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Pharmacologic Therapy for Type 2 Diabetes Mellitus

DeFronzo, Ralph A.·1999·Annals of Internal Medicine

DOI 10.7326/0003-4819-131-4-199908170-00008

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Abstract

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.

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Authors: DeFronzo, R. A.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
Corresponding author: DeFronzo, Ralph A.
ORCID: DeFronzo, Ralph A.
Venue: Annals of Internal Medicine
Publisher: American College of Physicians
Published: 1999-08-17
Volume: 131
Issue: 4
Pages: 281-303
ISSN: 0003-4819 (ISSN-L)
1539-3704
DOI: 10.7326/0003-4819-131-4-199908170-00008
OpenAlex: W2036939737
Cited by: 1,173
References: 172
Citations by year: 2026: 8 · 2025: 5 · 2024: 17 · 2023: 20 · 2022: 17 · 2021: 26 · 2020: 22 · 2019: 36 · 2018: 23 · 2017: 33 · 2016: 37 · 2015: 36 · 2014: 50 · 2013: 55 · 2012: 43
FWCI: 10.70
Type: journal article
Language: en
Open access: closed
Licence: www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations: Annals of Internal Medicine (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, oral antidiabetic drugs, glycemic control, insulin therapy, metformin, sulfonylureas, insulin resistance, insulin secretion, hepatic glucose production, microvascular complications, UKPDS, drug safety and efficacy, combination therapy
MeSH terms: Troglitazone, Administration, Oral, Algorithms, Carbamates, Chromans, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin, Metformin, Piperidines, Sulfonylurea Compounds, Thiazoles, Trisaccharides, Evidence-Based Medicine, Acarbose, Thiazolidinediones

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Pharmacologic Therapy for Type 2 Diabetes Mellitus

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