This JAMA Insights discusses continuous glucose monitoring use among individuals with type 2 diabetes, including types of devices, evidence of effectiveness, and adverse effects and contraindications.
Diverticulitis involves inflammation of outpouchings of the intestinal wall, a condition known as diverticulosis.
Risk factors for diverticulosis include being older than 65 years, obesity (body mass index [BMI] of 30 or more), high blood pressure, type 2 diabetes, certain medications (such as opioids, steroids, and nonsteroidal anti-inflammatory drugs [NSAIDs]), connective tissue diseases (such as polycystic kidney disease, Marfan syndrome, and Ehlers-Danlos syndrome), and specific genetic variants.1
By age 60 years, nearly 60% of people have diverticulosis, most often on the left side of the colon. About 1% to 4% of people with diverticulosis develop diverticulitis in their lifetime. Acute diverticulitis affects about 180 per 100 000 people in the US each year, resulting in approximately 200 000 hospitalizations annually.
Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction–associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers.
Observations The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis.
Conclusions A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis.
Importance Obesity affects 1 in 5 children and adolescents, increasing the risk of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the few pharmacotherapy options available for this population, necessitating a comprehensive evaluation of efficacy and safety.
Objective To assess the efficacy and safety of GLP-1 RAs in children and adolescents (<18 years) with obesity, prediabetes, or T2D.
Data Sources A systematic search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized clinical trials (RCTs) published from inception until February 28, 2025. Data analysis was completed from January 2025 to April 2025.
Study Selection RCTs comparing GLP-1 RAs to placebo in children and adolescents with obesity, overweight, prediabetes, or T2D with reported safety and efficacy data were included.
Data Extraction and Synthesis Two reviewers independently extracted data on sample size, population, interventions, follow-up, and outcomes. Risk of bias was assessed using version 2 of the Cochrane risk of bias tool (RoB2). Efficacy outcomes (except lipids) were analyzed as estimated treatment differences, lipids as estimated treatment ratios, and safety via rate ratios. A random-effects inverse variance model was used for all outcomes.
Main Outcomes and Measures The primary efficacy outcomes were change in hemoglobin A1c (HbA1c) (in percentage points), fasting glucose (in milligrams per deciliter), body weight (in kilograms), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), BMI z scores or percentiles, BMI standard deviation score (SDS), lipid outcomes, and blood pressure. Exploratory efficacy outcomes included obstructive sleep apnea and metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease. Safety outcomes included gastrointestinal adverse effects (GI AEs), infections, hepatobiliary disorders, suicidal ideation or behaviors, depression, hypoglycemia, and adverse event discontinuations.
Results A total of 18 RCTs (11 in obesity, 6 in T2D, and 1 in prediabetes) with 1402 participants (838 GLP-1 RA users and 564 placebo) were included (mean [range] age, 13.7 [6-17] years; 831 female participants (59.3%); median [IQR] treatment duration, 0.51 [0.25-1.00] years). GLP-1 RAs significantly reduced HbA1c (−0.44%; 95% CI, −0.68% to −0.21%), fasting glucose (−9.92 mg/dL; 95% CI, −16.20 to −3.64), body weight (−3.02 kg; 95% CI, −4.98 to −1.06), BMI (−1.45; 95% CI, −2.40 to −0.49), BMI SDS (−0.20; 95% CI, −0.36 to −0.05), BMI percentile (−7.24%; 95% CI, −12.97% to −1.51%), and systolic blood pressure (−2.73 mm Hg; 95% CI, −4.04 to −1.43) and increased GI AE (log[rate ratio] [RR], 0.75). Other AEs, including suicidal ideation or behaviors, showed no significant differences.
Conclusions and Relevance In this systematic review and meta-analysis of 18 trials, GLP-1 RAs significantly improved glycemic, weight, and cardiometabolic outcomes in children and adolescents with T2D or obesity. Available data over a relatively short follow-up suggested suicidal ideation or behaviors were not significantly different, although GI AEs warrant attention in long-term management.
Importance: Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking.
Objective: To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF.
