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Cited by 145Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Diagnosis and Treatment of Type 2 Diabetes in Adults

Open access
Kalyani, Rita R., Neumiller, Joshua J., Maruthur, Nisa M., Wexler, Deborah J.·2025·JAMA
DOI 10.1001/jama.2025.5956PMC PMC13014273
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Abstract

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 A 1C 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 A 1C 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 A 1C <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 A 1C 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.

AI snapshot

Written from the paper’s full text.

TL;DR

This JAMA review summarizes current evidence on diagnosis and treatment of type 2 diabetes in adults, emphasizing individualized glycemic targets, lifestyle and weight management, metformin as general first-line therapy, and early SGLT2i/GLP-1RA use for patients with cardiovascular or kidney disease or high cardiovascular risk. It reports global prevalence estimates up to 14%, diagnostic thresholds, and trial-based reductions in microvascular and macrovascular complications with intensive glucose lowering and newer agents.

Key findings

  • Type 2 diabetes accounts for 90% to 95% of diabetes cases globally, with worldwide estimates of 589 million to 828 million people and US adult prevalence of 15.8%; up to 14% of the global population is affected.
  • Diagnosis is based on fasting plasma glucose ≥126 mg/dL, HbA1c ≥6.5%, or 2-hour plasma glucose ≥200 mg/dL during 75-g oral glucose tolerance testing, with confirmation by repeat or different test.
  • Lifestyle interventions can improve outcomes: physical activity at an optimal dose of 1100 metabolic-equivalent minutes/week (≈244 minutes/week moderate-intensity) reduced HbA1c by 0.4% to 1.0%; the DiRECT trial achieved remission in 46% vs 4% at 12 months; Look AHEAD showed no primary cardiovascular outcome difference over median 9.6 years but sustained weight loss and other benefits.
  • For cardiovascular/kidney risk, SGLT2i and GLP-1RA trials showed benefits: SGLT2i meta-analysis of 46,969 participants reduced 3-point MACE (HR, 0.90 [95% CI, 0.85–0.95]); GLP-1RA meta-analysis of 56,004 participants reduced MACE (10.5% vs 11.8%; HR, 0.88 [95% CI, 0.82–0.94]); high-potency GLP-1RAs and dual GIP/GLP-1RAs produced >5% weight loss in most, sometimes >10%.

Methods

  • Narrative review: PubMed search for English-language articles published within 5 years before and through June 12, 2024, updated through February 14, 2025, using title keywords for diagnosis and treatment of type 2 diabetes; supplemented by references from selected articles and relevant practice guidelines.
  • Of 2016 articles identified, 126 were included: 47 randomized clinical trials, 22 observational studies, 21 systematic reviews and/or meta-analyses, 21 guidelines, 12 narrative reviews, and 3 drug or device reference guides.
  • Laboratory values are reported primarily in conventional units, with conversion factors provided for glucose and HbA1c.

Limitations

  • Stated: this is not a systematic review and the quality of included literature was not formally evaluated; relevant articles may have been missed; cardiovascular outcome trials generally did not include individuals at lower cardiovascular risk; trials of newer glucose-lowering drugs such as SGLT2is and GLP-1RAs were of relatively short duration, so long-term effects are unknown.
  • Evident: as a narrative review, the synthesis and recommendations may be subject to selection and interpretation bias, and no formal risk-of-bias or certainty-of-evidence assessment is reported.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jama.2025.5956

Cites

115 of 115 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

66 of 92 cited sources checked · 3 supported · 5 flagged · accuracy not yet measured

  • Premisecitation

    The Look AHEAD randomized clinical trial reported that a long-term behavioral weight loss intervention compared with diabetes self-management education and support resulted in no difference between groups for the primary cardiovascular outcome over a median of 9.6 years of follow-up.

    “The Action for Health in Diabetes (Look AHEAD) randomized clinical trial (including 5145 overweight persons with type 2 diabetes) reported that a long-term behavioral weight loss intervention including a goal of at least 175 minutes per week of moderate-intensity physical activity, compared with diabetes self-management education and support, resulted in no difference between groups for the”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [35] Wing RR; Look AHEAD Research Group. Does lifestyle intervention improve health of adults with overweight/obesity and type 2 diabetes? findings from the Look AHEAD randomized trial. Obesity (Silver Spring). 2021; 29(8): 1246– 1258. doi: 10.1002/oby.23158 33988896 source

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    In a trial of 7447 participants in Spain at high cardiovascular risk (50% with diabetes), the 5-year absolute risk of the cardiovascular primary end point was 3.8% (95% CI, 3.2%-4.4%) in the group randomized to receive a Mediterranean diet combined with extra virgin olive oil or nuts vs 5.7% (95% CI, 4.6%-6.9%) in the control group (intention-to-treat hazard ratio, 0.70 [95% CI, 0.55-0.89]).

    “In a trial of 7447 participants in Spain at high cardiovascular risk (50% with diabetes), the 5-year absolute risk of the cardiovascular primary end point (myocardial infarction, stroke, or death from cardiovascular causes) was 3.8% (95% CI, 3.2%–4.4%) in the group randomized to receive a Mediterranean diet combined with extra virgin olive oil or nuts vs 5.7% (95% CI, 4.6%–6.9%) in the control”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] Estruch R, Ros E, Salas-Salvadó J,; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018; 378(25): e34. doi: 10.1056/NEJMoa1800389 29897866 source

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  • Premisecitation

    In individuals with prediabetes, type 2 diabetes can be prevented or delayed with changes in health behaviors that lead to weight loss or pharmacotherapy.

    “In individuals with prediabetes, type 2 diabetes can be prevented or delayed with changes in health behaviors that lead to weight loss or pharmacotherapy.8”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Echouffo-Tcheugui JB, Perreault L, Ji L, Dagogo-Jack S. Diagnosis and management of prediabetes: a review. JAMA. 2023; 329(14): 1206– 1216. doi: 10.1001/jama.2023.4063 37039787 source

      The Methods (page unavailable) define prediabetes, and the Results report its prevalence, but neither addresses whether type 2 diabetes can be prevented or delayed. Searches for weight loss, lifestyle intervention, and pharmacotherapy found no passage supporting the attributed claim. (LLM, conf=0.76)

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  • Premisecitation

    Approximately one-third of patients with type 2 diabetes require treatment with insulin during their lifetime.

