscape.com.
Lifestyle coaching for obesity associated with improved cardiometabolic numbers in study
Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.
The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .
“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”
In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.
Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
Cholesterol changes in intervention vs. control group
HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).
Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.
There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
Funding barriers to obesity treatment
The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.
“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.
John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.
“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.
That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.
“You don’t necessarily need to be a physician to do this,” Dr. Flack said.
For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.
“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.
Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.
“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.
A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”
Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.
The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .
“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”
In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.
Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
Cholesterol changes in intervention vs. control group
HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).
Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.
There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
Funding barriers to obesity treatment
The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.
“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.
John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.
“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.
That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.
“You don’t necessarily need to be a physician to do this,” Dr. Flack said.
For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.
“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.
Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.
“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.
A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”
Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.
The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .
“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”
In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.
Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
Cholesterol changes in intervention vs. control group
HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).
Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.
There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
Funding barriers to obesity treatment
The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.
“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.
John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.
“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.
That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.
“You don’t necessarily need to be a physician to do this,” Dr. Flack said.
For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.
“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.
Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.
“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.
A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”
Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
