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Cited by 3,834Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

The DOI matches its Crossref record; 108 of the 108 references it cites were found in a registry or an index; none of the 113 sources its claims cite is checked for support yet.

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy

Open access
Nathan, David M., Buse, John B., Davidson, Mayer B., Ferrannini, Ele, Holman, Rury R., Sherwin, Robert, Zinman, Bernard·2009·Diabetes Care
DOI 10.2337/dc08-9025PMC PMC2606813
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Abstract

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This 2009 consensus update reaffirms an A1C goal of <7% and recommends lifestyle intervention plus metformin at diagnosis, with rapid addition of a second medication—usually insulin or a sulfonylurea—and further insulin intensification if targets are not met. It reviews glucose-lowering drug classes and advises against rosiglitazone while placing exenatide or pioglitazone in a second tier for selected patients.

Key findings

  • The consensus recommends achieving and maintaining A1C <7.0%, initiating lifestyle intervention and metformin at diagnosis, and adding a second medication within 2–3 months if glycemic goals are not achieved or sustained.
  • Metformin and sulfonylureas each typically lower A1C by ∼1.5 percentage points; TZDs by 0.5–1.4; DPP-4 inhibitors by 0.6–0.9; exenatide by 0.5–1; pramlintide by 0.5–0.7; and α-glucosidase inhibitors by 0.5–0.8.
  • The ACCORD study found excess CVD mortality in the intensive group targeting A1C <6.0% versus <7.9%, while ADVANCE and the Veterans Affairs Diabetes Trial did not show excess mortality with intensive regimens; none demonstrated benefit on primary CVD outcomes.
  • The consensus group unanimously advised against using rosiglitazone; exenatide or pioglitazone may be considered in selected settings, such as when hypoglycemia is particularly undesirable or weight loss is a major consideration.

Methods

  • Consensus guideline/algorithm derived from two sources: clinical trials addressing effectiveness and safety of diabetes therapies, and the writing group’s clinical judgement weighing benefits, risks, and costs.
  • The writing group reviewed studies of drugs used as monotherapy or in combination to lower glycemia, but did not conduct a systematic review or meta-analysis and collected no new primary data.
  • Recommendations are organized into a tiered algorithm: Tier 1 well-validated core therapies (lifestyle plus metformin, then add insulin or sulfonylurea, then intensify insulin) and Tier 2 less well-validated therapies (e.g., exenatide or pioglitazone in selected patients).

Limitations

  • Stated: the paucity of high-quality, well-controlled clinical trials directly comparing different diabetes treatment regimens remains a major impediment to recommending one class or combination over another.
  • Stated: the most appropriate day-to-day blood glucose and A1C targets have not been systematically studied, and evidence-based review was supplemented by subjective value judgements about benefits, risks, and costs.
  • Evident: as a consensus statement rather than a systematic review or original trial, the recommendations reflect panel opinion and may not be reproducible by other groups with different judgements.

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Integrity signals

Registry

Crossref · 10.2337/dc08-9025

Cites

108 of 108 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 113 cited sources checked · 0 supported · 0 flagged

Show all 56 claims

  • Probably not a substantial claim. 8
  • It may state two separate claims as one. 23
27 of 27

  • The authors state this as an assumption.

    The writing group's collective clinical judgement is an appropriate source for the recommendations.

    “The second source of material that informed our recommendations was clinical judgement, that is, our collective knowledge and clinical experience, which takes into account benefits, risks, and costs in the treatment of diabetes.”

  • The authors state this as an assumption.

    Value judgements are necessary to weigh the benefits of treatment against risks and costs in a subjective fashion.

    “As in all clinical decision making, an evidence-based review of the literature must also be supplemented by value judgements, where the benefits of treatment are weighed against risks and costs in a subjective fashion.”

  • The authors state this as an assumption.

    The recommendations made in this new iteration of the treatment algorithm will guide therapy and result in improved glycemic control and health status over time.

    “While we realize that others may have different judgements, we believe that the recommendations made in this new iteration of our treatment algorithm will guide therapy and result in improved glycemic control and health status over time.”

  • The authors state this as an assumption.

    There are enough data regarding the characteristics of the individual interventions to provide the guidelines despite the absence of rigorous, comprehensive studies that directly compare the efficacy of all available glucose-lowering treatments and their combinations.