    “Approximately one-third of patients with type 2 diabetes require treatment with insulin during their lifetime.”
    • Also stated in: § Glucose-Lowering Medications for Type 2 Diabetes · hedged
      “Insulin therapy is eventually required by up to one-third of adults with type 2 diabetes to maintain glycemic goals as β-cell function declines.14,103”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      The Results (Patient characteristics) describe the reviewed patients but give no proportion who required insulin. The Background discusses diabetes management without addressing lifetime insulin use; searches for insulin treatment and a one-third lifetime proportion found no supporting passage in our copy. The approximately 32.2% figure in the Abstract (Conclusions) refers to cardiovascular disease prevalence, not insulin treatment. (LLM, conf=0.73)

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    • cites [103] Centers for Disease Control and Prevention. United States Diabetes Surveillance System (USDSS). Accessed February 25, 2025. https://gis.cdc.gov/grasp/diabetes/diabetesatlas-surveillance.html source

      The Other Glucose-Lowering Medications section discusses insulin therapy but gives no estimate of how many people with type 2 diabetes require it during their lifetime. Searches for “one-third,” “30%,” and lifetime insulin use found no supporting passage in our copy, which is truncated at the end. (LLM, conf=0.72)

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  • Premisecitation

    In a randomized trial of 5047 patients with type 2 diabetes who were taking metformin, at 5 years of follow-up, the incidence of HbA1C greater than 7.0% was lower with the addition of insulin glargine or liraglutide (26.5 and 26.1 per 100 participant-years, respectively) than glimepiride or sitagliptin (30.4 and 38.1 per 100 participant-years, respectively) (P < .001 for a global test of

    “A randomized trial of 5047 patients with type 2 diabetes who were taking metformin assigned patients to receive a sulfonylurea (glimepiride), DPP-4 inhibitor (sitagliptin), GLP-1 receptor agonist (liraglutide), or basal insulin glargine. At 5 years of follow-up, the incidence of HbA1C greater than 7.0% was lower with the addition of insulin glargine or liraglutide (26.5 and 26.1 per 100”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [91] Nathan DM, Lachin JM, Balasubramanyam A,; GRADE Study Research Group. Glycemia reduction in type 2 diabetes: glycemic outcomes. N Engl J Med. 2022; 387(12): 1063– 1074. doi: 10.1056/NEJMoa2200433 36129996 PMC9829320 source

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    Premisecitation

    Trials of heart failure outcomes with dapagliflozin and empagliflozin, enrolling up to 50% of participants with type 2 diabetes, report reduction in cardiovascular death and improvement of heart failure among patients with heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, respectively, independent of diabetes status, compared with placebo.

    “Trials of HF outcomes with dapagliflozin and empagliflozin, enrolling up to 50% of participants with type 2 diabetes, report reduction in cardiovascular death and improvement of HF among patients with HF with reduced ejection fraction and HF with preserved ejection fraction, respectively, independent of diabetes status, compared with placebo.66–69,88”
    Quote in the paperSubstantial claim4 of 5 sources checked
    • cites [66] McMurray JJV, Solomon SD, Inzucchi SE,; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381(21): 1995– 2008. doi: 10.1056/NEJMoa1911303 31535829 source

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    • cites [67] Packer M, Anker SD, Butler J,; EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383(15): 1413– 1424. doi: 10.1056/NEJMoa2022190 32865377 source

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    • cites [68] Anker SD, Butler J, Filippatos G,; EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021; 385(16): 1451– 1461. doi: 10.1056/NEJMoa2107038 34449189 source

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    • cites [69] Solomon SD, McMurray JJV, Claggett B,; DELIVER Trial Committees and Investigators. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022; 387(12): 1089– 1098. doi: 10.1056/NEJMoa2206286 36027570 source
    • cites [88] Wiviott SD, Raz I, Bonaca MP,; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380(4): 347– 357. doi: 10.1056/NEJMoa1812389 30415602 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

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    Premisecitation

    The DiRECT Study reported that a very low-calorie formula diet (825-853 kcal/d) followed by stepped food reintroduction achieved remission of type 2 diabetes (HbA1C <6.5% without diabetes medications for at least 2 months) among 46% of participants in the intervention group vs 4% in the control group at 12 months (odds ratio, 19.7 [95% CI, 7.8-49.8]).

    “The DiRECT Study, an open-label, cluster-randomized trial of 306 individuals from 49 primary care practices in the UK, reported that a very low–calorie formula diet (825–853 kcal/d) followed by stepped food reintroduction achieved remission of type 2 diabetes (HbA1C <6.5% without diabetes medications for at least 2 months) among 46% of participants in the intervention group vs 4% in the control”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] Lean ME, Leslie WS, Barnes AC, Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018; 391(10120): 541– 551. doi: 10.1016/S0140-6736(17)33102-1 29221645 source

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    Premisecitation

    Diabetes-related comorbidities also include metabolic dysfunction-associated steatotic liver disease, cancers such as colorectal and breast, and dementia.

    “Diabetes-related comorbidities also include metabolic dysfunction–associated steatotic liver disease,19 cancers such as colorectal and breast,20 and dementia.21”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [19] Younossi ZM, Golabi P, Price JK, The global epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2024; 22(10): 1999– 2010.e8. doi: 10.1016/j.cgh.2024.03.006 38521116 source
    • cites [20] Casagrande SS, Menke A,, eds. Diabetes in America. 3rd ed. 2018. 33651524 source

      Citation 21 is attached to dementia, so that is the part assessed here. The Background discusses metabolic syndrome and heart-disease risk in people with type 2 diabetes, but neither it nor the retrieved passages address dementia (searched: dementia, cognitive decline, Alzheimer’s disease, cognitive impairment). (LLM, conf=0.76)

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    • cites [21] Pearson-Stuttard J, Buckley J, Cicek M, Gregg EW. The changing nature of mortality and morbidity in patients with diabetes. Endocrinol Metab Clin North Am. 2021; 50(3): 357– 368. doi: 10.1016/j.ecl.2021.05.001 34399950 source

      The Introduction discusses cardiovascular disease in people with diabetes, and the Discussion addresses DASH-related cardiometabolic outcomes. Searches for steatotic liver disease, colorectal and breast cancer, and dementia found no passage identifying them as diabetes-related comorbidities. (LLM, conf=0.72)

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    Premisecitation

    Most individuals with type 2 diabetes are asymptomatic at diagnosis, and routine screening is recommended.

