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Debate: Initial combination therapy for type 2 diabetes?
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
SAN DIEGO –
This question was debated by two well-known clinician-researchers in the diabetes world at the recent annual scientific sessions of the American Diabetes Association.
Ralph A. DeFronzo, MD, argued for combination therapy at the time of diagnosis, and David M. Nathan, MD, countered that sequential therapy is a better way to go.
‘The ominous octet’: Addressing multiple underlying defects
Of course, Dr. DeFronzo said, the right agents must be selected. “The drugs we’re going to use as combination at a minimum have to correct the underlying insulin resistance and beta-cell failure, or we are not going to be successful.”
In addition, he said, these drugs should also provide protection against cardiovascular, kidney, and fatty liver disease, because “[managing] diabetes is more than just controlling the glucose.”
Recent U.S. data suggest that half of people with diabetes have a hemoglobin A1c above 7%, and a quarter remain above 8%. “We’re not really doing a very good job in terms of glycemic control,” said Dr. DeFronzo, chief of the diabetes division at University of Texas, San Antonio.
One reason for this failure, he said, is the complex pathophysiology of type 2 diabetes represented by eight major defects, what he called the “ominous octet”: decreased pancreatic insulin secretion, gut incretin effects, glucose uptake in the muscle, increased lipolysis, glucose reabsorption in the kidney, hepatic glucose production, increased glucagon secretion, and neurotransmitter dysfunction.
“There are eight problems, so you’re going to need multiple drugs in combination ... not ones that just lower the A1c.”
And, Dr. DeFronzo said, these drugs “must be started early in the natural history of type 2 diabetes if progressive beta-cell failure is to be prevented.”
He pointed to the United Kingdom Prospective Diabetes Study (UKPDS), in which the sulfonylurea glyburide was used first, followed by metformin. With each drug, the A1c decreased initially but then rose within 3 years. By 15 years, 65% of participants were taking insulin.
More recently, the GRADE study examined the effects of adding four different glucose-lowering agents (glimepiride, sitagliptin, liraglutide, or insulin glargine) in people who hadn’t achieved target A1c with metformin.
“So, by definition, drug number one failed,” he observed.
During the study, all participants showed an initial A1c drop, followed by progressive failure, “again ... showing that stepwise therapy doesn’t work.”
All patients with type 2 diabetes at his center are treated using the “DeFronzo algorithm” consisting of three drug classes: a glucagon-like peptide-1 (GLP-1) agonist, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and pioglitazone, as each of them targets more than one of the “ominous octet” defects.
“The drugs that clearly do not work on a long-term basis are metformin and sulfonylureas,” he emphasized.
Several studies demonstrate the efficacy of combination therapy, he said. In one, DURATION 8, the combination of exenatide and dapagliflozin was superior to either agent individually in lowering A1c, cardiovascular events, and all-cause mortality over 2 years.
And in the 5-year VERIFY study, early combination therapy with vildagliptin plus metformin proved superior in A1c-lowering to starting patients on metformin and adding vildagliptin later.
Dr. DeFronzo’s own “knock-out punch” study, EDICT, in people with new-onset type 2 diabetes, compared the initial combination of metformin, pioglitazone, and exenatide with conventional sequential add-on therapy with metformin, glipizide, and insulin glargine.
The primary endpoint – the difference in the proportion of patients with A1c less than 6.5% – was 70% versus 29% with combination compared with sequential therapy, a difference “as robust as you can be going against the stepwise approach” at P < .00001, he said.
The combination therapy virtually normalized both insulin sensitivity and beta-cell function, whereas the conventional therapy did neither.
Also from Dr. DeFronzo’s group, in the Qatar study, which compared exenatide plus pioglitazone with basal-bolus insulin in people with about 10 years’ duration of type 2 diabetes and A1c above 7.5% taking sulfonylurea plus metformin, the combination therapy produced an A1c of 6.2% versus 7.1% with insulin.
Dr. DeFronzo pointed to new language added to the ADA Standards of Medical Care in Diabetes in 2022.
While still endorsing stepwise therapy, the document also says that “there are data to support initial combination therapy for more rapid attainment of glycemic targets and longer durability of glycemic effect.” The two references cited are EDICT and VERIFY.
“Finally, the American Diabetes Association has gotten the message,” he concluded.
Sequential therapy: Far more data, lower cost
Dr. Nathan began by pointing out that the ADA Standards of Care continue to advise use of metformin as first-line therapy for type 2 diabetes “because of its high efficacy in lowering A1c, minimal hypoglycemia risk when used as monotherapy, weight neutrality with the potential for modest weight loss, good safety profile, and low cost.”
He emphasized that he was not arguing “against the use of early or even initial combination therapy when there are co-existent morbidities [such as cardiovascular or chronic kidney disease] that merit use of demonstrably effective medications.” But Dr. Nathan pointed out, those patients are not the majority with type 2 diabetes.
He laid out four main arguments for choosing traditional sequential therapy over initial combination therapy. For one, it “enables determination of efficacy of adding individual medications, while initial combination precludes determining benefits of individual drugs.”
Second, traditional sequential therapy allows for assessment of side effects from individual drugs.
“With Dr. DeFronzo’s algorithm you throw everything at them, and if they get nausea, vomiting, or diarrhea, you won’t know which drug it is ... If they get an allergic reaction, you won’t know which medication it is,” observed Dr. Nathan, who is director of the clinical research center and the diabetes center at Massachusetts General Hospital, Boston.
Moreover, he said, traditional sequential therapy “promotes individualization, with selection of drugs, which is something we’re laboring to achieve. Initial combination obviously limits that.”
Further, sequential therapy is “parsimonious and cost-effective, whereas initial combination therapy is expensive, with modest advantages at most.”
And, there are “lots of data” supporting traditional sequential therapy and relatively little for initial combination therapy.
Dr. Nathan added that when he searched the literature for relevant randomized clinical trials, he found 16 investigating initial combination therapy versus monotherapy, but only three that examined combination versus sequential therapy.
“Very few of them, except for EDICT and VERIFY, actually include the sequential therapy that we would use in practice,” he said.
Moreover, he observed, except for the VERIFY study, most are less than half a year in duration. And in VERIFY, there was an initial 20% difference in the proportions of patients with A1c below 7.0%, but by 12 months, that difference had shrunk to just 5%-6%.
“So, looking over time is very important,” Dr. Nathan cautioned. “We really have to be careful ... Six months is barely enough time to see A1c equilibrate ... You really need to study a long-term, chronic, progressive disease like type 2 diabetes over a long enough period of time to be clinically meaningful.”
Dr. Nathan acknowledged to Dr. DeFronzo that the latter’s EDICT study was “well conducted” and “long enough,” and that the researchers did examine monotherapy versus sequential therapy. However, he pointed out that it was a small study with 249 patients and the dropout rate was high, with 58% of patients remaining in the study with triple therapy versus 68% for conventional treatment. “That’s a bit problematic,” Dr. Nathan noted.
At 2 years, the “trivial” difference in A1c was 6.5% with conventional therapy versus 6.0% with triple therapy. “This is all on the very flat complications curve with regard to A1c,” he observed.
Patients treated with sequential therapy with sulfonylurea and insulin had higher rates of hypoglycemia and weight gain, whereas the combination triple therapy group had more gastrointestinal side effects and edema.
However, the most dramatic difference was cost: the average wholesale price for sequential therapy totaled about $85 per month, compared with $1,310 for initial combination therapy. For the approximately 1.5 million patients with new-onset type 2 diabetes in the United States, that difference comes to an additional cost per year of about $22 billion, Dr. Nathan calculated.
“Although current sequential therapy leaves much to be desired ... initial combination therapy has generally only been tested for brief, clinically insufficient periods.
“And therefore, I think sequential therapy is still what is called for,” he concluded. “Well-powered, acceptable-duration studies need to be performed before we can adopt initial/early combination therapy as the standard of care.”
Dr. DeFronzo has reported receiving research support from Boehringer Ingelheim, AstraZeneca, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; and participation on a data safety monitoring board or advisory board for AstraZeneca, Intarcia, Novo Nordisk, and Boehringer Ingelheim. Dr. Nathan has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Spirometry predicts mortality in type 2 diabetes
Among adults with type 2 diabetes, the presence of preserved ratio impaired spirometry (PRISm) was significantly associated with increased risk of mortality and both macro- and microvascular complications, as well as increased mortality, based on data from more than 20,000 individuals.
Guochen Li, MD, of the Medical College of Soochow University, Suzhou, China, and colleagues wrote.
“A growing number of studies have demonstrated that impaired lung function and type 2 diabetes could trigger shared pathophysiological injuries, such as microangiopathy and chronic inflammation,” they said, but the potential role of PRISm as an early predictor of adverse outcomes in patients with type 2 diabetes has not been fully examined.
In a study published in the journal Chest, the researchers reviewed data from 20,047 individuals with type 2 diabetes in the UK Biobank, a population-based cohort of adults aged 37-73 years recruited between 2006 and 2010.
The main exposure was lung function based on spirometry. PRISm was defined as predicted forced expiratory volume per second (FEV1) less than 80%, with an FEV1/ forced vital capacity (FVC) ratio of at least 0.70. Individuals with normal spirometry (defined as predicted FEV1 ≥ 80% with an FEV1/FVC ratio ≥ 0.70) served as controls.
The primary outcomes were major complications of type 2 diabetes including macrovascular events (myocardial infarction, unstable angina, coronary heart disease [CHD], ischemic stroke, and any type of stroke), microvascular events (diabetic retinopathy and diabetic kidney disease) and mortality (all-cause, cardiovascular, and respiratory).
Overall, 16.9% of study participants (3385 patients) had obstructive spirometry and 22.6% (4521 patients) had PRISm. Compared with individuals with normal spirometry, those with PRISm were more likely to be current smokers, obese, and living in economically disadvantaged areas. Individuals with PRISm also were significantly more likely to be long-term patients with diabetes who were taking glucose-lowering or lipid-lowering drugs (P < .001 for all).
The median follow-up for each of the type 2 diabetes complications and mortality was approximately 12 years. Over this time, 5.0% of patients developed incident MI, 1.3% developed unstable angina, 15.6% had CHD, 3.5% had an ischemic stroke, and 4.7% had any type of stroke. As for microvascular events, 7.8% developed diabetic retinopathy and 6.7% developed diabetic kidney disease. A total of 2588 patients died during the study period (15.1%), including 544 from cardiovascular disease and 319 from respiratory disease.
PRISm was significantly associated with increased risk of each of the complications and mortality types. These associations persisted after adjusting for lifestyle and other factors. The fully adjusted hazard ratios for PRISm versus normal spirometry were 1.23 for MI, 1.23 for unstable angina, 1.21 for CHD, 1.38 for ischemic stroke, 1.41 for any type of stroke, 1.31 for diabetic retinopathy, and 1.38 for diabetic kidney disease. Adjusted HRs for mortality were 1.34, 1.60, and 1.56 for all-cause, cardiovascular, and respiratory mortality, respectively.
