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Cited by 2,375Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Glycemic Control With Diet, Sulfonylurea, Metformin, or Insulin in Patients With Type 2 Diabetes Mellitus<SUBTITLE>Progressive Requirement for Multiple Therapies (UKPDS 49)</SUBTITLE>

Turner, Robert C.·1999·JAMA
DOI 10.1001/jama.281.21.2005
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Abstract

CONTEXT: Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A1c (HbA1c) below 7% is unknown. OBJECTIVE: To assess how often each therapy can achieve the glycemic control target levels set by the American Diabetes Association. DESIGN: Randomized controlled trial conducted between 1977 and 1997. Patients were recruited between 1977 and 1991 and were followed up every 3 months for 3, 6, and 9 years after enrollment. SETTING: Outpatient diabetes clinics in 15 UK hospitals. PATIENTS: A total of 4075 patients newly diagnosed as having type 2 diabetes ranged in age between 25 and 65 years and had a median (interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA1c levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) kg/m2. INTERVENTIONS: After 3 months on a low-fat, high-carbohydrate, high-fiber diet, patients were randomized to therapy with diet alone, insulin, sulfonylurea, or metformin. MAIN OUTCOME MEASURES: Fasting plasma glucose and HbA1c levels, and the proportion of patients who achieved target levels below 7% HbA1c or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis. RESULTS: The proportion of patients who maintained target glycemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%, and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28%, and 24% achieved HbA1c levels below 7%. In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA1c levels below 7%. Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients. CONCLUSIONS: Each therapeutic agent, as monotherapy, increased 2- to 3-fold the proportion of patients who attained HbA1c below 7% compared with diet alone. However, the progressive deterioration of diabetes control was such that after 3 years approximately 50% of patients could attain this goal with monotherapy, and by 9 years this declined to approximately 25%. The majority of patients need multiple therapies to attain these glycemic target levels in the longer term.

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  • Type 2 diabetes is progressive, with glycaemic control deteriorating over time despite treatment.

    “This progressive nature of Type 2 diabetes has been further highlighted by two recent, large clinical studies performed on opposite sides of the Atlantic.”

    From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [15]

  • Metformin decreases fasting plasma glucose concentration and hemoglobin A1c by conserving β-cell function or by decreasing liver glucose production (hepatic gluconeogenesis).

    “A considerable number of studies have also found that metformin decreases fasting plasma glucose (PG) concentration and hemoglobin A1c by conserving the β-cell function or by decreasing liver glucose production (hepatic gluconeogenesis) (181–184).”

    From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [184]

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Authors
Turner, R. C.
Affiliations
University of Oxford (GB)
Corresponding author
Turner, Robert C.
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
1999-06-02
Volume
281
Issue
21
Pages
2005
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.281.21.2005
OpenAlex
W1975588287
Cited by
2,375
References
20
Citations by year
2026: 20 · 2025: 33 · 2024: 33 · 2023: 35 · 2022: 53 · 2021: 58 · 2020: 57 · 2019: 74 · 2018: 69 · 2017: 90 · 2016: 101 · 2015: 109 · 2014: 144 · 2013: 136 · 2012: 144
FWCI
31.23
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
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, glycemic control, HbA1c, fasting blood glucose, metformin, sulfonylureas, insulin therapy, dietary therapy, monotherapy, treatment persistence, glycemic targets, newly diagnosed diabetes, long-term follow-up, treatment effectiveness comparison, cost-effectiveness
MeSH terms
Adult, Blood Glucose, Combined Modality Therapy, Diabetes Mellitus, Type 2, Dietary Carbohydrates, Dietary Fiber, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Middle Aged, Prospective Studies, Sulfonylurea Compounds, Multivariate Analysis, Logistic Models, Diet, Fat-Restricted

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