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9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025

Open access
American Diabetes Association Professional Practice Committee, ElSayed, Nuha A., McCoy, Rozalina G., Aleppo, Grazia, Bajaj, Mandeep, Balapattabi, Kirthikaa, Beverly, Elizabeth A., Briggs Early, Kathaleen +19 more·2025·Diabetes Care
DOI 10.2337/dc25-s009PMC PMC11635045
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Abstract

The American Diabetes Association (ADA) “Standards of Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

AI snapshot

Written from the paper’s full text.

TL;DR

This is Section 9 of the American Diabetes Association's 2025 Standards of Care, an annually updated, evidence-graded clinical practice guideline covering pharmacologic treatment of type 1 and type 2 diabetes. It issues recommendations on insulin regimens and delivery technologies, noninsulin adjuncts, and person-centered selection of glucose-lowering medications based on comorbidities, weight, hypoglycemia risk, and cost.

Key findings

  • In type 1 diabetes, the DCCT showed intensive therapy achieving A1C of 7% produced ~50% reductions in microvascular complications over 6 years, but with more severe hypoglycemia (62 vs. 19 episodes per 100 person-years); benefits persisted over 20 years of follow-up. A meta-analysis found CSII lowered A1C modestly (−0.30% [95% CI −0.58 to −0.02]) and reduced severe hypoglycemia.
  • Adjunctive noninsulin agents in type 1 diabetes give modest benefit: pramlintide reduced A1C 0.3–0.4% with ~1 kg weight loss; liraglutide 1.8 mg reduced A1C ~0.4% and weight ~5 kg; metformin did not sustainably improve A1C. SGLT inhibitors improved A1C and weight but increased DKA (sotagliflozin: eightfold increase vs. placebo; SGLT inhibitor–associated DKA occurs in ~4% of people with type 1 diabetes, 5–17 times higher than untreated).
  • In type 2 diabetes, each new oral noninsulin class added to metformin lowers A1C ~0.7–1.0%, while GLP-1 RAs or the dual GIP/GLP-1 RA lower A1C by 1 to >2%. In GRADE, glargine and liraglutide were modestly more effective at maintaining A1C <7% than sitagliptin (least effective) or glimepiride, with more severe hypoglycemia on glargine/glimepiride; liraglutide showed lower cardiovascular disease risk (HR 0.7 [95% CI 0.6–0.9]).
  • For type 2 diabetes with ASCVD, HF, or CKD, SGLT2 inhibitors and/or GLP-1 RAs with demonstrated benefit are recommended irrespective of A1C; SGLT2 inhibitor glucose-lowering declines below eGFR 45 mL/min/1.73 m², and metformin should be stopped below eGFR 30 mL/min/1.73 m².

Methods

  • Guideline document produced by the ADA Professional Practice Committee (an interprofessional expert committee), updated annually or more frequently, using ADA's evidence-grading system (grades A, B, C, E) applied to numbered recommendations.
  • Evidence base is a narrative synthesis of randomized controlled trials, systematic reviews and meta-analyses, cardiovascular and kidney outcome trials, and real-world studies, supplemented by consensus reports (e.g., 2021 ADA/EASD type 1 diabetes consensus).
  • Content is organized by population and topic: insulin therapy and delivery in type 1 diabetes, noninsulin and surgical treatments, glucose-lowering therapy selection in type 2 diabetes (including combination therapy, insulin initiation/intensification, concentrated insulins, alternative routes), plus glucagon, medication costs, and special populations.

Limitations

  • Stated in the paper: most studies comparing multiple daily injections with CSII were relatively small and of short duration, and there is no consensus to guide choice of injection versus pump therapy; evidence for MASH benefits rests on phase 2 trials awaiting phase 3 confirmation; posttransplant diabetes data are limited by small sample sizes, short follow-up, and risk of bias from retrospective or single-arm designs; evidence is scarce for treating type 2 diabetes with baseline A1C above 10–12%.
  • Evident from the text: many recommendations carry the lowest evidence grade (E, expert consensus) rather than trial evidence; several cited comparisons are network meta-analyses rather than head-to-head trials; and drug cost tables use AWP/NADAC list prices that the authors note do not reflect actual patient costs.

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

Integrity signals

Registry

Crossref · 10.2337/dc25-s009

Cites

241 of 241 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

129 of 272 cited sources checked · 50 supported · 4 flagged · accuracy not yet measured

  • Findingcitation
    § If injectable therapy is needed to reduce A1C 1

    GLP-1 RAs and dual GIP and GLP-1 RA in these trials had a lower risk of hypoglycemia compared with insulin.

    “GLP-1 RAs and dual GIP and GLP-1 RA in these trials also had a lower risk of hypoglycemia and beneficial effects on body weight compared with insulin, albeit with greater gastrointestinal side effects.”
    Quote in the paperSubstantial claim3 of 8 sources checked
    • cites [123] Del Prato, 2021, Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial, Lancet source
    • cites [124] Singh, 2017, Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis, Diabetes Obes Metab source

      The Results (Safety outcomes; page unavailable) report lower odds of hypoglycaemia with two GLP-1 receptor agonists than with insulin glargine. The Discussion cautions that differing definitions limit interpretation. This paper does not study dual GIP/GLP-1 receptor agonists, so it cannot support that part of the claim. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [125] Levin, 2017, Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research, Diabetes Metab Syndr Obes source

      In “GLP-1RAs versus insulin products,” the review reports that hypoglycemia rates were generally lower with GLP-1RAs than with insulin, though some studies found similar rates. The cited review does not report the claimed comparison for dual GIP/GLP-1 receptor agonists, so it supports only the GLP-1RA portion. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [126] Abd El Aziz, 2017, A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients, Diabetes Obes Metab source
    • cites [127] Giorgino, 2015, Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2), Diabetes Care source
    • cites [128] Aroda, 2017, Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial, Lancet Diabetes Endocrinol source
    • cites [129] Davies, 2013, Once-weekly exenatide versus once- or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas, Diabetes Care source

      The Results (Safety and tolerability; page not provided) state that hypoglycemia incidence did not differ between once-weekly exenatide and insulin detemir. The Conclusions likewise report no difference in this trial and caution that the small number of events limits inference. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [130] Diamant, 2010, Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial, Lancet source
  • Premisecitation
    § Alternative Insulin Routes

    Inhaled insulin produces clinically meaningful A1C reductions compared with insulin aspart over 24 weeks.