    “However, most individuals with type 2 diabetes are asymptomatic at diagnosis, and routine screening is recommended (Box 2).14,22”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      The Discussion section on CVD risk assessment discusses screening people who already have type 2 diabetes for cardiovascular risk; it does not say that most people with type 2 diabetes are asymptomatic at diagnosis or recommend routine screening to diagnose diabetes. Searches for asymptomatic diagnosis and routine diabetes screening found no passage addressing those claims. (LLM, conf=0.76)

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    • cites [22] US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes: US Preventive Services Task Force recommendation statement. JAMA. 2021; 326(8): 736– 743. doi: 10.1001/jama.2021.12531 34427594 source

      Participant Selection and Randomization (p. 2) identifies type 2 diabetes as an eligibility criterion, and End Points (p. 7) defines how diabetes was classified. Neither addresses whether most people are asymptomatic at diagnosis or recommends routine diabetes screening; searches for those points found no supporting passage in our copy. (LLM, conf=0.76)

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    Premisecitation

    Although the global prevalence is rising (estimates range from 11%-14% of adult population), the incidence of type 2 diabetes has stabilized or decreased in most places worldwide.

    “Although the global prevalence is rising (estimates range from 11%–14% of adult population), the incidence of type 2 diabetes has stabilized or decreased in most places worldwide.6,7”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [6] Magliano DJ, Islam RM, Barr ELM, Trends in incidence of total or type 2 diabetes: systematic review. BMJ. 2019; 366: l5003. doi: 10.1136/bmj.l5003 31511236 PMC6737490 source

      The Introduction reports U.S. diabetes prevalence and a projected increase in the United States, not a global adult prevalence of 11%–14%. Searches for worldwide incidence trends and stabilized or declining incidence found no passage addressing those claims. The Results likewise concern U.S. prevalence, not global trends. (LLM, conf=0.76)

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    • cites [7] Global Burden of Disease Study 2021: results. Institute for Health Metrics Evaluation. Accessed February 23, 2025, https://vizhub.healthdata.org/gbd-results/ source

      The Introduction (page unavailable) describes type 2 diabetes as having a rising trend over past decades, supporting the general statement that its burden is rising. It does not give an 11%–14% prevalence estimate or say that incidence has stabilized or decreased in most places worldwide; the Results examine adiposity and diabetes risk, not global incidence trends. (LLM, conf=0.84)

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    Premisecitation

    The number of people with diabetes worldwide was estimated to be between 589 million and 828 million during 2022 to 2024.

    “The number of people with diabetes worldwide was estimated to be between 589 million and 828 million during 2022 to 2024,1,2”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [1] NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes prevalence and treatment from 1990 to 2022. Lancet. 2024; 404(10467): 2077– 2093. doi: 10.1016/S0140-6736(24)02317-1 39549716 PMC7616842 source

      The Results (page not provided) estimate that 828 million adults worldwide had diabetes in 2022. The cited paper does not give a 589 million estimate or an estimate for 2024, so it supports only the 2022 figure, not the stated range across 2022–2024. (LLM, conf=0.88)

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    • cites [2] International Diabetes Federation. IDF Diabetes Atlas, 11th edition. Accessed April 30, 2025. https://diabetesatlas.org/media/uploads/sites/3/2025/04/IDF_Atlas_11th_Edition_2025.pdf source

      The Summary reports diabetes prevalence in U.S. adults during August 2021–August 2023, not a worldwide count. Searches for worldwide estimates and the figures 589 million and 828 million found no passage addressing the claimed global estimate. (LLM, conf=0.78)

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    Premisecitation

    The prevalence of diabetes in US adults is 15.8%.

    “The prevalence of diabetes in US adults is 15.8%.4”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Gwira JA, Fryar CD, Gu Q. Prevalence of total, diagnosed, and undiagnosed diabetes in adults: United States, August 2021-August 2023. NCHS Data Brief. 2024; 516(516): CS354814. doi: 10.15620/cdc/165794 PMC12035661 40085919 source

      The Introduction discusses rising diabetes prevalence generally, while the Results report incidence trends, including US studies. Searches for “15.8” and US adult diabetes prevalence found no passage giving the claimed 15.8% estimate; our copy therefore does not verify it. (LLM, conf=0.76)

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    Premisecitation

    Diabetes is a leading cause of kidney failure, nontraumatic lower extremity amputation, and death (30.4 deaths per 100 000 population).

    “Diabetes is a leading cause of kidney failure, nontraumatic lower extremity amputation, and death (30.4 deaths per 100 000 population).3,18”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Centers for Disease Control and Prevention. National Diabetes Statistics Report 2024. Department of Health and Human Services; 2024. Accessed February 23, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html source
    • cites [18] Diabetes. Centers for Disease Control and Prevention National Center for Health Statistics. Accessed February 23, 2025. https://www.cdc.gov/nchs/fastats/diabetes.htm source

      The Methods (Participants) and Results passages describe diabetes classification and treatment in the DARE cohort, not population-level complications or mortality. Searches for kidney failure, lower-extremity amputation, and 30.4 deaths per 100,000 found no passage in our copy addressing the claim. Page numbers were not available. (LLM, conf=0.75)

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    Premisecitation

    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%.

    “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%.”
    • Also stated in: § Glucose-Lowering Medications for Type 2 Diabetes · plain
      “Newer, high-potency weekly GLP-1RAs (ie, high-dose semaglutide or dulaglutide) and dual GIP/GLP-1RAs (ie, tirzepatide) are associated with mean HbA1C reductions up to approximately 2% to 2.5% and weight reductions of greater than 5% from baseline in most individuals, with some exceeding 10%.80”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [80] Frías JP, Davies MJ, Rosenstock J,; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021; 385(6): 503– 515. doi: 10.1056/NEJMoa2107519 34170647 source

      The Effect on Cardiovascular Risk Factors section reports a 1.8 kg greater weight reduction with dapagliflozin than with placebo. It notes some GLP-1 receptor agonist use but does not report weight-loss outcomes for high-potency GLP-1RA or dual GIP/GLP-1RA medications. Searches for those medications and the claimed 5% and 10% thresholds found no supporting passage in our copy. (LLM, conf=0.77)

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    Premisecitation

    HbA1C generally has greater reliability than glucose levels, but may not accurately reflect time-averaged glucose levels in individuals with some hemoglobinopathies, pregnancy, HIV, recent blood transfusion, iron deficiency anemia, hemodialysis, or hemolytic anemia.

