HealthDay News — In a clinical report issued by the American Academy of Pediatrics and published online September 18 in Pediatrics, recommendations are presented for use of low-carbohydrate diets in children with type 1 diabetes, prediabetes, and type 2 diabetes.

Anna Neyman, MD, and Tamara S. Hannon, MD, from the Indiana University School of Medicine in Indianapolis, developed practical recommendations for pediatricians regarding use of low-carbohydrate diets in patients, including those with type 1 diabetes and those with obesity, prediabetes, and type 2 diabetes.

The authors note there are safety concerns to consider for youth with diabetes who are restricting carbohydrates, including growth deceleration, poor bone health, nutritional ketosis that cannot be distinguished from ketosis resulting from insulin deficiency, and disordered eating behaviors. Low-carbohydrate diets (<26% energy) and very low-carbohydrate (20 to 50g) diets are only recommended for children with type 1 diabetes under close supervision of a diabetes care team. For prevention and treatment of prediabetes and type 2 diabetes, reducing nutrient-poor carbohydrate intake by minimizing consumption of processed foods with high amounts of refined grains and added sugars is recommended. In children and adolescents, eliminating sugary beverages and juices significantly improves blood glucose and weight management. Dietary restriction of any kind has physical, metabolic, and psychological consequences, including risk for disordered eating, and poses additional risk for those with diabetes. A reduced-energy diet is most important for achieving weight loss among those for whom weight loss is medically indicated, irrespective of carbohydrate content.

“This statement is not about restrictive diets — it is about providing evidence to clinicians so they can support parents and families in making informed decisions,” Hannon said in a statement.

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The Food and Drug Administration (FDA) has cleared Abbott’s FreeStyle Libre 2^® and FreeStyle Libre 3^® continuous glucose monitoring (CGM) system sensors for integration with automated insulin delivery (AID) systems.

The Company is now working with insulin pump manufacturers to integrate their AID systems with the FreeStyle Libre 2 and FreeStyle Libre 3 sensors as soon as possible. The sensors were modified to allow for integration with AID systems.

The modified sensors were also cleared for use by pediatric patients as young as 2 years old and for wear time up to 15 days; the current version is approved for patients 4 years of age and older with a wear time of up to 14 days. Both the current and modified sensors have been cleared for use in pregnant women with all types of diabetes.

“Our goal is to make diabetes care as easy as possible,” said Jared Watkin, senior vice president for Abbott’s diabetes care business. “The FreeStyle Libre portfolio is already the most prescribed CGM in the United States and, with the integration of automated insulin delivery systems, people in the US will soon have an affordable option to pair with insulin pumps.”

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors will be available in the US later this year and will eventually replace the current versions.

Reference

US FDA clears Abbott’s FreeStyle Libre^® 2 and FreeStyle Libre^® 3 sensors for integration with automated insulin delivery systems. News release. Abbott. Accessed March 6, 2023. https://www.prnewswire.com/news-releases/us-fda-clears-abbotts-freestyle-libre-2-and-freestyle-libre-3-sensors-for-integration-with-automated-insulin-delivery-systems-301763020.html.

The Food and Drug Administration (FDA) has approved the Proclaim XR spinal cord stimulation (SCS) system for the treatment of painful diabetic peripheral neuropathy.

The Proclaim XR SCS system consists of an implantable pulse generator that delivers electrical pulses through leads to nerves along the spinal cord.  It was originally approved in 2019 for the treatment of chronic pain.

Clinical studies have shown that SCS treatment in patients with painful diabetic peripheral neuropathy (PDPN) can lead to significant reduction in pain and improved quality of life. When compared with conventional medical treatment alone, the addition of SCS reduced pain more effectively in patients with PDPN in the lower limbs.

Prior to implanting the SCS, a stimulation trial should be performed on a patient to confirm satisfactory pain relief. Patients who successfully complete the trial and undergo implantation of the Proclaim XR SCS device can then control their therapy using an Apple device. The system also pairs with Abbott’s NeuroSphere Virtual Clinic, allowing individuals to communicate with a clinician via a secure in-app video chat and receive remote programming adjustments.

Commenting on the expanded approval, Pedro Malha, vice president, neuromodulation, Abbott, said: “This new indication for Proclaim XR will drive meaningful change in the treatment of pain associated with diabetic peripheral neuropathy and will be an important tool for physicians and patients in managing this debilitating condition.”

