Rapid Increase in the Use of Oral Antidiabetic Drugs in the United States, 1990–2001

RESEARCH DESIGN AND METHODS

National data on drug products approved for treatment of type 2 diabetes were derived from two pharmaceutical marketing research databases purchased from IMS Health (National Prescription Audit Plus [NPA Plus] and National Disease and Therapeutic Index [NDTI]). NPA Plus provides national estimates of prescriptions dispensed by chain, independent, food store, mail order, and long-term care pharmacies (3). For the period 1996–2001, IMS Health’s pharmacy database consisted of ∼34,000 reporting pharmacy stores. The number of dispensed prescriptions was obtained from a sample of ∼22,000 randomly selected stores and projected nationally. The pharmacies in the database account for 40% of pharmacy stores and represent 45% of prescription coverage, according to estimates by IMS Health.

The design features and sampling frame of the NPA Plus have changed over time in the direction of greater representation and statistical accuracy. For the period of this report, the most significant changes occurred in 1992 with the addition to the sampling frame of food stores and the states of Alaska and Hawaii and the increase from 2,500 to 20,000 in the number of computerized pharmacies in the sample. The database accessed by FDA was also expanded in 1997 to include prescriptions from mail order houses and in 2001 from long-term care facilities. Although NPA sampling methodologies have changed over time, the data have always been projected to obtain national prescription estimates. The NPA Plus database was used to obtain the estimated annual number of dispensed outpatient prescriptions for each oral antidiabetic drug included in the Uniform System of Classification class 39200, oral agents for diabetes.

The second database, the NDTI, provides descriptive information on the patterns and treatments of diseases encountered in office-based medical practices in the U.S. (4). Data are obtained from a panel of 2,000–3,000 participating physicians who report on each patient-physician contact in the office, in the hospital, on the telephone, or elsewhere for 2 consecutive working days per calendar quarter. These data are also projected nationally. The sampling methodologies of the two databases are described elsewhere in more detail (5).

By convention, NDTI uses the term “mentions” for drug reports. A mention refers to a drug in association with a diagnosis during a patient-physician contact. Mentions are not directly equivalent to prescriptions because access to a drug product can be gained in a number of ways, including written prescriptions, authorized refills, office samples, etc. However, we have observed that for most drugs, mentions are primarily associated with written prescriptions. For instance, in 2001, 53% of mentions for Glucophage (metformin) were for issuance of a prescription or a prescription and a sample, 1% were for issuance of a sample, 2.5% involved a hospital order, 26% had no prescription (or sample) that visit (probably with discussion of continued therapy), and 16% were unspecified as to disposition (3). The category “recommended,” which is a small proportion of mentions for most drugs, was 1% for metformin.

RESULTS

In 1990, 23.4 million outpatient prescriptions for oral antidiabetic medications were dispensed in the U.S. By 2001, this number had increased 3.9-fold to 91.8 million prescriptions (Table 1). Through 1996, the market was dominated by the use of the second-generation sulfonylurea medications glipizide and glyburide. These two medications together accounted for ∼77% of prescriptions in 1990 and 75% in 1996. With the introduction of the biguanide metformin in 1995 and the thiazolidinedione insulin sensitizers in 1997, the proportion of prescriptions dispensed for sulfonylureas decreased, despite the marketing of a new sulfonylurea, glimepiride. By 2001, prescriptions for glipizide and glyburide accounted for 35.5% of market share, whereas metformin captured nearly 33%, and the thiazolidinedione insulin sensitizers rosiglitazone and pioglitazone together accounted for ∼17% (Table 1). Several new types of antidiabetic drugs, the glucosidase inhibitors (consisting of acarbose and miglitol) and the nonsulfonylurea insulin secretagogues (consisting of repaglinide and nateglinide), together accounted for only ∼3% of market share in 2001.