    “HbA1C generally has greater reliability than glucose levels, but may not accurately reflect time-averaged glucose levels in individuals with some hemoglobinopathies, pregnancy, HIV, recent blood transfusion, iron deficiency anemia, hemodialysis, or hemolytic anemia.14,23”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

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    • cites [23] Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus. World Health Organization; 1999. Accessed February 23, 2025. https://iris.who.int/bitstream/handle/10665/70523/WHO_NMH_CHP_CPM_11.1_eng.pdf 26158184 source

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    Premisecitation

    Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally.

    “Type 2 diabetes accounts for 90% to 95% of all cases of diabetes globally”
    • Also stated in: § CONCLUSIONS · plain
      “with type 2 diabetes comprising 90% to 95% of cases.1,3,4”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [1] NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes prevalence and treatment from 1990 to 2022. Lancet. 2024; 404(10467): 2077– 2093. doi: 10.1016/S0140-6736(24)02317-1 39549716 PMC7616842 source

      The Discussion (page unavailable) says that most diabetes cases in adults are type 2, but gives a range of 85–95%, not 90–95%. It does not extend that proportion to all diabetes cases across all ages globally. (LLM, conf=0.88)

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    • cites [3] Centers for Disease Control and Prevention. National Diabetes Statistics Report 2024. Department of Health and Human Services; 2024. Accessed February 23, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html source
    • cites [4] Gwira JA, Fryar CD, Gu Q. Prevalence of total, diagnosed, and undiagnosed diabetes in adults: United States, August 2021-August 2023. NCHS Data Brief. 2024; 516(516): CS354814. doi: 10.15620/cdc/165794 PMC12035661 40085919 source

      The Discussion (Principal findings; page unavailable) says type 2 diabetes incidence in adults is an order of magnitude greater than type 1 incidence. That supports the general point that type 2 predominates, but it does not establish that type 2 accounts for 90%–95% of all diabetes cases globally; the passage concerns adult incidence, not the global share of existing cases. (LLM, conf=0.76)

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    Premisecitation

    Risk factors for type 2 diabetes include overweight and obesity, physical inactivity, age, family history, race and ethnicity, history of gestational diabetes, and presence of other conditions (eg, hypertension, dyslipidemia, cardiovascular disease).

    “Risk factors for type 2 diabetes include overweight and obesity, physical inactivity, age, family history, race and ethnicity, history of gestational diabetes, and presence of other conditions (eg, hypertension, dyslipidemia, cardiovascular disease).9–14”
    Quote in the paperNot a substantial claim5 of 6 sources checked
    • cites [9] Moonesinghe R, Beckles GLA, Liu T, Khoury MJ. The contribution of family history to the burden of diagnosed diabetes, undiagnosed diabetes, and prediabetes in the United States: analysis of the National Health and Nutrition Examination Survey, 2009–2014. Genet Med. 2018; 20(10): 1159– 1166. doi: 10.1038/gim.2017.238 29369292 PMC6060023 source
    • cites [10] Jayedi A, Soltani S, Motlagh SZ, Anthropometric and adiposity indicators and risk of type 2 diabetes. BMJ. 2022; 376: e067516. doi: 10.1136/bmj-2021-067516 35042741 PMC8764578 source

      The Discussion identifies a history of gestational diabetes as a risk factor for later type 2 diabetes, and the Results quantify that increased risk. The paper does not substantiate the sentence’s full list of risk factors, including physical inactivity, overweight or obesity, and the listed other conditions; its race and age analyses did not find significant associations with the study effect size. Page numbers are not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [11] Cheng YJ, Kanaya AM, Araneta MRG, Prevalence of diabetes by race and ethnicity in the United States, 2011–2016. JAMA. 2019; 322(24): 2389– 2398. doi: 10.1001/jama.2019.19365 31860047 PMC6990660 source

      The Discussion reports an association between BMI and diabetes and differences in diabetes prevalence by race and ethnicity. It does not substantiate the rest of the listed risk factors—physical inactivity, age, family history, gestational diabetes, hypertension, dyslipidemia, or cardiovascular disease. Page numbers are not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [12] Aune D, Norat T, Leitzmann M, Tonstad S, Vatten LJ. Physical activity and the risk of type 2 diabetes. Eur J Epidemiol. 2015; 30(7): 529– 542. doi: 10.1007/s10654-015-0056-z 26092138 source

      The Main section identifies environment, lifestyle and heritability as T2D risk factors, and the Mechanistic clusters section links obesity-related processes and metabolic syndrome to T2D risk. The paper does not establish the full attributed list: it does not identify physical inactivity, age, family history or gestational diabetes as risk factors, and its analyses of ancestry groups and cardiovascular outcomes do not establish race or ethnicity or cardiovascular disease as risk factors for developing T2D. Page numbers are not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [13] Juan J, Sun Y, Wei Y, Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: systematic review and meta-analysis. Front Endocrinol (Lausanne). 2022; 13: 1012244. doi: 10.3389/fendo.2022.1012244 36277725 PMC9582268 source

      The “Genomic Risk Scores for Prediction and Personalization” section describes a type 2 diabetes prediction model using age, parental diabetes, BMI, blood pressure, HDL cholesterol, and triglycerides. The “Genomic Polygenic Prediction” section also links obesity to elevated risk. Our copy does not establish physical inactivity, gestational diabetes, or cardiovascular disease as risk factors, so it does not support the full list. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      The Discussion section, “Obesity as a risk factor for CVD” (page not provided), says that T2DM risk rises with BMI and discusses a difference between Asian and Caucasian populations. It does not establish the rest of the listed factors as risk factors for developing T2DM; much of its discussion instead concerns cardiovascular risk among people who already have T2DM. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In a meta-analysis and systematic review of 15 randomized clinical trials and observational studies (783 255 patients) comparing intensive control (HbA1C <7.5%) vs standard care in adults 60 years or older or frail adults of any age with type 2 diabetes, there was no difference in mortality, but intensive control was associated with both a reduction in microvascular and macrovascular complications

