Oral Agents in the Management of Type 2 Diabetes Mellitus.

Publication: American Family Physician

Publication Date: 01-MAY-01

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COPYRIGHT 2001 American Academy of Family Physicians

Despite exhaustive efforts to better manage patients with type 2 diabetes mellitus (formerly known as non-insulin-dependent diabetes mellitus), attempts at maintaining near normal blood glucose levels in these patients remains unsatisfactory. This continues to pose a real challenge to physicians as the prevalence of this disease in the United States continues to rise. Type 2 diabetes is defined as a syndrome characterized by insulin deficiency, insulin resistance and increased hepatic glucose output. Medications used to treat type 2 diabetes are designed to correct one or more of these metabolic abnormalities. Currently, there are five distinct classes of hypoglycemic agents available, each class displaying unique pharmacologic properties. These classes are the sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors. In patients for whom diet and exercise do not provide adequate glucose control, therapy with a single oral agent can be tried. When choosing an agent, it is prudent to consider both patient- and drug-specific characteristics. If adequate blood glucose control is not attained using a single oral agent, a combination of agents with different mechanisms of action may have additive therapeutic effects and result in better glycemic control. (Am Fam Physician 2001;63:1747-56,1759-80.)

The prevalence of type 2 diabetes mellitus (formerly known as non-insulin-dependent diabetes mellitus) in the United States has increased dramatically over the past two decades and continues to rise.(1) Despite the introduction of new agents to the armamentarium of hypoglycemic agents, efforts for better management of this disease have been disappointing and the control of blood glucose levels remains unsatisfactory.(2) Recently, the results of the United Kingdom Prospective Diabetes Study (UKPDS) were released.(3) This study, the largest and longest study of patients with type 2 diabetes, has reinforced the belief that improved control of blood glucose levels can substantially lower the overall morbidity associated with this disease, underscoring the urgency to obtain better glucose control in these patients. The focus of this review will be the management of patients with type 2 diabetes using one or more of the five available classes of oral hypoglycemic agents: sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors (Table 1). Options for monotherapy and combination therapy, efficacy of specific agents, adverse effects and special populations are some issues addressed in this review.

TABLE 1 Classes of Oral Hypoglycemic Agents Drug class Agent Sulfonylureas First generation Acetohexamide (Dymelor) Chlorpropamide (Diabinese) Tolazamide (Tolinase) Tolbutamide (Orinase) Second generation Glyburide (Micronase) Glipizide (Glucotrol) Glimepiride (Amaryl) Drug class Agent Meglitinides Repaglinide (Prandin) Nateglinide (Starlix) Biguanides Metformin (Glucophage) Thiazolidinediones Pioglitazone (Actos) Rosiglitazone (Avandia) Alpha-glucosidase Acarbose (Precose) inhibitors Miglitol (Glycet)

Type 2 diabetes can be described as a syndrome characterized by insulin deficiency, insulin resistance and increased hepatic glucose output.(4,5) With this in mind, therapies used to treat patients with this disease are aimed at correcting one or more of these physiologic abnormalities. Current recommendations of the American Diabetes Association include a trial of diet and exercise as first-line therapy for the treatment of patients with type 2 diabetes.(6) If the desired level of glycemic control is not achieved with diet and exercise within a three-month period, pharmacologic intervention is required.

Criteria for initiation of therapy with an oral agent versus insulin are debated among diabetologists, but the decision should be made jointly by the physician and patient to obtain the best results.(7) (Because of the apparently progressive nature of the beta cell defect in type 2 diabetes, current oral therapies may not prevent an eventual decline in glycemic control, and it is likely that many patients will ultimately require insulin therapy.) Once the decision is made to initiate therapy with an oral agent, it is prudent to consider patient-specific (age, weight, level of glycemic control) and agent-specific characteristics (relative potencies, duration of action, side-effect profiles, cost) to make the most appropriate choice (Tables 2 and 3(8)). Figure 1 illustrates a reasonable stepwise approach for initiating oral therapy in patients with type 2 diabetes and is consistent with the recommendations put forth by several expert committees and diabetes subspecialists.(4-6,9)

TABLE 2 Clinical Efficacy of Oral Hypoglycemic Agents Reduction Class of hypoglycemic agents in HbA1c (%) Sulfonylureas 0.8 to 2.0 Meglitinides 0.5 to 2.0 Biguanides 1.5 to 2.0 Thiazolidinediones 0.5 to 1.5 Alpha-glucosidase inhibitors 0.7 to 1.0 Reduction in FPG Class of hypoglycemic agents (mg per dL [mmol per L]) Sulfonylureas...

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