Design, setting, and participants: A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea. Enrolled patients had at least 1 non-sex-related stroke risk factor (determined using the CHA2DS2-VASc score [range, 0-9]) and no documented recurrence of atrial arrhythmia for at least 1 year after catheter ablation for AF. The CHA2DS2-VASc score is used as an assessment of stroke risk among patients with AF (calculated using point values for congestive heart failure, hypertension, ≥75 years of age, diabetes, stroke or transient ischemic attack, vascular disease, between 65 and 74 years of age, and sex category). The date of final follow-up was June 4, 2025.
Interventions: The patients were randomly assigned in a 1:1 ratio to discontinue oral anticoagulant therapy (n = 417) or continue oral anticoagulant therapy (with direct oral anticoagulants; n = 423).
Main outcomes and measures: The primary outcome was the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years. Individual components of the primary outcome (such as ischemic stroke and major bleeding) were assessed as secondary outcomes.
Results: Of the 840 adults randomized, the mean age was 64 (SD, 8) years, 24.9% were women, the mean CHA2DS2-VASc score was 2.1 (SD, 1.0), and 67.6% had paroxysmal AF. At 2 years, the primary outcome occurred in 1 patient (0.3%) in the discontinue oral anticoagulant therapy group vs 8 patients (2.2%) in the continue oral anticoagulant therapy group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P = .02). The 2-year cumulative incidence of ischemic stroke was 0.3% in the discontinue oral anticoagulant therapy group vs 0.8% in the continue oral anticoagulant therapy group (absolute difference, -0.5 percentage points [95% CI, -1.6 to 0.6]). Major bleeding occurred in 0 patients in the discontinue oral anticoagulant therapy group vs 5 patients (1.4%) in the continue oral anticoagulant therapy group (absolute difference, -1.4 percentage points [95% CI, -2.6 to -0.2]).
Conclusions and relevance: Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding vs continuing direct oral anticoagulant therapy.
Trial registration: ClinicalTrials.gov Identifier: NCT04432220.
Importance: A patent foramen ovale (PFO), an opening between the right and left atria during normal fetal development that fails to close after birth, is present in approximately 25% of all adults. Paradoxical embolism, a venous thromboembolism that travels to the systemic circulation typically through a PFO, accounts for about 5% of all strokes and 10% of strokes in younger patients.
Observations: Approximately 50% of patients 60 years or younger with an embolic stroke of undetermined source (cryptogenic stroke) have a PFO, compared with 25% of the general population. The Risk of Paradoxical Embolism (RoPE) score incorporates clinical characteristics (age, history of stroke or transient ischemic attack, diabetes, hypertension, smoking, cortical infarct on imaging) to predict the likelihood that embolic stroke of undetermined source was caused by a PFO. Among patients in the lowest RoPE score category (score <3), PFO prevalence was similar to that in the general population (23%), while PFO prevalence was 77% in patients with a RoPE score of 9 or 10. The PFO-Associated Stroke Causal Likelihood (PASCAL) classification system combines the RoPE score and anatomical criteria from echocardiography (large shunt, atrial septal aneurysm) to classify PFO as the “probable,” “possible,” or “unlikely” cause of otherwise cryptogenic stroke. PFO closure reduces recurrent ischemic stroke in patients 60 years or younger with cryptogenic stroke. In a pooled analysis of 6 trials (3740 patients), the annualized incidence of stroke over a median follow-up of 57 months was 0.47% (95% CI, 0.35%-0.65%) with PFO closure vs 1.09% (95% CI, 0.88%-1.36%) with medical therapy (adjusted hazard ratio, 0.41 [95% CI, 0.28-0.60]). However, the benefits and harms of closure were highly heterogeneous across the trial populations. In patients categorized as PASCAL “probable” (ie, younger patients without vascular risk factors and high-risk PFO anatomical features), there was a 90% decreased relative rate of recurrent ischemic stroke after PFO closure at 2 years (hazard ratio, 0.10 [95% CI, 0.03-0.35]; absolute risk reduction, 2.1% [95% CI, 0.9%-3.4%]). PASCAL “unlikely” patients (eg, older patients with vascular risk factors and no high-risk PFO anatomical features) did not have a lower recurrent stroke rate with PFO closure but had higher risk of procedure- and device-related adverse events, such as atrial fibrillation.
