Diabetes

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

“The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries,” investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told this news organization.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.
 

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Dr. Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Dr. Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

“In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend,” Dr. Khalid said.
 

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Dr. Khalid noted. 

“The idea is that it could be the fact there is sarcopenia or muscle loss that’s taking place in conjunction with fat loss that’s causing that to happen,” Dr. Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Dr. Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it’s not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but “the odds of a class effect are high,” Dr. Khalid said. 

Commenting on the findings, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

“It’s an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery,” Dr. Sivakumar said. “It’s thought-provoking and a great first start.” 

Dr. Sivakumar also observed that frailty is a hot topic in all of neurosurgery. “That’s a major, major point that’s showing an impact on all surgical outcomes and it’s being heavily studied in the neurosurgical subsets right now. So that’s definitely a possible correlating factor.”

Dr. Khalid reported no financial relationships. Dr. Sivakumar reported serving as a consultant for Stryker. 
 

A version of this article appeared on Medscape.com.

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

“The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries,” investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told this news organization.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.
 

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Dr. Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Dr. Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

“In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend,” Dr. Khalid said.
 

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Dr. Khalid noted. 

“The idea is that it could be the fact there is sarcopenia or muscle loss that’s taking place in conjunction with fat loss that’s causing that to happen,” Dr. Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Dr. Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it’s not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but “the odds of a class effect are high,” Dr. Khalid said. 

Commenting on the findings, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

“It’s an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery,” Dr. Sivakumar said. “It’s thought-provoking and a great first start.” 

Dr. Sivakumar also observed that frailty is a hot topic in all of neurosurgery. “That’s a major, major point that’s showing an impact on all surgical outcomes and it’s being heavily studied in the neurosurgical subsets right now. So that’s definitely a possible correlating factor.”

Dr. Khalid reported no financial relationships. Dr. Sivakumar reported serving as a consultant for Stryker. 
 

A version of this article appeared on Medscape.com.

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

“The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries,” investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told this news organization.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.
 

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Dr. Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Dr. Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

“In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend,” Dr. Khalid said.
 

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Dr. Khalid noted. 

“The idea is that it could be the fact there is sarcopenia or muscle loss that’s taking place in conjunction with fat loss that’s causing that to happen,” Dr. Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Dr. Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it’s not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but “the odds of a class effect are high,” Dr. Khalid said. 

Commenting on the findings, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

“It’s an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery,” Dr. Sivakumar said. “It’s thought-provoking and a great first start.” 

Dr. Sivakumar also observed that frailty is a hot topic in all of neurosurgery. “That’s a major, major point that’s showing an impact on all surgical outcomes and it’s being heavily studied in the neurosurgical subsets right now. So that’s definitely a possible correlating factor.”

Dr. Khalid reported no financial relationships. Dr. Sivakumar reported serving as a consultant for Stryker. 
 

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.

On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 

The document was also presented simultaneously at the ACP annual meeting. 

And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
 

General Agreement but Some Differences

The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone. 

The new ACP document gives two general recommendations:

1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. 

*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.

ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.” 

The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely. 

This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”

Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.” 

In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness. 

In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”

Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”

However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.

“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”

Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.

A version of this article first appeared on Medscape.com.

Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.

On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 

The document was also presented simultaneously at the ACP annual meeting. 

And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
 

General Agreement but Some Differences

The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone. 

The new ACP document gives two general recommendations:

1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. 

*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.

ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.” 

The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely. 

This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”

Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.” 

In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness. 

In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”

Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”

However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.

“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”

Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.

A version of this article first appeared on Medscape.com.

Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.

On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors. 

The document was also presented simultaneously at the ACP annual meeting. 

And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
 

General Agreement but Some Differences

The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone. 

The new ACP document gives two general recommendations:

1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. 

*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.

*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.

2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.

ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.” 

The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely. 

This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”

Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.” 

In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness. 

In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”

Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”

However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.

“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”

Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has designated the Eversense (Sensionics, Inc; Ascencia Diabetes Care) implanted continuous glucose monitor (CGM) an “integrated CGM,” meaning it can be used in conjunction with insulin pumps as part of an automated insulin delivery system (AID). 