The researchers also found that adding PRISm to an office-based risk score significantly improved the risk classification and predictive power for type 2 diabetes complications with the exception of unstable angina and mortality. They found little evidence for an association with sex, smoking, or PRISm duration and any mortality types. However, in subgroup analyses by age, sex, and duration of diabetes, PRISm remained associated with increased risk of macrovascular and microvascular complications, as well as mortality.
Potential mechanisms for the association between PRISm and diabetes complications include the role of insulin resistance in the exacerbation of lung damage in patients with type 2 diabetes, the increased rate of supplemental oxygen use among individuals with PRISm, and the increased prevalence of pulmonary artery enlargement in the PRISm subjects, the researchers wrote.
The findings were limited by several factors including the prospective design, the homogeneous population of individuals primarily of British or Irish ancestry, and the exclusion of diabetic neuropathy from the analysis, the researchers noted.
However, the results were strengthened by the large cohort, use of professional spirometry, and relatively long follow-up. “The findings underscore the relevance of PRISm for prognostic classification in type 2 diabetes and its potential for optimizing prevention strategies in this condition,” they concluded.
The study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The researchers reported no relevant financial relationships.
A version of this article first appeared on Medscape.com
Among adults with type 2 diabetes, the presence of preserved ratio impaired spirometry (PRISm) was significantly associated with increased risk of mortality and both macro- and microvascular complications, as well as increased mortality, based on data from more than 20,000 individuals.
Guochen Li, MD, of the Medical College of Soochow University, Suzhou, China, and colleagues wrote.
“A growing number of studies have demonstrated that impaired lung function and type 2 diabetes could trigger shared pathophysiological injuries, such as microangiopathy and chronic inflammation,” they said, but the potential role of PRISm as an early predictor of adverse outcomes in patients with type 2 diabetes has not been fully examined.
In a study published in the journal Chest, the researchers reviewed data from 20,047 individuals with type 2 diabetes in the UK Biobank, a population-based cohort of adults aged 37-73 years recruited between 2006 and 2010.
The main exposure was lung function based on spirometry. PRISm was defined as predicted forced expiratory volume per second (FEV1) less than 80%, with an FEV1/ forced vital capacity (FVC) ratio of at least 0.70. Individuals with normal spirometry (defined as predicted FEV1 ≥ 80% with an FEV1/FVC ratio ≥ 0.70) served as controls.
The primary outcomes were major complications of type 2 diabetes including macrovascular events (myocardial infarction, unstable angina, coronary heart disease [CHD], ischemic stroke, and any type of stroke), microvascular events (diabetic retinopathy and diabetic kidney disease) and mortality (all-cause, cardiovascular, and respiratory).
Overall, 16.9% of study participants (3385 patients) had obstructive spirometry and 22.6% (4521 patients) had PRISm. Compared with individuals with normal spirometry, those with PRISm were more likely to be current smokers, obese, and living in economically disadvantaged areas. Individuals with PRISm also were significantly more likely to be long-term patients with diabetes who were taking glucose-lowering or lipid-lowering drugs (P < .001 for all).
The median follow-up for each of the type 2 diabetes complications and mortality was approximately 12 years. Over this time, 5.0% of patients developed incident MI, 1.3% developed unstable angina, 15.6% had CHD, 3.5% had an ischemic stroke, and 4.7% had any type of stroke. As for microvascular events, 7.8% developed diabetic retinopathy and 6.7% developed diabetic kidney disease. A total of 2588 patients died during the study period (15.1%), including 544 from cardiovascular disease and 319 from respiratory disease.
PRISm was significantly associated with increased risk of each of the complications and mortality types. These associations persisted after adjusting for lifestyle and other factors. The fully adjusted hazard ratios for PRISm versus normal spirometry were 1.23 for MI, 1.23 for unstable angina, 1.21 for CHD, 1.38 for ischemic stroke, 1.41 for any type of stroke, 1.31 for diabetic retinopathy, and 1.38 for diabetic kidney disease. Adjusted HRs for mortality were 1.34, 1.60, and 1.56 for all-cause, cardiovascular, and respiratory mortality, respectively.
The researchers also found that adding PRISm to an office-based risk score significantly improved the risk classification and predictive power for type 2 diabetes complications with the exception of unstable angina and mortality. They found little evidence for an association with sex, smoking, or PRISm duration and any mortality types. However, in subgroup analyses by age, sex, and duration of diabetes, PRISm remained associated with increased risk of macrovascular and microvascular complications, as well as mortality.
Potential mechanisms for the association between PRISm and diabetes complications include the role of insulin resistance in the exacerbation of lung damage in patients with type 2 diabetes, the increased rate of supplemental oxygen use among individuals with PRISm, and the increased prevalence of pulmonary artery enlargement in the PRISm subjects, the researchers wrote.
The findings were limited by several factors including the prospective design, the homogeneous population of individuals primarily of British or Irish ancestry, and the exclusion of diabetic neuropathy from the analysis, the researchers noted.
However, the results were strengthened by the large cohort, use of professional spirometry, and relatively long follow-up. “The findings underscore the relevance of PRISm for prognostic classification in type 2 diabetes and its potential for optimizing prevention strategies in this condition,” they concluded.
The study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The researchers reported no relevant financial relationships.
A version of this article first appeared on Medscape.com
Among adults with type 2 diabetes, the presence of preserved ratio impaired spirometry (PRISm) was significantly associated with increased risk of mortality and both macro- and microvascular complications, as well as increased mortality, based on data from more than 20,000 individuals.
Guochen Li, MD, of the Medical College of Soochow University, Suzhou, China, and colleagues wrote.
“A growing number of studies have demonstrated that impaired lung function and type 2 diabetes could trigger shared pathophysiological injuries, such as microangiopathy and chronic inflammation,” they said, but the potential role of PRISm as an early predictor of adverse outcomes in patients with type 2 diabetes has not been fully examined.
In a study published in the journal Chest, the researchers reviewed data from 20,047 individuals with type 2 diabetes in the UK Biobank, a population-based cohort of adults aged 37-73 years recruited between 2006 and 2010.
The main exposure was lung function based on spirometry. PRISm was defined as predicted forced expiratory volume per second (FEV1) less than 80%, with an FEV1/ forced vital capacity (FVC) ratio of at least 0.70. Individuals with normal spirometry (defined as predicted FEV1 ≥ 80% with an FEV1/FVC ratio ≥ 0.70) served as controls.
The primary outcomes were major complications of type 2 diabetes including macrovascular events (myocardial infarction, unstable angina, coronary heart disease [CHD], ischemic stroke, and any type of stroke), microvascular events (diabetic retinopathy and diabetic kidney disease) and mortality (all-cause, cardiovascular, and respiratory).
Overall, 16.9% of study participants (3385 patients) had obstructive spirometry and 22.6% (4521 patients) had PRISm. Compared with individuals with normal spirometry, those with PRISm were more likely to be current smokers, obese, and living in economically disadvantaged areas. Individuals with PRISm also were significantly more likely to be long-term patients with diabetes who were taking glucose-lowering or lipid-lowering drugs (P < .001 for all).
The median follow-up for each of the type 2 diabetes complications and mortality was approximately 12 years. Over this time, 5.0% of patients developed incident MI, 1.3% developed unstable angina, 15.6% had CHD, 3.5% had an ischemic stroke, and 4.7% had any type of stroke. As for microvascular events, 7.8% developed diabetic retinopathy and 6.7% developed diabetic kidney disease. A total of 2588 patients died during the study period (15.1%), including 544 from cardiovascular disease and 319 from respiratory disease.
PRISm was significantly associated with increased risk of each of the complications and mortality types. These associations persisted after adjusting for lifestyle and other factors. The fully adjusted hazard ratios for PRISm versus normal spirometry were 1.23 for MI, 1.23 for unstable angina, 1.21 for CHD, 1.38 for ischemic stroke, 1.41 for any type of stroke, 1.31 for diabetic retinopathy, and 1.38 for diabetic kidney disease. Adjusted HRs for mortality were 1.34, 1.60, and 1.56 for all-cause, cardiovascular, and respiratory mortality, respectively.
The researchers also found that adding PRISm to an office-based risk score significantly improved the risk classification and predictive power for type 2 diabetes complications with the exception of unstable angina and mortality. They found little evidence for an association with sex, smoking, or PRISm duration and any mortality types. However, in subgroup analyses by age, sex, and duration of diabetes, PRISm remained associated with increased risk of macrovascular and microvascular complications, as well as mortality.
Potential mechanisms for the association between PRISm and diabetes complications include the role of insulin resistance in the exacerbation of lung damage in patients with type 2 diabetes, the increased rate of supplemental oxygen use among individuals with PRISm, and the increased prevalence of pulmonary artery enlargement in the PRISm subjects, the researchers wrote.
The findings were limited by several factors including the prospective design, the homogeneous population of individuals primarily of British or Irish ancestry, and the exclusion of diabetic neuropathy from the analysis, the researchers noted.
However, the results were strengthened by the large cohort, use of professional spirometry, and relatively long follow-up. “The findings underscore the relevance of PRISm for prognostic classification in type 2 diabetes and its potential for optimizing prevention strategies in this condition,” they concluded.
The study was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The researchers reported no relevant financial relationships.
A version of this article first appeared on Medscape.com
FROM THE JOURNAL CHEST
Evidence weighed for suicide/self-harm with obesity drugs
Following reports that the European Medicines Agency is looking into instances of suicide or self-harm after patients took the weight loss drugs semaglutide or liraglutide, the manufacturer, Novo Nordisk, issued a statement to this news organization in which it says it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”
U.S. experts say they haven’t personally seen this adverse effect in any patients except for one isolated case. An increase in suicidal ideation, particularly among younger people, has been reported following bariatric surgery for weight loss.
In the United States, the two drugs – both GLP-1 agonists – already come with a warning about the potential for these adverse effects on the branded versions approved for weight loss, Wegovy and Saxenda. (Years earlier, both drugs, marketed as Ozempic and Victoza, were also approved for treatment of type 2 diabetes.)
Of more than 1,200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and 7 suicide attempts have been reported since 2018, according to the Food and Drug Administration’s Adverse Event Reporting System (FAERS) public database. For liraglutide, there were 71 cases of suicidal ideation, 28 suicide attempts, and 25 completed suicides out of more than 35,000 reports of adverse reactions.
The FAERS website cautions users that the data may be duplicated or incomplete, that rates of occurrence cannot be established using the data, that reports have not been verified, and that the existence of a report cannot establish causation.
The EMA is looking into about 150 reports of possible cases of self-injury and suicidal thoughts, according to a press release from the agency.
“It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors,” it says. The medicines are widely used in the European Union, according to the press release.
The review of Ozempic, Saxenda, and Wegovy, which started on July 3, 2023, has been extended to include other GLP-1 receptor agonists, which include dulaglutide, exenatide, and lixisenatide. This review is expected to conclude in November 2023.