Conclusions and Relevance: Patent foramen ovale is present in approximately 25% of all adults and is a common cause of stroke in young and middle-aged patients. The PASCAL classification system can help guide patient selection for PFO closure. Percutaneous PFO closure substantially reduces the risk of stroke recurrence in well-selected patients younger than 60 years after cryptogenic stroke.
Importance: Type 2 diabetes involves progressive loss of insulin secretion from pancreatic β cells in the setting of insulin resistance and manifests clinically as hyperglycemia. Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally, with estimates ranging from 589 million to 828 million people worldwide. In the US, type 2 diabetes affects approximately 1 in 6 adults.
Observations: Risk factors for type 2 diabetes include older age, family history, overweight or obesity, physical inactivity, gestational diabetes, Hispanic ethnicity, and American Indian or Alaska Native, Asian, or Black race. Diabetes is diagnosed if fasting plasma glucose is greater than or equal to 126 mg/dL, hemoglobin A1C is greater than or equal to 6.5%, or 2-hour glucose during 75-g oral glucose tolerance testing is greater than or equal to 200 mg/dL. Approximately one-third of adults with type 2 diabetes have cardiovascular disease and 10.1% have severe vision difficulty or blindness. The prevalence of type 2 diabetes is 39.2% among patients with kidney failure. Although weight management is an important component of treatment for type 2 diabetes, no specific diet has been proven to be most effective for improving health outcomes. Physical activity can reduce hemoglobin A1C by 0.4% to 1.0% and improve cardiovascular risk factors (ie, hypertension and dyslipidemia). Randomized clinical trials have reported absolute reductions in microvascular disease (3.5%), such as retinopathy and nephropathy, myocardial infarction (3.3%-6.2%), and mortality (2.7%-4.9%), with intensive glucose-lowering strategies (hemoglobin A1C <7%) vs conventional treatment 2 decades after trial completion. First-line medications for type 2 diabetes include metformin and, in patients with cardiovascular or kidney comorbidities or at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is). Common add-on medications include dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RAs, dipeptidyl peptidase-4 inhibitors, sulfonylureas, and thiazolidinediones. Approximately one-third of patients with type 2 diabetes require treatment with insulin during their lifetime. Several randomized clinical trials have demonstrated benefits of specific SGLT2i and GLP-1RA medications compared with placebo for atherosclerotic cardiovascular disease (12%-26% risk reduction), heart failure (18%-25% risk reduction), and kidney disease (24%-39% risk reduction) over 2 to 5 years. Most trial participants with type 2 diabetes were taking metformin. High-potency GLP-1RA and dual GIP/GLP-1RA medications result in weight loss of greater than 5% in most individuals with type 2 diabetes, and weight loss may exceed 10%.
Conclusions: Type 2 diabetes affects up to 14% of the global population and is associated with preventable long-term complications, such as cardiovascular disease, kidney failure, vision loss, and increased mortality. In addition to lifestyle modifications including diet, exercise, and weight management, metformin is generally first-line therapy for attainment of hemoglobin A1C targets. For individuals with type 2 diabetes and cardiovascular or kidney disease or at high cardiovascular risk, guidelines recommend early treatment with SGLT2i and/or GLP-1RA medications.
Importance: Obesity affects approximately 21% of US adolescents and is associated with insulin resistance, hypertension, dyslipidemia, sleep disorders, depression, and musculoskeletal problems. Obesity during adolescence has also been associated with an increased risk of mortality from cardiovascular disease and type 2 diabetes in adulthood.
