Endocrinology (all articles)
RCT: Liraglutide for Children Aged 6 to <12 Years with Obesity
14 Sep, 2024 | 19:40h | UTCSummary:
A recent phase 3a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine examined the efficacy and safety of liraglutide in children aged 6 to less than 12 years with obesity. Currently, no medications are approved for treating nonmonogenic, nonsyndromic obesity in this age group, making this study particularly noteworthy.
Methods:
- Participants: 82 children with obesity (BMI ≥95th percentile for age and sex).
- Design: Participants were randomized in a 2:1 ratio to receive once-daily subcutaneous liraglutide (up to 3.0 mg) or placebo, alongside lifestyle interventions, over a 56-week treatment period, followed by a 26-week follow-up.
- Primary Endpoint: Percentage change in BMI from baseline to week 56.
- Secondary Endpoints: Percentage change in body weight and the proportion achieving a ≥5% reduction in BMI.
Results:
- BMI Reduction: At week 56, the liraglutide group experienced a mean BMI reduction of –5.8%, compared to a +1.6% increase in the placebo group. The estimated difference was –7.4 percentage points (95% CI, –11.6 to –3.2; P<0.001).
- Body Weight: Mean body weight increased by 1.6% in the liraglutide group versus 10.0% in the placebo group, a difference of –8.4 percentage points (95% CI, –13.4 to –3.3; P=0.001).
- BMI Reduction ≥5%: Achieved by 46% of participants in the liraglutide group versus 9% in the placebo group (adjusted odds ratio, 6.3; 95% CI, 1.4 to 28.8; P=0.02).
- Adverse Events: Reported in 89% of the liraglutide group and 88% of the placebo group. Gastrointestinal events were more common with liraglutide (80% vs. 54%).
Discussion:
While the study suggests that liraglutide can lead to a statistically significant reduction in BMI among children aged 6 to less than 12 years with obesity, several considerations should temper our enthusiasm:
- Sample Size and Diversity: The trial included only 82 participants, with a predominantly White population (72%), which may limit the generalizability of the findings to broader, more diverse populations.
- Duration and Long-Term Effects: The study spanned 56 weeks, with a 26-week follow-up. The long-term efficacy and safety of liraglutide in this age group remain uncertain, particularly concerning growth, development, and potential rebound weight gain after discontinuation.
- Clinical Significance: Although the reduction in BMI was statistically significant, the clinical significance—especially regarding long-term health outcomes and obesity-related comorbidities—is less clear. Obesity is a chronic and relapsing condition, and a modest reduction in BMI may not translate into substantial health benefits without sustained intervention.
- Adverse Events: The high incidence of gastrointestinal adverse events raises questions about the tolerability of liraglutide in young children. Managing these side effects in a pediatric population can be challenging and may affect adherence.
- Lack of Consensus on BMI Reduction: There’s no international consensus on what constitutes a clinically meaningful BMI reduction in children, complicating the interpretation of the results.
Conclusion:
This trial provides preliminary evidence that liraglutide, combined with lifestyle interventions, may help reduce BMI in children under 12 with obesity. However, given the limitations—including small sample size, short duration, and safety concerns—it’s prudent to approach these findings with cautious optimism. More extensive studies with longer follow-up periods and more diverse populations are necessary to fully assess the long-term efficacy and safety of liraglutide in this vulnerable age group.
Takeaway:
While liraglutide shows promise as an adjunct therapy for pediatric obesity, it’s essential to weigh the benefits against the potential risks and uncertainties. Clinicians should continue to prioritize established lifestyle interventions and consider pharmacotherapy on a case-by-case basis, pending further evidence.
Polled Analysis: Semaglutide Reduces Heart Failure Events in Obese Patients with HFpEF
12 Sep, 2024 | 13:39h | UTCStudy Design and Population: This post-hoc pooled analysis combined data from four randomized, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) involving 3,743 participants with heart failure and preserved or mildly reduced ejection fraction (HFpEF). The participants had various comorbidities including obesity, diabetes, and atherosclerotic cardiovascular disease. They were randomized to receive either semaglutide or placebo.
Main Findings: Semaglutide significantly reduced the risk of the composite endpoint of cardiovascular death or worsening heart failure events compared to placebo (HR 0.69, 95% CI 0.53–0.89, p=0.0045). It also reduced worsening heart failure events alone (HR 0.59, 95% CI 0.41–0.82, p=0.0019). However, no significant reduction in cardiovascular death alone was observed (HR 0.82, 95% CI 0.57–1.16, p=0.25). Semaglutide was generally well tolerated, with fewer serious adverse events compared to placebo.