The Eversense now joins Dexcom’s G6 and G7 and the Freestyle Libre 2 Plus in being compatible with multiple different branded insulin pumps as part of AID systems, and it is the only implantable one. 

The sensor device is inserted under the skin of the patient’s upper arm by a healthcare provider and a transmitter is worn over it on the skin. The FDA approved the Eversense in June 2018 for 3-month use and in February 2022  for use up to 6 months. It is indicated for people with diabetes aged 18 years and older.

Fingerstick blood glucose measurements are still required for calibration once a day after day 21, when symptoms don’t match the CGM information, or when taking tetracycline medications. 

According to Sensionics, the Eversense is “the most accurate CGM in the critical low glucose ranges with essentially no compression lows.” The latter refers to ‘false low’ alarms that sometimes occur when a person presses on the device, such as during sleep.

“As we look ahead, we are focused on progressing our partnership discussions and software developments, and look forward to providing more updates,” Sensionics said in a statement.
 

A version of this article first appeared on Medscape.com.

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

A version of this article first appeared on Medscape.com.

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

A version of this article first appeared on Medscape.com.

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

A version of this article first appeared on Medscape.com.

TOPLINE: 

Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).

METHODOLOGY:

• Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
• Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
• The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
• The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
• The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.

TAKEAWAY:

• Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
• The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
• Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
• However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.

IN PRACTICE:

“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.” 

SOURCE:

Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.

LIMITATIONS:

Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).

METHODOLOGY:

• Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
• Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
• The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
• The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
• The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.

TAKEAWAY:

• Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
• The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
• Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
• However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.

IN PRACTICE:

“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.” 

SOURCE:

Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.

LIMITATIONS:

Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).

METHODOLOGY:

• Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
• Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
• The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
• The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
• The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.

TAKEAWAY:

• Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
• The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
• Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
• However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.

IN PRACTICE:

“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.” 

SOURCE:

Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.

LIMITATIONS:

Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — Sarcopenic obesity, which is characterized by excess adiposity and muscle loss, is an “underestimated and underdiagnosed” condition, said the panelists at a session of the XV Latin American Obesity Congress (FLASO 2024) and II Paraguayan Congress of Obesity. The condition often affects older adults but can also occur at any age as a result of unhealthy habits or intensive or repeated weight loss efforts. 

“The drugs currently used for managing obesity promote significant weight loss, but by losing fat, muscle is also lost,” said Fabiola Romero Gómez, MD, a professor of medicine at the National University of Asunción and president of the Paraguayan Society of Endocrinology and Metabolism. “We must handle [these drugs] with extreme care. When we employ a strategy that achieves this significant weight loss, we must ensure that the patient receives a good protein intake and engages in resistance exercises, because otherwise, the cure may be worse than the disease.”

Some patients develop sarcopenic obesity after using glucagon-like peptide-1 (GLP-1) analogs, undergoing bariatric surgery, or pursuing restrictive diets, Dr. Romero said in an interview. The condition is more common when there are long-standing cycles of weight loss and subsequent gain, “which accounts for the majority of our patients,” she said.

“An important, largely ignored aspect of weight loss, whether through pharmacological or lifestyle intervention, is that a portion of the weight loss comprises lean muscle,” according to a recent editorial in Nature Medicine. “Weight regain, however, is almost entirely fat. People with chronic obesity often lose and regain weight in repeated cycles, each of which results in body-composition changes (even if they experience some net weight loss). This cycling puts people unable to sustain weight loss at risk of being metabolically less healthy than they were before the initial weight loss was achieved — in effect, at risk of developing sarcopenic obesity.”
 

A ‘Hidden’ Problem

Sarcopenic obesity is “something hidden, something that we often do not see. Why? Because if we do not make measurements of body composition, we will not realize it,” said Dr. Romero.

According to the 2022 consensus of the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity, clinical signs or factors suggesting sarcopenic obesity include age over 70 years, diagnosis of a chronic disease, repeated falls or weakness, and nutritional events such as recent weight loss or rapid gain, long-standing restrictive diets, and bariatric surgery. 