Reference

FDA approves Abbott’s spinal cord stimulation for people living with painful diabetic peripheral neuropathy. News release. January 26, 2023. https://www.prnewswire.com/news-releases/fda-approves-abbotts-spinal-cord-stimulation-for-people-living-with-painful-diabetic-peripheral-neuropathy-301731127.html

HealthDay News — A coordinated, multifaceted intervention increases prescription of 3 groups of evidence-based therapies in adults with type 2 diabetes and atherosclerotic cardiovascular disease (CVD), according to a study published online March 6 in the Journal of the American Medical Association to coincide with the annual meeting of the American College of Cardiology, held from March 4 to 6 in New Orleans.

Neha J. Pagidipati, MD, MPH, from the Duke Clinical Research Institute in Durham, North Carolina, and colleagues assessed the effect of a coordinated, multifaceted intervention of assessment, education, and feedback vs usual care on the proportion of adults with type 2 diabetes and atherosclerotic CVD prescribed all 3 groups of recommended, evidence-based therapies (high-intensity statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [ACEIs or ARBs], and sodium-glucose cotransporter 2 inhibitors and/or glucagon-like peptide 1 receptor agonists [SGLT2 inhibitors and/or GLP-1RAs]). The analysis included 1049 participants treated at 43 US cardiology clinics (July 2019 through May 2022).

The researchers found that patients in the intervention group were more likely to be prescribed all 3 therapies (37.9%) vs individuals in the usual-care group (14.5%; adjusted odds ratio, 4.38) and were more likely to be prescribed each of the three therapies (adjusted odds ratios, 1.73, 1.82, and 3.11 for high-intensity statins, ACEIs or ARBs, and SGLT2 inhibitors and/or GLP-1RAs, respectively). No changes in atherosclerotic CVD risk factors were seen with the intervention.

“An absolute increase of 23.4 percent in prescriptions for all three recommended therapies in the intervention group versus the usual-care group, which was more than twice the improvement the trial was designed to detect, is clinically meaningful and, based on clinical trial evidence for these therapies, should result in a substantial improvement in patient outcomes over time,” the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.

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Mikhail N. Kosiborod, MD, from Saint Luke’s Mid America Heart Institute in Kansas City, Missouri, and colleagues randomly assigned 616 patients who had heart failure with preserved ejection fraction, a body mass index of 30 kg/m² or more, and type 2 diabetes to receive semaglutide or placebo once a week for 52 weeks. The change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight were the primary endpoints.

The researchers found that the mean change in KCCQ-CSS was 13.7 and 6.4 points with semaglutide and placebo, respectively, and the corresponding mean percentage changes in body weight were −9.8% and −3.4%. For the confirmatory secondary endpoints, including the estimated between-group difference in change in 6-minute walk distance and estimated treatment ratio for change in C-reactive protein level, the results favored semaglutide over placebo. Serious adverse events were reported in 17.7% and 28.8% of those in the semaglutide and placebo groups, respectively.

“Once-weekly semaglutide at a dose of 2.4 mg led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 52 weeks,” the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Novo Nordisk, which manufactures semaglutide and funded the study.

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Amir Qaseem, MD, PhD, from ACP in Philadelphia, and colleagues developed clinical guidelines based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients’ values and preferences, and costs for type 2 diabetes treatments. The effectiveness and harms of newer pharmacologic treatments, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins were reviewed.

For adults with type 2 diabetes and inadequate glycemic control, the authors recommend the addition of an SGLT-2 inhibitor or GLP-1 agonist to metformin and lifestyle modifications (strong recommendation). An SGLT-2 inhibitor can reduce the risk for all-cause mortality, major adverse cardiovascular events, chronic kidney disease progression, and hospitalization due to congestive heart failure. Use of a GLP-1 agonist can reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. To reduce morbidity and all-cause mortality, the addition of a DPP-4 inhibitor to metformin and lifestyle modification is not recommended for adults with type 2 diabetes and inadequate glycemic control (strong recommendation).

“ACP continues to recommend starting treatment with metformin and adding other agents only when glycemic goals are not met or comorbid conditions warrant their use,” Fatima Z. Syed, M.D., from Duke University in Durham, North Carolina, writes in an accompanying editorial.

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Updated by the ADA Professional Practice Committee, the guidelines are intended to provide a comprehensive overview of diabetes care, including recommendations for evaluating and treating type 1 and type 2 diabetes, gestational diabetes, and prediabetes. This year’s guidelines include several updated recommendations based on the latest research and clinical trials.