Implications for Practice: These findings suggest semaglutide may be an effective therapy to reduce heart failure-related events in obese patients with HFpEF. Although semaglutide did not reduce cardiovascular death, its ability to lower the risk of heart failure hospitalizations makes it a potential therapeutic option for managing HFpEF in this population, a condition with limited treatment choices.
RCT: Once-Weekly Insulin Efsitora Non-Inferior to Insulin Degludec for HbA1c Control but Increases Hypoglycemia in Adults with Type 1 Diabetes
12 Sep, 2024 | 13:06h | UTCStudy Design and Population: This 52-week, randomized, open-label non-inferiority trial included 692 adults with type 1 diabetes from 82 global sites. Participants were randomly assigned to receive once-weekly insulin efsitora (n=343) or once-daily insulin degludec (n=349), both in combination with insulin lispro. The primary objective was to assess the change in HbA1c from baseline to week 26, with a non-inferiority margin of 0.4%.
Main Findings: HbA1c reduction was similar between the groups at 26 weeks (–0.51% for efsitora vs. –0.56% for degludec; p=0.43). However, participants on efsitora experienced higher rates of level 2 or 3 hypoglycemia (14.03 vs. 11.59 events per patient year, p=0.016) and a greater incidence of severe hypoglycemia (10% for efsitora vs. 3% for degludec). Overall, the safety profile was similar, with no treatment-related deaths.
Implications for Practice: Once-weekly insulin efsitora offers comparable glycemic control to daily degludec, but its association with increased hypoglycemia, especially during dose titration, indicates that closer monitoring and optimization are necessary. This treatment could reduce the burden of daily injections, but its hypoglycemia risks must be managed carefully.
Updated ESC Hypertension Guidelines 2024: Intensified Blood Pressure Targets and New Categories – Eur Heart J
31 Aug, 2024 | 19:54h | UTCIntroduction:
The 2024 ESC Guidelines for managing elevated blood pressure (BP) and hypertension were developed by the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). These guidelines introduce significant updates to BP management, including more intensive treatment targets and the introduction of a new category for “Elevated BP.”
Key Points:
1 – New Intensive BP Target: For most patients receiving BP-lowering medication, the guidelines now recommend a systolic BP treatment target range of 120-129 mmHg. This marks a significant shift from previous guidelines, which suggested a less aggressive initial target.
2 – New ‘Elevated BP’ Category: The guidelines introduce a new category, “Elevated BP,” defined as a systolic BP of 120-139 mmHg and/or diastolic BP of 70-89 mmHg. This aims to identify more patients at risk of cardiovascular events, such as heart attacks and strokes, before they meet the traditional threshold for hypertension.
3 – Pragmatic BP Management: For patients who cannot tolerate the intensive BP target, the guidelines recommend aiming for a BP that is “as low as reasonably achievable” (ALARA), particularly in frail or older individuals.
4 – Lifestyle Modifications: The guidelines emphasize lifestyle interventions, including dietary changes like potassium supplementation and new exercise recommendations, as first-line strategies for managing BP.
5 – Renal Denervation: For the first time, the guidelines include recommendations on the use of renal denervation—a procedure for patients with resistant hypertension that has not responded to standard treatments. This is not recommended as a first-line treatment but may be considered in specific high-risk cases.
Conclusion:
These new guidelines represent a major update in the management of hypertension, particularly in promoting more aggressive BP targets to reduce cardiovascular risks. The inclusion of a new BP category and recommendations for renal denervation highlight the guidelines’ focus on early intervention and advanced treatment options.
RCT: Chelation Fails to Reduce Cardiovascular Events in Post-MI Patients with Diabetes – JAMA
18 Aug, 2024 | 19:11h | UTCStudy Design and Population: This double-masked, placebo-controlled randomized clinical trial (RCT) included 959 participants aged 50 or older with diabetes and a history of myocardial infarction (MI) from 88 sites in the US and Canada. Participants were randomly assigned to receive either 40 weekly infusions of an EDTA-based chelation solution or a placebo infusion. The median follow-up period was 48 months.
Main Findings: The trial found no significant reduction in major adverse cardiovascular events (MACE) with EDTA-based chelation compared to placebo. The primary endpoint, a composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina, occurred in 35.6% of the chelation group and 35.7% of the placebo group (HR, 0.93; 95% CI, 0.76-1.16; P = .53). However, chelation did reduce median blood lead levels by 61%, from 9.0 μg/L at baseline to 3.5 μg/L by the 40th infusion (P < .001).
Implications for Practice: Despite the significant reduction in blood lead levels, EDTA-based chelation did not reduce cardiovascular events in this high-risk population. These findings suggest that while chelation therapy may lower lead levels, it does not translate into cardiovascular benefits for patients with diabetes and a history of MI, challenging its use in this context.