In a statement, Novo Nordisk did not directly dispute a potential link between the drugs and suicidal ideation.
“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation,” the statement indicates. “This event had been reported in clinical trials with other weight management products.”
It adds: “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”
Important to know the denominator
“What’s important to know is the denominator,” said Holly Lofton, MD, a clinical associate professor of surgery and medicine and the director of the medical weight management program at NYU Langone, New York. “It needs a denominator with the total population on the medication so we can determine if that’s really a significant risk.”
Dr. Lofton described an isolated, anecdotal case of a patient who had no history of depression or mental health problems but developed suicidal thoughts after taking Saxenda for several months. In that case, the 25-year-old was experiencing problems in a personal relationship and with social media.
Two other weight loss specialists contacted by this news organization had not had patients who had experienced suicidal ideation with the drugs. “These are not very common in practice,” Dr. Lofton said in an interview.
The U.S. prescribing information for Saxenda, which contains liraglutide and has been approved as an adjunct to diet and exercise for chronic weight management, recommends monitoring for the emergence of depression and suicidal thoughts. In the clinical trials, 6 of the 3,384 patients who took the drug reported suicidal ideation; none of the 1,941 patients who received placebo did so, according to the FDA.
Similarly, the U.S. prescribing information for Wegovy, which contains semaglutide, recommends monitoring for the emergence of suicidal thoughts or depression, but this recommendation was based on clinical trials of other weight management products. The prescribing information for Ozempic, the brand name for semaglutide for type 2 diabetes, does not include this recommendation.
Is it the weight loss, rather than the meds? Seen with bariatric surgery too
Speculating what the link, if any, might be, Dr. Lofton suggested dopamine release could be playing a role. Small trials in humans as well as animal studies hint at a blunting of dopamine responses to usual triggers – including addictive substances and possibly food – that may also affect mood.
Young people (aged 18-34) who undergo bariatric surgery are at an increased risk of suicide during follow-up compared to their peers who don’t have surgery. And a study found an increase in events involving self-harm after bariatric surgery, especially among patients who already had a mental health disorder.
For a patient who derives comfort from food, not being able to eat in response to a stressful event may lead that patient to act out in more serious ways, according to Dr. Lofton. “That’s why, again, surgical follow-up is so important and their presurgical psychiatric evaluation is so important.”
A version of this article originally appeared on Medscape.com.
Following reports that the European Medicines Agency is looking into instances of suicide or self-harm after patients took the weight loss drugs semaglutide or liraglutide, the manufacturer, Novo Nordisk, issued a statement to this news organization in which it says it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”
U.S. experts say they haven’t personally seen this adverse effect in any patients except for one isolated case. An increase in suicidal ideation, particularly among younger people, has been reported following bariatric surgery for weight loss.
In the United States, the two drugs – both GLP-1 agonists – already come with a warning about the potential for these adverse effects on the branded versions approved for weight loss, Wegovy and Saxenda. (Years earlier, both drugs, marketed as Ozempic and Victoza, were also approved for treatment of type 2 diabetes.)
Of more than 1,200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and 7 suicide attempts have been reported since 2018, according to the Food and Drug Administration’s Adverse Event Reporting System (FAERS) public database. For liraglutide, there were 71 cases of suicidal ideation, 28 suicide attempts, and 25 completed suicides out of more than 35,000 reports of adverse reactions.
The FAERS website cautions users that the data may be duplicated or incomplete, that rates of occurrence cannot be established using the data, that reports have not been verified, and that the existence of a report cannot establish causation.
The EMA is looking into about 150 reports of possible cases of self-injury and suicidal thoughts, according to a press release from the agency.
“It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors,” it says. The medicines are widely used in the European Union, according to the press release.
The review of Ozempic, Saxenda, and Wegovy, which started on July 3, 2023, has been extended to include other GLP-1 receptor agonists, which include dulaglutide, exenatide, and lixisenatide. This review is expected to conclude in November 2023.
In a statement, Novo Nordisk did not directly dispute a potential link between the drugs and suicidal ideation.
“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation,” the statement indicates. “This event had been reported in clinical trials with other weight management products.”
It adds: “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”
Important to know the denominator
“What’s important to know is the denominator,” said Holly Lofton, MD, a clinical associate professor of surgery and medicine and the director of the medical weight management program at NYU Langone, New York. “It needs a denominator with the total population on the medication so we can determine if that’s really a significant risk.”
Dr. Lofton described an isolated, anecdotal case of a patient who had no history of depression or mental health problems but developed suicidal thoughts after taking Saxenda for several months. In that case, the 25-year-old was experiencing problems in a personal relationship and with social media.
Two other weight loss specialists contacted by this news organization had not had patients who had experienced suicidal ideation with the drugs. “These are not very common in practice,” Dr. Lofton said in an interview.
The U.S. prescribing information for Saxenda, which contains liraglutide and has been approved as an adjunct to diet and exercise for chronic weight management, recommends monitoring for the emergence of depression and suicidal thoughts. In the clinical trials, 6 of the 3,384 patients who took the drug reported suicidal ideation; none of the 1,941 patients who received placebo did so, according to the FDA.
Similarly, the U.S. prescribing information for Wegovy, which contains semaglutide, recommends monitoring for the emergence of suicidal thoughts or depression, but this recommendation was based on clinical trials of other weight management products. The prescribing information for Ozempic, the brand name for semaglutide for type 2 diabetes, does not include this recommendation.
Is it the weight loss, rather than the meds? Seen with bariatric surgery too
Speculating what the link, if any, might be, Dr. Lofton suggested dopamine release could be playing a role. Small trials in humans as well as animal studies hint at a blunting of dopamine responses to usual triggers – including addictive substances and possibly food – that may also affect mood.
Young people (aged 18-34) who undergo bariatric surgery are at an increased risk of suicide during follow-up compared to their peers who don’t have surgery. And a study found an increase in events involving self-harm after bariatric surgery, especially among patients who already had a mental health disorder.
For a patient who derives comfort from food, not being able to eat in response to a stressful event may lead that patient to act out in more serious ways, according to Dr. Lofton. “That’s why, again, surgical follow-up is so important and their presurgical psychiatric evaluation is so important.”
A version of this article originally appeared on Medscape.com.
Following reports that the European Medicines Agency is looking into instances of suicide or self-harm after patients took the weight loss drugs semaglutide or liraglutide, the manufacturer, Novo Nordisk, issued a statement to this news organization in which it says it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”
U.S. experts say they haven’t personally seen this adverse effect in any patients except for one isolated case. An increase in suicidal ideation, particularly among younger people, has been reported following bariatric surgery for weight loss.
In the United States, the two drugs – both GLP-1 agonists – already come with a warning about the potential for these adverse effects on the branded versions approved for weight loss, Wegovy and Saxenda. (Years earlier, both drugs, marketed as Ozempic and Victoza, were also approved for treatment of type 2 diabetes.)
Of more than 1,200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and 7 suicide attempts have been reported since 2018, according to the Food and Drug Administration’s Adverse Event Reporting System (FAERS) public database. For liraglutide, there were 71 cases of suicidal ideation, 28 suicide attempts, and 25 completed suicides out of more than 35,000 reports of adverse reactions.
The FAERS website cautions users that the data may be duplicated or incomplete, that rates of occurrence cannot be established using the data, that reports have not been verified, and that the existence of a report cannot establish causation.
The EMA is looking into about 150 reports of possible cases of self-injury and suicidal thoughts, according to a press release from the agency.
“It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors,” it says. The medicines are widely used in the European Union, according to the press release.
The review of Ozempic, Saxenda, and Wegovy, which started on July 3, 2023, has been extended to include other GLP-1 receptor agonists, which include dulaglutide, exenatide, and lixisenatide. This review is expected to conclude in November 2023.
In a statement, Novo Nordisk did not directly dispute a potential link between the drugs and suicidal ideation.
“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation,” the statement indicates. “This event had been reported in clinical trials with other weight management products.”
It adds: “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”
Important to know the denominator
“What’s important to know is the denominator,” said Holly Lofton, MD, a clinical associate professor of surgery and medicine and the director of the medical weight management program at NYU Langone, New York. “It needs a denominator with the total population on the medication so we can determine if that’s really a significant risk.”
Dr. Lofton described an isolated, anecdotal case of a patient who had no history of depression or mental health problems but developed suicidal thoughts after taking Saxenda for several months. In that case, the 25-year-old was experiencing problems in a personal relationship and with social media.
Two other weight loss specialists contacted by this news organization had not had patients who had experienced suicidal ideation with the drugs. “These are not very common in practice,” Dr. Lofton said in an interview.
The U.S. prescribing information for Saxenda, which contains liraglutide and has been approved as an adjunct to diet and exercise for chronic weight management, recommends monitoring for the emergence of depression and suicidal thoughts. In the clinical trials, 6 of the 3,384 patients who took the drug reported suicidal ideation; none of the 1,941 patients who received placebo did so, according to the FDA.
Similarly, the U.S. prescribing information for Wegovy, which contains semaglutide, recommends monitoring for the emergence of suicidal thoughts or depression, but this recommendation was based on clinical trials of other weight management products. The prescribing information for Ozempic, the brand name for semaglutide for type 2 diabetes, does not include this recommendation.
Is it the weight loss, rather than the meds? Seen with bariatric surgery too
Speculating what the link, if any, might be, Dr. Lofton suggested dopamine release could be playing a role. Small trials in humans as well as animal studies hint at a blunting of dopamine responses to usual triggers – including addictive substances and possibly food – that may also affect mood.
Young people (aged 18-34) who undergo bariatric surgery are at an increased risk of suicide during follow-up compared to their peers who don’t have surgery. And a study found an increase in events involving self-harm after bariatric surgery, especially among patients who already had a mental health disorder.
For a patient who derives comfort from food, not being able to eat in response to a stressful event may lead that patient to act out in more serious ways, according to Dr. Lofton. “That’s why, again, surgical follow-up is so important and their presurgical psychiatric evaluation is so important.”
A version of this article originally appeared on Medscape.com.
FDA clears the Tandem Mobi insulin pump
The product is half the size of the company’s t:slim X2 and is now the smallest of the commercially available durable tubed pumps. It is fully controllable from a mobile app through a user’s compatible iPhone.
Features of the Mobi include a 200-unit insulin cartridge and an on-pump button that can be used instead of the phone for bolusing insulin. The device can be clipped to clothing or worn on-body with an adhesive sleeve that is sold separately.
The Mobi is compatible with all existing Tandem-branded infusion sets manufactured by the Convatec Group, and there is a new 5-inch tubing option made just for the Tandem Mobi.
The Mobi is part of a hybrid-closed loop automated delivery system, along with the current Control-IQ technology and a compatible continuous glucose monitor (CGM). The CGM sensor predicts glucose values 30 minutes ahead and adjusts insulin delivery every 5 minutes to prevent highs and lows. Users must still manually bolus for meals. The system can deliver automatic correction boluses for up to 1 hour to prevent hyperglycemia.