    “In a meta-analysis and systematic review of 15 randomized clinical trials and observational studies (783 255 patients) comparing intensive control (HbA1C <7.5%) vs standard care in adults 60 years or older or frail adults of any age with type 2 diabetes, there was no difference in mortality, but intensive control was associated with both a reduction in microvascular and macrovascular complications”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [45] Crabtree T, Ogendo JJ, Vinogradova Y, Gordon J, Idris I. Intensive glycemic control and macrovascular, microvascular, hypoglycemia complications and mortality in older (age ≥60years) or frail adults with type 2 diabetes: a systematic review and meta-analysis from randomized controlled trial and observation studies. Expert Rev Endocrinol Metab. 2022; 17(3): 255– 267. doi: 10.1080/17446651.2022.2079495 35614863 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Studies have been limited by small sample sizes in combination therapy subgroups and trials have not consistently shown benefit for the combination of SGLT2is and GLP-1RAs on cardiovascular and kidney outcomes.

    “Studies have been limited by small sample sizes in combination therapy subgroups and trials have not consistently shown benefit for the combination of SGLT2is and GLP-1RAs on cardiovascular and kidney outcomes.73,112”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [73] Perkovic V, Tuttle KR, Rossing P,; FLOW Trial Committees and Investigators. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024; 391(2): 109– 121. doi: 10.1056/NEJMoa2403347 38785209 source

      The Trial Participants and Limitations sections describe a linagliptin-versus-glimepiride trial, not studies of combined SGLT2 inhibitors and GLP-1 receptor agonists. Searches for that combination, small subgroups, and cardiovascular or kidney outcomes found no passage addressing the claim. Page numbers were unavailable in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [112] Apperloo EM, Neuen BL, Fletcher RA, Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists. Lancet Diabetes Endocrinol. 2024; 12(8): 545– 557. doi: 10.1016/S2213-8587(24)00155-4 38991584 source

  • May combine two claims.

    Premisecitation

    The Look AHEAD weight loss intervention was associated with sustained weight loss, lower HbA1C, delayed progression of kidney disease, and improvements in quality of life, depression, sleep apnea, urinary incontinence, and health care utilization and costs.

    “However, the weight loss intervention was associated with sustained weight loss, lower HbA1C, delayed progression of kidney disease, and improvements in quality of life, depression, sleep apnea, urinary incontinence, and health care utilization and costs.35”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [35] Wing RR; Look AHEAD Research Group. Does lifestyle intervention improve health of adults with overweight/obesity and type 2 diabetes? findings from the Look AHEAD randomized trial. Obesity (Silver Spring). 2021; 29(8): 1246– 1258. doi: 10.1002/oby.23158 33988896 source

      The Results and Discussion describe intensive glucose control in veterans, not the Look AHEAD weight-loss intervention. Although they report lower HbA1c and less progression of albuminuria with intensive glucose control, those findings cannot verify outcomes attributed to Look AHEAD. Searches for Look AHEAD, sustained weight loss, and the listed quality-of-life and cost outcomes found no relevant passage in our copy; page numbers were unavailable. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In meta-analyses of people with diabetes (type 1 and 2), clinically meaningful HbA1C reductions have been reported for Mediterranean-style vs control diets (difference in HbA1C, −0.39% [95% CI, −0.58% to −0.20%]), the Dietary Approaches to Stop Hypertension vs control diets (difference in HbA1C, −0.53% [95% CI, −0.62% to −0.43%]), and low- vs high-carbohydrate diets (difference in HbA1C at 6 mo, −

    “In meta-analyses of people with diabetes (type 1 and 2), clinically meaningful HbA1C reductions have been reported for Mediterranean-style vs control diets (difference in HbA1C, −0.39% [95% CI, −0.58% to −0.20%]), the Dietary Approaches to Stop Hypertension vs control diets (difference in HbA1C, −0.53% [95% CI, −0.62% to −0.43%]), and low- vs high-carbohydrate diets (difference in HbA1C at 6 mo, −”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [25] Sainsbury E, Kizirian NV, Partridge SR, Effect of dietary carbohydrate restriction on glycemic control in adults with diabetes. Diabetes Res Clin Pract. 2018; 139: 239– 252. doi: 10.1016/j.diabres.2018.02.026 29522789 source

      The Conclusions list A1C and healthy eating as outcomes of diabetes self-management education, and the References cite a nutrition-therapy consensus report. Neither passage reports meta-analyses comparing Mediterranean, DASH, or low-carbohydrate diets, or the quoted HbA1C differences. Searches for those diet names and figures found no supporting passage in this paper. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [26] Zheng X, Zhang W, Wan X, The effects of Mediterranean diet on cardiovascular risk factors, glycemic control and weight loss in patients with type 2 diabetes: a meta-analysis. BMC Nutr. 2024; 10(1): 59. doi: 10.1186/s40795-024-00836-y 38641818 PMC11027355 source
    • cites [27] Chiavaroli L, Viguiliouk E, Nishi SK, DASH dietary pattern and cardiometabolic outcomes: an umbrella review of systematic reviews and meta-analyses. Nutrients. 2019; 11(2): 338. doi: 10.3390/nu11020338 30764511 PMC6413235 source

      The Discussion reports HbA1c reductions associated with physical activity in people with type 2 diabetes, not dietary comparisons. Searches of our copy for Mediterranean-style, DASH, and low- versus high-carbohydrate diets found no passage reporting the attributed estimates or addressing outcomes in people with type 1 and type 2 diabetes together. Page numbers were not provided for the indexed passages. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In ACCORD, compared with standard care, the intensive glycemic control group had increased hypoglycemia (10.5% vs 3.5%; P < .001), weight gain greater than 10% (28% vs 14%; P < .001), and mortality (5% vs 4%; hazard ratio, 1.22 [95% CI, 1.01-1.46]), prompting early trial discontinuation.