Cohort Study: Long-Term Multivitamin Use Not Linked to Reduced Mortality in Over 390,000 US Adults
18 Aug, 2024 | 15:07h | UTCtudy Design and Population: This cohort study examined the association between daily multivitamin (MV) use and mortality risk using data from three large prospective cohorts in the United States. The study included 390,124 generally healthy adults with no prior history of cancer or major chronic diseases. Participants were followed for up to 27 years, with baseline MV use assessed between 1993 and 2001 and follow-up assessments from 1998 to 2004.
Main Findings: Daily MV use was not associated with a reduction in all-cause mortality. In fact, the study found a 4% higher risk of mortality among daily MV users compared to nonusers during the first half of the follow-up period (HR, 1.04; 95% CI, 1.02-1.07), although this risk was not significant in the second half. The findings were consistent across major causes of death, including heart disease, cancer, and cerebrovascular diseases.
Implications for Practice: These findings suggest that long-term MV use does not confer a mortality benefit among generally healthy adults. Healthcare providers may need to reconsider recommending MVs for longevity purposes, as the evidence does not support their efficacy in reducing mortality risk.
CDC Updates Contraceptive Guidelines for 2024 – Centers for Disease Control and Prevention
18 Aug, 2024 | 13:51h | UTCIntroduction: The Centers for Disease Control and Prevention (CDC) has released updated recommendations in the “U.S. Selected Practice Recommendations for Contraceptive Use, 2024” and “U.S. Medical Eligibility Criteria for Contraceptive Use, 2024.” These guidelines provide healthcare providers with the latest evidence-based recommendations to support patient-centered contraceptive care, aiming to remove unnecessary barriers and ensure equitable access to contraception.
Key Points:
1 – Intrauterine Device (IUD) Placement:
– Routine use of misoprostol is not recommended for IUD placement, except in selected cases. Lidocaine (topical or paracervical block) is newly recommended to reduce patient pain during IUD placement.
2 – Bleeding Irregularities with Implants:
– Hormonal treatments and antifibrinolytic agents may improve bleeding irregularities associated with implant use, although bleeding often recurs after stopping treatment. NSAIDs and selective estrogen-receptor modulators may also be effective, with benefits persisting post-treatment.
3 – Testosterone Use and Pregnancy Risk:
– Testosterone therapy may not prevent pregnancy in transgender, gender-diverse, and nonbinary individuals with a uterus. Contraceptive counseling and services should be offered to those at risk of pregnancy who do not desire it.
4 – Self-Administration of Injectable Contraceptives:
– Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) should be available for self-administration, providing an additional option for those seeking injectable contraception.
5 – Updates in Medical Eligibility Criteria:
– The 2024 guidelines include revised recommendations for patients with chronic kidney disease, updates for those who are breastfeeding, postpartum, or post-abortion, and considerations for individuals with obesity, cardiovascular conditions, and other comorbidities.
6 – Patient-Centered Counseling:
– The guidelines emphasize the importance of providing contraceptive care in a noncoercive manner, supporting the individual’s values, goals, and reproductive autonomy. Healthcare providers are encouraged to recognize and address structural inequities and avoid discrimination in contraceptive counseling.
Conclusion: These updated guidelines from the CDC are designed to support healthcare providers in delivering equitable, patient-centered contraceptive care. By removing unnecessary barriers and providing clear guidance on managing complex contraceptive issues, the recommendations aim to improve access to contraception and support informed, autonomous decision-making among patients.
Guideline Reference: Curtis, K. M., Nguyen, A. T., Tepper, N. K., et al. (2024). U.S. Selected Practice Recommendations for Contraceptive Use, 2024. MMWR Recommendations and Reports, 73(3).
Meta-Analysis: Long-Term Low-Carbohydrate Diets Improve Dyslipidemia but Not Glycemic Control in Type 2 Diabetes – J Diabetes Investig
17 Aug, 2024 | 19:14h | UTCStudy Design and Population: This systematic review and meta-analysis examined the impact of long-term low-carbohydrate diets (LCD) on glycemic control and other metabolic parameters in adults with type 2 diabetes. Six randomized controlled trials (RCTs) involving 524 participants were included, with intervention durations ranging from 12 to 24 months.
Main Findings: The meta-analysis found no significant difference in glycated hemoglobin (HbA1c) levels between participants on long-term LCD and those on control diets (SMD -0.11, 95% CI -0.33 to 0.11, P = 0.32). Similarly, there were no significant differences in weight loss, blood pressure, or low-density lipoprotein (LDL) cholesterol levels. However, LCDs were associated with a significant increase in high-density lipoprotein (HDL) cholesterol (SMD 0.22, 95% CI 0.04 to 0.41, P = 0.02) and a decrease in triglyceride levels (SMD -0.19; 95% CI -0.37 to -0.02; P = 0.03).