    “Studies comparing inhaled insulin with injectable insulin have demonstrated its faster onset and shorter duration compared with the RAA insulin lispro as well as clinically meaningful A1C reductions and weight reductions compared with the RAA insulin aspart over 24 weeks (186-188).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [186] Akturk, 2018, Improved postprandial glucose with inhaled technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: the STAT study, Diabetes Technol Ther source

      The Results report that this was a four-week trial, not a 24-week trial. Over those four weeks, the aspart group had a significantly greater HbA1c decrease than the inhaled-insulin group—the opposite of the claimed comparative reduction. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [187] Hoogwerf, 2021, Results of a 24-week trial of technosphere insulin versus insulin aspart in type 2 diabetes, Endocr Pract source
    • cites [188] Grant, 2022, Comparison of pharmacokinetics and pharmacodynamics of inhaled technosphere insulin and subcutaneous insulin lispro in the treatment of type 1 diabetes mellitus, Clin Pharmacokinet source

      The Results (Patient Demographics; page unavailable) report baseline glycated hemoglobin, not a change in A1C. The Discussion (Clinical Use; page unavailable) discusses glucose control compared with insulin aspart, and the References list a 24-week trial, but our copy does not report whether inhaled insulin produced clinically meaningful A1C reductions over 24 weeks. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
  • Findingcitation
    § If injectable therapy is needed to reduce A1C 1

    In individuals intensified to insulin therapy, combination therapy with a GLP-1 RA or dual GIP and GLP-1 RA has hypoglycemia benefits compared with insulin alone.

    “In individuals who are intensified to insulin therapy, combination therapy with a GLP-1 RA or a dual GIP and GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effects, as well as weight and hypoglycemia benefits, than treatment intensification with insulin alone (89,131).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [89] Davies, 2022, 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 source

      The Other Glucose-Lowering Medications section reports lower hypoglycemia rates with basal insulin plus a GLP-1 RA than with intensified insulin regimens, including fewer events in studies comparing the combination with basal insulin alone. Its discussion of the dual GIP and GLP-1 RA tirzepatide does not establish a hypoglycemia benefit when it is combined with insulin; that part of the claim is unsupported by the passages found. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [131] Dahl, 2022, Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial, JAMA source

      The paper's safety results (section labeled “Downloaded From,” page not provided) do not show a hypoglycemia benefit from adding tirzepatide to insulin glargine. Hypoglycemia incidence was 14.2%–19.3% in the combination groups versus 12.5% with insulin glargine plus placebo; all three severe episodes occurred in the tirzepatide groups. (LLM, conf=0.87)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Evidence suggests that an AID hybrid closed-loop system is superior to AID sensor-augmented pump therapy for increased percentage of time in range and reduction of hypoglycemia.

    “Evidence suggests that an AID hybrid closed-loop system is superior to AID sensor-augmented pump therapy for increased percentage of time in range and reduction of hypoglycemia (34,35).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [34] Brown, 2019, Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes, N Engl J Med source
    • cites [35] Collyns, 2021, Improved glycemic outcomes with Medtronic MiniMed advanced hybrid closed-loop delivery: results from a randomized crossover trial comparing automated insulin delivery with predictive low glucose suspend in people with type 1 diabetes, Diabetes Care source
  • Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    In general, individuals with type 1 diabetes require approximately 30-50% of their daily insulin as basal and the remainder as prandial.

    “In general, individuals with type 1 diabetes require approximately 30-50% of their daily insulin as basal and the remainder as prandial (43).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [43] Lal, 2019, Optimizing basal insulin dosing, J Pediatr source
  • May combine two claims. 38
  • Classified as probably not a substantial claim. 2

  • May combine two claims.

    Findingcitation
    § Choice of Glucose-Lowering Therapy

    In an observational study emulating GRADE, liraglutide was more effective at achieving and maintaining A1C below 7% than sitagliptin, canagliflozin, or glimepiride, which all had comparable effectiveness.

    “An observational study that emulated many of GRADE's design features and included canagliflozin as a comparator arm, but did not include insulin glargine, found that liraglutide was more effective at achieving and maintaining A1C below 7% than sitagliptin, canagliflozin, or glimepiride, which all had comparable effectiveness (108).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [108] Nathan, 2022, Glycemia reduction in type 2 diabetes–glycemic outcomes, N Engl J Med source

      The Methods (Treatments) and Results (Participant Retention and Adherence) describe randomly assigned treatments, including insulin glargine, rather than an observational emulation that excluded it; the Methods also say SGLT2 inhibitors were not included. The Results (Efficacy) report significantly different outcomes for sitagliptin and glimepiride, not comparable effectiveness. Although liraglutide performed better than both, this paper does not report the study described in the claim. (LLM, conf=0.91)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Integration of continuous glucose monitoring (CGM) into the treatment plan soon after diagnosis improves glycemic outcomes, decreases hypoglycemic events, and improves quality of life for individuals with type 1 diabetes.

    “Integration of continuous glucose monitoring (CGM) into the treatment plan soon after diagnosis improves glycemic outcomes, decreases hypoglycemic events, and improves quality of life for individuals with type 1 diabetes (18-23).”
    Quote in the paperSubstantial claim1 of 6 sources checked
    • cites [18] Mulinacci, 2019, Glycemic outcomes with early initiation of continuous glucose monitoring system in recently diagnosed patients with type 1 diabetes, Diabetes Technol Ther source
    • cites [19] Elbalshy, 2022, Effect of divergent continuous glucose monitoring technologies on glycaemic control in type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials, Diabet Med source

      The Abstract Conclusions report improved glycaemic outcomes, including HbA1c, time in range, and time below range; the Discussion links CGM to minimising hypoglycaemia. The paper does not establish that starting CGM soon after diagnosis produces these benefits or report an improvement in quality of life. The supplied passages have no page numbers. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [20] Champakanath, 2022, Continuous glucose monitoring initiation within first year of type 1 diabetes diagnosis is associated with improved glycemic outcomes: 7-year follow-up study, Diabetes Care source
    • cites [21] Weinstock, 2013, Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry, J Clin Endocrinol Metab source
    • cites [22] Tamborlane, 2008, Continuous glucose monitoring and intensive treatment of type 1 diabetes, N Engl J Med source
    • cites [23] Polonsky, 2017, The impact of continuous glucose monitoring on markers of quality of life in adults with type 1 diabetes: further findings from the DIAMOND randomized clinical trial, Diabetes Care source

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    SGLT2 inhibitors have been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C, reduced body weight, and improved blood pressure; however, SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA.

    “Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C, reduced body weight, and improved blood pressure (78); however, SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA (79).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [78] Rao, 2021, Sodium-glucose cotransporter 2 inhibitors as an add-on therapy to insulin for type 1 diabetes mellitus: meta-analysis of randomized controlled trials, Acta Diabetol source
    • cites [79] Li, 2023, The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: a systematic review and meta-analysis, J Diabetes Complications source

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    The addition of metformin in adults with type 1 diabetes was associated with small reductions in body weight, insulin dose, and lipid levels but did not sustainably improve A1C.

    “The addition of metformin in adults with type 1 diabetes was associated with small reductions in body weight, insulin dose, and lipid levels but did not sustainably improve A1C (69,70).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [69] Meng, 2018, Effect of metformin on glycaemic control in patients with type 1 diabetes: a meta-analysis of randomized controlled trials, Diabetes Metab Res Rev source
    • cites [70] Petrie, 2017, Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial, Lancet Diabetes Endocrinol source

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    The SGLT1/2 inhibitor sotagliflozin has been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C and body weight; however, sotagliflozin use was associated with an eightfold increase in DKA compared with placebo.

