Prediabetic State

RPR Commentary: Continuous glucose monitoring is a tool that should be used to address specific glucose management challenges. There are significant hazards with overuse. James W. Mold, MD, MPH

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Importance Continuous glucose monitoring (CGM), initially recommended primarily for people with type 1 diabetes, has rapidly expanded to patients with type 2 diabetes and, more recently, even to individuals without diabetes. This broadening use underscores the importance of critically examining the evidence supporting CGM across populations, clarifying where benefits are established, where they are modest, and where they remain uncertain.

Observations We reviewed systematic reviews and meta-analyses of randomized trials and clinical guidelines evaluating CGM use beyond type 1 diabetes, with particular attention to glycemic outcomes, hypoglycemia, patient-reported outcomes, and potential unintended consequences in nonpregnant adults. In adults with type 2 diabetes, evidence from randomized trials consistently demonstrated that CGM use was associated, on average, with a modest yet consistent reduction in hemoglobin A1c of approximately 0.3% compared with finger-stick monitoring or usual care; some patients benefited considerably more. Only limited and indirect evidence supported the adoption of CGM in people with type 2 diabetes not receiving glucose-lowering therapy or in those with prediabetes or obesity.

Conclusions and Relevance CGM should be deployed in response to a specific patient problem rather than as a default intervention. Deliberate, equitable deployment of CGM that is aligned with patient goals, clinical context, and system capacity will be necessary to ensure that those most likely to benefit are not left behind, while avoiding overuse in populations for whom benefit remains unproven.

Author/s:

Dower, Justin A., Johansson, Minna, Camp, Anne W.

Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults: A Review

Megan George — Tue, 11 Nov 2025 14:43:19 +0000

Date Added:

November 11, 2025

Journal/Publication:

JAMA

Publication Date:

November 10, 2025

URL:

Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.19615

Keywords

liver disease

steatotic liver disease

MASLD

Steatohepatitis

PMID (1):

41212550

MeSH

Glucagon-Like Peptide-1 Receptor Agonists

semaglutide

cardiovascular diseases

prevalence

diabetes mellitus

diabetes mellitus, type 2

Prediabetic State

liver cirrhosis

A review of metabolic dysfunction–associated steatotic liver disease in adults. James W. Mold, MD, MPH

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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.

Author/s:

Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher

Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis

Megan George — Tue, 16 Sep 2025 13:46:37 +0000

Date Added:

September 16, 2025

Journal/Publication:

JAMA Pediatrics

Publication Date:

September 15, 2025

URL:

Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamapediatrics.2025.3243

Keywords

diabetes

Diabetes and Endocrinology

PMID (1):

40952752

MeSH

diabetes mellitus, type 2

Glycated Hemoglobin

overweight

Glucagon-Like Peptide-1 Receptor Agonists

glucagon-like peptide 1

Prediabetic State

blood pressure

pediatric obesity

Digestive System Diseases

A review of what we know about the use of GLP-1 RAs in children and adolescents. James W. Mold, MD, MPH

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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.

Author/s:

Pareeta Kotecha, Wenxi Huang, Ya-Yun Yeh

Testosterone Treatment in Middle-Aged and Older Men with Hypogonadism

Megan George — Tue, 02 Sep 2025 13:52:11 +0000

Date Added:

September 2, 2025

Journal/Publication:

The New England Journal of Medicine

Publication Date:

August 6, 2025

URL:

Testosterone Treatment in Middle-Aged and Older Men with Hypogonadism

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1056/NEJMra2404637

Keywords

PMID (1):

40768717

MeSH

cardiovascular diseases

Urinary Retention

Hypogonadism

prostatic neoplasms

Cognitive Dysfunction* / therapy

pulmonary embolism

Lower Urinary Tract Symptoms

Anemia

A review of testosterone replacement in middle-aged and older men with hypogonadism. James W. Mold, MD, MPH

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•
In clinical trials involving middle-aged and older men with hypogonadism, testosterone treatment led to improved sexual activity and libido, correction of anemia, and modestly improved energy, mood, and walking ability. (The following key points also refer to findings from clinical trials involving this patient population.)
•
Testosterone treatment did not improve cognition in men without a previously diagnosed cognitive disorder and did not prevent progression to diabetes in men with prediabetes or improve glycemic control in those with diabetes.
•
Testosterone treatment did not increase the risk of major cardiovascular events among men with preexisting cardiovascular disease.
•
Testosterone treatment did not increase the risk of prostate cancer or acute urinary retention and did not worsen lower urinary tract symptoms.
•
Testosterone treatment was associated with an increased risk of clinical fractures and pulmonary embolism.
•
The decision to administer testosterone treatment in a man with hypogonadism should be based on the severity of the hypogonadism and an assessment of the potential benefits and risks of treatment.

Author/s:

Shalender Bhasin, Peter J Snyder

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

Aubrey Delammermore — Thu, 23 Feb 2023 06:00:00 +0000

Date Added:

February 23, 2023

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

February 7, 2023

URL:

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

0.7326/M22-3018

Keywords

Kidney

Cholecalciferol

Intention to Treat Analysis

type 2 diabetes

Randomized Controlled Trials as Topic

PMID (1):

36745886

MeSH

diabetes mellitus, type 2

In patients with prediabetes, Vitamin D supplementation appears to improve blood glucose levels and reduce progression to diabetes. James W. Mold, MD, MPH

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Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data sources: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.

