CHANGING LANDSCAPE OF DIABETES CARE
Significant shifts in diabetes treatment since 1994 are evident from our analysis of the IMS Health NDTI data. Notable changes are: (1) increased numbers of total annual visits for diabetes (decrease in visits per patient), (2) increased use of oral therapies until the early 2000s with a subsequent shift back toward insulin with the advent of ultrashort-acting and long-acting preparations, (3) rapid growth of metformin and glitazones (thiazolidinediones) in the late 1990s, (4) rapid early growth of incretins and DPP-4 inhibitors in the past 2 years, (5) a continuous decrease in sulfonylurea use, (6) increasing use of both combination products and multiple products per patient, and (7) substantially increased aggregate drug expenditures and price per prescription.
TRENDS IN VISITS FOR DIABETES
Estimated US patient visits to office-based physicians for type 2 diabetes remained relatively stable between 1994 (29 million; 95% CI, 27 million to 31 million) and 1997 (28 million) but increased to 37 million (35 million to 39 million) in 2000 and then to 45 million (42 million to 48 million) by 2007. During this period, several notable changes occurred in the characteristics of patients and of the physicians providing treatment at these visits. The proportion of visits for diabetes by patients of ethnic minorities increased from 23% in 1994 to 28% in 2000 to 33% in 2007. Between 1994 and 2007, visits by Asian (1% to 5%) and Hispanic (5% to 10%) patients increased most rapidly. Changes also were noted in the proportion of visits by women (45% in 1994 to 51% in 2007), patients younger than 60 years (32% to 41%), and patients covered by Medicare (47% to 38%). Little change was seen by US region or by the specialties of the physicians treating the patients with diabetes. The mean number of annual physician visits per patient decreased from 2.9 (95% CI, 2.7–3.1) visits in 1994 to 2.7 (2.5–2.7) visits in 2000 and to 2.4 (2.3–2.5) visits in 2007. The estimated number of individual patients with type 2 diabetes seen by US office-based physicians increased from 10 million (95% CI, 9 million to 11 million) in 1994 to 14 million (13 million to 15 million) in 2000 and to 19 million (17 million to 21 million) in 2007.
OVERALL TRENDS IN TREATMENT
The number of visits for which a diabetes therapy was reported (treatment visits) increased from 25 million (95% CI, 23 million to 27 million) in 1994 to 30 million (28 million to 32 million) in 2000 and to 36 million (34 million to 38 million) in 2007. The proportion of total diabetes visits for which no medication therapy was reported increased from 15% (95% CI, 13%–17%) in 1994 to 18% (16%–20%) in 2000 and to 20% (18%–22%) in 2007. The mean number of medications prescribed per treatment visit increased from 1.06 medications per visit in 1994 to 1.45 in 2007. When individual components of combination products were counted separately, an increase was seen from 1.14 components per visit in 1994 to 1.63 in 2007.
CHANGES IN MEDICATION CLASSES USED AS DIABETES THERAPY
Significant shifts occurred in the medications used for diabetes therapy ( and ). In 1994, pharmacotherapy for diabetes was divided between insulin preparations (38%; 95% CI, 34%–42% of treatment visits) and sulfonylureas (67%; 67%–73%). By 2007, a variety of newer drug classes also were used to treat diabetes. In 2007, the most frequent therapies were metformin (the only available biguanide; 54%; 95% CI, 49%–59% of treatment visits), sulfonylureas (34%; 31%–37%), glitazones (28%; 25%–31%), insulin (28%; 25%–31%), sitagliptin phosphate (only available DPP-4 inhibitor; 8%; 7%–9%), and exenatide (only available incretin; 4%; 3%–4%).
Figure 1 National trends in the use of different therapeutic drug classes to treat diabetes, 1997–2004. Data are from the IMS Health National Disease and Therapeutic Index; drugs from most new therapeutic classes (eg, dipeptidyl-peptidase-IV inhibitors) (more ...)
Insulin use decreased from 38% (95% CI, 34%–42%) of treatment visits in 1994 to a nadir of 25% (22%–27%) in 2000, only to increase to 28% (25%–31%) by 2007. Nearly all insulin use in 1994 was in the form of regular and intermediate-acting (eg, NPH) preparations. In 1994, 25% of treatment visits involved patients receiving a prescription for regular insulin and 21% involved patients receiving a prescription for intermediate-acting insulin, with approximately one-third of regular insulin use in combination products (). By 2000, use of each of these preparations had decreased, particularly for regular insulin (14% of treatment visits) compared with NPH (18%).