    “The SGLT1/2 inhibitor sotagliflozin has been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C and body weight (80); however, sotagliflozin use was associated with an eightfold increase in DKA compared with placebo (81).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [80] Chen, 2020, Efficacy and safety of sotagliflozin adjuvant therapy for type 1 diabetes mellitus: a systematic review and meta-analysis, Medicine (Baltimore) 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 [81] U.S. Food and Drug Administration . FDA Introductory Remarks: January 17, 2019: Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2019. Accessed 23 August 2024. Available from https://wayback.archive-it.org/7993/20190207212714/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM629782.pdf

      Not checked in the free run.

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

    Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Further adjustment of prandial insulin doses for nutritional intake of protein and fat, in addition to carbohydrates, may be more feasible for individuals using CSII than for those using multiple daily injections.

    “Further adjustment of prandial insulin doses for nutritional intake of protein and fat, in addition to carbohydrates, is recommended but may be more feasible for individuals using CSII than for those using multiple daily injections (55).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [55] Al Balwi, 2022, Efficacy of insulin dosing algorithms for high-fat high-protein mixed meals to control postprandial glycemic excursions in people living with type 1 diabetes: A systematic review and meta-analysis, Pediatr Diabetes source

      The Introduction recommends fat-and-protein counting for high-fat, high-protein meals, and the Abstract reports that adding fat and protein to carbohydrate counting improves postprandial glucose control. The Abstract also calls for further research on dosing equations particularly for people using multiple daily injections. Neither passage establishes that adjusting doses is more feasible with CSII than with multiple daily injections; page numbers are unavailable in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation
    § Choice of Glucose-Lowering Therapy

    Metformin is inexpensive and widely available.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [92] Adler, 2024, 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 source
    • cites [94] Holman, 2008, 10-year follow-up of intensive glucose control in type 2 diabetes, N Engl J Med source
    • cites [95] Bahardoust, 2024, Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis, J Diabetes Metab Disord source

      The Introduction describes metformin as low cost, supporting “inexpensive.” It also calls metformin widely used and a first-line treatment, but does not establish that it is widely available. Page numbers were not provided in our copy. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation
    § Choice of Glucose-Lowering Therapy

    In GRADE, at 5 years, all therapies decreased A1C levels but glargine and liraglutide were modestly more effective in achieving and maintaining A1C below 7%, while sitagliptin was least effective.

    “It found that at 5 years, all therapies decreased A1C levels but glargine and liraglutide were modestly more effective in achieving and maintaining A1C below 7%, while sitagliptin was least effective.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [108] Nathan, 2022, Glycemia reduction in type 2 diabetes–glycemic outcomes, N Engl J Med source

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    Higher C-peptide levels have been associated with better A1C, lower risk of retinopathy, lower risk of nephropathy, and lower risk of severe hypoglycemia.

    “Higher C-peptide levels have been associated with better A1C, lower risk of retinopathy, lower risk of nephropathy, and lower risk of severe hypoglycemia (85).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [85] Lachin, 2014, Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial, Diabetes source

      The Discussion reports that higher C-peptide was associated with lower HbA1c, less severe hypoglycemia, and less risk of retinopathy. The Results (Intensive Therapy, 1–5-Year Duration) report a lower observed risk of nephropathy, but the reduction was not statistically significant, so that part of the claim needs qualification. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation
    § Choice of Glucose-Lowering Therapy

    There is evidence that people with type 2 diabetes and severe hyperglycemia can also be effectively treated with a sulfonylurea, a GLP-1 RA, or dual GIP and GLP-1 RA, though evidence is scarce for individuals with baseline A1C above 10-12%.

    “Additionally, there is evidence that people with type 2 diabetes and severe hyperglycemia can also be effectively treated with a sulfonylurea, a GLP-1 RA, or dual GIP and GLP-1 RA, though evidence is scarce for individuals with baseline A1C above 10-12% (104,109-111).”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [104] Frías, 2021, Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes, N Engl J Med source
    • cites [109] Babu, 2009, Safe and simple emergency department discharge therapy for patients with type 2 diabetes mellitus and severe hyperglycemia, Endocr Pract source
    • cites [110] Buse, 2015, Is insulin the most effective injectable antihyperglycaemic therapy?, Diabetes Obes Metab source

      The Conclusion (p. 6) supports GLP-1 receptor agonists as a possible treatment for selected people with type 2 diabetes and HbA1c above 9%. The limitations discussion (p. 5) cautions that results may differ above 11%, consistent with limited evidence at very high baseline HbA1c. The paper treats sulphonylurea as background therapy, not as an alternative tested here, and does not address dual GIP/GLP-1 receptor agonists. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [111] D’Alessio, 2015, Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes, Diabetes Obes Metab source

  • May combine two claims.

    Findingcitation
    § Choice of Glucose-Lowering Therapy

    Metformin is effective and safe.

    “Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92,94,95).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [92] Adler, 2024, 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 source
    • cites [94] Holman, 2008, 10-year follow-up of intensive glucose control in type 2 diabetes, N Engl J Med source
    • cites [95] Bahardoust, 2024, Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis, J Diabetes Metab Disord source

      The Introduction describes metformin as glucose-lowering and having a low risk of hypoglycemia, supporting effectiveness and one aspect of safety. It does not establish the broader, unqualified claim that metformin is safe. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Concentrated Insulins

    U-300 glargine has a longer duration of action than U-100 glargine but modestly lower efficacy per unit administered.

    “U-300 glargine has a longer duration of action than U-100 glargine but modestly lower efficacy per unit administered (179-181).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [179] Becker, 2015, New insulin glargine 300 units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 units · mL-1, Diabetes Care source
    • cites [180] Riddle, 2015, One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension, Diabetes Obes Metab source
    • cites [181] Yki-Järvinen, 2014, New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2), Diabetes Care source

  • May combine two claims.

    Findingcitation
    § Glucose-Lowering Therapy for People With Metabolic Comorbidities

    Metabolic surgery, especially Roux-en-Y gastric bypass and sleeve gastrectomy, are very effective interventions to achieve both weight and glycemic goals and have additional health benefits beyond improving metabolism.

    “Metabolic surgery, especially Roux-en-Y gastric bypass and sleeve gastrectomy, are very effective interventions to achieve both weight and glycemic goals and have additional health benefits beyond improving metabolism (162).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [162] Schauer, 2017, Bariatric surgery versus intensive medical therapy for diabetes–5-year outcomes, N Engl J Med source

  • May combine two claims.

    Findingcitation
    § Glucose-Lowering Therapy for People With Metabolic Comorbidities

    Of currently available agents, tirzepatide and semaglutide have the highest efficacy in terms of glucose lowering as well as weight loss, followed by dulaglutide, liraglutide, and extended-release exenatide.