    “In ACCORD, compared with the standard care group, the intensive glycemic control group had increased hypoglycemia (10.5% vs 3.5%; P < .001), weight gain greater than 10% (28% vs 14%; P < .001), and mortality (5% vs 4%; hazard ratio, 1.22 [95% CI, 1.01–1.46]), prompting early trial discontinuation.39,43”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [39] Gerstein HC, Miller ME, Byington RP,; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358(24): 2545– 2559. doi: 10.1056/NEJMoa0802743 18539917 PMC4551392 source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [43] Park L, Wexler D. Update in diabetes and cardiovascular disease: synthesizing the evidence from recent trials of glycemic control to prevent cardiovascular disease. Curr Opin Lipidol. 2010; 21(1): 8– 14. doi: 10.1097/MOL.0b013e328332dfaa 19829110 PMC2871337 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Newer, high-potency weekly GLP-1RAs (ie, high-dose semaglutide or dulaglutide) and dual GIP/GLP-1RAs (ie, tirzepatide) are associated with mean HbA1C reductions up to approximately 2% to 2.5% and weight reductions of greater than 5% from baseline in most individuals, with some exceeding 10%.

    “Newer, high-potency weekly GLP-1RAs (ie, high-dose semaglutide or dulaglutide) and dual GIP/GLP-1RAs (ie, tirzepatide) are associated with mean HbA1C reductions up to approximately 2% to 2.5% and weight reductions of greater than 5% from baseline in most individuals, with some exceeding 10%.80”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [80] Frías JP, Davies MJ, Rosenstock J,; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021; 385(6): 503– 515. doi: 10.1056/NEJMoa2107519 34170647 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The 2-hour plasma glucose level is more sensitive for diagnosis than fasting glucose or HbA1C in identifying individuals with diabetes, and is the preferred test to diagnose cystic fibrosis-related diabetes or posttransplant diabetes; however, it is more cumbersome to perform and has greater day-to-day variability.

    “The 2-hour plasma glucose level is more sensitive for diagnosis than fasting glucose or HbA1C in identifying individuals with diabetes, and is the preferred test to diagnose cystic fibrosis-related diabetes or posttransplant diabetes; however, it is more cumbersome to perform and has greater day-to-day variability.14”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    A meta-analysis of 7 trials of 6 injectable GLP-1RAs and 1 oral GLP-1RA among 56 004 participants with type 2 diabetes (76% with established cardiovascular disease) over a median follow-up of 1.3 to 5.4 years reported a reduction in both the primary major adverse cardiovascular events outcome (10.5% with GLP-1RA treatment vs 11.8% with placebo; hazard ratio, 0.88 [95% CI, 0.82-0.94]) and secondary

    “Similarly, a meta-analysis of 7 trials of 6 injectable GLP-1RAs and 1 oral GLP-1RA among 56 004 participants with type 2 diabetes (76% with established cardiovascular disease) over a median follow-up of 1.3 to 5.4 years reported a reduction in both the primary major adverse cardiovascular events outcome (10.5% with GLP-1RA treatment vs 11.8% with placebo; hazard ratio, 0.88 [95% CI, 0.82–0.94])”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [108] Kristensen SL, Rørth R, Jhund PS, Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2019; 7(10): 776– 785. doi: 10.1016/S2213-8587(19)30249-9 31422062 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Adult-onset type 1 diabetes and other types of diabetes, such as monogenic diabetes syndromes or diabetes secondary to medical conditions such as pancreatitis, may be misdiagnosed as type 2 diabetes, which can potentially delay initiation of appropriate treatment.

    “Adult-onset type 1 diabetes and other types of diabetes, such as monogenic diabetes syndromes or diabetes secondary to medical conditions such as pancreatitis, may be misdiagnosed as type 2 diabetes, which can potentially delay initiation of appropriate treatment.24”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Thomas NJ, Lynam AL, Hill AV, Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes. Diabetologia. 2019; 62(7): 1167– 1172. doi: 10.1007/s00125-019-4863-8 30969375 PMC6559997 source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Intensive glycemic control reduced retinopathy progression in ACCORD (7.3% vs 10.4%; P = .003) and incidence of nephropathy in ADVANCE (4.1% vs 5.2%; P = .006).

    “Intensive control reduced retinopathy progression in ACCORD (7.3% vs 10.4%; P = .003)42 and incidence of nephropathy in ADVANCE (4.1% vs 5.2%; P = .006).40”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [42] Chew EY, Ambrosius WT, Davis MD,; ACCORD Study Group; ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010; 363(3): 233– 244. doi: 10.1056/NEJMoa1001288 20587587 PMC4026164 source

      Citation 42 is attached to the ACCORD retinopathy result; the ADVANCE result has a separate citation. Searches of our copy for ACCORD, retinopathy progression, and the reported percentages found no supporting passage. The Methods and Results instead describe a 52-week comparison of insulin detemir and glargine, with glycaemic control and hypoglycaemia outcomes; no page numbers were available. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [40] Patel A, MacMahon S, Chalmers J,; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358(24): 2560– 2572. doi: 10.1056/NEJMoa0802987 18539916 source

  • May combine two claims.

    Premisecitation

    In a randomized clinical trial of 224 participants with type 2 diabetes taking insulin, CGM decreased hypoglycemic episodes, reducing time with blood glucose less than 70 mg/dL by 0.47 hours per day compared with BGM.

    “In a randomized clinical trial of 224 participants with type 2 diabetes taking insulin, CGM decreased hypoglycemic episodes, reducing time with blood glucose less than 70 mg/dL by 0.47 hours per day compared with BGM.50”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [50] Haak T, Hanaire H, Ajjan R, Hermanns N, Riveline JP, Rayman G. Flash glucose-sensing technology as a replacement for blood glucose monitoring for the management of insulin-treated type 2 diabetes. Diabetes Ther. 2017; 8(1): 55– 73. doi: 10.1007/s13300-016-0223-6 28000140 PMC5306122 source

      The Results > Hypoglycaemia section reports hypoglycaemia with tirzepatide versus placebo or basal insulin, not CGM versus BGM. Searches for CGM, 224 participants, and 0.47 hours per day found no passage in our copy addressing the cited trial or its reported result; page numbers were not available. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Sulfonylureas are inexpensive and have high HbA1C-lowering efficacy.