    “However, even in the absence of rigorous, comprehensive studies that directly compare the efficacy of all available glucose-lowering treatments and their combinations, we feel that there are enough data regarding the characteristics of the individual interventions to provide the guidelines below.”

  • The paper relies on this without support.

    For most individuals with type 2 diabetes, lifestyle interventions fail to achieve or maintain metabolic goals because of failure to lose weight, weight regain, progressive disease, or a combination.

    “The authors recognize that for most individuals with type 2 diabetes, lifestyle interventions fail to achieve or maintain the metabolic goals either because of failure to lose weight, weight regain, progressive disease, or a combination of factors.”

  • The paper relies on this without support.

    Antihyperglycemic drugs with different mechanisms of action have the greatest synergy.

    “In general, antihyperglycemic drugs with different mechanisms of action will have the greatest synergy.”

  • The paper relies on this without support.

    Some patients with severely uncontrolled diabetes have unrecognized type 1 diabetes; others have type 2 diabetes with severe insulin deficiency.

    “Some patients with these characteristics will have unrecognized type 1 diabetes; others will have type 2 diabetes with severe insulin deficiency.”

  • The paper relies on this without support.

    Insulin can be titrated rapidly and is associated with the greatest likelihood of returning glucose levels rapidly to target levels.

    “Insulin can be titrated rapidly and is associated with the greatest likelihood of returning glucose levels rapidly to target levels.”

  • The paper relies on this without support.

    After symptoms are relieved and glucose levels decreased, oral agents can often be added and insulin may be withdrawn.

    “After symptoms are relieved and glucose levels decreased, oral agents can often be added and it may be possible to withdraw insulin, if preferred.”

  • The paper relies on this without support.

    Current-day management has failed to achieve and maintain the glycemic levels most likely to provide optimal healthcare status for people with diabetes.

    “Although new classes of medications and numerous combinations have been demonstrated to lower glycemia, current-day management has failed to achieve and maintain the glycemic levels most likely to provide optimal healthcare status for people with diabetes.”

  • The paper relies on this without support.

    10–20% of patients with type 2 diabetes are not obese or overweight.

    “For the 10–20% of patients with type 2 diabetes who are not obese or overweight, modification of dietary composition and activity levels may play a supporting role, but medications are still generally required early in the course of diabetes (see special considerations/patients below).”

  • The paper relies on this without support.

    Metformin has a favorable profile: effect on glycemia, absence of weight gain or hypoglycemia, generally low side effects, high acceptance, and relatively low cost.

    “Metformin is recommended as the initial pharmacological therapy, in the absence of specific contraindications, for its effect on glycemia, absence of weight gain or hypoglycemia, generally low level of side effects, high level of acceptance, and relatively low cost.”

  • The paper relies on this without support.

    Insulin secretagogues (sulfonylurea or glinides) are not synergistic with insulin.

    “When insulin injections are started, insulin secretagogues (sulfonylurea or glinides) should be discontinued, or tapered and then discontinued, since they are not considered to be synergistic.”
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Metadata

Authors
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B.
Affiliations
  • Harvard University (US)
  • University of North Carolina at Chapel Hill (US)
  • Charles R. Drew University of Medicine and Science (US)
  • University of Pisa (IT)
  • University of Oxford (GB)
  • Yale University (US)
  • Mount Sinai Hospital (CA)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2009-01-01
Volume
32
Issue
1
Pages
193-203
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc08-9025
PMC
PMC2606813
OpenAlex
W2146901298
Semantic Scholar
1cf454a7ca554873302c894d16550f4a80a5f19a
Cited by
3,834
References
107
Citations by year
2026: 35 · 2025: 66 · 2024: 67 · 2023: 62 · 2022: 88 · 2021: 95 · 2020: 101 · 2019: 121 · 2018: 109 · 2017: 144 · 2016: 203 · 2015: 221 · 2014: 299 · 2013: 349 · 2012: 458
FWCI
316.41
Type
journal article
Language
en
Open access
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • Insulet Corporation
  • Novo Nordisk
  • Servier
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, hyperglycemia, medical management, consensus algorithms, thiazolidinediones, drug safety
MeSH terms
Algorithms, Blood Glucose, Diabetes Mellitus, Diabetes Mellitus, Type 2, Humans, Hyperglycemia, Hypoglycemic Agents, Controlled Clinical Trials as Topic

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