    “Of the currently available agents, tirzepatide and semaglutide have the highest efficacy in terms of glucose lowering as well as weight loss, followed by dulaglutide, liraglutide, and extendedrelease exenatide (157-161).”
    Quote in the paperSubstantial claim3 of 5 sources checked
    • cites [157] Garvey, 2023, Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial, Lancet source

      The Discussion (page unavailable) reports that tirzepatide produced greater weight loss than reported for semaglutide and liraglutide in trials involving people with obesity and type 2 diabetes. The Results (page unavailable) also report improved HbA1c with tirzepatide versus placebo. The paper does not establish the claimed ranking of all five agents for both glucose lowering and weight loss; in particular, it does not compare dulaglutide or extended-release exenatide. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [158] Davies, 2021, Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source
    • cites [159] Bonora, 2021, Effect of dulaglutide 3.0 and 4.5 mg on weight in patients with type 2 diabetes: exploratory analyses of AWARD-11, Diabetes Obes Metab source

      The Introduction and Discussion (page not specified) state that dulaglutide lowers glucose and is associated with weight loss in people with type 2 diabetes. The paper compares dulaglutide doses, but does not establish the claimed efficacy ranking against tirzepatide, semaglutide, liraglutide, or extended-release exenatide. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [160] Davies, 2015, Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial, JAMA source

      The Results and Discussion (page not supplied) show that liraglutide reduced weight and improved glycemic measures in adults with type 2 diabetes compared with placebo. This trial does not establish the claimed efficacy ranking among tirzepatide, semaglutide, dulaglutide, liraglutide, and extended-release exenatide. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [161] Ahmann, 2018, Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial, Diabetes Care source

  • May combine two claims.

    Findingcitation
    § Glucose-Lowering Therapy for People With Cardiovascular Disease or Risk Factors for Cardiovascular Disease

    In GRADE, no significant differences were found for major adverse cardiovascular events, hospitalization for HF, or cardiovascular death.

    “although no significant differences were found for major adverse cardiovascular events, hospitalization for HF, or cardiovascular death (133).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [133] Nathan, 2022, Glycemia reduction in type 2 diabetes–microvascular and cardiovascular outcomes, N Engl J Med source

  • May combine two claims.

    Premisecitation
    § Alternative Insulin Routes

    Inhaled insulin has faster onset and shorter duration compared with the rapid-acting insulin analog lispro.

    “Studies comparing inhaled insulin with injectable insulin have demonstrated its faster onset and shorter duration compared with the RAA insulin lispro as well as clinically meaningful A1C reductions and weight reductions compared with the RAA insulin aspart over 24 weeks (186-188).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [186] Akturk, 2018, Improved postprandial glucose with inhaled technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: the STAT study, Diabetes Technol Ther source
    • cites [187] Hoogwerf, 2021, Results of a 24-week trial of technosphere insulin versus insulin aspart in type 2 diabetes, Endocr Pract source

      The Introduction says Technosphere inhaled insulin has a faster onset and shorter duration than subcutaneously injected rapid-acting insulin analogs. The paper does not identify lispro as the comparator; its 24-week trial compares Technosphere insulin with insulin aspart. Thus it supports the general pharmacologic comparison, but not the lispro-specific attribution. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [188] Grant, 2022, Comparison of pharmacokinetics and pharmacodynamics of inhaled technosphere insulin and subcutaneous insulin lispro in the treatment of type 1 diabetes mellitus, Clin Pharmacokinet source

  • May combine two claims.

    Premisecitation
    § Concentrated Insulins

    U-500 regular insulin has similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin.

    “U-500 regular insulin has distinct pharmacokinetics with similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin; thus, it has characteristics more like a premixed intermediate-acting (NPH) and regular insulin product and can be used as two or three daily injections (177,178).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [177] de la Peña, 2011, Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects, Diabetes Care source

      The Results report similar onset, lower peak effect, and prolonged duration for U-500R versus U-100R. However, the Abstract Results and Conclusions specify that time to maximum effect was significantly delayed only at the 100-unit dose; the claim presents that delay without the dose qualification. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [178] Wysham, 2016, Effect of total daily dose on efficacy, dosing, and safety of 2 dose titration regimens of human regular U500 insulin in severely insulin-resistant patients with type 2 diabetes, Endocr Pract source

  • May combine two claims.

    Findingcitation
    § Glucose-Lowering Therapy for People With Cardiovascular Disease or Risk Factors for Cardiovascular Disease

    While greater reductions in HF hospitalization risk are observed with SGLT2 inhibitor therapy in individuals with higher baseline HF risk, some benefit is observed across the full range of HF risk.

    “Similarly, while greater reductions in HF hospitalization risk are observed with SGLT2 inhibitor therapy in individuals with higher baseline HF risk, some benefit is observed across the full range of HF risk (135).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [135] Berg, 2019, Heart failure risk stratification and efficacy of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus, Circulation source

  • May combine two claims.

    Premisecitation
    § Therapeutic Strategies for Individuals With Other Types of Diabetes

    Individuals with neonatal diabetes due to KCNJ22 and ABCC8 mutations can be treated with high-dose sulfonylureas, while those with INS, GATA6, EIF2AK3, and FOXP3 mutations require insulin therapy.

    “Individuals with neonatal diabetes due to KCNJ22 and ABCC8 mutations can be treated with high-dose sulfonylureas, while those with INS, GATA6, EIF2AK3, and FOXP3 mutations require insulin therapy (234).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [234] Greeley, 2022, ISPAD Clinical Practice Consensus Guidelines 2022: the diagnosis and management of monogenic diabetes in children and adolescents, Pediatr Diabetes source

      The section on KATP-channel neonatal diabetes identifies KCNJ11—not the claim’s KCNJ22—and ABCC8, and says about 90% of affected children can switch from insulin to sulfonylureas, often at doses higher than those used for adults with type 2 diabetes (page unavailable). The INS subsection says affected individuals are insulin dependent. Our copy links GATA6, EIF2AK3, and FOXP3 to neonatal diabetes but does not establish the claimed insulin-therapy requirement for all three; its IPEX section discusses other treatment for FOXP3-related disease. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Therapeutic Strategies for Individuals Receiving Cancer Treatment

    ICI-diabetes is an insulin-deficient phenotype that presents as acute severe hyperglycemia or DKA and appears to occur more abruptly than type 1 diabetes.

    “ICI-diabetes is an insulin-deficient phenotype that presents as acute severe hyperglycemia or DKA and appears to occur more abruptly than type 1 diabetes (216-218).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [216] Byun, 2020, Immune checkpoint inhibitor-associated diabetes: a single-institution experience, Diabetes Care source
    • cites [217] Barroso-Sousa, 2018, Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis, JAMA Oncol source

      The 'Incidence of Primary Adrenal Insufficiency and Insulin Deficient Diabetes' section identifies insulin-deficient diabetes following ICI treatment and reports its incidence. It does not describe acute severe hyperglycemia or DKA, or compare the abruptness of onset with type 1 diabetes; searches for those clinical features found no supporting passage in our copy. No page number was provided for the indexed passage. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [218] Liu, 2020, Reporting of immune checkpoint inhibitor therapy-associated diabetes, 2015-2019, Diabetes Care source

      In the paper’s main text (page unavailable), 338 of 735 ICI-diabetes cases presented with DKA or diabetic ketosis, supporting that part of the claim. The paper does not establish an insulin-deficient phenotype, document acute severe hyperglycemia, or compare onset speed with type 1 diabetes; it says clinical-course and C-peptide data were unavailable. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § SGLT Inhibition and Risk of Ketosis

    Individuals with type 1 diabetes and insulin-deficient type 2 diabetes are at increased risk for DKA with SGLT inhibitor therapy.