  Updates related to drug therapy include:

• Guidance and screening on the use of teplizumab-mzwv. Teplizumab is approved under the brand name Tzield to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years of age and older who have stage 2 type 1 diabetes. The treatment is administered by intravenous infusion once daily for 14 consecutive days. Findings from a phase 2 clinical trial showed teplizumab delayed the median onset of stage 3 type 1 diabetes by 25 months compared with placebo.
• Additional guidance on the use of obesity medications. The recommendations state that a glucagon-like peptide 1 receptor agonist (GLP-1 RA; eg, semaglutide) or a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA (eg, tirzepatide) are the preferred pharmacotherapy for patients with diabetes who are overweight or obese. Both drug classes aid in weight loss and have led to improvements in glycemic control and cardiometabolic outcomes.

Other notable updates include new screening recommendations for heart failure and peripheral arterial disease, as well as additional information on preventing and managing hypoglycemia and evaluating patients for nonalcoholic fatty liver disease and fracture risk. The guidelines also emphasize the importance of utilizing diabetes technology, including artificial intelligence for retinal screenings and digital tools for diabetes self-management education.

“These changes reflect our ongoing commitment to optimizing patient outcomes through informed, adaptable, and patient-centered health care practices,” said Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer. “The ADA’s Standards of Care ensures health care professionals, especially our primary care workforce, provide the best possible care to those living with diabetes.”

The full guideline can be accessed here.

Published every 5 years, the ADA’s Economic Costs of Diabetes in the US in 2022 includes data on the total direct medical costs associated with diabetes, as well as the average annual medical expenditures. The report was authored by a group of experts in the field of diabetes care and costs. In 2022, around 7.6% of the total US population was diagnosed with diabetes (~25.5 million people) and approximately 339,000 deaths were attributed to the disease.

According to the report, the direct medical costs associated with diabetes increased by 7% from $287.0 billion in 2017 to $306.6 billion in 2022; glucose-lowering medications and diabetes supplies accounted for approximately 17% ($51.3 billion) of these costs. Findings also showed that from 2017 to 2022, after adjusting for inflation, the cost of insulin increased by 24% and the total cost of insulin and other medications for glucose management went up by 26%. For patients living with diabetes, the average annual medical costs amounted to $19,736.

Though the prevalence of diabetes was lower among women, they spent more on average than men on annual diabetes health care. Additionally, health care expenditures attributable to diabetes were found to be higher among Black patients and individuals over the age of 65 when compared with other patients living with diabetes in the US. 

The authors also looked at the indirect costs associated with diabetes. These included reduced employment due to disability, presenteeism or reduced work productivity, and premature mortality. In total, these indirect costs accounted for $106.3 billion of the total estimated national cost of diabetes. 

“Reducing the cost of diabetes is essential to improving the lives of all people with diabetes,” said Charles Henderson, the ADA’s CEO. “November is American Diabetes Month, and as we continue our fight to end diabetes, we urge policymakers and the entire health care system to see this report as a call to action to prioritize affordable diabetes care.”

HealthDay News — For adults with type 2 diabetes, glycemic control is significantly better with once-weekly icodec than once-daily insulin glargine U100, according to a study published online June 24 in the New England Journal of Medicine to coincide with the annual meeting of the American Diabetes Association, held from June 23 to 26 in San Diego.

Julio Rosenstock, MD, from Velocity Clinical Research at Medical City in Dallas, and colleagues conducted a 78-week phase 3a trial involving adults with type 2 diabetes who had not previously received insulin. Participants were randomly assigned to receive once-weekly insulin icodec or once-daily insulin glargine U100 (492 in each group).

The researchers found that at 52 weeks, the mean reduction in glycated hemoglobin level was greater with icodec than with glargine U100 (from 8.50 to 6.93% and from 8.44 to 7.12%, respectively); the estimated between-group difference of −0.19 percentage points (95% CI, −0.36 to −0.03) confirmed the noninferiority and superiority of icodec. Compared with glargine U100, the percentage of time spent in the glycemic range of 70 to 180mg/dL was significantly higher with icodec (71.9 vs 66.9%), which confirmed superiority. The rates of combined clinically significant or severe hypoglycemia were 0.30 and 0.16 events per person-year of exposure with icodec and glargine U100, respectively, at week 52, and 0.30 and 0.16 per person-year of exposure, respectively, at week 83 (estimated rate ratios, 1.64 [95% CI 0.98 to 2.75] and 1.63 [95% CI, 1.02 to 2.61], respectively).