Compared with 1990, in 2001 a larger proportion of patients who were prescribed oral antidiabetic drugs were in the 40- to 59-year-old age group (Table 2). However, rates of diabetes increase with age, and older individuals remain the largest group of consumers of these drugs. Also, compared with 1990 levels, in 2001 an increasing proportion of patients began rather than continued therapy, which reflects the number of new drugs and is also consistent with the observed increase in incidence of type 2 diabetes in the U.S. For 1990, 1996, and 2001, the proportion of prescriptions that were refills was similar, ranging from 66 to 69%. Associated with the introduction of metformin in 1995, there has been a substantial increase in the co-prescribing of oral antidiabetic drugs. Consistently throughout the period of 1990 through 2001, mentions for these drugs were made most often in visits to internists and family and general practitioners.

CONCLUSIONS

The period of 1990 through 2001 saw the approval and marketing of many new oral antidiabetic medications for the management of type 2 diabetes in the U.S. In the early 1990s, the sulfonylurea drugs glyburide and glipizide were the primary medications prescribed for this condition. The introduction of metformin in 1995 and of the thiazolidinedione insulin sensitizers rosiglitazone and pioglitazone in 1999 contributed to a percent decline in prescriptions for glyburide and glipizide in 2001. Nevertheless, these two medications continued to capture more than one-third of the market of oral antidiabetic drugs in 2001, whereas metformin captured nearly one-third, and the thiazolidinedione insulin sensitizers accounted for 17%. All the other drugs combined accounted for only 15% of the market share.

During the 11-year period from 1990 to 2001, a 3.9-fold increase (from 23.4 million to nearly 92 million) occurred in dispensings of outpatient prescriptions for oral antidiabetic drugs. Only 21.5 million prescriptions were dispensed in 1986 (1). This rapid increase in prescriptions coexists with the increase in the incidence of type 2 diabetes in the U.S. In the data presented here, the largest proportionate increase in prescriptions between 1990 and 2001 was for 40- to 59-year-old individuals.

The prevalence of diagnosed diabetes in U.S. adults increased from 4.9% in 1990 to 6.9% in 1999 (6). Because obesity and duration of obesity are major risk factors of type 2 diabetes (7–9), the increase in prevalence of this disease and consequent use of oral antidiabetic drugs correspond to the increase in the prevalence of obesity. The age-adjusted prevalence of obesity (BMI >30 kg/m²) in the U.S. increased from nearly 23% in the period 1988–1994 to 30.5% in 1999–2000 (10). Other factors that have contributed to the increase in the prevalence of diabetes include a change in the definition of diabetes to lower blood glucose levels (11) and the aging and ethnic composition of the population (12).

Besides the increasing prevalence of type 2 diabetes, the increase in prescriptions for oral antidiabetic drugs is also attributable to an increase in the frequency of co-prescribing drugs in this class. Such co-prescribing of these drugs and insulin was shown by the U.K. Prospective Diabetes Study (UKPDS) to increase the probability of achieving glycemic control (13), which delays the onset and slows the progression of diabetic complications (11,13–15). The importance of achieving glycemic control was determined by the landmark UKPDS and the Diabetes Control and Complications Trial (11,13–15), which were conducted in the 1990s.

The prescription data presented in this article are limited by the following methodological considerations: the data are based on prescriptions rather than persons; the data do not address duration of use; and the sampling schemes are not statistical samples, so the results may not be representative. Furthermore, the sampling schemes have changed over time and these changes could affect trend data. Pertinent to the data presented in this report, the mail order and long-term care channels were added during the 1990s; however, they constitute a relatively small proportion of total prescriptions, and inclusion of these channels is in the direction of greater population coverage and more accurate estimates. For less-popular singular drugs, the descriptive information from NDTI is based on relatively small samples with wide confidence intervals about the estimates; in contrast, NDTI estimates for the class of oral antidiabetic drugs included in this article are based on large numbers of patient-physician visits, which result in narrow confidence intervals and more accurate estimates. The IMS Health data are purchased by pharmaceutical companies, the FDA, and other government agencies to obtain timely drug use information. The IMS Health databases yield results that are generally consistent with other health surveys and databases.

With these data, we are able to track drug use over time. Since their introduction some 40 years ago, the first-generation (primarily chlorpropamide) and then the second-generation (glyburide and glipizide) sulfonylurea drugs have been the mainstays of type 2 diabetes management. With the approval in 1995 through 2001 of new medications with different mechanisms of action, options for management of type 2 diabetes have expanded.