Implications for Practice: While long-term LCDs do not appear to improve glycemic control in individuals with type 2 diabetes, they may be beneficial for managing dyslipidemia, specifically by increasing HDL cholesterol and reducing triglycerides. These findings suggest that LCDs could be considered as part of a strategy for addressing cardiovascular risk factors in this population, but they should not be relied upon for glycemic management.
Meta-Analysis: Renal Denervation Modestly Reduces Blood Pressure in Uncontrolled Hypertension – J Am Heart Assoc
17 Aug, 2024 | 16:14h | UTCStudy Design and Population: This updated meta-analysis evaluated 15 randomized clinical trials, encompassing 2,581 patients, to assess the efficacy and safety of catheter-based renal denervation (RDN) in patients with uncontrolled hypertension. The trials included both patients on antihypertensive medications (ON-Med) and those off medications (OFF-Med), with comparisons made between RDN and sham or standard therapy.
Main Findings: RDN led to a modest but statistically significant reduction in blood pressure across both ON-Med and OFF-Med groups. In the OFF-Med group, 24-hour ambulatory systolic BP was reduced by 3.7 mm Hg (95% CI, -5.41 to -2.00). In the ON-Med group, the reduction was 2.23 mm Hg (95% CI, -3.56 to -0.90). Sham-controlled trials reinforced these findings, showing consistent BP reductions, thus validating the effect of RDN. However, the degree of BP reduction is modest and may be clinically limited.
Implications for Practice: While RDN appears to have a favorable safety profile and provides consistent BP reductions, the modest nature of these reductions suggests that its clinical utility may be more limited. Further research is needed to identify which patient populations might benefit the most from RDN and to optimize procedural techniques for greater efficacy.
Meta-analysis: SSRIs Significantly Reduce Symptoms but Increase Adverse Events in Premenstrual Syndrome – Cochrane Database Syst Rev
17 Aug, 2024 | 16:04h | UTCStudy Design and Population: This systematic review and meta-analysis included 34 randomized controlled trials (RCTs) involving 4,563 women diagnosed with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). The studies primarily focused on evaluating the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) compared to placebo. The trials involved a diverse population, predominantly from Western countries, with participants aged between 18 and 49 years.
Main Findings: SSRIs likely reduce overall self-rated premenstrual symptoms in women with PMS and PMDD, with a standardized mean difference (SMD) of -0.57 (95% CI: -0.72 to -0.42). Continuous SSRI administration was more effective than luteal phase administration (SMD -0.69 vs. -0.39). However, SSRIs were associated with a higher risk of adverse events, including nausea (OR 3.30), insomnia (OR 1.99), sexual dysfunction (OR 2.32), and fatigue (OR 1.52).
Implications for Practice: SSRIs are an effective treatment option for reducing premenstrual symptoms in women with PMS and PMDD, particularly when administered continuously. However, the increased risk of adverse events must be carefully considered, and patients should be monitored closely. Further research is necessary to confirm these findings and explore long-term safety.
RCT: Dietary Acid Reduction with Fruits and Vegetables Slows CKD Progression and Lowers CVD Risk in Hypertensive Patients – Am J Med
17 Aug, 2024 | 15:49h | UTCStudy Design and Population: This five-year randomized control trial included 153 hypertensive patients with macroalbuminuria and normal kidney function. Participants were randomly assigned to one of three groups: a diet rich in base-producing fruits and vegetables, oral sodium bicarbonate (NaHCO3), or Usual Care. The primary objective was to assess the effects of dietary acid reduction on chronic kidney disease (CKD) progression and cardiovascular disease (CVD) risk.
Main Findings: The study found that both fruits and vegetables and NaHCO3 slowed CKD progression compared to Usual Care, with significantly higher estimated glomerular filtration rates in the intervention groups. However, only the fruits and vegetables group showed significant reductions in systolic blood pressure, LDL cholesterol, and body mass index, leading to greater improvements in CVD risk indices.
Implications for Practice: The results support using fruits and vegetables as a foundational treatment for hypertension to reduce CKD progression and lower CVD risk, potentially with reduced reliance on pharmacological interventions.
Systematic Review: Uncertain Impact of Vitamin D Supplementation During Pregnancy on Key Maternal and Neonatal Outcomes – Cochrane Database Syst Rev
11 Aug, 2024 | 12:42h | UTCStudy Design and Population: This Cochrane systematic review evaluates the effects of vitamin D supplementation alone or in combination with calcium and other vitamins/minerals during pregnancy. The analysis included 10 randomized controlled trials (RCTs) with a total of 2,313 pregnant women. The review excluded 20 studies from previous versions due to trustworthiness concerns and incorporated one new study.