    “Individuals with type 1 diabetes (84,236) and insulin-deficient type 2 diabetes are at increased risk for DKA with SGLT inhibitor therapy.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [84] Danne, 2019, International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors, Diabetes Care source
    • cites [236] Umpierrez, 2024, Hyperglycemic crises in adults with diabetes: a consensus report, Diabetes Care source

  • May combine two claims.

    Premisecitation
    § Therapeutic Strategies for Individuals With Other Types of Diabetes

    Individuals with maturity-onset diabetes of the young due to HNF1A and HNF4A mutations can be treated with low-dose sulfonylurea therapy but may ultimately require insulin therapy.

    “Individuals with maturity-onset diabetes of the young due to HNF1A and HNF4A mutations can be treated with low-dose sulfonylurea therapy but may ultimately require insulin therapy (234)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [234] Greeley, 2022, ISPAD Clinical Practice Consensus Guidelines 2022: the diagnosis and management of monogenic diabetes in children and adolescents, Pediatr Diabetes source

      The section on HNF1A-MODY and HNF4A-MODY (page unavailable) recommends a low initial sulfonylurea dose and says patients can remain on low doses for decades. It does not say they may ultimately require insulin therapy; instead, it says sulfonylureas usually provide better glycemic management than insulin. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Therapeutic Strategies for Individuals Receiving Cancer Treatment

    Immune checkpoint inhibitors suppress physiologic blocks on immune responses, which can result in autoimmune toxicities, including autoimmune diabetes, with an incidence approximately ≤1%.

    “Immune checkpoint inhibitors (ICIs) (agents that block programmed cell death protein 1 [PD-1] and programmed cell death protein ligand 1 [PD-L1]) suppress physiologic blocks on immune responses, which can result in autoimmune toxicities, including autoimmune diabetes (incidence approximately #1%).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [216] Byun, 2020, Immune checkpoint inhibitor-associated diabetes: a single-institution experience, Diabetes Care source
    • cites [217] Barroso-Sousa, 2018, Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis, JAMA Oncol source
    • cites [218] Liu, 2020, Reporting of immune checkpoint inhibitor therapy-associated diabetes, 2015-2019, Diabetes Care source

      The paper’s opening section identifies PD-1 and PD-L1 inhibitors and says ICI therapy can cause immune-related adverse effects, including diabetes. It does not explain the effect as suppression of physiologic blocks on immune responses, and its reported overall ICI-associated diabetes incidence is approximately 1.27% (735 of 57,683), rather than ≤1%. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Therapeutic Strategies for Individuals Receiving Cancer Treatment

    Hyperglycemia occurs early during alpelisib therapy, with a median time of onset of about 2 weeks from initiation, an incidence of ≥60% overall, and typically resolves upon treatment cessation.

    “Hyperglycemia occurs early during therapy (median time of onset of about 2 weeks from initiation of alpelisib) with an incidence of $60% overall and typically resolves upon treatment cessation (220-222).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [220] André, 2019, Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer, N Engl J Med source

      The Safety section (page not available in our copy) reports hyperglycemia in 63.7% of alpelisib-treated patients, supporting the incidence claim. The End Points section describes early glucose monitoring but gives no median time to onset. The Discussion says adverse events were generally reversible, but does not establish that hyperglycemia typically resolves upon treatment cessation. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [221] André, 2021, Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1, Ann Oncol source

      Table 3 reports hyperglycemia in 64.8% of patients receiving alpelisib plus fulvestrant, supporting the stated incidence. The Discussion says adverse events were reversible and manageable, but neither it nor the Safety section gives a median onset of about two weeks or establishes that hyperglycemia typically resolves specifically upon treatment cessation. Page numbers are unavailable in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [222] Rugo, 2020, Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer, Ann Oncol source

      The ‘Time to onset and improvement of AESIs’ section reports a median onset of 15 days for grade ≥3 hyperglycemia, not for hyperglycemia of all grades. The ‘Supportive medications to manage hyperglycemia’ section reports 187 affected patients in the alpelisib cohort, consistent with an overall incidence above 60%, and ‘Hyperglycemia by baseline diabetic status’ reports that all affected patients had grade 0 or 1 hyperglycemia after discontinuation. The omitted grade qualifier limits support for the claimed median onset. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation
    § Glucose-Lowering Therapy for People With Metabolic Comorbidities

    Combination therapy with pioglitazone plus GLP-1 RA is safe and effective and has been shown to reduce hepatic steatosis in adults with type 2 diabetes with biopsy-proven MASH or those at higher risk of clinically significant liver fibrosis identified with noninvasive tests.

    “Combination therapy with pioglitazone plus GLP-1 RA should also be considered for treatment of hyperglycemia in adults with type 2 diabetes with biopsyproven MASH or those at higher risk of clinically significant liver fibrosis identified with noninvasive tests, as such therapy is safe and effective and has been shown to reduce hepatic steatosis (154-156).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [154] Sathyanarayana, 2011, Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes, Obesity (Silver Spring) source
    • cites [155] Abdul-Ghani, 2020, Combination therapy with pioglitazone/exenatide improves beta-cell function and produces superior glycaemic control compared with basal/bolus insulin in poorly controlled type 2 diabetes: a 3-year follow-up of the Qatar study, Diabetes Obes Metab source
    • cites [156] Lavynenko, 2022, Combination therapy with pioglitazone/exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: the efficacy and durability of initial combination therapy for type 2 diabetes (EDICT), Diabetes Obes Metab source

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    Liraglutide treatment had no impact on C-peptide in individuals with type 1 diabetes and residual b-cell function, and with liraglutide discontinuation there was worsening of C-peptide loss compared with placebo.

    “During treatment there was no impact, and with liraglutide discontinuation there was worsening of Cpeptide loss compared with placebo (73).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] von Herrath, 2021, Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial, Lancet Diabetes Endocrinol source

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

    Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook notes 0.5 units/kg/day as a typical starting dose in adults with type 1 diabetes who are metabolically stable, with approximately one-half administered as prandial insulin and the remaining portion as basal insulin.

    “The American Diabetes Association/ JDRF Type 1 Diabetes Sourcebook notes 0.5 units/kg/day as a typical starting dose in adults with type 1 diabetes who are metabolically stable, with approximately one-half administered as prandial insulin given to manage blood glucose after meals and the remaining portion as basal insulin to manage glycemia in the periods between meal absorption (49).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Peters, 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Randomized controlled trials and real-world studies have demonstrated the ability of commercially available AID systems to improve achievement of glycemic goals while reducing the risk of hypoglycemia.

    “Randomized controlled trials and real-world studies have demonstrated the ability of commercially available systems to improve achievement of glycemic goals while reducing the risk of hypoglycemia (26)(27)(28)(29)(30)(31).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (26)(27)(28)(29)(30)(31)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § PHARMACOLOGIC THERAPY FOR ADULTS WITH TYPE 1 DIABETES

    In people with type 1 diabetes, treatment with analog insulins is associated with less hypoglycemia and weight gain and lower A1C compared with injectable human insulins.