“The findings of the current trial highlight the totality of evidence for glycemic control with icodec,” the authors write.

Several authors disclosed ties to pharmaceutical companies, including Novo Nordisk, which manufactures once-weekly insulin icodec and funded the study.

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HealthDay News — Oral semaglutide 50mg once daily leads to a superior and clinically meaningful reduction in body weight for adults with overweight or obesity without type 2 diabetes, according to a study published online June 25 in The Lancet to coincide with the annual meeting of the American Diabetes Association, held from June 23 to 26 in San Diego.

Filip K. Knop, MD, from the University of Copenhagen in Denmark, and colleagues conducted a randomized, phase 3 superiority trial involving adults with a body mass index of at least 30 kg/m² or at least 27 kg/m² with bodyweight-related complications and comorbidities, without type 2 diabetes, in a trial conducted at 50 outpatient clinics in 9 countries. A total of 667 participants were randomly assigned to oral semaglutide 50mg or placebo (334 or 333, respectively) once per day for 68 weeks, plus lifestyle intervention.

The researchers found that from baseline to week 68, the estimated mean bodyweight change was −15.1 and −2.4% with semaglutide and placebo, respectively. Compared with placebo, in the semaglutide group, more participants reached bodyweight reductions of at least 5% (85 vs 26%; odds ratio, 12.6), 10% (69 vs 12%; odds ratio, 14.7); 15% (54 vs 6%; odds ratio, 17.9), and 20% (34 vs 3%; odds ratio, 18.5).

“These results indicate that oral semaglutide 50mg could provide an effective, future option for people with overweight or obesity who would benefit from a glucagon-like peptide-1 receptor agonist,” the authors write.

Several authors disclosed ties to pharmaceutical companies, including Novo Nordisk, which manufactures semaglutide and funded the study.

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HealthDay News — For patients with insulin-naive type 2 diabetes, once-weekly icodec is superior for reduction in hemoglobin A1c (HbA1c), according to a study published online June 24 in the Journal of the American Medical Association to coincide with the annual meeting of the American Diabetes Association, held from June 23 to 26 in San Diego.

Ildiko Lingvay, MD, MPH, from the University of Texas Southwestern Medical Center in Dallas, and colleagues examined the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes in a phase 3a trial conducted at 92 sites in 11 countries. Participants were randomly assigned to once-weekly icodec and once-daily placebo or once-daily degludec and once-weekly placebo (294 patients in each group).

The researchers found that the mean HbA1c level decreased from 8.6 to 7.0% at 26 weeks in the icodec group and from 8.5 to 7.2%% in the degludec group (estimated treatment difference, −0.2 percentage points), confirming noninferiority and superiority. No significant between-group differences were seen in the change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, or change in body weight from baseline to week 26. The icodec group had combined level 2 or 3 hypoglycemia rates that were numerically higher from week 0 to 31 and statistically significantly higher from week 0 to 26.

“When considering treatment with icodec insulin in clinical practice, the small added glycemic benefit and convenience of the once-weekly administration should be weighed against the small absolute risk of hypoglycemia,” the authors write.

Several authors disclosed ties to pharmaceutical companies, including Novo Nordisk, which manufactures once-weekly insulin icodec and funded the study.

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HealthDay News — Once-weekly tirzepatide provides substantial and clinically meaningful reductions in body weight in adults with obesity and type 2 diabetes, according to a study published online June 26 in the The Lancet to coincide with the annual meeting of the American Diabetes Association, held from June 23 to 26 in San Diego.

W. Timothy Garvey, MD, from the UAB Diabetes Research Center at the University of Alabama at Birmingham, and colleagues examined the efficacy and safety of tirzepatide versus placebo for weight management for people with obesity and type 2 diabetes in a phase 3 trial conducted in seven countries. Adults with a body mass index of 27kg/m² or higher and glycated hemoglobin of 7 to 10% were randomly assigned to receive once-weekly, subcutaneous tirzepatide (10 or 15mg) or placebo for 72 weeks (312, 311, and 315, respectively).

The researchers found that the least-squares mean change in bodyweight at week 72 was −12.8, −14.7, and −3.2%, respectively, with tirzepatide 10mg and 15mg, and placebo. Bodyweight reduction thresholds of 5% or higher were met by more participants treated with tirzepatide versus placebo (79 to 83% vs 32%). Gastrointestinal-related adverse events were the most frequent adverse events reported with tirzepatide, and included nausea, diarrhea, and vomiting; most were mild to moderate in severity, and few led to treatment discontinuation (<5%).