Main Findings: The evidence regarding vitamin D supplementation alone was very uncertain for its impact on pre-eclampsia, gestational diabetes, preterm birth, and nephritic syndrome. There is low-certainty evidence suggesting that vitamin D may reduce the risk of severe postpartum hemorrhage and low birthweight, though the possibility of increased risk cannot be excluded. Supplementation with vitamin D plus calcium showed very uncertain effects on preterm birth and low birthweight, with no conclusive data on pre-eclampsia, gestational diabetes, or maternal adverse events. The combination of vitamin D, calcium, and other vitamins/minerals also yielded very uncertain evidence for all outcomes examined.
Implications for Practice: The current evidence does not provide strong support for routine vitamin D supplementation during pregnancy due to the low and very uncertain evidence on key outcomes. Further high-quality RCTs are needed to better understand the effects, particularly concerning maternal adverse events and neonatal health.
Consensus Recommendations: Cardiovascular Risks in People With Narcolepsy – J Am Hear Assoc
10 Aug, 2024 | 21:48h | UTCIntroduction: The Journal of the American Heart Association recently published a consensus guideline by a panel of sleep and cardiology experts to address the heightened cardiovascular risks in individuals with narcolepsy. Given the increased prevalence of hypertension and cardiometabolic comorbidities in this population, the panel developed recommendations aimed at mitigating these risks.
Key Points:
1 – Increased Cardiovascular Risk in Narcolepsy:
– Individuals with narcolepsy, both Type 1 (NT1) and Type 2 (NT2), exhibit higher rates of cardiovascular and cardiometabolic diseases, such as hypertension, obesity, and diabetes, compared to the general population.
– The association of narcolepsy with conditions like obstructive sleep apnea (OSA) and restless legs syndrome further elevates cardiovascular risk.
2 – Monitoring and Early Detection:
– Clinicians should annually monitor blood pressure, weight, and waist circumference in patients with narcolepsy, even in the absence of existing cardiovascular disease.
– Screening for lipid levels and hemoglobin A1c is recommended, especially in patients with risk factors like hypertension, obesity, and diabetes.
3 – Lifestyle and Therapeutic Interventions:
– Patients should be educated about the link between narcolepsy and cardiovascular disease. Emphasis should be placed on maintaining optimal sleep duration, regular exercise, healthy eating, and reducing sodium intake.
– The American Heart Association’s “Life’s Essential 8” guidelines should be followed to enhance overall cardiovascular health.
4 – Medication Management:
– Narcolepsy medications, particularly stimulants and sodium oxybate, can increase cardiovascular risk. Clinicians should consider the patient’s cardiovascular profile when prescribing these treatments and explore alternatives with lower cardiovascular impact if necessary.
5 – Sodium Reduction:
– High sodium intake, from both diet and certain narcolepsy medications, is associated with increased blood pressure and cardiovascular disease. Patients should be advised to reduce sodium intake, and clinicians should consider prescribing lower-sodium alternatives when possible.
Conclusion: These expert consensus recommendations underscore the importance of proactive cardiovascular risk management in patients with narcolepsy. By implementing these guidelines, clinicians can help mitigate the long-term cardiovascular risks associated with this chronic sleep disorder.
Retrospective Study: Automated Multiorgan CT Markers Predict Diabetes and Cardiometabolic Comorbidities – Radiology
10 Aug, 2024 | 21:36h | UTCStudy Design and Population: This retrospective study analyzed data from 32,166 Korean adults (mean age, 45 years) who underwent health screenings, including fluorodeoxyglucose PET/CT scans, between 2012 and 2015. The study aimed to evaluate the predictive ability of automated CT-derived markers, such as visceral and subcutaneous fat, muscle area, bone density, liver fat, and aortic calcification, for diabetes and associated cardiometabolic conditions.
Main Findings: Visceral fat index showed the highest predictive performance for both prevalent and incident diabetes, with an AUC of 0.70 for men and 0.82 for women in cross-sectional analyses. Combining visceral fat, muscle area, liver fat, and aortic calcification improved prediction, yielding a C-index of 0.69 for men and 0.83 for women. Additionally, the study found that these CT markers were effective in identifying metabolic syndrome, fatty liver, coronary artery calcium scores >100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95.
Implications for Practice: Automated CT-derived markers can effectively predict diabetes and multiple cardiometabolic comorbidities, surpassing traditional anthropometric measures. These findings suggest that integrating such automated assessments into routine clinical practice could enhance risk stratification and preventive care, particularly through opportunistic screening during routine CT scans.