The European guidelines also propose screening in individuals at risk to check for an increased body mass index (BMI) or waist circumference and suspicion parameters of sarcopenia. In this group of patients, the diagnosis should be made based on the analysis of alterations in muscle-skeletal functional parameters, such as grip or pinch strength or the 30-second chair stand test, followed by a determination of body mass alteration using dual-energy x-ray absorptiometry or electrical bioimpedance. 

Electrical bioimpedance is Dr. Romero’s preferred method. It is an economical, simple, and easily transportable test that calculates lean muscle mass, fat mass, and body water based on electrical conductivity, she said. Experts have pointed out that bioimpedance scales “will revolutionize the way we measure obesity,” she added. 

In an as-yet-unpublished study that received an honorable mention at the 3rd Paraguayan Congress of Endocrinology, Diabetes, and Metabolism last year, Dr. Romero and colleagues studied 126 patients (median age, 45 years) with obesity defined by percentage of fat mass determined by bioimpedance. When their BMI was analyzed, 11.1% were “normal” weight, and 35.7% were “overweight.” Even waist circumference measurement suggested that about 15% of participants were without obesity. Moreover, almost one in four participants presented with sarcopenia, “implying a decrease in quality of life and physical disability in the future if not investigated, diagnosed, and treated correctly,” said Dr. Romero. 
 

Prevention and Recommendations

Exercise and nutrition are two key components in the prevention and management of sarcopenic obesity. Physicians prescribing GLP-1 receptor agonists “must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan, as well as ensuring they eat a high-protein diet,” Yoon Ji Ahn, MD, and Vibha Singhal, MD, MPH, of the Weight Management Center of Massachusetts General Hospital in Boston, wrote in a commentary published by this news organization.

Paraguayan nutritionist Patricia López Soto, a diabetes educator with postgraduate degrees in obesity, diabetes, and bariatric surgery from Favaloro University in Buenos Aires, shared with this news organization the following general recommendations to prevent sarcopenic obesity in patients undergoing weight loss treatment: 

• Follow a healthy and balanced Mediterranean or DASH-style diet.
• Increase protein intake at the three to four main meals to a minimum of 1.4-1.5 g/kg/day.
• Try to make the protein intake mostly of high biological value: Beef, chicken, fish, eggs, seafood, cheese, skim milk, and yogurt.
• Ensure protein intake at each meal of between 25 g and 30 g to increase protein synthesis. For example, a 150 g portion of meat or chicken provides 30 g of protein.
• If the protein intake is not achieved through food, a supplement measure like isolated and hydrolyzed whey protein is a good option.
• Engage in strength or resistance training (weightlifting) three to four times per week and 30 minutes of cardiovascular exercise every day.
• To improve adherence, treatment should be carried out with a multidisciplinary team that includes a physician, nutritionist, and physical trainer, with frequent check-ups and body composition studies by bioimpedance.

Dr. Romero and Ms. López declared no relevant financial relationships. 
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — Sarcopenic obesity, which is characterized by excess adiposity and muscle loss, is an “underestimated and underdiagnosed” condition, said the panelists at a session of the XV Latin American Obesity Congress (FLASO 2024) and II Paraguayan Congress of Obesity. The condition often affects older adults but can also occur at any age as a result of unhealthy habits or intensive or repeated weight loss efforts. 

“The drugs currently used for managing obesity promote significant weight loss, but by losing fat, muscle is also lost,” said Fabiola Romero Gómez, MD, a professor of medicine at the National University of Asunción and president of the Paraguayan Society of Endocrinology and Metabolism. “We must handle [these drugs] with extreme care. When we employ a strategy that achieves this significant weight loss, we must ensure that the patient receives a good protein intake and engages in resistance exercises, because otherwise, the cure may be worse than the disease.”

Some patients develop sarcopenic obesity after using glucagon-like peptide-1 (GLP-1) analogs, undergoing bariatric surgery, or pursuing restrictive diets, Dr. Romero said in an interview. The condition is more common when there are long-standing cycles of weight loss and subsequent gain, “which accounts for the majority of our patients,” she said.