    “In people with type 1 diabetes, treatment with analog insulins is associated with less hypoglycemia and weight gain and lower A1C compared with injectable human insulins (5)(6)(7).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (5)(6)(7)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Starting insulin doses and those soon after diagnosis may be higher if an individual presents with ketoacidosis, or lower (0.2-0.6 units/kg), particularly in young children and those with continued endogenous insulin production.

    “Starting doses and those soon after diagnosis may be higher, if an individual presents with ketoacidosis, or lower (0.2-0.6 units/kg), particularly in young children and those with continued endogenous insulin production (during the partial remission phase or”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (49)(50)(51)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § TIVE INSULIN ROUTES IN PHARMACOLOGIC THERAPY FOR

    A systematic review and meta-analysis concluded that CSII via pump therapy has modest advantages for lowering A1C (À0.30% [95% CI À0.58 to À0.02]) and for reducing severe hypoglycemia rates in children and adults.

    “A systematic review and meta-analysis concluded that CSII via pump therapy has modest advantages for lowering A1C (À0.30% [95% CI À0.58 to À0.02]) and for reducing severe hypoglycemia rates in children and adults (15).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Yeh, 2012, Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis, Ann Intern Med source

  • May combine two claims.

    Premisecitation
    § TIVE INSULIN ROUTES IN PHARMACOLOGIC THERAPY FOR

    Newer insulin formulations may cause less hypoglycemia while improving postprandial glucose excursions and administration flexibility compared with RAA.

    “These newer formulations may cause less hypoglycemia while improving postprandial glucose excursions and administration flexibility (in relation to prandial intake) compared with RAA (10)(11)(12).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (10)(11)(12)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    The largest clinical trials of GLP-1 RAs in type 1 diabetes have been conducted with liraglutide 1.8 mg daily, and results showed modest A1C reductions (≥0.4%), decreases in weight (≥5 kg), and reductions in insulin doses.

    “The largest clinical trials of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in type 1 diabetes have been conducted with liraglutide 1.8 mg daily, and results showed modest A1C reductions ($0.4%), decreases in weight ($5 kg), and reductions in insulin doses (71,72).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [71] Mathieu, 2016, Efficacy and safety of liraglutide added to insulin treatment in type 1 diabetes: the ADJUNCT ONE treat-to-target randomized trial, Diabetes Care source
    • cites [72] Ahrén, 2016, Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes: the ADJUNCT TWO randomized trial, Diabetes Care source

  • May combine two claims.

    Premisecitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Reduction of nocturnal hypoglycemia in individuals with type 1 diabetes using insulin pumps with CGM is improved by automatic suspension of insulin delivery at a preset glucose level, with further improvements when using devices with predictive low-glucose insulin delivery suspension.

    “Reduction of nocturnal hypoglycemia in individuals with type 1 diabetes using insulin pumps with CGM is improved by automatic suspension of insulin delivery at a preset glucose level, with further improvements when using devices with predictive low-glucose insulin delivery suspension (24,25).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Bergenstal, 2013, Threshold-based insulin-pump interruption for reduction of hypoglycemia, N Engl J Med source
    • cites [25] Forlenza, 2018, Predictive low-glucose suspend reduces hypoglycemia in adults, adolescents, and children with type 1 diabetes in an at-home randomized crossover study: results of the PROLOG trial, Diabetes Care source

  • May combine two claims.

    Premisecitation
    § PHARMACOLOGIC THERAPY FOR ADULTS WITH TYPE 1 DIABETES

    The DCCT demonstrated that intensive therapy with multiple daily injections or continuous subcutaneous insulin infusion (CSII) reduced A1C and was associated with improved long-term outcomes.

    “The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy with multiple daily injections or continuous subcutaneous insulin infusion (CSII) reduced A1C and was associated with improved long-term outcomes (1)(2)(3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (1)(2)(3)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation
    § Noninsulin Treatments for Type 1 Diabetes

    Clinical trials have demonstrated a modest reduction in A1C (0.3-0.4%) and modest weight loss (≥1 kg) with pramlintide in adults with type 1 diabetes.

    “Clinical trials have demonstrated a modest reduction in A1C (0.3-0.4%) and modest weight loss ($1 kg) with pramlintide (68).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Qiao, 2017, Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis, Oncotarget source

  • May combine two claims.

    Interpretationcitation
    § S182 Pharmacologic Approaches to Glycemic Treatment

    Automated insulin delivery (AID) systems are safe and effective for people with type 1 diabetes.

    “Automated insulin delivery (AID) systems are safe and effective for people with type 1 diabetes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (26)(27)(28)(29)(30)(31)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning
    § Choice of Glucose-Lowering Therapy

    GLP-1 RAs and tirzepatide have additional benefits over insulin and sulfonylureas, including lower risks for hypoglycemia and favorable weight effects.

    “GLP-1 RAs and tirzepatide have additional benefits over insulin and sulfonylureas, specifically lower risks for hypoglycemia (both) and favorable weight (both), cardiovascular (GLP-1 RAs), kidney (GLP-1 RAs), and liver (both) end points.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § SGLT Inhibition and Risk of Ketosis

    SGLT inhibitor-associated DKA occurs in approximately 4% of people with type 1 diabetes; the risk can be 5-17 times higher than in people with type 1 diabetes not treated with SGLT inhibitors.

    “SGLT inhibitor-associated DKA occurs in approximately 4% of people with type 1 diabetes; the risk can be 5-17 times higher than that in people with T1D not treated with SGLT inhibitors (237).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [237] Wolfsdorf, 2019, SGLT inhibitors for type 1 diabetes: proceed with extreme caution, Diabetes Care source
39 of 39

  • The paper relies on this without support.

    The hallmark of type 1 diabetes is absent or near-absent b-cell function.

    “Insulin treatment is essential for individuals with type 1 diabetes because the hallmark of type 1 diabetes is absent or near-absent b-cell function.”

  • The paper relies on this without support.

    Basal insulin analogs have longer duration of action with flatter, more constant and consistent plasma concentrations and activity profiles than NPH insulin; rapid-acting analogs (RAA) have a quicker onset and peak and shorter duration of action than regular human insulin.

    “Basal insulin analogs have longer duration of action with flatter, more constant and consistent plasma concentrations and activity profiles than NPH insulin; rapidacting analogs (RAA) have a quicker onset and peak and shorter duration of action than regular human insulin.”

  • The paper relies on this without support.

    Most studies comparing multiple daily injections with CSII have been relatively small and of short duration.

    “Most studies comparing multiple daily injections with CSII have been relatively small and of short duration.”

  • The paper relies on this without support.

    Total daily insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1 unit/kg/day.

    “Total daily insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1 unit/ kg/day.”

  • The paper relies on this without support.

    Higher insulin amounts may be required during puberty, menses, and medical illness.

    “Higher amounts may be required during puberty, menses, and medical illness.”

  • The paper relies on this without support.

    Typical multidose treatment plans for individuals with type 1 diabetes combine premeal use of prandial insulins with a longer-acting formulation.