Limited release of the Tandem Mobi is expected in late 2023, followed by full commercial availability in early 2024.
A version of this article originally appeared on Medscape.com.
The product is half the size of the company’s t:slim X2 and is now the smallest of the commercially available durable tubed pumps. It is fully controllable from a mobile app through a user’s compatible iPhone.
Features of the Mobi include a 200-unit insulin cartridge and an on-pump button that can be used instead of the phone for bolusing insulin. The device can be clipped to clothing or worn on-body with an adhesive sleeve that is sold separately.
The Mobi is compatible with all existing Tandem-branded infusion sets manufactured by the Convatec Group, and there is a new 5-inch tubing option made just for the Tandem Mobi.
The Mobi is part of a hybrid-closed loop automated delivery system, along with the current Control-IQ technology and a compatible continuous glucose monitor (CGM). The CGM sensor predicts glucose values 30 minutes ahead and adjusts insulin delivery every 5 minutes to prevent highs and lows. Users must still manually bolus for meals. The system can deliver automatic correction boluses for up to 1 hour to prevent hyperglycemia.
Limited release of the Tandem Mobi is expected in late 2023, followed by full commercial availability in early 2024.
A version of this article originally appeared on Medscape.com.
The product is half the size of the company’s t:slim X2 and is now the smallest of the commercially available durable tubed pumps. It is fully controllable from a mobile app through a user’s compatible iPhone.
Features of the Mobi include a 200-unit insulin cartridge and an on-pump button that can be used instead of the phone for bolusing insulin. The device can be clipped to clothing or worn on-body with an adhesive sleeve that is sold separately.
The Mobi is compatible with all existing Tandem-branded infusion sets manufactured by the Convatec Group, and there is a new 5-inch tubing option made just for the Tandem Mobi.
The Mobi is part of a hybrid-closed loop automated delivery system, along with the current Control-IQ technology and a compatible continuous glucose monitor (CGM). The CGM sensor predicts glucose values 30 minutes ahead and adjusts insulin delivery every 5 minutes to prevent highs and lows. Users must still manually bolus for meals. The system can deliver automatic correction boluses for up to 1 hour to prevent hyperglycemia.
Limited release of the Tandem Mobi is expected in late 2023, followed by full commercial availability in early 2024.
A version of this article originally appeared on Medscape.com.
Link between low co-pays for new diabetes drugs and patient adherence
Findings from a recent study indicate that the less U.S. patients pay out of pocket for drugs that often have high co-pays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagonlike peptide-1 (GLP-1) agonists, the more they adhere to taking these medications.
The study, led by Utibe R. Essien, MD, from University of California, Los Angeles, and Balvindar Singh, MD, PhD, from University of Pittsburgh, was published online in JAMA Cardiology.
Patient data from Clinformatics Data Mart, a health insurance claims database, was analyzed for the study. The information for 90,041 adults from the United States who had commercial and Medicare health insurance, and who started taking a GLP-1 agonist or SGLT2 inhibitor between 2014 and 2020 was reviewed. Participants had type 2 diabetes, heart failure, or both.
The primary outcome showed patients with a lower drug co-pay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher co-pay. These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
After full adjustments were made and after the 12 months, patients with a high co-pay of $50 per month or more were 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a co-pay of less than $10 per month for these agents.
“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” the authors conclude.
The authors acknowledge the study’s limitations, including the inability to exclude residual confounding, uncertain generalizability for those without health insurance or with public insurance and possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities. Additionally, this study did not have information on patients’ preferences associated with medication use, including specific reasons for poor adherence, and could not assess how co-payments influenced initial prescription receipt or abandonment at the pharmacy, or other factors including possible price inflation.
The study received no commercial funding. One author (not a lead author) is an adviser to several drug companies including ones that market SGLT2 inhibitors or GLP-1 agonists.
Findings from a recent study indicate that the less U.S. patients pay out of pocket for drugs that often have high co-pays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagonlike peptide-1 (GLP-1) agonists, the more they adhere to taking these medications.
The study, led by Utibe R. Essien, MD, from University of California, Los Angeles, and Balvindar Singh, MD, PhD, from University of Pittsburgh, was published online in JAMA Cardiology.
Patient data from Clinformatics Data Mart, a health insurance claims database, was analyzed for the study. The information for 90,041 adults from the United States who had commercial and Medicare health insurance, and who started taking a GLP-1 agonist or SGLT2 inhibitor between 2014 and 2020 was reviewed. Participants had type 2 diabetes, heart failure, or both.
The primary outcome showed patients with a lower drug co-pay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher co-pay. These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
After full adjustments were made and after the 12 months, patients with a high co-pay of $50 per month or more were 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a co-pay of less than $10 per month for these agents.
“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” the authors conclude.
The authors acknowledge the study’s limitations, including the inability to exclude residual confounding, uncertain generalizability for those without health insurance or with public insurance and possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities. Additionally, this study did not have information on patients’ preferences associated with medication use, including specific reasons for poor adherence, and could not assess how co-payments influenced initial prescription receipt or abandonment at the pharmacy, or other factors including possible price inflation.
The study received no commercial funding. One author (not a lead author) is an adviser to several drug companies including ones that market SGLT2 inhibitors or GLP-1 agonists.
Findings from a recent study indicate that the less U.S. patients pay out of pocket for drugs that often have high co-pays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagonlike peptide-1 (GLP-1) agonists, the more they adhere to taking these medications.
The study, led by Utibe R. Essien, MD, from University of California, Los Angeles, and Balvindar Singh, MD, PhD, from University of Pittsburgh, was published online in JAMA Cardiology.
Patient data from Clinformatics Data Mart, a health insurance claims database, was analyzed for the study. The information for 90,041 adults from the United States who had commercial and Medicare health insurance, and who started taking a GLP-1 agonist or SGLT2 inhibitor between 2014 and 2020 was reviewed. Participants had type 2 diabetes, heart failure, or both.
The primary outcome showed patients with a lower drug co-pay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher co-pay. These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
After full adjustments were made and after the 12 months, patients with a high co-pay of $50 per month or more were 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a co-pay of less than $10 per month for these agents.
“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” the authors conclude.
The authors acknowledge the study’s limitations, including the inability to exclude residual confounding, uncertain generalizability for those without health insurance or with public insurance and possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities. Additionally, this study did not have information on patients’ preferences associated with medication use, including specific reasons for poor adherence, and could not assess how co-payments influenced initial prescription receipt or abandonment at the pharmacy, or other factors including possible price inflation.
The study received no commercial funding. One author (not a lead author) is an adviser to several drug companies including ones that market SGLT2 inhibitors or GLP-1 agonists.
FROM JAMA CARDIOLOGY
FDA approves cognitive-behavioral app for adults with type 2 diabetes
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
Aging and type 1 diabetes: ‘Complete picture’ 40 years on
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Weighing childhood obesity interventions
A teenager who weighed 300 lb and was homeschooled because he was too big to fit in a classroom chair is among the patients Manal Habib, MD, has seen in her pediatric endocrinology practice.
The boy, a social butterfly who hated isolation and blamed himself for his “poor choices,” turned out to have an MC4R mutation that interfered with proper metabolism and satiation signals.
“People often blame obese and overweight people for not having enough willpower, but it’s often a physiological problem,” said Dr. Habib, who works at the University of California, Los Angeles.
She is among the clinicians offering more aggressive forms of weight management, prescribing medications, including metformin, semaglutide, and liraglutide – often off-label – to help children and teens with obesity who do not respond to lifestyle changes.
The results of intensive interventions can be life-changing: The teen Dr. Habib treated is back at school, playing sports, and no longer needs drugs to reduce cholesterol and blood pressure. He now takes a low maintenance dose of a weight-loss medication.
But the long-term effects of these new agents on children and teens are poorly understood, and both medication and surgery are associated with significant complications. Pediatricians treating kids pre- or post-intervention should be alert to a range of physical, psychological, and behavioral risks and complications.
Keeping bones healthy
Pediatricians should be aware of the risk to bone health in patients who undergo surgery, according to Misra Madhusmita, MD, chief of pediatric endocrinology at Massachusetts General Hospital in Boston. In a recent study, Dr. Madhusmita and her colleagues found that sleeve gastrectomy reduced vertebral bone strength in adolescents and young adults.
“This is a time of life when bone mass is typically accruing rapidly,” Dr. Madhusmita told this news organization. “A deleterious effect on bone accrual at this time of life raises concerns about suboptimal acquisition of peak bone mass, which is typically attained in early adult life and is a key factor determining bone health and fracture risk in later life.”
Reduced skeletal loading and muscle mass can weaken bones, as can malabsorption of nutrients. Fat loss can trigger lower levels of bioavailable androgens and their subsequent conversion to estrogen, negatively affecting bone density. And sleeve gastrectomy in particular lowers ghrelin, another hormone influencing skeletal health.
Clinicians should advise patients who have had surgery to follow a healthy diet and consume sufficient levels of calcium and vitamin D, said Dr. Madhusmita. Weight-bearing exercises, weight training, and resistance training are also imperative to build bone mass and muscle. Any preexisting conditions or lifestyle factors that weaken the bones should be taken into consideration.
Managing expectations
The long-term effects of weight loss medications on children are less documented than with surgery, according to Caren Mangarelli, MD, a former primary care physician who is now medical director of both the adolescent bariatric program and the children’s wellness and weight management clinic at Lurie Children’s Hospital in Chicago, Ill.
But one significant known risk is the potential for rebound weight gain and the complications like high blood pressure and high blood sugar that go with it if the patient stops medication. Dr. Mangarelli said that many clinicians lack the training required to safely facilitate weight loss medications for kids.
“We have to remember that obesity is a chronic disease, especially for those with more severe forms,” she said. “They’re not likely to outgrow it. It’s not like, ‘Oh, we’ll just put a patient on medication, they’ll lose weight, and we’ll take them off of it,’ because you could create a bad cycle of losing weight, followed by metabolism slowing down, hunger cues going up, and weight going back up.”
Making the risks of stopping medication clear and supporting compliance are essential, especially when it comes to injectables like semaglutide, which can be more burdensome than taking pills, requiring weekly subcutaneous injections. Pediatricians should ensure that families understand that medication is a long-term solution, Dr. Habib said.
Many families and patients “want a quick result. They’re focused on a specific size or weight, and they want to take the medication for a short period without changing anything else,” Dr. Habib said.
But children with genetic abnormalities or severe obesity could be on medication for their entire lives. Patients who make significant healthy lifestyle changes have a greater chance of weaning off drug therapy.
But “it’s hard with children because they’re dependent on their family,” Dr. Habib said. “One of the first things that I talk about with families is that it’s very important for everyone to be involved in making healthy changes, especially the parents, because the kids are going to follow their lifestyle and choices, not necessarily what they tell them to do.”