Erythritol Ingestion Increases Platelet Reactivity and Thrombosis Potential in Healthy Adults – Arterioscler Thromb Vasc Biol
10 Aug, 2024 | 21:11h | UTCStudy Design and Population: This interventional study evaluated the effects of erythritol versus glucose on platelet reactivity and thrombosis potential in 20 healthy volunteers, with 10 participants in each group. Researchers measured erythritol plasma levels and assessed platelet function through aggregometry and granule marker analysis both before and after ingestion of 30 g of erythritol or glucose.
Main Findings: Erythritol ingestion resulted in a more than 1000-fold increase in plasma erythritol concentration and significantly enhanced stimulus-dependent platelet aggregation and release of serotonin and CXCL4, markers of platelet activation. In contrast, glucose ingestion did not significantly alter platelet reactivity or granule marker release, highlighting erythritol’s unique pro-thrombotic effects.
Implications for Practice: These findings raise concerns regarding the safety of erythritol as a non-nutritive sweetener, particularly its potential to enhance thrombosis risk. The results suggest a need to reevaluate erythritol’s safety status and consider its impact on cardiovascular health in regulatory guidelines.
Cohort Studies: Metformin During Early Pregnancy or Spermatogenesis is Safe Regarding Congenital Malformation Risks – Ann Intern Med
10 Aug, 2024 | 20:05h | UTCStudy Design and Population: Two observational cohort studies assessed the safety of metformin, focusing on early pregnancy and paternal use during spermatogenesis. The first study involved 12,489 pregnant women with pregestational type 2 diabetes, comparing those on insulin monotherapy to those on insulin plus metformin. The second study analyzed 383,851 live births in Israel, examining the impact of paternal metformin use during spermatogenesis on congenital malformations in newborns.
Main Findings: The first study found no significant increase in the risk of nonlive births when continuing metformin in early pregnancy compared to switching to insulin monotherapy. The risk of congenital malformations was also comparable between the two groups. The second study showed that paternal metformin use in monotherapy did not raise the risk of major congenital malformations, though a slight risk increase was observed with metformin in polytherapy, potentially due to underlying cardiometabolic conditions.
Implications for Practice: These findings suggest that metformin use, either during early pregnancy or spermatogenesis, poses minimal risk for congenital malformations. However, clinicians should consider the overall cardiometabolic profile and diabetes management when prescribing metformin, especially in combination with other antidiabetic medications.
References:
RCT: Dapagliflozin Does Not Improve Outcomes in Critically Ill Patients With Acute Organ Dysfunction – JAMA
10 Aug, 2024 | 19:58h | UTCStudy Design and Population: This multicenter, open-label, randomized clinical trial conducted across 22 ICUs in Brazil evaluated the effect of adding dapagliflozin to standard care in 507 critically ill patients with at least one acute organ dysfunction (respiratory, cardiovascular, or kidney). The study took place between November 2022 and September 2023, with participants randomly assigned to either 10 mg of dapagliflozin plus standard care or standard care alone for up to 14 days or until ICU discharge.
Main Findings: The primary outcome, a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay, showed no significant difference between the dapagliflozin and control groups (win ratio, 1.01; 95% CI, 0.90 to 1.13; P = .89). Secondary outcomes also did not demonstrate significant benefits, although dapagliflozin had a slightly higher probability of reducing the need for kidney replacement therapy.
Implications for Practice: The addition of dapagliflozin to standard care in critically ill patients with acute organ dysfunction did not improve overall clinical outcomes. Although the study did not find significant benefits, the wide confidence intervals suggest that further research could be warranted to explore potential effects more definitively.
RCT: Tirzepatide Significantly Improves MASH Resolution Without Worsening Fibrosis Over 52 Weeks – N Engl J Med
10 Aug, 2024 | 19:53h | UTCStudy Design and Population: This phase 2, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of tirzepatide in 190 participants with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and moderate to severe liver fibrosis (stage F2 or F3). Participants were assigned to receive subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo weekly for 52 weeks.
Main Findings: Tirzepatide significantly improved MASH resolution without worsening fibrosis compared to placebo. Resolution rates were 44% for 5 mg, 56% for 10 mg, and 62% for 15 mg, versus 10% for placebo. Improvement in fibrosis stage without worsening MASH was also higher in tirzepatide groups (51-55%) than in the placebo group (30%). The most common adverse events were mild to moderate gastrointestinal symptoms.
Implications for Practice: Tirzepatide shows promise as a treatment for MASH with moderate to severe fibrosis, significantly improving disease resolution without worsening fibrosis. However, further research with larger and longer trials is needed to confirm these findings and evaluate long-term safety.