“An important, largely ignored aspect of weight loss, whether through pharmacological or lifestyle intervention, is that a portion of the weight loss comprises lean muscle,” according to a recent editorial in Nature Medicine. “Weight regain, however, is almost entirely fat. People with chronic obesity often lose and regain weight in repeated cycles, each of which results in body-composition changes (even if they experience some net weight loss). This cycling puts people unable to sustain weight loss at risk of being metabolically less healthy than they were before the initial weight loss was achieved — in effect, at risk of developing sarcopenic obesity.”
 

A ‘Hidden’ Problem

Sarcopenic obesity is “something hidden, something that we often do not see. Why? Because if we do not make measurements of body composition, we will not realize it,” said Dr. Romero.

According to the 2022 consensus of the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity, clinical signs or factors suggesting sarcopenic obesity include age over 70 years, diagnosis of a chronic disease, repeated falls or weakness, and nutritional events such as recent weight loss or rapid gain, long-standing restrictive diets, and bariatric surgery. 

The European guidelines also propose screening in individuals at risk to check for an increased body mass index (BMI) or waist circumference and suspicion parameters of sarcopenia. In this group of patients, the diagnosis should be made based on the analysis of alterations in muscle-skeletal functional parameters, such as grip or pinch strength or the 30-second chair stand test, followed by a determination of body mass alteration using dual-energy x-ray absorptiometry or electrical bioimpedance. 

Electrical bioimpedance is Dr. Romero’s preferred method. It is an economical, simple, and easily transportable test that calculates lean muscle mass, fat mass, and body water based on electrical conductivity, she said. Experts have pointed out that bioimpedance scales “will revolutionize the way we measure obesity,” she added. 

In an as-yet-unpublished study that received an honorable mention at the 3rd Paraguayan Congress of Endocrinology, Diabetes, and Metabolism last year, Dr. Romero and colleagues studied 126 patients (median age, 45 years) with obesity defined by percentage of fat mass determined by bioimpedance. When their BMI was analyzed, 11.1% were “normal” weight, and 35.7% were “overweight.” Even waist circumference measurement suggested that about 15% of participants were without obesity. Moreover, almost one in four participants presented with sarcopenia, “implying a decrease in quality of life and physical disability in the future if not investigated, diagnosed, and treated correctly,” said Dr. Romero. 
 

Prevention and Recommendations

Exercise and nutrition are two key components in the prevention and management of sarcopenic obesity. Physicians prescribing GLP-1 receptor agonists “must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan, as well as ensuring they eat a high-protein diet,” Yoon Ji Ahn, MD, and Vibha Singhal, MD, MPH, of the Weight Management Center of Massachusetts General Hospital in Boston, wrote in a commentary published by this news organization.

Paraguayan nutritionist Patricia López Soto, a diabetes educator with postgraduate degrees in obesity, diabetes, and bariatric surgery from Favaloro University in Buenos Aires, shared with this news organization the following general recommendations to prevent sarcopenic obesity in patients undergoing weight loss treatment: 

• Follow a healthy and balanced Mediterranean or DASH-style diet.
• Increase protein intake at the three to four main meals to a minimum of 1.4-1.5 g/kg/day.
• Try to make the protein intake mostly of high biological value: Beef, chicken, fish, eggs, seafood, cheese, skim milk, and yogurt.
• Ensure protein intake at each meal of between 25 g and 30 g to increase protein synthesis. For example, a 150 g portion of meat or chicken provides 30 g of protein.
• If the protein intake is not achieved through food, a supplement measure like isolated and hydrolyzed whey protein is a good option.
• Engage in strength or resistance training (weightlifting) three to four times per week and 30 minutes of cardiovascular exercise every day.
• To improve adherence, treatment should be carried out with a multidisciplinary team that includes a physician, nutritionist, and physical trainer, with frequent check-ups and body composition studies by bioimpedance.