    “Sulfonylureas are inexpensive and have high HbA1C-lowering efficacy.38,81”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [38] Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91). Lancet. 2024; 404(10448): 145– 155. doi: 10.1016/S0140-6736(24)00537–3 38772405 source
    • cites [81] Rosenstock J, Kahn SE, Johansen OE,; CAROLINA Investigators. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA. 2019; 322(12): 1155– 1166. doi: 10.1001/jama.2019.13772 31536101 PMC6763993 source

      Section 7 (Managing metformin in the elderly; page unavailable) describes sulphonylureas as having efficacy similar to metformin, supporting their glucose-lowering efficacy, but does not characterize their HbA1c-lowering efficacy as high. The Introduction says metformin has a very low cost; it does not say sulphonylureas are inexpensive. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Expected benefits of metabolic surgery include improved quality of life, reduced cardiovascular events, and decreased risk of hepatocellular, colorectal, pancreatic, gallbladder, breast, endometrial, and ovarian cancers.

    “In addition to weight reduction and decreased glycemia (with diabetes remission in some patients), expected benefits of metabolic surgery include improved quality of life, reduced cardiovascular events, and decreased risk of hepatocellular, colorectal, pancreatic, gallbladder, breast, endometrial, and ovarian cancers.14,123–126”
    Quote in the paperSubstantial claim4 of 5 sources checked
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      The Results and Discussion passages address cardiovascular disease prevalence and the relationship between obesity and cardiovascular risk in people with type 2 diabetes. Searches for metabolic or bariatric surgery and the named cancers found no passage assessing whether surgery improves quality of life or reduces cardiovascular events or cancer risk. No page numbers were supplied for these passages. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [123] Schauer PR, Bhatt DL, Kirwan JP,; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes. N Engl J Med. 2017; 376(7): 641– 651. doi: 10.1056/NEJMoa1600869 28199805 PMC5451258 source

      The Results (Quality of Life) and Discussion report better quality-of-life outcomes after surgery than after medical therapy at five years. The Discussion says the trial was too small and short to detect differences in cardiovascular events; it does not establish a reduction in those events. Our copy does not address risk reductions for the listed cancers. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [124] Courcoulas AP, Patti ME, Hu B, Long-term outcomes of medical management vs bariatric surgery in type 2 diabetes. JAMA. 2024; 331(8): 654– 664. doi: 10.1001/jama.2024.0318 38411644 PMC10900968 source

      The “Metabolic Surgery” for Diabetes section supports weight reduction, improved glycemic control, and remission in some patients. The copy lists quality of life and cardiovascular events as outcomes to assess, but does not establish improved quality of life or fewer cardiovascular events; it also does not report reduced risk for the named cancers. No page numbers are available for these passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [125] Sjöholm K, Carlsson LMS, Svensson PA, Association of bariatric surgery with cancer incidence in patients with obesity and diabetes. Diabetes Care. 2022; 45(2): 444– 450. doi: 10.2337/dc21-1335 34799430 PMC8914410 source
    • cites [126] Wilson RB, Lathigara D, Kaushal D. Systematic review and meta-analysis of the impact of bariatric surgery on future cancer risk. Int J Mol Sci. 2023; 24(7): 6192. doi: 10.3390/ijms24076192 37047163 PMC10094585 source

      The Conclusions (page not provided) report significantly decreased incidence of all seven listed cancers after bariatric surgery. The Introduction mentions improved cardiovascular risk factors, not fewer cardiovascular events; the Discussion mentions impaired quality of life with obesity, not improved quality of life after surgery. Those two benefits are therefore not supported by this source. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    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.

    “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.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [14] American Diabetes Association Professional Practice Committee. Standards of care in diabetes: 2025. Diabetes Care. 2025; 48(1)(suppl 1): S1– S5. doi: 10.2337/dc25-SINT 39651982 PMC11635031 source

      The Background (page unavailable) says diabetes guidelines address CVD prevention and that certain antidiabetic treatments lower CVD risk. It does not say guidelines recommend early SGLT2i or GLP-1RA treatment for people with cardiovascular or kidney disease or high cardiovascular risk. The Discussion (page unavailable) instead describes newer drugs as often intended for second- or third-line use. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [116] Davies MJ, Aroda VR, Collins BS, Management of hyperglycemia in type 2 diabetes, 2022: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022; 45(11): 2753– 2786. doi: 10.2337/dci22-0034 36148880 PMC10008140 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Type 2 diabetes affects up to 14% of the global population.

    “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.”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [1] NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes prevalence and treatment from 1990 to 2022. Lancet. 2024; 404(10467): 2077– 2093. doi: 10.1016/S0140-6736(24)02317-1 39549716 PMC7616842 source

      The Results (page not provided) report approximately 14% age-standardised diabetes prevalence worldwide in 2022, separately for adult women and men. The Discussion (page not provided) says the surveys generally did not distinguish diabetes types and that 85–95% of adult cases are type 2. The paper therefore does not establish that type 2 diabetes affects 14% of the global population. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [2] International Diabetes Federation. IDF Diabetes Atlas, 11th edition. Accessed April 30, 2025. https://diabetesatlas.org/media/uploads/sites/3/2025/04/IDF_Atlas_11th_Edition_2025.pdf source

      The Abstract reports an age-adjusted diabetes prevalence of 14.3% among U.S. adults, which is close to the cited figure. It does not estimate prevalence in the global population or report a separate figure for type 2 diabetes, so it cannot support those qualifiers. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [3] Centers for Disease Control and Prevention. National Diabetes Statistics Report 2024. Department of Health and Human Services; 2024. Accessed February 23, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Globally, 32.2% of people with type 2 diabetes have cardiovascular disease.

    “Globally, 32.2% of people with type 2 diabetes have cardiovascular disease.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes. Cardiovasc Diabetol. 2018; 17(1): 83. doi: 10.1186/s12933-018-0728-6 29884191 PMC5994068 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The prevalence of type 2 diabetes is 39.2% among patients with kidney failure.

    “The prevalence of type 2 diabetes is 39.2% among patients with kidney failure.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the US, 1 in 10 individuals with diabetes have severe vision loss or blindness.

    “In the US, 1 in 10 individuals with diabetes have severe vision loss or blindness.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Centers for Disease Control and Prevention. National Diabetes Statistics Report 2024. Department of Health and Human Services; 2024. Accessed February 23, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html source

  • May combine two claims.

    Premisecitation

    Physical activity can reduce HbA1C by 0.4% to 1.0% and improve cardiovascular risk factors (hypertension and dyslipidemia).