The behavioral and mental
One of Dr. Habib’s most striking cases was a 6-year-old patient with autism spectrum disorder experiencing early-onset puberty. Her condition made it difficult for her parents to enforce behavioral and lifestyle changes, making medication the best option to normalize the young girl’s body.
“The goal in this case is not necessarily to help her lose weight, but to prevent her from having severe health risks at such a young age,” said Habib.
Though medication may be the best solution when other options have failed, the ease of using medication may mean clinicians fail to address the complex emotional and psychosocial factors that can both cause and result from obesity.
“A lot of families think that if just this one thing were better, everything else would fall into place,” Habib said. “But there often are multiple layers to treating the patient.”
According to Cambria Garrell, MD, a pediatrician at the UCLA Fit for Healthy Weight Program in Los Angeles, pediatricians should be aware of the psychosocial and mental health factors such as undiagnosed mental illness or family dysfunction.
Dr. Garrell sometimes cares for children with undiagnosed mental health disorders. Children with conditions like attention-deficit/hyperactivity disorder and autism spectrum disorders may struggle with eating because of impulse control and sensory processing issues. Family functioning, issues at school, and lack of sleep are also major contributors to obesity to screen for.
“We really like to think about the environmental and psychosocial factors contributing to obesity instead of just pathologizing the weight,” Dr. Garrell said.
Risk for alcohol abuse
Bariatric and metabolic surgeries are associated with an increased risk for alcohol use disorder (AUD). Pediatricians treating children pre- or post-op should ensure that patients receive behavioral and mental health services to minimize the risk for alcohol abuse.
The risk for AUD is likely the result of changes to the way the body metabolizes alcohol, resulting in heightened sensitivity to it, although research is not conclusive, according to Dr. Mangarelli.
The risk for AUD is likely multifactorial, Dr. Mangarelli said.
“We don’t totally understand all of it, but if you’re experiencing a high more easily, that may lead to misuse,” Dr. Mangarelli said. “It’s also important to remember that this population of patients has experienced stigma for a very long time, and they often have associated mental health and body image issues.”
“Those problems don’t disappear on their own,” she added. “You want to make sure that patients are hooked into behavioral and mental health services before surgery so that they have somebody who’s following them after surgery.”
A version of this article first appeared on Medscape.com.
A teenager who weighed 300 lb and was homeschooled because he was too big to fit in a classroom chair is among the patients Manal Habib, MD, has seen in her pediatric endocrinology practice.
The boy, a social butterfly who hated isolation and blamed himself for his “poor choices,” turned out to have an MC4R mutation that interfered with proper metabolism and satiation signals.
“People often blame obese and overweight people for not having enough willpower, but it’s often a physiological problem,” said Dr. Habib, who works at the University of California, Los Angeles.
She is among the clinicians offering more aggressive forms of weight management, prescribing medications, including metformin, semaglutide, and liraglutide – often off-label – to help children and teens with obesity who do not respond to lifestyle changes.
The results of intensive interventions can be life-changing: The teen Dr. Habib treated is back at school, playing sports, and no longer needs drugs to reduce cholesterol and blood pressure. He now takes a low maintenance dose of a weight-loss medication.
But the long-term effects of these new agents on children and teens are poorly understood, and both medication and surgery are associated with significant complications. Pediatricians treating kids pre- or post-intervention should be alert to a range of physical, psychological, and behavioral risks and complications.
Keeping bones healthy
Pediatricians should be aware of the risk to bone health in patients who undergo surgery, according to Misra Madhusmita, MD, chief of pediatric endocrinology at Massachusetts General Hospital in Boston. In a recent study, Dr. Madhusmita and her colleagues found that sleeve gastrectomy reduced vertebral bone strength in adolescents and young adults.
“This is a time of life when bone mass is typically accruing rapidly,” Dr. Madhusmita told this news organization. “A deleterious effect on bone accrual at this time of life raises concerns about suboptimal acquisition of peak bone mass, which is typically attained in early adult life and is a key factor determining bone health and fracture risk in later life.”
Reduced skeletal loading and muscle mass can weaken bones, as can malabsorption of nutrients. Fat loss can trigger lower levels of bioavailable androgens and their subsequent conversion to estrogen, negatively affecting bone density. And sleeve gastrectomy in particular lowers ghrelin, another hormone influencing skeletal health.
Clinicians should advise patients who have had surgery to follow a healthy diet and consume sufficient levels of calcium and vitamin D, said Dr. Madhusmita. Weight-bearing exercises, weight training, and resistance training are also imperative to build bone mass and muscle. Any preexisting conditions or lifestyle factors that weaken the bones should be taken into consideration.
Managing expectations
The long-term effects of weight loss medications on children are less documented than with surgery, according to Caren Mangarelli, MD, a former primary care physician who is now medical director of both the adolescent bariatric program and the children’s wellness and weight management clinic at Lurie Children’s Hospital in Chicago, Ill.
But one significant known risk is the potential for rebound weight gain and the complications like high blood pressure and high blood sugar that go with it if the patient stops medication. Dr. Mangarelli said that many clinicians lack the training required to safely facilitate weight loss medications for kids.
“We have to remember that obesity is a chronic disease, especially for those with more severe forms,” she said. “They’re not likely to outgrow it. It’s not like, ‘Oh, we’ll just put a patient on medication, they’ll lose weight, and we’ll take them off of it,’ because you could create a bad cycle of losing weight, followed by metabolism slowing down, hunger cues going up, and weight going back up.”
Making the risks of stopping medication clear and supporting compliance are essential, especially when it comes to injectables like semaglutide, which can be more burdensome than taking pills, requiring weekly subcutaneous injections. Pediatricians should ensure that families understand that medication is a long-term solution, Dr. Habib said.
Many families and patients “want a quick result. They’re focused on a specific size or weight, and they want to take the medication for a short period without changing anything else,” Dr. Habib said.
But children with genetic abnormalities or severe obesity could be on medication for their entire lives. Patients who make significant healthy lifestyle changes have a greater chance of weaning off drug therapy.
But “it’s hard with children because they’re dependent on their family,” Dr. Habib said. “One of the first things that I talk about with families is that it’s very important for everyone to be involved in making healthy changes, especially the parents, because the kids are going to follow their lifestyle and choices, not necessarily what they tell them to do.”
The behavioral and mental
One of Dr. Habib’s most striking cases was a 6-year-old patient with autism spectrum disorder experiencing early-onset puberty. Her condition made it difficult for her parents to enforce behavioral and lifestyle changes, making medication the best option to normalize the young girl’s body.
“The goal in this case is not necessarily to help her lose weight, but to prevent her from having severe health risks at such a young age,” said Habib.
Though medication may be the best solution when other options have failed, the ease of using medication may mean clinicians fail to address the complex emotional and psychosocial factors that can both cause and result from obesity.
“A lot of families think that if just this one thing were better, everything else would fall into place,” Habib said. “But there often are multiple layers to treating the patient.”
According to Cambria Garrell, MD, a pediatrician at the UCLA Fit for Healthy Weight Program in Los Angeles, pediatricians should be aware of the psychosocial and mental health factors such as undiagnosed mental illness or family dysfunction.
Dr. Garrell sometimes cares for children with undiagnosed mental health disorders. Children with conditions like attention-deficit/hyperactivity disorder and autism spectrum disorders may struggle with eating because of impulse control and sensory processing issues. Family functioning, issues at school, and lack of sleep are also major contributors to obesity to screen for.
“We really like to think about the environmental and psychosocial factors contributing to obesity instead of just pathologizing the weight,” Dr. Garrell said.
Risk for alcohol abuse
Bariatric and metabolic surgeries are associated with an increased risk for alcohol use disorder (AUD). Pediatricians treating children pre- or post-op should ensure that patients receive behavioral and mental health services to minimize the risk for alcohol abuse.
The risk for AUD is likely the result of changes to the way the body metabolizes alcohol, resulting in heightened sensitivity to it, although research is not conclusive, according to Dr. Mangarelli.
The risk for AUD is likely multifactorial, Dr. Mangarelli said.
“We don’t totally understand all of it, but if you’re experiencing a high more easily, that may lead to misuse,” Dr. Mangarelli said. “It’s also important to remember that this population of patients has experienced stigma for a very long time, and they often have associated mental health and body image issues.”
“Those problems don’t disappear on their own,” she added. “You want to make sure that patients are hooked into behavioral and mental health services before surgery so that they have somebody who’s following them after surgery.”
A version of this article first appeared on Medscape.com.
A teenager who weighed 300 lb and was homeschooled because he was too big to fit in a classroom chair is among the patients Manal Habib, MD, has seen in her pediatric endocrinology practice.
The boy, a social butterfly who hated isolation and blamed himself for his “poor choices,” turned out to have an MC4R mutation that interfered with proper metabolism and satiation signals.
“People often blame obese and overweight people for not having enough willpower, but it’s often a physiological problem,” said Dr. Habib, who works at the University of California, Los Angeles.
She is among the clinicians offering more aggressive forms of weight management, prescribing medications, including metformin, semaglutide, and liraglutide – often off-label – to help children and teens with obesity who do not respond to lifestyle changes.
The results of intensive interventions can be life-changing: The teen Dr. Habib treated is back at school, playing sports, and no longer needs drugs to reduce cholesterol and blood pressure. He now takes a low maintenance dose of a weight-loss medication.
But the long-term effects of these new agents on children and teens are poorly understood, and both medication and surgery are associated with significant complications. Pediatricians treating kids pre- or post-intervention should be alert to a range of physical, psychological, and behavioral risks and complications.
Keeping bones healthy
Pediatricians should be aware of the risk to bone health in patients who undergo surgery, according to Misra Madhusmita, MD, chief of pediatric endocrinology at Massachusetts General Hospital in Boston. In a recent study, Dr. Madhusmita and her colleagues found that sleeve gastrectomy reduced vertebral bone strength in adolescents and young adults.
“This is a time of life when bone mass is typically accruing rapidly,” Dr. Madhusmita told this news organization. “A deleterious effect on bone accrual at this time of life raises concerns about suboptimal acquisition of peak bone mass, which is typically attained in early adult life and is a key factor determining bone health and fracture risk in later life.”
Reduced skeletal loading and muscle mass can weaken bones, as can malabsorption of nutrients. Fat loss can trigger lower levels of bioavailable androgens and their subsequent conversion to estrogen, negatively affecting bone density. And sleeve gastrectomy in particular lowers ghrelin, another hormone influencing skeletal health.
Clinicians should advise patients who have had surgery to follow a healthy diet and consume sufficient levels of calcium and vitamin D, said Dr. Madhusmita. Weight-bearing exercises, weight training, and resistance training are also imperative to build bone mass and muscle. Any preexisting conditions or lifestyle factors that weaken the bones should be taken into consideration.