Dr. Romero and Ms. López declared no relevant financial relationships. 
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

ASUNCIÓN, PARAGUAY — Sarcopenic obesity, which is characterized by excess adiposity and muscle loss, is an “underestimated and underdiagnosed” condition, said the panelists at a session of the XV Latin American Obesity Congress (FLASO 2024) and II Paraguayan Congress of Obesity. The condition often affects older adults but can also occur at any age as a result of unhealthy habits or intensive or repeated weight loss efforts. 

“The drugs currently used for managing obesity promote significant weight loss, but by losing fat, muscle is also lost,” said Fabiola Romero Gómez, MD, a professor of medicine at the National University of Asunción and president of the Paraguayan Society of Endocrinology and Metabolism. “We must handle [these drugs] with extreme care. When we employ a strategy that achieves this significant weight loss, we must ensure that the patient receives a good protein intake and engages in resistance exercises, because otherwise, the cure may be worse than the disease.”

Some patients develop sarcopenic obesity after using glucagon-like peptide-1 (GLP-1) analogs, undergoing bariatric surgery, or pursuing restrictive diets, Dr. Romero said in an interview. The condition is more common when there are long-standing cycles of weight loss and subsequent gain, “which accounts for the majority of our patients,” she said.

“An important, largely ignored aspect of weight loss, whether through pharmacological or lifestyle intervention, is that a portion of the weight loss comprises lean muscle,” according to a recent editorial in Nature Medicine. “Weight regain, however, is almost entirely fat. People with chronic obesity often lose and regain weight in repeated cycles, each of which results in body-composition changes (even if they experience some net weight loss). This cycling puts people unable to sustain weight loss at risk of being metabolically less healthy than they were before the initial weight loss was achieved — in effect, at risk of developing sarcopenic obesity.”
 

A ‘Hidden’ Problem

Sarcopenic obesity is “something hidden, something that we often do not see. Why? Because if we do not make measurements of body composition, we will not realize it,” said Dr. Romero.

According to the 2022 consensus of the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity, clinical signs or factors suggesting sarcopenic obesity include age over 70 years, diagnosis of a chronic disease, repeated falls or weakness, and nutritional events such as recent weight loss or rapid gain, long-standing restrictive diets, and bariatric surgery. 

The European guidelines also propose screening in individuals at risk to check for an increased body mass index (BMI) or waist circumference and suspicion parameters of sarcopenia. In this group of patients, the diagnosis should be made based on the analysis of alterations in muscle-skeletal functional parameters, such as grip or pinch strength or the 30-second chair stand test, followed by a determination of body mass alteration using dual-energy x-ray absorptiometry or electrical bioimpedance. 

Electrical bioimpedance is Dr. Romero’s preferred method. It is an economical, simple, and easily transportable test that calculates lean muscle mass, fat mass, and body water based on electrical conductivity, she said. Experts have pointed out that bioimpedance scales “will revolutionize the way we measure obesity,” she added. 

In an as-yet-unpublished study that received an honorable mention at the 3rd Paraguayan Congress of Endocrinology, Diabetes, and Metabolism last year, Dr. Romero and colleagues studied 126 patients (median age, 45 years) with obesity defined by percentage of fat mass determined by bioimpedance. When their BMI was analyzed, 11.1% were “normal” weight, and 35.7% were “overweight.” Even waist circumference measurement suggested that about 15% of participants were without obesity. Moreover, almost one in four participants presented with sarcopenia, “implying a decrease in quality of life and physical disability in the future if not investigated, diagnosed, and treated correctly,” said Dr. Romero. 
 

Prevention and Recommendations

Exercise and nutrition are two key components in the prevention and management of sarcopenic obesity. Physicians prescribing GLP-1 receptor agonists “must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan, as well as ensuring they eat a high-protein diet,” Yoon Ji Ahn, MD, and Vibha Singhal, MD, MPH, of the Weight Management Center of Massachusetts General Hospital in Boston, wrote in a commentary published by this news organization.