Phase 2 Trial: Survodutide Improves MASH Without Worsening Fibrosis, But Increases GI Side Effects – N Engl J Med
10 Aug, 2024 | 19:47h | UTCStudy Design and Population: This 48-week, phase 2 randomized trial evaluated the efficacy and safety of survodutide, a dual agonist of the glucagon and GLP-1 receptors, in 293 adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis (F1-F3 stages). Participants were randomized to receive weekly injections of survodutide (2.4, 4.8, or 6.0 mg) or placebo.
Main Findings: Survodutide significantly improved MASH without worsening fibrosis compared to placebo, with 47% to 62% of participants in the survodutide groups achieving histologic improvement versus 14% in the placebo group. A reduction in liver fat content by at least 30% was observed in 57% to 67% of participants receiving survodutide, compared to 14% in the placebo group. However, adverse events such as nausea, diarrhea, and vomiting were more common with survodutide.
Implications for Practice: The findings suggest that survodutide could be a promising treatment for MASH, with potential benefits for liver histology and fat content. However, the increased gastrointestinal side effects warrant careful consideration in future phase 3 trials to better evaluate the drug’s safety profile and long-term efficacy.
Randomized Trials: Tirzepatide Reduces Apnea-Hypopnea Index and Body Weight in Patients with Obstructive Sleep Apnea and Obesity – N Engl J Med
10 Aug, 2024 | 19:38h | UTCStudy Design and Population: This study comprises two phase 3, double-blind, randomized trials involving adults with moderate-to-severe obstructive sleep apnea (OSA) and obesity. Participants were either using or not using positive airway pressure (PAP) therapy at baseline and received tirzepatide or placebo over 52 weeks.
Main Findings: Tirzepatide significantly reduced the apnea-hypopnea index (AHI) by 20-24 events per hour compared to placebo and also lowered body weight, hypoxic burden, and systolic blood pressure.
Implications for Practice: Tirzepatide offers a promising treatment for reducing OSA severity and associated obesity-related complications, but further research is needed to confirm long-term benefits.
New Guidelines Recommend Against Routine Vitamin D Testing and Treatment for Healthy Adults – J Clin Endocrinol Metab
4 Aug, 2024 | 19:19h | UTCIntroduction: The Endocrine Society has developed new clinical practice guidelines focused on the use of vitamin D for the prevention of various diseases. These guidelines were created by a multidisciplinary panel, including experts in adult and pediatric endocrinology, internal medicine, obstetrics and gynecology, nutrition, and epidemiology.
Key Points:
1 – Empiric Vitamin D Supplementation in Children and Adolescents:
– Recommended to prevent nutritional rickets.
– May lower the risk of respiratory tract infections.
– Dosage in trials ranged from 300 to 2000 IU daily, with an average of about 1200 IU per day.
2 – Empiric Vitamin D Supplementation or Testing in Adults Under 75:
– Not recommended for generally healthy adults without specific indications.
3 – Empiric Vitamin D Supplementation in Adults Over 75:
– Suggested due to its potential to lower the risk of mortality.
– Treatment should be empirical, no testing recommended if there are no established indications for testing (e.g., hypocalcemia).
– Recommended daily rather than intermittent high doses. Dosage in clinical trials ranged from 400 to 3333 IU daily equivalent.
4 – Vitamin D Supplementation During Pregnancy:
– Suggested to lower the risk of preeclampsia, intrauterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality.
– Empiric supplementation recommended without routine 25(OH)D testing unless there are established indications for testing.
– Dosages in trials ranged from 600 to 5000 IU daily equivalent, with an average of about 2500 IU per day.
5 – Vitamin D and High-Risk Prediabetes:
– Suggested to reduce the progression to diabetes.
– In clinical trials, vitamin D dosages ranged from 842 to 7543 IU daily. The estimated weighted average was approximately 3500 IU per day.
6 – Routine 25(OH)D Testing:
– Not recommended for the general population, including those with obesity or dark complexion.
– No clear evidence defining optimal target levels for disease prevention.
Conclusion: These guidelines emphasize the importance of targeted vitamin D supplementation for specific age groups and conditions, while advising against routine testing for vitamin D levels in the general population. Empiric supplementation is considered beneficial, particularly in children, pregnant women, and older adults, and is feasible, cost-effective, and generally acceptable.