Managing expectations
The long-term effects of weight loss medications on children are less documented than with surgery, according to Caren Mangarelli, MD, a former primary care physician who is now medical director of both the adolescent bariatric program and the children’s wellness and weight management clinic at Lurie Children’s Hospital in Chicago, Ill.
But one significant known risk is the potential for rebound weight gain and the complications like high blood pressure and high blood sugar that go with it if the patient stops medication. Dr. Mangarelli said that many clinicians lack the training required to safely facilitate weight loss medications for kids.
“We have to remember that obesity is a chronic disease, especially for those with more severe forms,” she said. “They’re not likely to outgrow it. It’s not like, ‘Oh, we’ll just put a patient on medication, they’ll lose weight, and we’ll take them off of it,’ because you could create a bad cycle of losing weight, followed by metabolism slowing down, hunger cues going up, and weight going back up.”
Making the risks of stopping medication clear and supporting compliance are essential, especially when it comes to injectables like semaglutide, which can be more burdensome than taking pills, requiring weekly subcutaneous injections. Pediatricians should ensure that families understand that medication is a long-term solution, Dr. Habib said.
Many families and patients “want a quick result. They’re focused on a specific size or weight, and they want to take the medication for a short period without changing anything else,” Dr. Habib said.
But children with genetic abnormalities or severe obesity could be on medication for their entire lives. Patients who make significant healthy lifestyle changes have a greater chance of weaning off drug therapy.
But “it’s hard with children because they’re dependent on their family,” Dr. Habib said. “One of the first things that I talk about with families is that it’s very important for everyone to be involved in making healthy changes, especially the parents, because the kids are going to follow their lifestyle and choices, not necessarily what they tell them to do.”
The behavioral and mental
One of Dr. Habib’s most striking cases was a 6-year-old patient with autism spectrum disorder experiencing early-onset puberty. Her condition made it difficult for her parents to enforce behavioral and lifestyle changes, making medication the best option to normalize the young girl’s body.
“The goal in this case is not necessarily to help her lose weight, but to prevent her from having severe health risks at such a young age,” said Habib.
Though medication may be the best solution when other options have failed, the ease of using medication may mean clinicians fail to address the complex emotional and psychosocial factors that can both cause and result from obesity.
“A lot of families think that if just this one thing were better, everything else would fall into place,” Habib said. “But there often are multiple layers to treating the patient.”
According to Cambria Garrell, MD, a pediatrician at the UCLA Fit for Healthy Weight Program in Los Angeles, pediatricians should be aware of the psychosocial and mental health factors such as undiagnosed mental illness or family dysfunction.
Dr. Garrell sometimes cares for children with undiagnosed mental health disorders. Children with conditions like attention-deficit/hyperactivity disorder and autism spectrum disorders may struggle with eating because of impulse control and sensory processing issues. Family functioning, issues at school, and lack of sleep are also major contributors to obesity to screen for.
“We really like to think about the environmental and psychosocial factors contributing to obesity instead of just pathologizing the weight,” Dr. Garrell said.
Risk for alcohol abuse
Bariatric and metabolic surgeries are associated with an increased risk for alcohol use disorder (AUD). Pediatricians treating children pre- or post-op should ensure that patients receive behavioral and mental health services to minimize the risk for alcohol abuse.
The risk for AUD is likely the result of changes to the way the body metabolizes alcohol, resulting in heightened sensitivity to it, although research is not conclusive, according to Dr. Mangarelli.
The risk for AUD is likely multifactorial, Dr. Mangarelli said.
“We don’t totally understand all of it, but if you’re experiencing a high more easily, that may lead to misuse,” Dr. Mangarelli said. “It’s also important to remember that this population of patients has experienced stigma for a very long time, and they often have associated mental health and body image issues.”
“Those problems don’t disappear on their own,” she added. “You want to make sure that patients are hooked into behavioral and mental health services before surgery so that they have somebody who’s following them after surgery.”
A version of this article first appeared on Medscape.com.
Treating obesity: Will new drugs end the crisis?
This is the second in a three-part series on the obesity crisis. Part one tackles a complicated question – why does the obesity rate keep rising despite our efforts to stop it? – and can be found here. Part three shows how doctors and patients can make treatment better and can be found here.
In the mid-1980s, Louis J. Aronne, MD, strolled into a lab at Rockefeller University in New York where a colleague was breeding mice. “I will never forget what he showed me,” said Dr. Aronne, now the director of obesity research and treatment at Weill Cornell Medicine in New York. “He had a cage with 10 mice, one severely obese and the others normal weight. He took blood from one of the thin mice and gave it to the fat mouse.”
When Dr. Aronne returned 3 days later, that obese mouse had turned thin.
It was proof of something Dr. Aronne already suspected: Obesity had biological causes and wasn’t just a failure of willpower.
Years later, in 1994, that research led to the discovery of leptin, a hormone released from fat cells that’s involved in the regulation of body weight. It was a watershed moment in obesity research.
Since then, Dr. Aronne and others have worked to build the clinical field of obesity medicine, attempting to shift the public and medical view of obesity from a purely behavioral issue to a disease worthy of medical treatment.
All the while, the U.S. obesity rate soared.
Now, another watershed moment: We finally have highly effective obesity drugs. The hype is real, and so are the weight loss results.
“I’ve been saying for 30 years that when we find treatments that really work, people aren’t going to believe the results,” Dr. Aronne said. “It took longer than I expected, but it’s gratifying now to see.”
The big question
The emerging class of obesity medications known as GLP-1 agonists is indeed a game changer. The weight loss drug semaglutide (Ozempic, Wegovy) showed groundbreaking results, and studies suggest a parade of even more impressive drugs is on the way.
Yes, the drugs offer new hope to millions with obesity complications. But to truly turn the tide on our 42% obesity rate, much more work remains to be done, researchers said, including answering a big question:
How do these weight loss drugs work?
“We have new blockbuster drugs, and we don’t even know why they reduce body weight,” said Samuel Klein, MD, professor of medicine and nutritional science at Washington University in St. Louis. “It was by accident that this was discovered.”
Oops, we created a weight loss drug
Developed to treat diabetes, the GLP-1 drugs’ weight loss effects were a surprise. Now that those effects are confirmed, pharmaceutical companies and researchers are racing to figure out how these drugs work.
In the 1960s, scientists discovered the incretin effect – when you eat glucose (sugar), your body makes more insulin than it does if glucose is given intravenously. Glucose passes through the GI tract and the gut releases hormones that stimulate insulin secretion. It’s “essentially a feed-forward signal to your pancreas to tell it, ‘By the way, you need to be ready because there’s a bunch of glucose coming,’ ” said Randy Seeley, MD, director of the Michigan Nutrition Obesity Research Center, funded by the National Institutes of Health.
One of these hormones – or “incretins” – is GLP-1. In experiments, people with type 2 diabetes who were hooked up to GLP-1 saw their blood sugar go down.
“That led to the idea that if we could take this native hormone and make it last longer, we’d have a therapy for type 2 diabetes,” said Dr. Seeley. Thanks to a GLP-1-like compound in the saliva of the Gila monster, that idea became reality in the 2000s.
Along the way, a surprising side finding came to light: In early trials, diabetes patients on these drugs dropped weight.
Both Ozempic and Wegovy – brand names for semaglutide – are once-weekly injections (pill forms to treat obesity are on the way), but the latter is a higher dose.
“That dose results in about 40% of patients in the clinical trials achieving a 20% weight loss. We’ve just had nothing like that in terms of efficacy before,” said Dr. Seeley, who has worked with some of the drug companies (including Novo Nordisk, the maker of Ozempic and Wegovy, and Eli Lilly, maker of Mounjaro) that market the GLP-1s.
By contrast, semaglutide’s once-a-day predecessor liraglutide (Saxenda, made by Novo Nordisk) can lead to about 10% weight loss.
“And one of the ironies is, we don’t really know why,” Dr. Seeley said. “We don’t know why semaglutide is a better molecule for weight loss than liraglutide.”
Initially, scientists believed that the drugs, in addition to telling the pancreas to secrete more insulin, were also signaling the brain that you’re full. “Turns out that’s not really the way it works,” Dr. Seeley said. “GLP-1 made from your gut probably doesn’t get into your brain very much. But you make GLP-1 in your brain as well.”
For weight loss, it’s the brain’s GLP-1 system, not the gut’s, that the drugs are thought to hijack. But exactly which parts of the brain they affect and how is unknown. “That’s something lots of people are working on, including our own lab,” Dr. Seeley said. (Another surprise: The drugs may have potential as an anti-addiction treatment.)
The diabetes medication tirzepatide (Mounjaro), expected to be approved for weight loss as early as this year, is also a weekly injection, but it has a unique feature: It starts a response not just for GLP-1 but also for another incretin called GIP. Turns out, two is better than one: Trial participants on tirzepatide lost up to 22.5% of their body weight.
More of these hybrid drugs are on the way, Dr. Seeley said. In mid-stage clinical trials, the drug retatrutide, which targets three hormones, led to 24% weight loss. “The idea is the more bullets we can load into the gun, the more we can push the biology into a place where it’s easier to lose weight.”
Shifting from prevention to damage control
Less invasive and more scalable than surgery (only 1% of the eligible population gets bariatric surgery), the drugs offer doctors a safe, effective way to treat many patients with obesity. That’s cause for excitement, but concerns remain because they are expensive, costing about $800 to $1,300 per month out of pocket. Many health insurers, including Medicare, do not cover them for weight loss.
“You have this significant advance in obesity treatment, but very few will be able to access it,” said Gary Foster, PhD, adjunct professor of psychology in psychiatry at the University of Pennsylvania, Philadelphia, and chief scientific officer at WW (formerly Weight Watchers).
There is a push, including a proposed bill, to get Medicare to cover obesity medication. But given the expense of the drugs, the health economics do not support that move, according to an editorial in the New England Journal of Medicine. If Medicare were to cover obesity meds, the budget impact would likely be huge, potentially driving up premiums. If other payers followed suit, the impact could be felt across the U.S. health care system.
Other drawbacks include side effects – including nausea, diarrhea, stomach pain, and vomiting – that can be so bad that some patients can’t tolerate them.
And critically, the drugs do not deal with the root cause of the problem, said Robert Lustig, MD, an endocrinologist and pediatrician at the University of California, San Francisco, who has suggested that excess insulin is driving obesity. “No one has the disease that these drugs are treating. No one has GLP-1 deficiency. They’re bypassing the problem. They’re band-aiding the problem.”
Because the drugs work by mimicking starvation – they appear to curb hunger, so you eat less – people on them lose not just fat but also healthy lean mass, Dr. Lustig said.
Concerns about pancreatitis did not really bear out in postmarketing reports. (The drugs are still not recommended in people with pancreatitis or multiple endocrine neoplasia.) But predicting longer-term outcomes can be difficult, noted Dr. Lustig.