Paraguayan nutritionist Patricia López Soto, a diabetes educator with postgraduate degrees in obesity, diabetes, and bariatric surgery from Favaloro University in Buenos Aires, shared with this news organization the following general recommendations to prevent sarcopenic obesity in patients undergoing weight loss treatment: 

• Follow a healthy and balanced Mediterranean or DASH-style diet.
• Increase protein intake at the three to four main meals to a minimum of 1.4-1.5 g/kg/day.
• Try to make the protein intake mostly of high biological value: Beef, chicken, fish, eggs, seafood, cheese, skim milk, and yogurt.
• Ensure protein intake at each meal of between 25 g and 30 g to increase protein synthesis. For example, a 150 g portion of meat or chicken provides 30 g of protein.
• If the protein intake is not achieved through food, a supplement measure like isolated and hydrolyzed whey protein is a good option.
• Engage in strength or resistance training (weightlifting) three to four times per week and 30 minutes of cardiovascular exercise every day.
• To improve adherence, treatment should be carried out with a multidisciplinary team that includes a physician, nutritionist, and physical trainer, with frequent check-ups and body composition studies by bioimpedance.

Dr. Romero and Ms. López declared no relevant financial relationships. 
 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Excessive intrapancreatic fat deposition (IPFD) leading to fatty change of the pancreas (FP) was prevalent in almost 18% of participants in a large population-based cohort, and both IPFD and FP were associated with an increased risk for diabetes, acute pancreatitis, and pancreatic cancer.

METHODOLOGY:

• Excessive IPFD is a common pancreatic disorder in the general population; however, there is a paucity of longitudinal studies investigating the relationship between FP and the risk for exocrine and endocrine pancreatic diseases.
• This prospective cohort study conducted from July 2014 to January 2023 investigated the prevalence of FP and the link between IPFD and pancreatic diseases in 42,599 participants (median age, 65 years; 46.6% men) from the UK Biobank who underwent abdominal Dixon MRI.
• IPFD levels were measured using MRI and a deep learning-based framework called nnUNet.
• The outcomes assessed in this study were diseases of the exocrine pancreas and endocrine pancreas, including acute pancreatitis, pancreatic cancer, diabetes, and other pancreatic conditions.

TAKEAWAY:

• The prevalence of FP was 17.86%.
• Elevation in IPFD levels by one quintile increased the risk for the development of acute pancreatitis by 51.3% (P = .001), pancreatic cancer by 36.5% (P = .017), diabetes by 22.1% (P < .001), and all pancreatic diseases by 22.7% (P < .001).
• FP increased the risk for acute pancreatitis by 298.2% (P < .001), pancreatic cancer by 97.6% (P = .034), diabetes by 33.7% (P = .001), and all pancreatic diseases by 44.1% (P < .001).
• An increasing trend in the prevalence of FP with advancing age was observed in both men and women.

IN PRACTICE:

“FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas,” the authors wrote.

SOURCE:

This study, led by Xiaowu Dong, MD, of the Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The authors acknowledged that most of the enrolled participants were White and older than 45 years. A low response rate to recruitment invitations in the UK Biobank database may have introduced self-selection bias. The median follow-up duration of 4.61 years was short and may be insufficient to fully capture the impact of IPFD. Additionally, the use of the average fat fraction for the entire pancreas may have led to spatial variations being ignored.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, Cultivation Foundation of Yangzhou Municipal Key Laboratory, The Medical Research Project of Jiangsu Provincial Health Commission, Yangzhou key research and development plan, and Suzhou Innovation Platform Construction Projects-Municipal Key Laboratory Construction. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Excessive intrapancreatic fat deposition (IPFD) leading to fatty change of the pancreas (FP) was prevalent in almost 18% of participants in a large population-based cohort, and both IPFD and FP were associated with an increased risk for diabetes, acute pancreatitis, and pancreatic cancer.

METHODOLOGY:

• Excessive IPFD is a common pancreatic disorder in the general population; however, there is a paucity of longitudinal studies investigating the relationship between FP and the risk for exocrine and endocrine pancreatic diseases.
• This prospective cohort study conducted from July 2014 to January 2023 investigated the prevalence of FP and the link between IPFD and pancreatic diseases in 42,599 participants (median age, 65 years; 46.6% men) from the UK Biobank who underwent abdominal Dixon MRI.
• IPFD levels were measured using MRI and a deep learning-based framework called nnUNet.
• The outcomes assessed in this study were diseases of the exocrine pancreas and endocrine pancreas, including acute pancreatitis, pancreatic cancer, diabetes, and other pancreatic conditions.