“We are encouraged by these weight loss and glycemic control results, especially as weight loss interventions are typically less effective in patients in diabetes,” Garvey said in a statement.

Several authors disclosed ties to pharmaceutical companies, including Eli Lilly, which manufactures tirzepatide and funded the study.

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HealthDay News — For individuals with diabetes without preexisting cardiovascular disease, the addition of glucagon-like peptide 1 receptor agonists (GLP1-RA) is associated with a lower risk for major adverse cardiac events (MACE) and heart failure, according to a study published online May 9 in the Annals of Internal Medicine.

Tadarro L. Richardson Jr., MD, from the VA Tennessee Valley Healthcare System Geriatric Research Education Clinical Center in Nashville, and colleagues examined whether MACE incidence is lower with the addition of GLP1-RA or sodium-glucose cotransporter 2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) onto metformin, sulfonylurea, or insulin treatment alone or in combination. A total of 28,759 GLP1-RA versus 28,628 DPP4i weighted pairs and 21,200 SGLT2i vs 21,170 DPP4i weighted pairs were included in the study.

The researchers found lower MACE and heart failure risk in association with GLP1-RA vs DPP4i (adjusted hazard ratio, 0.82; 95% CI, 0.72 to 0.94), for an adjusted risk difference of 3.2 events per 1000 person-years. There was no association observed for SGLT2i versus DPP4i with MACE and heart failure (adjusted hazard ratio, 0.91; 95% CI, 0.78 to 1.08).

“These findings are hypothesis generating, and further evaluation of these medications as part of primary [cardiovascular disease] prevention strategy is needed,” the authors write.

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In its new presidential advisory, the American Heart Association (AHA) has shined a spotlight on cardiovascular-kidney-metabolic (CKM) syndrome. CKM is a newly described multisystem syndrome highlighting the interactions among risk factors linked to poor health, organ damage, cardiovascular events, and early death. This includes obesity, type 2 diabetes and other metabolic abnormalities, chronic kidney disease (CKD), and cardiovascular disease risk.

According to the advisory, “rather than simply considering cardiorenal syndrome and cardiometabolic disease as separate entities, it is increasingly clear that we need to consider their overlap as a broader construct of CKM syndrome.

“Nearly every major organ system is affected as a consequence of CKM syndrome, with associated clinical challenges including kidney failure, premature cognitive decline, metabolic dysfunction-associated steatotic liver disease (previously nonalcoholic fatty liver disease), obstructive sleep apnea, and increased risk for cancer. However, the greatest clinical impact of CKM syndrome with regard to morbidity and premature mortality is through the disproportionate burden of [cardiovascular disease].”

More than 90 million adults, or 1 in 3 individuals, in the US have at least 3 risk factors for CKM syndrome, according to Chiadi Ndumele, MD, PhD, MHS, a cardiologist and member of the advisory writing committee. Social determinants of health and risk enhancers also play a role in who is prone to developing these risk factors and who receives adequate care, Dr Ndumele, an associate professor at Johns Hopkins University in Baltimore, Maryland, pointed out. Prevention efforts and early life screening for risk factors are major goals of this initiative, he said.

The advisory, published in Circulation, takes an interdisciplinary approach to preventing and managing CKM syndrome throughout a patient’s lifetime from youth to adulthood. It provides guidance on CKM syndrome prevention, staging, prediction, and approaches to holistic and equitable care.

CKM Syndrome Staging

The advisory details a CKM syndrome staging framework designed to help clinicians slow progression by considering the totality of patients’ individual risk exposures. The frequency and intensity of screening should increase with the CKM syndrome stage. The framework outlines how and when to use specific therapies.