Then there are philosophical questions, said James Hill, PhD, director of the Nutrition Obesity Research Center at the University of Alabama at Birmingham.. “If you’re continuing to not exercise and eat not healthy foods and take a medication, is that success? Have we won when people are at a lower weight but not doing a healthy behavior?”
‘We can’t treat our way out of this’
The fact is, ending the obesity epidemic is a tall order, even for drugs as impressive as these.
“We can’t treat our way out of this,” said Jamy Ard, MD, codirector of Wake Forest Baptist Health Weight Management Center in Winston-Salem, N.C. “The treatments we have now are great, and there will be more coming. But we do need to figure out the prevention side of things.”
Dr. Seeley agreed but added that we can’t diet-and-exercise our way out either.
“There’s no switch to be flipped,” Dr. Seeley said. “If you told me we shouldn’t spend all this money on these drugs, we should spend it on prevention – great! What would we do?”
And prevention efforts won’t help the millions already living with health problems from obesity, Dr. Aronne said.
“Getting people to stop smoking prevents lung cancer. But stopping smoking doesn’t treat lung cancer,” Dr. Aronne said. “Once the physical changes occur in the lung that cause a tumor to grow, it’s too late. You have to think of obesity the same way.”
Dr. Seeley pointed out that “fearmongering” around the drugs highlights our lingering bias that obesity is a lifestyle issue that should not be medically treated.
“People say, ‘When you stop taking it, you’re going to gain the weight back,’ ” Dr. Seeley said. “There’s truth to that, but when you stop taking your hypertension medication, your blood pressure goes up. We don’t think of that as a [reason] for why you shouldn’t take your blood pressure medication. But that gets trumpeted into all these conversations about whether people [with obesity] should be treated at all.”
Like obesity, blood pressure was once thought to be a behavioral problem, Dr. Aronne said. But blood pressure meds prevent heart attacks and strokes. And it’s likely obesity meds will do the same.
One 55-year-old patient on the road to kidney failure lost weight on obesity medications, including semaglutide, Dr. Aronne said. Now, 6 years later, his kidney function is back to normal. “Normally, we think of kidney disease as irreversible,” Dr. Aronne said.
In that respect, these drugs should save money in the long run by virtue of heading off those health care costs, said Dr. Seeley, who imagines a future where obesity is not gone but better managed, like high blood pressure is now.
In the end, the drugs are another step toward what Dr. Aronne and many others have always pushed for: Treating obesity as a disease.
A version of this article originally appeared on WebMD.com.
This is the second in a three-part series on the obesity crisis. Part one tackles a complicated question – why does the obesity rate keep rising despite our efforts to stop it? – and can be found here. Part three shows how doctors and patients can make treatment better and can be found here.
In the mid-1980s, Louis J. Aronne, MD, strolled into a lab at Rockefeller University in New York where a colleague was breeding mice. “I will never forget what he showed me,” said Dr. Aronne, now the director of obesity research and treatment at Weill Cornell Medicine in New York. “He had a cage with 10 mice, one severely obese and the others normal weight. He took blood from one of the thin mice and gave it to the fat mouse.”
When Dr. Aronne returned 3 days later, that obese mouse had turned thin.
It was proof of something Dr. Aronne already suspected: Obesity had biological causes and wasn’t just a failure of willpower.
Years later, in 1994, that research led to the discovery of leptin, a hormone released from fat cells that’s involved in the regulation of body weight. It was a watershed moment in obesity research.
Since then, Dr. Aronne and others have worked to build the clinical field of obesity medicine, attempting to shift the public and medical view of obesity from a purely behavioral issue to a disease worthy of medical treatment.
All the while, the U.S. obesity rate soared.
Now, another watershed moment: We finally have highly effective obesity drugs. The hype is real, and so are the weight loss results.
“I’ve been saying for 30 years that when we find treatments that really work, people aren’t going to believe the results,” Dr. Aronne said. “It took longer than I expected, but it’s gratifying now to see.”
The big question
The emerging class of obesity medications known as GLP-1 agonists is indeed a game changer. The weight loss drug semaglutide (Ozempic, Wegovy) showed groundbreaking results, and studies suggest a parade of even more impressive drugs is on the way.
Yes, the drugs offer new hope to millions with obesity complications. But to truly turn the tide on our 42% obesity rate, much more work remains to be done, researchers said, including answering a big question:
How do these weight loss drugs work?
“We have new blockbuster drugs, and we don’t even know why they reduce body weight,” said Samuel Klein, MD, professor of medicine and nutritional science at Washington University in St. Louis. “It was by accident that this was discovered.”
Oops, we created a weight loss drug
Developed to treat diabetes, the GLP-1 drugs’ weight loss effects were a surprise. Now that those effects are confirmed, pharmaceutical companies and researchers are racing to figure out how these drugs work.
In the 1960s, scientists discovered the incretin effect – when you eat glucose (sugar), your body makes more insulin than it does if glucose is given intravenously. Glucose passes through the GI tract and the gut releases hormones that stimulate insulin secretion. It’s “essentially a feed-forward signal to your pancreas to tell it, ‘By the way, you need to be ready because there’s a bunch of glucose coming,’ ” said Randy Seeley, MD, director of the Michigan Nutrition Obesity Research Center, funded by the National Institutes of Health.
One of these hormones – or “incretins” – is GLP-1. In experiments, people with type 2 diabetes who were hooked up to GLP-1 saw their blood sugar go down.
“That led to the idea that if we could take this native hormone and make it last longer, we’d have a therapy for type 2 diabetes,” said Dr. Seeley. Thanks to a GLP-1-like compound in the saliva of the Gila monster, that idea became reality in the 2000s.
Along the way, a surprising side finding came to light: In early trials, diabetes patients on these drugs dropped weight.
Both Ozempic and Wegovy – brand names for semaglutide – are once-weekly injections (pill forms to treat obesity are on the way), but the latter is a higher dose.
“That dose results in about 40% of patients in the clinical trials achieving a 20% weight loss. We’ve just had nothing like that in terms of efficacy before,” said Dr. Seeley, who has worked with some of the drug companies (including Novo Nordisk, the maker of Ozempic and Wegovy, and Eli Lilly, maker of Mounjaro) that market the GLP-1s.
By contrast, semaglutide’s once-a-day predecessor liraglutide (Saxenda, made by Novo Nordisk) can lead to about 10% weight loss.
“And one of the ironies is, we don’t really know why,” Dr. Seeley said. “We don’t know why semaglutide is a better molecule for weight loss than liraglutide.”
Initially, scientists believed that the drugs, in addition to telling the pancreas to secrete more insulin, were also signaling the brain that you’re full. “Turns out that’s not really the way it works,” Dr. Seeley said. “GLP-1 made from your gut probably doesn’t get into your brain very much. But you make GLP-1 in your brain as well.”
For weight loss, it’s the brain’s GLP-1 system, not the gut’s, that the drugs are thought to hijack. But exactly which parts of the brain they affect and how is unknown. “That’s something lots of people are working on, including our own lab,” Dr. Seeley said. (Another surprise: The drugs may have potential as an anti-addiction treatment.)
The diabetes medication tirzepatide (Mounjaro), expected to be approved for weight loss as early as this year, is also a weekly injection, but it has a unique feature: It starts a response not just for GLP-1 but also for another incretin called GIP. Turns out, two is better than one: Trial participants on tirzepatide lost up to 22.5% of their body weight.
More of these hybrid drugs are on the way, Dr. Seeley said. In mid-stage clinical trials, the drug retatrutide, which targets three hormones, led to 24% weight loss. “The idea is the more bullets we can load into the gun, the more we can push the biology into a place where it’s easier to lose weight.”
Shifting from prevention to damage control
Less invasive and more scalable than surgery (only 1% of the eligible population gets bariatric surgery), the drugs offer doctors a safe, effective way to treat many patients with obesity. That’s cause for excitement, but concerns remain because they are expensive, costing about $800 to $1,300 per month out of pocket. Many health insurers, including Medicare, do not cover them for weight loss.
“You have this significant advance in obesity treatment, but very few will be able to access it,” said Gary Foster, PhD, adjunct professor of psychology in psychiatry at the University of Pennsylvania, Philadelphia, and chief scientific officer at WW (formerly Weight Watchers).
There is a push, including a proposed bill, to get Medicare to cover obesity medication. But given the expense of the drugs, the health economics do not support that move, according to an editorial in the New England Journal of Medicine. If Medicare were to cover obesity meds, the budget impact would likely be huge, potentially driving up premiums. If other payers followed suit, the impact could be felt across the U.S. health care system.
Other drawbacks include side effects – including nausea, diarrhea, stomach pain, and vomiting – that can be so bad that some patients can’t tolerate them.
And critically, the drugs do not deal with the root cause of the problem, said Robert Lustig, MD, an endocrinologist and pediatrician at the University of California, San Francisco, who has suggested that excess insulin is driving obesity. “No one has the disease that these drugs are treating. No one has GLP-1 deficiency. They’re bypassing the problem. They’re band-aiding the problem.”
Because the drugs work by mimicking starvation – they appear to curb hunger, so you eat less – people on them lose not just fat but also healthy lean mass, Dr. Lustig said.
Concerns about pancreatitis did not really bear out in postmarketing reports. (The drugs are still not recommended in people with pancreatitis or multiple endocrine neoplasia.) But predicting longer-term outcomes can be difficult, noted Dr. Lustig.
Then there are philosophical questions, said James Hill, PhD, director of the Nutrition Obesity Research Center at the University of Alabama at Birmingham.. “If you’re continuing to not exercise and eat not healthy foods and take a medication, is that success? Have we won when people are at a lower weight but not doing a healthy behavior?”
‘We can’t treat our way out of this’
The fact is, ending the obesity epidemic is a tall order, even for drugs as impressive as these.
“We can’t treat our way out of this,” said Jamy Ard, MD, codirector of Wake Forest Baptist Health Weight Management Center in Winston-Salem, N.C. “The treatments we have now are great, and there will be more coming. But we do need to figure out the prevention side of things.”
Dr. Seeley agreed but added that we can’t diet-and-exercise our way out either.
“There’s no switch to be flipped,” Dr. Seeley said. “If you told me we shouldn’t spend all this money on these drugs, we should spend it on prevention – great! What would we do?”
And prevention efforts won’t help the millions already living with health problems from obesity, Dr. Aronne said.
“Getting people to stop smoking prevents lung cancer. But stopping smoking doesn’t treat lung cancer,” Dr. Aronne said. “Once the physical changes occur in the lung that cause a tumor to grow, it’s too late. You have to think of obesity the same way.”
Dr. Seeley pointed out that “fearmongering” around the drugs highlights our lingering bias that obesity is a lifestyle issue that should not be medically treated.
“People say, ‘When you stop taking it, you’re going to gain the weight back,’ ” Dr. Seeley said. “There’s truth to that, but when you stop taking your hypertension medication, your blood pressure goes up. We don’t think of that as a [reason] for why you shouldn’t take your blood pressure medication. But that gets trumpeted into all these conversations about whether people [with obesity] should be treated at all.”