TAKEAWAY:

• The prevalence of FP was 17.86%.
• Elevation in IPFD levels by one quintile increased the risk for the development of acute pancreatitis by 51.3% (P = .001), pancreatic cancer by 36.5% (P = .017), diabetes by 22.1% (P < .001), and all pancreatic diseases by 22.7% (P < .001).
• FP increased the risk for acute pancreatitis by 298.2% (P < .001), pancreatic cancer by 97.6% (P = .034), diabetes by 33.7% (P = .001), and all pancreatic diseases by 44.1% (P < .001).
• An increasing trend in the prevalence of FP with advancing age was observed in both men and women.

IN PRACTICE:

“FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas,” the authors wrote.

SOURCE:

This study, led by Xiaowu Dong, MD, of the Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The authors acknowledged that most of the enrolled participants were White and older than 45 years. A low response rate to recruitment invitations in the UK Biobank database may have introduced self-selection bias. The median follow-up duration of 4.61 years was short and may be insufficient to fully capture the impact of IPFD. Additionally, the use of the average fat fraction for the entire pancreas may have led to spatial variations being ignored.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, Cultivation Foundation of Yangzhou Municipal Key Laboratory, The Medical Research Project of Jiangsu Provincial Health Commission, Yangzhou key research and development plan, and Suzhou Innovation Platform Construction Projects-Municipal Key Laboratory Construction. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Excessive intrapancreatic fat deposition (IPFD) leading to fatty change of the pancreas (FP) was prevalent in almost 18% of participants in a large population-based cohort, and both IPFD and FP were associated with an increased risk for diabetes, acute pancreatitis, and pancreatic cancer.

METHODOLOGY:

• Excessive IPFD is a common pancreatic disorder in the general population; however, there is a paucity of longitudinal studies investigating the relationship between FP and the risk for exocrine and endocrine pancreatic diseases.
• This prospective cohort study conducted from July 2014 to January 2023 investigated the prevalence of FP and the link between IPFD and pancreatic diseases in 42,599 participants (median age, 65 years; 46.6% men) from the UK Biobank who underwent abdominal Dixon MRI.
• IPFD levels were measured using MRI and a deep learning-based framework called nnUNet.
• The outcomes assessed in this study were diseases of the exocrine pancreas and endocrine pancreas, including acute pancreatitis, pancreatic cancer, diabetes, and other pancreatic conditions.

TAKEAWAY:

• The prevalence of FP was 17.86%.
• Elevation in IPFD levels by one quintile increased the risk for the development of acute pancreatitis by 51.3% (P = .001), pancreatic cancer by 36.5% (P = .017), diabetes by 22.1% (P < .001), and all pancreatic diseases by 22.7% (P < .001).
• FP increased the risk for acute pancreatitis by 298.2% (P < .001), pancreatic cancer by 97.6% (P = .034), diabetes by 33.7% (P = .001), and all pancreatic diseases by 44.1% (P < .001).
• An increasing trend in the prevalence of FP with advancing age was observed in both men and women.

IN PRACTICE:

“FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas,” the authors wrote.

SOURCE:

This study, led by Xiaowu Dong, MD, of the Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The authors acknowledged that most of the enrolled participants were White and older than 45 years. A low response rate to recruitment invitations in the UK Biobank database may have introduced self-selection bias. The median follow-up duration of 4.61 years was short and may be insufficient to fully capture the impact of IPFD. Additionally, the use of the average fat fraction for the entire pancreas may have led to spatial variations being ignored.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, Cultivation Foundation of Yangzhou Municipal Key Laboratory, The Medical Research Project of Jiangsu Provincial Health Commission, Yangzhou key research and development plan, and Suzhou Innovation Platform Construction Projects-Municipal Key Laboratory Construction. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.