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Cited by 728Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes Management and Education

The DOI matches its Crossref record; 241 of the 241 references it cites were found in a registry or an index; 129 of the 272 sources its claims cite were checked for support.

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, Bruemmer, Dennis, Echouffo-Tcheugui, Justin B., Ekhlaspour, Laya, Gaglia, Jason L., Garg, Rajesh, Girotra, Monica, Khunti, Kamlesh, Lal, Rayhan, Lingvay, Ildiko, Matfin, Glenn, Neumiller, Joshua J., Pandya, Naushira, Pekas, Elizabeth J., Pilla, Scott J., Polsky, Sarit, Segal, Alissa R., Seley, Jane Jeffrie, Stanton, Robert C., Bannuru, Raveendhara R.·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.

Overview

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.

Verification

Claims the paper makes

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

  • It may state two separate claims as one. 38
  • Probably not a substantial claim. 2
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

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

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Metadata

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
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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