Observations: Obesity in adolescents aged 12 to younger than 18 years is commonly defined as a body mass index (BMI) at the 95th or greater age- and sex-adjusted percentile. Comprehensive treatment in adolescents includes lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Lifestyle modification therapy, which includes dietary, physical activity, and behavioral counseling, is first-line treatment; as monotherapy, lifestyle modification requires more than 26 contact hours over 1 year to elicit approximately 3% mean BMI reduction. Newer antiobesity medications, such as liraglutide, semaglutide, and phentermine/topiramate, in combination with lifestyle modification therapy, can reduce mean BMI by approximately 5% to 17% at 1 year of treatment. Adverse effects vary, but severe adverse events from these newer antiobesity medications are rare. Surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) for severe adolescent obesity (BMI ≥120% of the 95th percentile) reduces mean BMI by approximately 30% at 1 year. Minor and major perioperative complications, such as reoperation and hospital readmission for dehydration, are experienced by approximately 15% and 8% of patients, respectively. Determining the long-term durability of all obesity treatments warrants future research.
Conclusions and relevance: The prevalence of adolescent obesity is approximately 21% in the US. Treatment options for adolescents with obesity include lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Intensive lifestyle modification therapy reduces BMI by approximately 3% while pharmacotherapy added to lifestyle modification therapy can attain BMI reductions ranging from 5% to 17%. Surgery is the most effective intervention for adolescents with severe obesity and has been shown to achieve BMI reduction of approximately 30%.
Effective diabetes management, particularly in older and frail adults, requires a nuanced approach that balances the benefits of antihyperglycemic medications with the risks of intensive glycemic control. While certain diabetes medications are important to the prevention of chronic complications of diabetes, intensive glycemic management can increase the risk of hypoglycemia, potentially leading to serious adverse outcomes (eg, falls, seizures, hospitalizations, death). In patients aged 65 or older and those with frailty, a tailored approach to diabetes care is crucial. A patient-centred approach might include individualizing glycemic targets and reducing the intensity of both pharmacologic treatment and routine monitoring to prioritize patient safety and quality of life. Implementing such patient-centred care requires clinicians to thoroughly consider each patient’s overall health, preferences, and social context, thus ensuring that treatment decisions align with the patient’s personal goals of care and life circumstances.
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.
Methods: This was a collaborative trial-level meta-analysis from the SGLT2i Meta-analysis Cardio-Renal Trialists Consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across 3 patient populations (patients with diabetes at high risk for atherosclerotic cardiovascular disease, heart failure [HF], or chronic kidney disease). The outcomes of interest were MACE (composite of cardiovascular death, myocardial infarction , or stroke), individual components of MACE (inclusive of fatal and nonfatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i versus placebo were meta-analyzed across trials and examined across key subgroups (established atherosclerotic cardiovascular disease, previous myocardial infarction, diabetes, previous HF, albuminuria, chronic kidney disease stages, and risk groups).
Results: A total of 78 607 patients across 11 trials were included: 42 568 (54.2%), 20 725 (26.4%), and 15 314 (19.5%) were included from trials of patients with diabetes at high risk for atherosclerotic cardiovascular disease, HF, or chronic kidney disease, respectively. SGLT2i reduced the rate of MACE by 9% (hazard ration [HR], 0.91 [95% CI, 0.87-0.96], P<0.0001) with a consistent effect across all 3 patient populations (I2=0%) and across all key subgroups. This effect was primarily driven by a reduction in cardiovascular death (HR, 0.86 [95% CI, 0.81-0.92], P<0.0001), with no significant effect for myocardial infarction in the overall population (HR, 0.95 [95% CI, 0.87-1.04], P=0.29), and no effect on stroke (HR, 0.99 [95% CI, 0.91-1.07], P=0.77). The benefit for cardiovascular death was driven primarily by reductions in HF death and sudden cardiac death (HR, 0.68 [95% CI, 0.46-1.02] and HR, 0.86 [95% CI, 0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (Pinteraction=0.02).
Conclusions: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of atherosclerotic cardiovascular disease, diabetes, kidney function, or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of cardiovascular death, particularly HF death and sudden cardiac death, without a significant effect on myocardial infarction in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.
Keywords: diabetes mellitus; heart failure; meta-analysis; metabolic syndrome; renal insufficiency, chronic; sodium-glucose cotransporter-2 inhibitors.