• Stage 0 describes healthy adults with no risk factors whom clinicians can encourage to preserve cardiovascular health through AHA’s life’s essential 8: eating healthy, staying active, maintaining healthy weight, avoiding smoking, and maintaining normal range blood pressure, blood sugar, and lipids. Clinicians should screen these adults every 3 to 5 years to assess blood pressure, triglycerides, HDL cholesterol, and blood sugar. At every stage, clinicians should perform yearly measurement of waist circumference and body mass index and encourage healthy lifestyle behaviors.
• Stage 1 describes adults with excess or dysfunctional adipose tissue from overweight, obesity, abdominal obesity, and/or impaired glucose tolerance. (Women with gestational diabetes fall into this category.) Clinicians should screen every 2 to 3 years for blood pressure, triglycerides, cholesterol, and blood sugar. The goal is at least 5% weight loss, with treatment for glucose intolerance if needed.
• Stage 2 describes adults with metabolic risk factors or CKD. These individuals have type 2 diabetes, hypertension, hypertriglyceridemia, metabolic syndrome, and/or metabolic or nonmetabolic etiologies of CKD. Yearly assessment of blood pressure, triglycerides, cholesterol, and blood sugar is warranted. Kidney function should be assessed at least yearly and more frequently in those at risk for kidney failure. CKD screening should include blood and urine testing for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).

Stage 2 warrants intensified lifestyle medication and targeted therapies to control blood pressure, blood sugar, and cholesterol, protect kidney function, and reduce the risk of heart failure. Medications may include glucagon-like peptide 1 (GLP-1) receptor agonists or sodium glucose contransporter 2 inhibitors (SGLT2i).

• Stage 3 describes adults with subclinical atherosclerotic cardiovascular disease or subclinical heart failure. It also includes those with risk equivalents including patients with stage 4 to 5 CKD and those with high predicted cardiovascular risk.

The goal of care in stage 3 is increasing or changing medications or lifestyle efforts to prevent progression to symptomatic cardiovascular disease (eg, heart failure) and kidney failure. Regression may be possible. Clinicians should use coronary artery calcium screening to guide decisions about cholesterol-lowering statin therapy if necessary.

• Stage 4 describes patients with clinical cardiovascular disease including coronary heart disease, heart failure, atrial fibrillation, stroke, or peripheral arterial disease. People may have already had a heart attack or stroke. Stage 4b patients also have end-stage kidney disease (ESKD) and are therefore at the highest risk for cardiovascular events, hospitalizations, and premature death. The goal of management in stage 4 is individualized treatment to optimize care and secondary prevention.

Read more: Heart Failure Medications

Enhancing Risk Prediction With a New Tool

The AHA will be unveiling a new risk calculator that includes CKM components such as cardiovascular disease, CKD, and metabolic disorders. It will gauge an individual’s risk for heart failure in addition to heart attack and stroke.

The new tool – to be presented at AHA’s Scientific Sessions in Philadelphia, Pennsylvania on November 11-13, 2023 – goes beyond the current pooled cohort equation. It starts younger (at age 30 years) and reflects risk in various ethnicities. The calculator will include blood sugar measurement results, eGFR, UACR, and social determinants of health.

The risk calculator will calculate both 10-year and 30-year cardiovascular disease risk.

Risk-Enhancing Factors

The advisory noted specific factors and medical history that can increase the likelihood that CKM syndrome progresses to a more advanced stage. These factors might adversely affect predisposition, lifestyle behaviors, medication exposures, and more.

• Family history of diabetes or kidney failure
• High-sensitivity C-reactive protein of 2.0mg/L or higher
• Chronic inflammatory conditions such as lupus and HIV/AIDS
• High-risk demographic groups such as South Asians and individuals of low socioeconomic status
• Adverse social determinants of health (eg, economic instability, low education, poor health care access, under-resourced neighborhoods, and low social/community context due to racism, etc)
• Mental health disorders
• Sleep disorders
• Sex-specific factors (eg, erectile dysfunction, premature menopause, hypertensive disorders of pregnancy, preterm birth, polycystic ovarian syndrome)

Major goals are to find optimal strategies to support lifestyle change and weight loss at every stage, tailored approaches to selecting cardioprotective anti-hyperglycemic therapies in at-risk patients and those with existing cardiovascular disease, the use of lipid-lowering therapies beyond statins in those with diabetes and/or high risk for CKM syndrome, and management of cardiovascular disease in patients with CKD.

The call to action centers on addressing research gaps and improving patients’ social determinants of health, access to pharmacotherapies, CKM syndrome education, interdisciplinary care, obesity management, and community support.

“We actually now have therapies that converge together and meaningfully improve outcomes, whether from a metabolic, cardiovascular, or kidney perspective,” said Janani Rangaswamy, MD, a nephrologist and coauthor of the paper. She is also professor of medicine at the George Washington University School of Medicine in Washington, DC. Dr Rangaswamy mentioned, for example, that high-level evidence supports SGLT2i for cardio-kidney protection in patients who have CKD with and without diabetes across albuminuria categories and patients who have heart failure with preserved or reduced ejection fraction. Combined use of SGLT2i and GLP-1 RA may be considered for those with multiple CKM syndrome risk factors in the setting of high predicted cardiovascular risk. In patients with CKD and diabetes, finerenone, a nonsteroidal mineralocorticoid receptor antagonist, shows benefit on top of renin angiotensin aldosterone system inhibitors.