Cohort Study: GLP1 receptor agonist use not associated with significant increase in thyroid cancer risk – The BMJ
25 May, 2024 | 19:51h | UTCA large Scandinavian cohort study investigated the association between glucagon-like peptide 1 (GLP1) receptor agonist use and thyroid cancer risk in Denmark, Norway, and Sweden from 2007 to 2021. The study compared 145,410 patients treated with GLP1 receptor agonists to 291,667 patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors and included an additional analysis with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Results showed no significant increase in thyroid cancer risk among GLP1 users over a mean follow-up of 3.9 years, with a hazard ratio of 0.93 (95% CI, 0.66 to 1.31) compared to DPP4 inhibitor users. The study utilized nationwide cancer registers and employed an active-comparator, new user design to minimize confounding, using Cox regression models adjusted by propensity score weighting. The findings suggest that while small risk increases cannot be definitively ruled out, the use of GLP1 receptor agonists does not substantially elevate thyroid cancer risk.
Reference (link to free full-text):
New ACC/AHA Guidelines for the Management of Lower Extremity Peripheral Artery Disease
16 May, 2024 | 11:05h | UTCIntroduction
The 2024 ACC/AHA guidelines, along with several associated societies, highlight the significance of peripheral artery disease (PAD) as a major public health issue, often underestimated, and linked to high risks of amputation and serious cardiovascular events. This document is crucial for clinicians seeking to optimize treatment and improve the quality of life for affected patients.
Key Points
1 – Risk Assessment: It is crucial to evaluate risks associated with PAD and health disparities that may impact treatment outcomes.
2 – Diagnosis: Diagnosis of PAD typically involves physical examination, medical history, and the resting ankle-brachial index.
3 – Medical Therapy: Management includes antiplatelet therapy (usually single), high-intensity statins, antihypertensive therapy, diabetes management, and smoking cessation. Rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin (81 mg) has proven effective and can be included in the therapy for patients at low risk of bleeding.
4 – Structured Exercise: A central component of care, including supervised exercise therapy and community-based programs.
5 – Revascularization: Indicated to prevent limb loss in chronic limb-threatening ischemia and can improve quality of life in cases of claudication.
6 – Multidisciplinary Care: Optimized care involves a team of multiple specialties, especially for chronic limb-threatening ischemia.
New Guidelines for the Management of Corticosteroid-Induced Adrenal Insufficiency – J Clin Endocrinol Metab
15 May, 2024 | 11:21h | UTCIntroduction:
The European Society of Endocrinology and the Endocrine Society have co-published the first joint clinical guideline, focusing on the diagnosis and therapy for glucocorticoid-induced adrenal insufficiency. This document serves as an essential tool for health professionals involved in the care of patients undergoing chronic glucocorticoid therapy.
Key Points:
- Patient Education: Clinicians are recommended to inform patients about the endocrine effects of glucocorticoid treatment, particularly in relation to adrenal insufficiency.
- No Tapering in Short-Term Therapies: It is suggested not to taper glucocorticoid therapies of short duration (<3-4 weeks), regardless of the dose.
- Careful Tapering: For long-term therapies, tapering should be done gradually, especially when approaching physiological daily equivalent doses (e.g., 4-6 mg of prednisone).
- Monitoring Withdrawal Syndrome: Consideration of glucocorticoid withdrawal syndrome that may occur during tapering, adjusting the dose as needed to alleviate symptoms.
- Testing for Adrenal Insufficiency: Morning serum cortisol is recommended as the first test in the suspicion of disorders in the recovery of the HPA axis after cessation of glucocorticoids.
These guidelines offer practical and evidence-based guidance for managing patients who develop adrenal insufficiency due to prolonged use of glucocorticoids, emphasizing the importance of patient education and careful monitoring during the tapering process.
Reference (link to free full-text):
Meta-analysis reveals 24% prevalence of eating disorders among individuals with insulin-dependent diabetes – Eat Behav
11 May, 2024 | 13:41h | UTCThis systematic review and meta-analysis evaluated the prevalence of eating disorder symptoms (EDS) in individuals aged 16 and older with insulin-dependent diabetes, covering both type 1 and type 2 diabetes. The study involved an extensive search across several databases including PubMed, Embase, Scopus, PsycINFO, and CINAHL, culminating in the inclusion of 45 studies. The meta-analysis revealed a pooled prevalence of EDS at 24% (95% CI 0.21–0.28), with prevalence reaching 27% (95% CI 0.24–0.31) among studies using the Diabetes Eating Problem Survey-Revised (DEPS-R), the most frequently utilized screening tool. Notably, the prevalence of EDS varied based on the screening tool used and was significantly associated with sex distribution; studies with a higher percentage of female participants (over 58%) reported a higher prevalence of EDS (30% vs. 18%, prevalence ratio 1.7). The study also highlighted a concerning prevalence of insulin omission, reported at 21% (95% CI 0.13–0.33). This analysis underscores the substantial occurrence of eating disorder symptoms among this patient population, emphasizing the need for tailored screening and interventions.
Reference (link to abstract – $ for full-text):