Study selection: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

Data extraction: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.

Data synthesis: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).

Limitations: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.

Conclusion: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

Primary funding source: None. (PROSPERO: CRD42020163522).

Author/s:

Pittas, A. G., Kawahara, T., Jorde, R., Dawson-Hughes, B., Vickery, E. M., Angellotti, E., Nelson, J., Trikalinos, T. A., Balk, E. M.

Screening for Prediabetes and Type 2 Diabetes

Bethie Seay — Thu, 26 Aug 2021 05:00:00 +0000

Date Added:

August 26, 2021

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1001/jama.2021.12531

The U.S. Preventive Services Advisory Committee recommends screening nonpregnant adults aged 35 – 70 with BMI >25 for prediabetes and diabetes. While there is no recommendation regarding how often to screen, they mention that every 3 years seems reasonable based upon the evidence they reviewed.

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IMPORTANCE An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5%
meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older
adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps
because of differences in the definition of prediabetes or the heterogeneity of prediabetes.
Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the
US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver
disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause
of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2
diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of
improving health outcomes.
OBJECTIVE To update its 2015 recommendation, the USPSTF commissioned a systematic
review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic,
nonpregnant adults and preventive interventions for those with prediabetes.
POPULATION Nonpregnant adults aged 35 to 70 years seen in primary care settings who have
overweight or obesity (defined as a body mass index 25 and 30, respectively) and no
symptoms of diabetes.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that screening for
prediabetes and type 2 diabetes and offering or referring patients with prediabetes to
effective preventive interventions has a moderate net benefit.
CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for prediabetes
and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians
should offer or refer patients with prediabetes to effective preventive interventions.
(B recommendation)

Author/s:

US Preventative Services task Force

Summary of Revisions: Standards of Medical Care in Diabetes—2020

John Bayhi — Sat, 14 Mar 2020 19:35:38 +0000

Date Added:

March 14, 2020

Journal/Publication:

Diabetes Care

Publisher:

American Diabetes Association

Publication Date:

January 1, 2020

Issue:

Supplement 1

Volume:

Pages:

S4-S6

URL:

Summary of Revisions: Standards of Medical Care in Diabetes—2020

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.2337/dc20-Srev

Keywords

PMID (1):

31862743

MeSH

Sodium-Glucose Transporter 2 Inhibitors

Diabetic Ketoacidosis

Ficus

Glucagon-Like Peptide-1 Receptor

glycated hemoglobin a

cardiovascular diseases

Consensus

Farmers

Cystic Fibrosis

Transients and Migrants

Pharmaceutical Preparations

depression

Smell

Patient Comfort

electronic nicotine delivery systems

Blood Glucose Self-Monitoring

celiac disease

follow-up studies

Latent Autoimmune Diabetes in Adults

seasons

social determinants of health

Standard of Care

Time-to-Treatment

united states food and drug administration

risk reduction behavior

Centers for Disease Control and Prevention

glucagon-like peptide 1

anxiety disorders

Feeding and Eating Disorders

thyroid diseases

Infections

This is a three-page summary of the 2020 updates to the ADA Guidelines for Type 2 diabetes. James W. Mold, MD, MPH

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No abstract available.

Standards of Medical Care in Diabetes—2019 Abridged for Primary Care Providers

John Bayhi — Fri, 02 Aug 2019 17:59:06 +0000

Date Added:

August 2, 2019

Journal/Publication:

Clinical Diabetes

Publisher:

American Diabetes Association

Publication Date:

January 1, 2019

Issue:

Volume:

Pages:

11-34

URL:

Standards of Medical Care in Diabetes — 2019 Abridged for Primary Care Providers

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.2337/cd18-0105

Keywords

PMID (1):

30705493

MeSH

diabetes mellitus

diabetes mellitus, type 2

diabetes mellitus, type 1

blood glucose

Prediabetic State

Glucose Tolerance Test

Treatment Adherence and Compliance

Standard of Care

self-management

This is the 2019 version of the ADA Guidelines for managing diabetes in primary care. James W. Mold, MD, MPH

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The American Diabetes Association’s (ADA’s) Standards of Medical Care in Diabetes is updated and published annually in a supplement to the January issue of Diabetes Care. The ADA’s Professional Practice Committee, which includes physicians, diabetes educators, registered dietitians (RDs), and public health experts, develops the Standards. The Standards include the most current evidence-based recommendations for diagnosing and treating adults and children with all forms of diabetes. ADA’s grading system uses A, B, C, or E to show the evidence level that supports each recommendation.

A—Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered
B—Supportive evidence from well-conducted cohort studies
C—Supportive evidence from poorly controlled or uncontrolled studies
E—Expert consensus or clinical experience

This is an abridged version of the 2019 Standards containing the evidence-based recommendations most pertinent to primary care. The tables and figures have been renumbered from the original document to match this version. The complete 2019 Standards of Care document, including all supporting references, is available at professional.diabetes.org/standards.

Author/s:

American Diabetes Association