    “Typical multidose treatment plans for individuals with type 1 diabetes combine premeal use of prandial insulins with a longer-acting formulation.”

  • The paper relies on this without support.

    The long-acting basal dose is titrated to regulate overnight and fasting glucose.

    “The long-acting basal dose is titrated to regulate overnight and fasting glucose.”

  • The paper relies on this without support.

    Postprandial glucose excursions are best managed by a well-timed injection or inhalation of prandial insulin.

    “Postprandial glucose excursions are best managed by a well-timed injection or inhalation of prandial insulin.”

  • The paper relies on this without support.

    The optimal time to administer prandial insulin varies based on the pharmacokinetics of the formulation, the premeal blood glucose level, and carbohydrate consumption.

    “Prandial insulin should ideally be administered prior to meal consumption; however, the optimal time to administer varies based on the pharmacokinetics of the formulation (regular, RAA, or inhaled), the premeal blood glucose level, and carbohydrate consumption.”

  • The paper relies on this without support.

    Physiologic insulin secretion varies with glycemia, meal size, meal composition, and tissue demand for glucose.

    “Physiologic insulin secretion varies with glycemia, meal size, meal composition, and tissue demand for glucose.”

  • The paper relies on this without support.

    Strategies have evolved to adjust prandial doses based on predicted needs to address variability in people treated with insulin.

    “To address this variability in people treated with insulin, strategies have evolved to adjust prandial doses based on predicted needs.”

  • The paper relies on this without support.

    Ensuring that individuals and/or caregivers understand correct insulin administration technique is important to optimize glycemic management and insulin use safety.

    “Ensuring that individuals and/or caregivers understand correct insulin administration technique is important to optimize glycemic management and insulin use safety.”

  • The paper relies on this without support.

    Exogenously delivered insulin should be injected or infused into subcutaneous tissue, not intramuscularly.

    “Exogenously delivered insulin should be injected or infused into subcutaneous tissue, not intramuscularly.”

  • The paper relies on this without support.

    Insulin absorption from IM sites differs from that in subcutaneous sites and is also influenced by the activity of the muscle.

    “Insulin absorption from IM sites differs from that in subcutaneous sites and is also influenced by the activity of the muscle.”

  • The paper relies on this without support.

    Inadvertent IM injection can lead to unpredictable insulin absorption and variable effects on glucose and is associated with frequent and unexplained hypoglycemia.

    “Inadvertent IM injection can lead to unpredictable insulin absorption and variable effects on glucose and is associated with frequent and unexplained hypoglycemia.”

  • The paper relies on this without support.

    Risk for IM insulin delivery is increased in younger, leaner individuals when injecting into the limbs rather than truncal sites and when using longer needles.

    “Risk for IM insulin delivery is increased in younger, leaner individuals when injecting into the limbs rather than truncal sites (abdomen and buttocks) and when using longer needles.”

  • The paper relies on this without support.

    Injection or infusion site rotation is necessary to avoid lipohypertrophy.

    “Injection or infusion site rotation is additionally necessary to avoid lipohypertrophy, an accumulation of subcutaneous fat in response to the adipogenic actions of insulin at a site of multiple injections.”

  • The paper relies on this without support.

    Lipohypertrophy can contribute to erratic insulin absorption, increased glycemic variability, and unexplained hypoglycemic episodes.

    “Lipohypertrophy appears as soft, smooth raised areas several centimeters in breadth and can contribute to erratic insulin absorption, increased glycemic variability, and unexplained hypoglycemic episodes.”

  • The paper relies on this without support.

    Proper insulin injection, infusion, or inhalation technique may lead to more effective use of this therapy and holds the potential for improved clinical outcomes.

    “Proper insulin injection, infusion, or inhalation technique may lead to more effective use of this therapy and, as such, holds the potential for improved clinical outcomes.”

  • The paper relies on this without support.

    Injectable and oral noninsulin glucose-lowering medications have been studied for their efficacy as adjuncts to insulin treatment of type 1 diabetes.

    “Injectable and oral noninsulin glucoselowering medications have been studied for their efficacy as adjuncts to insulin treatment of type 1 diabetes.”

  • The paper relies on this without support.

    Pramlintide is based on the naturally occurring b-cell peptide amylin and is approved for use in adults with type 1 diabetes.

    “Pramlintide is based on the naturally occurring b-cell peptide amylin and is approved for use in adults with type 1 diabetes.”

  • The paper relies on this without support.

    Similar results (modest A1C reduction and weight loss) have been reported for several agents currently approved only for the treatment of type 2 diabetes.

    “Similar results have been reported for several agents currently approved only for the treatment of type 2 diabetes.”

  • The paper relies on this without support.

    There are currently no approved therapies for preservation of C-peptide or delaying the progression of symptomatic type 1 diabetes.

    “There are currently no approved therapies for preservation of C-peptide or delaying the progression of symptomatic type 1 diabetes.”

  • The paper relies on this without support.

    Various therapies, including verapamil, menin inhibitors, Janus kinase inhibitors, antithymocyte globulin, several monoclonal antibodies including teplizumab, and cell therapies, are currently under active investigation.

    “Various therapies, including verapamil, menin inhibitors, Janus kinase inhibitors, antithymocyte globulin, several monoclonal antibodies including teplizumab, and cell therapies, are currently under active investigation.”

  • The paper relies on this without support.

    Successful pancreas and islet transplantation can normalize glucose levels and mitigate microvascular complications of type 1 diabetes.

    “Successful pancreas and islet transplantation can normalize glucose levels and mitigate microvascular complications of type 1 diabetes.”

  • The paper relies on this without support.

    People receiving pancreas or islet transplantation require lifelong immunosuppression to prevent graft rejection and/or recurrence of autoimmune islet destruction.

    “However, people receiving these treatments require lifelong immunosuppression to prevent graft rejection and/or recurrence of autoimmune islet destruction.”

  • The paper relies on this without support.

    Person-specific factors that affect choice of treatment include individualized glycemic goals, individualized weight goals, the individual's risk for hypoglycemia, and the individual's history of or risk factors for cardiovascular, kidney, liver, and other comorbidities and complications of diabetes.

    “Person-specific factors that affect choice of treatment include individualized glycemic goals (see Section 6,”

  • The paper relies on this without support.

    Type 2 diabetes is a progressive disease.

    “Because type 2 diabetes is a progressive disease, maintenance of glycemic goals often requires combination therapy.”

  • The paper relies on this without support.

    The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea.

    “The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extendedrelease formulation.”

  • The paper relies on this without support.

    For people with an eGFR of 30-45 mL/min/1.73m2, there is an increased risk for periodic decreases of eGFR to ≤30 mL/min/1.73m2 which heightens the risk of lactic acidosis.

    “For people with an eGFR of 30-45 mL/min/1.73m 2 , there is an increased risk for periodic decreases of eGFR to #30 mL/min/1.73m 2 which heightens the risk of lactic acidosis.”

  • The paper relies on this without support.

    Obesity is present in over 90% of people with type 2 diabetes.

    “Obesity is present in over 90% of people with type 2 diabetes, and in these individuals weight management is a key treatment goal, along with glucose lowering.”