Like obesity, blood pressure was once thought to be a behavioral problem, Dr. Aronne said. But blood pressure meds prevent heart attacks and strokes. And it’s likely obesity meds will do the same.
One 55-year-old patient on the road to kidney failure lost weight on obesity medications, including semaglutide, Dr. Aronne said. Now, 6 years later, his kidney function is back to normal. “Normally, we think of kidney disease as irreversible,” Dr. Aronne said.
In that respect, these drugs should save money in the long run by virtue of heading off those health care costs, said Dr. Seeley, who imagines a future where obesity is not gone but better managed, like high blood pressure is now.
In the end, the drugs are another step toward what Dr. Aronne and many others have always pushed for: Treating obesity as a disease.
A version of this article originally appeared on WebMD.com.
This is the second in a three-part series on the obesity crisis. Part one tackles a complicated question – why does the obesity rate keep rising despite our efforts to stop it? – and can be found here. Part three shows how doctors and patients can make treatment better and can be found here.
In the mid-1980s, Louis J. Aronne, MD, strolled into a lab at Rockefeller University in New York where a colleague was breeding mice. “I will never forget what he showed me,” said Dr. Aronne, now the director of obesity research and treatment at Weill Cornell Medicine in New York. “He had a cage with 10 mice, one severely obese and the others normal weight. He took blood from one of the thin mice and gave it to the fat mouse.”
When Dr. Aronne returned 3 days later, that obese mouse had turned thin.
It was proof of something Dr. Aronne already suspected: Obesity had biological causes and wasn’t just a failure of willpower.
Years later, in 1994, that research led to the discovery of leptin, a hormone released from fat cells that’s involved in the regulation of body weight. It was a watershed moment in obesity research.
Since then, Dr. Aronne and others have worked to build the clinical field of obesity medicine, attempting to shift the public and medical view of obesity from a purely behavioral issue to a disease worthy of medical treatment.
All the while, the U.S. obesity rate soared.
Now, another watershed moment: We finally have highly effective obesity drugs. The hype is real, and so are the weight loss results.
“I’ve been saying for 30 years that when we find treatments that really work, people aren’t going to believe the results,” Dr. Aronne said. “It took longer than I expected, but it’s gratifying now to see.”
The big question
The emerging class of obesity medications known as GLP-1 agonists is indeed a game changer. The weight loss drug semaglutide (Ozempic, Wegovy) showed groundbreaking results, and studies suggest a parade of even more impressive drugs is on the way.
Yes, the drugs offer new hope to millions with obesity complications. But to truly turn the tide on our 42% obesity rate, much more work remains to be done, researchers said, including answering a big question:
How do these weight loss drugs work?
“We have new blockbuster drugs, and we don’t even know why they reduce body weight,” said Samuel Klein, MD, professor of medicine and nutritional science at Washington University in St. Louis. “It was by accident that this was discovered.”
Oops, we created a weight loss drug
Developed to treat diabetes, the GLP-1 drugs’ weight loss effects were a surprise. Now that those effects are confirmed, pharmaceutical companies and researchers are racing to figure out how these drugs work.
In the 1960s, scientists discovered the incretin effect – when you eat glucose (sugar), your body makes more insulin than it does if glucose is given intravenously. Glucose passes through the GI tract and the gut releases hormones that stimulate insulin secretion. It’s “essentially a feed-forward signal to your pancreas to tell it, ‘By the way, you need to be ready because there’s a bunch of glucose coming,’ ” said Randy Seeley, MD, director of the Michigan Nutrition Obesity Research Center, funded by the National Institutes of Health.
One of these hormones – or “incretins” – is GLP-1. In experiments, people with type 2 diabetes who were hooked up to GLP-1 saw their blood sugar go down.
“That led to the idea that if we could take this native hormone and make it last longer, we’d have a therapy for type 2 diabetes,” said Dr. Seeley. Thanks to a GLP-1-like compound in the saliva of the Gila monster, that idea became reality in the 2000s.
Along the way, a surprising side finding came to light: In early trials, diabetes patients on these drugs dropped weight.
Both Ozempic and Wegovy – brand names for semaglutide – are once-weekly injections (pill forms to treat obesity are on the way), but the latter is a higher dose.
“That dose results in about 40% of patients in the clinical trials achieving a 20% weight loss. We’ve just had nothing like that in terms of efficacy before,” said Dr. Seeley, who has worked with some of the drug companies (including Novo Nordisk, the maker of Ozempic and Wegovy, and Eli Lilly, maker of Mounjaro) that market the GLP-1s.
By contrast, semaglutide’s once-a-day predecessor liraglutide (Saxenda, made by Novo Nordisk) can lead to about 10% weight loss.
“And one of the ironies is, we don’t really know why,” Dr. Seeley said. “We don’t know why semaglutide is a better molecule for weight loss than liraglutide.”
Initially, scientists believed that the drugs, in addition to telling the pancreas to secrete more insulin, were also signaling the brain that you’re full. “Turns out that’s not really the way it works,” Dr. Seeley said. “GLP-1 made from your gut probably doesn’t get into your brain very much. But you make GLP-1 in your brain as well.”
For weight loss, it’s the brain’s GLP-1 system, not the gut’s, that the drugs are thought to hijack. But exactly which parts of the brain they affect and how is unknown. “That’s something lots of people are working on, including our own lab,” Dr. Seeley said. (Another surprise: The drugs may have potential as an anti-addiction treatment.)
The diabetes medication tirzepatide (Mounjaro), expected to be approved for weight loss as early as this year, is also a weekly injection, but it has a unique feature: It starts a response not just for GLP-1 but also for another incretin called GIP. Turns out, two is better than one: Trial participants on tirzepatide lost up to 22.5% of their body weight.
More of these hybrid drugs are on the way, Dr. Seeley said. In mid-stage clinical trials, the drug retatrutide, which targets three hormones, led to 24% weight loss. “The idea is the more bullets we can load into the gun, the more we can push the biology into a place where it’s easier to lose weight.”
Shifting from prevention to damage control
Less invasive and more scalable than surgery (only 1% of the eligible population gets bariatric surgery), the drugs offer doctors a safe, effective way to treat many patients with obesity. That’s cause for excitement, but concerns remain because they are expensive, costing about $800 to $1,300 per month out of pocket. Many health insurers, including Medicare, do not cover them for weight loss.
“You have this significant advance in obesity treatment, but very few will be able to access it,” said Gary Foster, PhD, adjunct professor of psychology in psychiatry at the University of Pennsylvania, Philadelphia, and chief scientific officer at WW (formerly Weight Watchers).
There is a push, including a proposed bill, to get Medicare to cover obesity medication. But given the expense of the drugs, the health economics do not support that move, according to an editorial in the New England Journal of Medicine. If Medicare were to cover obesity meds, the budget impact would likely be huge, potentially driving up premiums. If other payers followed suit, the impact could be felt across the U.S. health care system.
Other drawbacks include side effects – including nausea, diarrhea, stomach pain, and vomiting – that can be so bad that some patients can’t tolerate them.
And critically, the drugs do not deal with the root cause of the problem, said Robert Lustig, MD, an endocrinologist and pediatrician at the University of California, San Francisco, who has suggested that excess insulin is driving obesity. “No one has the disease that these drugs are treating. No one has GLP-1 deficiency. They’re bypassing the problem. They’re band-aiding the problem.”
Because the drugs work by mimicking starvation – they appear to curb hunger, so you eat less – people on them lose not just fat but also healthy lean mass, Dr. Lustig said.
Concerns about pancreatitis did not really bear out in postmarketing reports. (The drugs are still not recommended in people with pancreatitis or multiple endocrine neoplasia.) But predicting longer-term outcomes can be difficult, noted Dr. Lustig.
Then there are philosophical questions, said James Hill, PhD, director of the Nutrition Obesity Research Center at the University of Alabama at Birmingham.. “If you’re continuing to not exercise and eat not healthy foods and take a medication, is that success? Have we won when people are at a lower weight but not doing a healthy behavior?”
‘We can’t treat our way out of this’
The fact is, ending the obesity epidemic is a tall order, even for drugs as impressive as these.
“We can’t treat our way out of this,” said Jamy Ard, MD, codirector of Wake Forest Baptist Health Weight Management Center in Winston-Salem, N.C. “The treatments we have now are great, and there will be more coming. But we do need to figure out the prevention side of things.”
Dr. Seeley agreed but added that we can’t diet-and-exercise our way out either.
“There’s no switch to be flipped,” Dr. Seeley said. “If you told me we shouldn’t spend all this money on these drugs, we should spend it on prevention – great! What would we do?”
And prevention efforts won’t help the millions already living with health problems from obesity, Dr. Aronne said.
“Getting people to stop smoking prevents lung cancer. But stopping smoking doesn’t treat lung cancer,” Dr. Aronne said. “Once the physical changes occur in the lung that cause a tumor to grow, it’s too late. You have to think of obesity the same way.”
Dr. Seeley pointed out that “fearmongering” around the drugs highlights our lingering bias that obesity is a lifestyle issue that should not be medically treated.
“People say, ‘When you stop taking it, you’re going to gain the weight back,’ ” Dr. Seeley said. “There’s truth to that, but when you stop taking your hypertension medication, your blood pressure goes up. We don’t think of that as a [reason] for why you shouldn’t take your blood pressure medication. But that gets trumpeted into all these conversations about whether people [with obesity] should be treated at all.”
Like obesity, blood pressure was once thought to be a behavioral problem, Dr. Aronne said. But blood pressure meds prevent heart attacks and strokes. And it’s likely obesity meds will do the same.
One 55-year-old patient on the road to kidney failure lost weight on obesity medications, including semaglutide, Dr. Aronne said. Now, 6 years later, his kidney function is back to normal. “Normally, we think of kidney disease as irreversible,” Dr. Aronne said.
In that respect, these drugs should save money in the long run by virtue of heading off those health care costs, said Dr. Seeley, who imagines a future where obesity is not gone but better managed, like high blood pressure is now.
In the end, the drugs are another step toward what Dr. Aronne and many others have always pushed for: Treating obesity as a disease.
A version of this article originally appeared on WebMD.com.
GLP-1 agonists offer multiple benefits in type 2 diabetes with liver cirrhosis
Topline
, new observational data show.
Methodology
- Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
- Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
- All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.
Takeaway
- During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
- GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
- A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.
In practice
“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.
Study details
The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.
Limitations
Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.
Disclosures
The authors disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Topline
, new observational data show.
Methodology
- Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
- Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
- All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.
Takeaway
- During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
- GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
- A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.
In practice
“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.
Study details
The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.
Limitations
Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.
Disclosures
The authors disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Topline
, new observational data show.
Methodology
- Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
- Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
- All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.
Takeaway
- During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
- GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
- A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.
In practice
“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.
Study details
The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.
Limitations
Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.
Disclosures
The authors disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.