The advisory proposed value-based care whereby patients with at least 2 criteria for CKM syndrome see a multidisciplinary care team that includes representation from primary care, cardiology, nephrology, and endocrinology with oversight from a care coordinator. The goal is upfront, guideline-recommended treatment.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

A. Michael Lincoff, MD, from the Cleveland Clinic, and colleagues assessed whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes. The analysis included 17,604 patients (aged 45 years and older) with preexisting cardiovascular disease and a body mass index 27kg/m² or greater who were randomly assigned to once-weekly subcutaneous semaglutide at a dose of 2.4mg or placebo.

The researchers found that during a mean duration of exposure to semaglutide or placebo of 34.2 months and a mean follow-up of 39.8 months, a primary cardiovascular end-point event (death or nonfatal heart attack or stroke) occurred in 6.5% of the semaglutide group and in 8.0 percent of the placebo group (hazard ratio, 0.80). Discontinuation due to adverse events occurred in 16.6 percent of participants in the semaglutide group and among 8.2% in the placebo group.

“The magnitude of the effect of semaglutide in the current trial was similar to that among patients with diabetes in previous studies (within the constraints of between-trial comparisons), which suggests that treatment with semaglutide could be applied more broadly for secondary prevention of cardiovascular events in the expanding population of patients with overweight and obesity and atherosclerotic vascular disease,” the authors write.

The study was funded by Novo Nordisk, the manufacturer of semaglutide.

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Using a sodium-glucose cotransport 2 (SGLT2) inhibitor instead of a dipeptidyl peptidase 4 (DPP4) inhibitor may reduce the risk of acute kidney injury (AKI) and AKI requiring dialysis in patients with type 2 diabetes, new study findings suggest.

Among 104,462 propensity-score matched patients (44.1% female; mean age 58 years) with type 2 diabetes treated with SGLT2 or DPP4 inhibitors in Taiwan’s 2016-2018 National Health Insurance Research Database, 856 patients (0.8%) experienced AKI and 102 patients (less than 0.1%) had AKI requiring dialysis over 2.5 years of follow-up.  

SGLT2 inhibitor users had significant 34% and 44% lower risks of AKI and AKI requiring dialysis compared with DPP4 inhibitor users, Chi-Jung Chung, PhD, China Medical University in Taichung, Taiwan, and colleagues reported in JAMA Network Open. The risks of AKI and AKI requiring dialysis were a significant 39% and 46% lower with dapagliflozin, respectively, and 30% and 41% lower with empagliflozin, respectively. Results for canagliflozin were not significant or not applicable.

Among potential causes of AKI, investigators documented heart disease, sepsis, respiratory failure, and shock in 22.7%, 23.6%, 6.5%, and 2.8% of patients, respectively. SGLT2 inhibitor use was significantly associated with a 58% lower risk of AKI among patients with respiratory failure and a 52% lower risk of AKI among patients with shock, the investigators reported. They found no relationship between AKI and heart disease or sepsis in the SGLT2 inhibitor group.

The risk of developing advanced chronic kidney disease (CKD) within 90 days of AKI was a significant 6.5% lower in the SGLT2 vs DPP inhibitor group, Dr Chung and colleagues reported. At baseline, 9.2% of patients had stage 1-3 CKD.

“Despite the warning of the US Food and Drug Administration Adverse Event Reporting System regarding the association between SGLT2i and the risk of AKI, an increasing number of clinical trials and clinical database studies have found that SGLT2i use was associated with a decreased risk of AKI,” Dr Chung’s team wrote.

The investigators suggested SGLT2 inhibitor use decreases intraglomerular pressure, podocyte stress, and proteinuria; improves renal cortical oxygenation; and reduces hypoxic injury through cellular signaling and decreased inflammation.

According to Dr Chung’s team, these findings suggest that SGLT2 inhibitors may be an effective way to prevent AKI and AKI requiring dialysis and improve outcomes.