  • The paper relies on this without support.

    Insulins, sulfonylureas, and thiazolidinediones can promote weight gain.

    “Insulins, sulfonylureas, and thiazolidinediones can promote weight gain and should be used judiciously and at the lowest possible dose.”

  • The paper relies on this without support.

    Other glucose-lowering medications (metformin, SGLT2 inhibitors, DPP-4 inhibitors, dopamine agonists, bile acid sequestrants, and alpha-glucosidase inhibitors) are weight neutral or have a modest beneficial effect on weight.

    “Other glucoselowering medications (metformin, SGLT2 inhibitors, DPP-4 inhibitors, dopamine agonists, bile acid sequestrants, and aglucosidase inhibitors) are weight neutral or have a modest beneficial effect on weight.”

  • The paper relies on this without support.

    Sulfonylureas, meglitinides, and DPP-4 inhibitors do not have additional beneficial effects on cardiovascular, kidney, weight, or liver outcomes.

    “Use of sulfonylureas, meglitinides, and DPP-4 inhibitors should be limited or discontinued, as these medications do not have additional beneficial effects on cardiovascular, kidney, weight, or liver outcomes and (for sulfonylureas and meglitinides) increase risk of hypoglycemia and weight gain.”

  • The paper relies on this without support.

    Sulfonylureas and meglitinides increase risk of hypoglycemia and weight gain.

    “Use of sulfonylureas, meglitinides, and DPP-4 inhibitors should be limited or discontinued, as these medications do not have additional beneficial effects on cardiovascular, kidney, weight, or liver outcomes and (for sulfonylureas and meglitinides) increase risk of hypoglycemia and weight gain.”

  • The paper relies on this without support.

    Pioglitazone may help improve glycemia and reduce the amount of insulin needed.

    “Adjunctive use of pioglitazone may help to improve glycemia and reduce the amount of insulin needed, although potential side effects should be considered.”

  • The paper relies on this without support.

    Human insulins are often less costly alternatives to insulin analogs.

    “Moreover, human insulins, separately, self-mixed, or as premixed NPH/regular (for example, 70/30) formulations, are often less costly alternatives to insulin analogs.”

  • The paper relies on this without support.

    Use of inhaled insulin may result in a decline in lung function (reduced FEV1).

    “Use of inhaled insulin may result in a decline in lung function (reduced forced expiratory volume in 1 s [FEV 1 ]).”

  • The paper relies on this without support.

    Individuals with high-deductible health plans and those without insurance coverage can incur very high out-of-pocket expenses for glucose-lowering therapies.

    “individuals with high-deductible health plans and those without insurance coverage can incur very high out-of-pocket expenses for glucoselowering therapies.”

  • The paper relies on this without support.

    No caps exist for diabetes durable medical equipment or for noninsulin medications.

    “Moreover, no such caps exist for diabetes durable medical equipment (i.e., equipment for glucose monitoring and insulin administration) or for noninsulin medications.”

  • The paper relies on this without support.

    mTOR kinase inhibitors, including everolimus, cause hyperglycemia by interfering with insulin signaling, leading to impaired insulin secretion and increased insulin resistance.

    “mTOR kinase inhibitors, including everilomus, cause hyperglycemia by interfering with insulin signaling, leading to impaired insulin secretion and increased insulin resistance.”

  • The paper relies on this without support.

    SGLT2 inhibitors appear to be safe and effective in posttransplantation diabetes.

    “SGLT2 inhibitors may be similarly preferred for individuals with ASCVD, HF, and CKD and appear to be safe and effective in posttransplantation diabetes.”

  • The paper relies on this without support.

    There is increased risk of genitourinary tract infection with SGLT2 inhibitors, which is a concern in individuals receiving immunosuppression and in those who have undergone kidney transplantation.

    “However, there is increased risk of genitourinary tract infection, which is a concern in individuals receiving immunosuppression and in those who have undergone kidney transplantation.”

  • The paper relies on this without support.

    SGLT2 inhibitors are not approved for use in people with type 1 diabetes.

    “It is important to note that SGLT2 inhibitors are not approved for use in people with type 1 diabetes.”

  • The paper relies on this without support.

    Medications that impact gastrointestinal emptying time (e.g., GLP-1 RAs or dual GIP and GLP-1 RA) may affect the absorption of orally administered medications, including oral contraception.

    “Medications that impact gastrointestinal emptying time (e.g., GLP-1 RAs or dual GIP and GLP-1 RA) may affect the absorption of orally administered medications, including oral contraception.”

  • The paper relies on this without support.

    Studies on the efficacy and safety of glucose-lowering medications exclude individuals who are pregnant and require individuals of childbearing potential to use one or two forms of contraception.

    “Studies on the efficacy and safety of glucose-lowering medications exclude individuals who are pregnant and require individuals of childbearing potential to use one or two forms of contraception.”

  • The paper relies on this without support.

    Hyperglycemia due to chemotherapy may either be transient or represent permanent diabetes.

    “Hyperglycemia due to chemotherapy may either be transient (improving upon treatment cessation) or represent permanent diabetes.”

  • The paper relies on this without support.

    Individuals with pancreatogenic diabetes may require early insulin initiation to achieve and maintain glycemic goals.

    “Individuals with pancreatogenic diabetes may require early insulin initiation to achieve and maintain glycemic goals.”

  • The paper relies on this without support.

    While immediately posttransplant many individuals require insulin therapy, noninsulin therapies can be used for long-term management.

    “While immediately posttransplant many individuals require insulin therapy, noninsulin therapies can be used for long-term management.”

  • The paper relies on this without support.

    GLP-1 RAs have demonstrated benefit on cardiovascular, kidney, weight, and liver outcomes.

    “GLP-1 RA therapy may be preferred for many individuals due to the demonstrated benefit of GLP-1 RAs on cardiovascular, kidney, weight, and liver outcomes.”
50 of 50

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Peters, 2013, The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook.

Cited by

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Related

Authors
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., Ekhlaspour, L., Gaglia, J. L., Garg, R., Girotra, M., Khunti, K., Lal, R., Lingvay, I., Matfin, G., Neumiller, J. J., Pandya, N., Pekas, E. J., Pilla, S. J., Polsky, S., Segal, A. R., Seley, J. J., Stanton, R. C., & Bannuru, R. R.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2024-12-09
Volume
48
Issue
Supplement_1
Pages
S181-S206
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc25-s009
PMC
PMC11635045
OpenAlex
W4405187712
Semantic Scholar
36383ae6e317f20a2223b5702a4f60004fe2727f
Cited by
728
References
229
Citations by year
2026: 280 · 2025: 375 · 2024: 61 · 2023: 11
FWCI
42.74
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/journals/pages/license (vor)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
National Institutes of Health (5k23dk121942-05)
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 Management and Education
Keywords
glycemic control, pharmacotherapy, diabetes mellitus, antidiabetic drugs, clinical guidelines, treatment goals, quality of care
MeSH terms
Glycemic Control, Blood Glucose, Diabetes Mellitus, Humans, Hypoglycemic Agents, Practice Guidelines as Topic, Standard of Care

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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.

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