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REVIEW
HAROLD E. LEBOVITZ, MD*
Professor of Medicine, Division of Endocrinology and Metabolism/Diabetes, State University of New York (SUNY) Health Sciences Center, Brooklyn

Treating hyperglycemia in type 2 diabetes: New goals and strategies
s A B S T R AC T
To achieve glycemic goals in type 2 diabetes, one must usually use combinations of oral agents or oral agents plus insulin. Thispaper discusses the metabolic derangements of type 2 diabetes, the different classes of antihyperglycemic drugs, and strategies for using these drugs rationally.
type 2 diabetes W lot more seriously than in themellitus a past, and
E ARE TAKING

s KEY POINTS
The American Diabetes Association calls for a goal hemoglobin A1c level of 7.0% in type 2 diabetes; other organizations set the goal at 6.5%.Plasma glucose levels that correspond to a hemoglobin A1c level of 6.5% are a fasting level less than 110 mg/dL and a 2-hour postprandial level less than 140 mg/dL. Both fasting and postprandial glucose levels need to be monitored and controlled, as do components of the metabolic syndrome such as insulin resistance, dyslipidemia, hypertension, and a procoagulant state. Agents that decreasefasting plasma glucose levels selectively (eg, sulfonylureas and metformin) or in conjunction with lowering postprandial glucose excursions (eg, repaglinide, pioglitazone, and rosiglitazone) lower mean hemoglobin A1c levels 1.5 to 2.0 percentage points. Agents that primarily lower postprandial hyperglycemia are the alpha-glucosidase inhibitors and nateglinide. These decrease mean hemoglobin A1c levelsby 0.5 to 1.0 percentage points.

treating it more aggressively. For starters, forget about the old term for the disease, “non–insulin-dependent diabetes.” Many patients with type 2 or adultonset diabetes do need insulin. In fact, some need basal insulin treatment with intermediate-acting or long-acting insulins, while a few may need pre-meal insulin treatment to control postprandialhyperglycemia in addition to basal treatment. We now have a menu of oral antihyperglycemic drugs and new insulin preparations that, if used rationally, can greatly improve metabolic control and decrease complications in most patients. This review provides a practical perspective on how to use the new drugs, discussing how they work, their effect on components of the metabolic syndrome, their adverse effects,and how they can be used in combination. s CONSEQUENCES OF TYPE 2 DIABETES Type 2 diabetes is one of the major problems confronting the health care system. By 2010, its prevalence will have increased approximately 2.5-fold from 1990 figures.1 It is the leading cause of new blindness2 and end-stage renal disease,3 it accounts for slightly more than one half of lower-extremity amputations,4 and itis a major risk factor for cardiovascular disease.5
*The

author has indicated that he has received grant or research support from the Bristol-Myers Squibb, GlaxoSmithKline, and Novo Nordisk corporations; serves as a consultant for the Amylin, AstraZeneca, Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica, MerckLipha, Novartis, Novo Nordisk, Pfizer, and Takeda corporations; ison the speakers’ bureaus of all of the above plus the Aventis corporation; and is a major stock shareholder in the Bayer, Bristol-Myers Squibb, and GlaxoSmithKline corporations.

CLEVELAND CLINIC JOURNAL OF MEDICINE

VOLUME 69 • NUMBER 10

OCTOBER 2002

809

TYPE 2 DIABETES DRUGS

LEBOVITZ

TA B L E 1

Antihyperglycemic drugs for type 2 diabetes
DRUG DOSE MECHANISM OF ACTIONInsulin secretogogues work only if enough beta cells remain

Insulin secretogogues Sulfonylureas (one or two divided doses) Glipizide 2.5–25 mg/day* Glipizide GITS 2.5–10 mg/day* Glyburide 1.25–15 mg/day* Micronized form 1–12 mg/day Glimepiride 1–8 mg/day Rapid-acting Nateglinide 60–120 mg with each meal Repaglinide 0.5–4.0 mg with each meal Basal insulins Highly variable NPH Lente Ultralente...