Reference

Chung MC, Hung PH, Hsiao PJ, et al. Sodium-glucose transport protein 2 inhibitor use for type 2 diabetes and the incidence of acute kidney injury in Taiwan. JAMA Netw Open. Published online February 22, 2023. doi:10.1001/jamanetworkopen.2023.0453

Rajiv Agarwal, MD, from Indiana University in Indianapolis, and colleagues quantified the proportion of kidney and cardiovascular risk reductions seen during a 4-year period mediated by a change in kidney injury in a post-hoc analysis using pooled data from two phase 3 trials of finerenone. Data were included for 12,512 patients with CKD and type 2 diabetes who received finerenone and placebo (1:1 ratio).

The researchers found that the median urine albumin-to-creatinine ratio (UACR) was 514mg/g at baseline. Overall, 53.2 and 27.0% of patients in the finerenone and placebo groups, respectively, had a 30% or greater reduction in UACR. Eighty-four and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively, was mediated by a reduction in UACR (analyzed as a continuous variable). The corresponding proportions mediated were 64 and 26% when change in UACR was assessed as a binary variable (whether the 30% reduction threshold was met).

“The current results emphasize the importance of monitoring UACR after initiating treatment, as it can serve as a valuable surrogate indicator of the early treatment efficacy and offer insights into potential long-term kidney and cardiovascular benefits,” the authors write.

The study was funded by Bayer, the manufacturer of finerenone.

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HealthDay News — As demand for the wildly popular weight-loss drug Wegovy continues to climb, drug maker Novo Nordisk said Thursday that it will continue restrictions on starter doses of the medication into 2024. The new plan extends by months existing restrictions and means patients who are not already taking the medication will have to wait to start.

“We are going to continue to supply the market, but it’s just going to be on a limited form so we can have that continuity of care,” Doug Langa, executive vice president of North America Operations for Novo Nordisk, told CNN. “We’re still producing all strengths and we’re still supplying all strengths to the market.” The company had previously expected the restriction to last through September.

Eli Lilly is also struggling with supply and demand issues for its type 2 diabetes medication Mounjaro. That medication does not yet have US Food and Drug Administration approval as a weight-loss drug. “Supply will likely remain tight in the coming months and quarters due to significant demand,” Eli Lilly Chief Financial Officer Anat Ashkenazi told CNN.

Prescriptions for Ozempic are now at almost 500,000, about 200,000 higher than last year, CNN reported. Meanwhile, about 80,000 people use Wegovy. Wegovy was shown in a recent trial to also reduce the risk for heart attack, stroke, or heart-related death by 20%.

Based on body mass index, 120 million Americans would qualify to take Wegovy, Langa said. A person must have a BMI of 27 or higher, plus a weight-related health condition. “This is categorically the largest unmet need that I know of in life science,” Langa said. “We’re super happy to be able to be bringing something that is so meaningful.”

CNN Article

Treatment with analog rather than human insulin may result in better clinical outcomes in patients with type 2 diabetes receiving maintenance hemodialysis (HD), investigators suggest.

In the multinational Analyzing Data, Recognizing Excellence and Optimizing Outcomes (ARO) ii study, investigators compared outcomes between 713 analog insulin and 733 human insulin users. In adjusted multivariable analyses, significantly lower proportions of the analog than human insulin group experienced major adverse cardiovascular events (MACE, 26.8% vs 35.9%), hospitalization (58.2% vs 75.0%), and all-cause mortality (22.0% vs 31.4%), James Fotheringham, PhD, of the University of Sheffield in Sheffield, UK, and colleagues reported in the American Journal of Kidney Diseases. Analog users had significant 18.3%, 24.3%, 19.2% lower risks for these outcomes, respectively. MACE was defined as hospitalization for coronary, cerebral, or peripheral arterial events, heart failure, or cardiac arrest.

Hypoglycemia (less than 3.0 mmol/L) occurred at comparable rates among analog and human insulin users: 14.1% vs 15.0%.

Insulin therapy is the “cornerstone” of antihyperglycemic treatment in kidney failure since these patients are ineligible for sodium-glucose contransporter 2 inhibitors, Dr Fotheringham’s team noted.

“Both long- and short-acting analogues, therefore, could significantly reduce glycemic variability, which has been linked to mortality in people on HD, without necessarily modifying HbA1c.”

Human insulin, they noted, has been linked with postprandial hyperglycemia followed by hypoglycemia and weight gain.

Since this was an observational study, residual confounding could not be ruled out, such as the cost and availability of each insulin type.

Disclosure: This research was supported by Amgen. Please see the original reference for a full list of disclosures.