    “Physical activity can reduce hemoglobin A1C by 0.4% to 1.0% and improve cardiovascular risk factors (ie, hypertension and dyslipidemia).”
    • Also stated in: § Health Behaviors · plain
      “Dose-associated HbA1C reductions with this level of activity ranged from 0.4% to 1.0%.33”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Gallardo-Gómez D, Salazar-Martínez E, Alfonso-Rosa RM, Optimal dose and type of physical activity to improve glycemic control in people diagnosed with type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2024; 47(2): 295– 303. doi: 10.2337/dc23-0800 38241499 source

  • May combine two claims.

    Premisenone given

    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.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    More than 600 genetic variants are associated with an increased risk of type 2 diabetes.

    “More than 600 genetic variants are associated with an increased risk of type 2 diabetes.15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Suzuki K, Hatzikotoulas K, Southam L,; VA Million Veteran Program. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature. 2024; 627(8003): 347– 357. doi: 10.1038/s41586-024-07019-6 38374256 PMC10937372 source

  • May combine two claims.

    Premisenone given

    Randomized clinical trials have reported absolute reductions in microvascular disease (3.5%), myocardial infarction (3.3%-6.2%), and mortality (2.7%-4.9%) with intensive glucose-lowering strategies (HbA1C <7%) vs conventional treatment 2 decades after trial completion.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Although body mass index has a stronger association with type 2 diabetes than genetic risk scores, approximately 10% of individuals with type 2 diabetes do not have overweight or obesity.

    “Although body mass index has a stronger association with type 2 diabetes than genetic risk scores,16 approximately 10% of individuals with type 2 diabetes do not have overweight or obesity.3”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Meigs JB. The genetic epidemiology of type 2 diabetes: opportunities for health translation. Curr Diab Rep. 2019; 19(8): 62. doi: 10.1007/s11892-019-1173-y 31332628 PMC8059416 source
    • cites [3] Centers for Disease Control and Prevention. National Diabetes Statistics Report 2024. Department of Health and Human Services; 2024. Accessed February 23, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html source

  • May combine two claims.

    Premisecitation

    An observational study with median 17.5 years follow-up on 1489 of 1525 surviving participants reported reductions in all-cause mortality (2.7%-4.9%), myocardial infarction (3.3%-6.2%), and microvascular disease (3.5%) in those previously randomized to receive intensive treatment vs conventional therapy (P < .05 for all comparisons).

    “An observational study that published follow-up data (median of 17.5 years [range, 0–42 years]) on 1489 (97.6%) of the 1525 surviving participants reported reductions in all-cause mortality (2.7%–4.9%), myocardial infarction (3.3%–6.2%), and microvascular disease defined as vitreous hemorrhage, retinal photocoagulation, death due to kidney disease, or kidney failure (3.5%) in those previously”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91). Lancet. 2024; 404(10448): 145– 155. doi: 10.1016/S0140-6736(24)00537–3 38772405 source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Randomized clinical trials investigating cardiovascular outcomes did not generally include individuals at lower risk of cardiovascular disease.

    “Third, randomized clinical trials investigating cardiovascular outcomes did not generally include individuals at lower risk of cardiovascular disease.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Clinical trials of newer glucose-lowering drugs such as SGLT2is and GLP1RAs were of relatively short duration.

    “Fourth, clinical trials of newer glucose-lowering drugs such as SGLT2is and GLP1RAs were of relatively short duration, and long-term effects of these medications are currently unknown.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The review focused on high-quality studies and supplemented the search by identifying additional articles from references of selected articles and reviewed relevant current practice guidelines.

    “We focused on high-quality studies and supplemented our search by identifying additional articles from references of selected articles and reviewed relevant current practice guidelines.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    This review is not a systematic review, and the quality of included literature was not formally evaluated.

    “First, it is not a systematic review, and the quality of included literature was not formally evaluated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Relevant articles may have been missed.

    “Second, relevant articles may have been missed.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The review searched PubMed for English-language articles published within 5 years before and through June 12, 2024, and updated the search for additional articles published through February 14, 2025, using title keywords for diagnosis and treatment of type 2 diabetes.

    “We searched PubMed for English-language articles published within 5 years before and through June 12, 2024, and updated the search for additional articles published through February 14, 2025, using title keywords for diagnosis and treatment of type 2 diabetes (Supplement).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Of 2016 articles identified, 126 were included, consisting of 47 randomized clinical trials, 22 observational studies, 21 systematic reviews and/or meta-analyses, 21 guidelines, 12 narrative reviews, and 3 drug or device reference guides.

    “Of 2016 articles identified, 126 were included, consisting of 47 randomized clinical trials, 22 observational studies, 21 systematic reviews and/or meta-analyses, 21 guidelines, 12 narrative reviews, and 3 drug or device reference guides.”
    Quote in the paperNot a substantial claim
44 of 44

Cites

Flagged first, then by citations

1 of the 116 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. 1999, Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus
  2. 2023, Practical Insulin: A Handbook or Prescribing Providers
  3. International Diabetes Federation. IDF Diabetes Atlas, 11th edition. Accessed April 30, 2025. https://diabetesatlas.org/media/uploads/sites/3/2025/04/IDF_Atlas_11th_Edition_2025.pdf

Cited by

Sorted by citations

Related

Authors
Kalyani, R. R., Neumiller, J. J., Maruthur, N. M., & Wexler, D. J.
Affiliations
  • Johns Hopkins University (US)
  • Washington State University Spokane (US)
  • Harvard University (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2025-09-16
Volume
334
Issue
11
Pages
984
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2025.5956
PMC
PMC13014273
OpenAlex
W4411540721
Cited by
145
References
116
Citations by year
2026: 121 · 2025: 24
FWCI
85.66
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • American Diabetes Association
  • Novo Nordisk
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK135043)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, insulin resistance, beta-cell dysfunction, hyperglycemia, diabetes diagnosis, diabetes risk factors, cardiovascular risk, tight glycemic control, metformin, SGLT2 inhibitors, GLP-1 receptor agonists, GIP/GLP-1 dual agonist, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, insulin therapy
MeSH terms
Global Burden of Disease, Adult, Age Factors, Blood Glucose, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Hyperglycemia, Hypoglycemic Agents, Insulin Resistance, Life Style, Medical History Taking, Obesity, Risk Factors, Exercise, Prevalence, Overweight, Sedentary Behavior

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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