National trends in the use of different types of insulin to treat diabetes, 1994 to 2007. Data are from the IMS Health National Disease and Therapeutic Index and include combination products that contain these medications.
Since 2001, the use of newer insulin preparations has been rapidly increasing. Ultrashort-acting insulin analogues (available in 1996) and combinations that include them have increased from 2% of treatment visits in 2001 to 7% in 2007, with approximately half in the form of combination products. Likewise, long-acting insulin analogues (available in 2000) increased from 2% in 2001 to 12% in 2007. With the increase of these newer insulins, use of older insulin preparations has continued to decrease. In 2007, the use of regular insulin (5% of treatment visits) and NPH (5%), including their combinations, together constituted only 30% of all treatment visits with insulin. The use of single-component insulin monotherapy (eg, NPH alone) decreased from 48% of all insulin treatment visits in 1994 to 22% in 2007. Inhaled insulin was introduced in January 2006 but, because of its limited adoption (less than 1% of treatment visits in 2007), this product was removed from the market in November 2007. The most common individual insulin therapies in 2007 were insulin glargine and insulin lispro.
Once the mainstay of diabetes therapy (67%; 95% CI, 61%–73%), sulfonylureas were used in only 34% (31%–37%) of treatment visits in 2007. This change was notably slower between 1994 and 1999 (60%) and more rapid recently. Combination drugs, including sulfonylureas, were first available in 2000. These drugs increased to 11% of treatment visits by 2003 but decreased to 6% in 2007. Most combination therapy in 2007 was a sulfonylurea combined with metformin (5% of treatment visits). Combination therapy accounted for 18% of all sulfonylurea use in 2007. Sulfonylurea monotherapy declined from 94% of all sulfonylurea use in 1994 to 30% in 2007. In 1994, the most common individual sulfonylurea was glyburide. In 2007, the most common individual noncombination sulfonylurea was glipizide, whereas those most common in combination products were glyburide (with metformin) and glimepiride (with glitazones).
As a safer biguanide than phenformin (removed from the market in 1977), metformin was released in the United States in 1995. This drug was rapidly adopted (18% of treatment visits in 1996 and 38% in 2000). After surpassing sulfonylureas as the leading class of diabetes treatment in 2004 (48%; 95% CI, 44%–52%), metformin use has continued to increase (2007: 54%; 49%–59%). Metformin-containing combination products were introduced in 2000 (with sulfonylureas), 2002 (with glitazones), and 2007 (with sitagliptin). In 2007, these combinations accounted for 12% of treatment visits or 23% of all metformin use, including metformin and sulfonylurea (5% of treatment visits), metformin and glitazone (6%), and metformin and sitagliptin (1%).
The first glitazone, troglitazone, was approved in 1997. This drug was adopted rapidly so that by 1998 it accounted for 10% (95% CI, 8%–12%) of treatment visits. Because of hepatotoxicity, however, troglitazone was removed from the market in 2000. With the addition of rosiglitazone maleate (1999) and pioglitazone hydrochloride (1999), this class continued to increase until peaking at 34% (95% CI, 31%–37%) of treatment visits by 2005, then decreased to 28% (25%–31%) by 2007. A significant reduction in use was evident during 2007. The use of glitazone combinations (introduced in 2002) has increased to constitute 24% of all glitazone uses in 2007. Glitazone use as monotherapy increased from 1997 (2% of treatment visits) to 2004 (9%), then decreased to 7% of treatment visits during 2007 (25% of all glitazone use). The most commonly used individual glitazone has shifted from troglitazone in 1999 to rosiglitazone (59% of glitazone uses by 2004) to pioglitazone (64%) in 2007. In 2007, a further shift was seen toward pioglitazone, with an associated 63% decrease in rosiglitazone use.
NEWLY AVAILABLE MEDICATIONS
Several recently released medications have shown rapid early adoption into practice, although several more years of data will provide a more accurate assessment of their places in therapy. Sitagliptin, a DPP-4 inhibitor released in October 2006, increased to 10% of treatment visits by the fourth quarter of 2007 (8%; 95% CI, 7%–9%; for all of 2007). Exenatide, an injectable incretin initially derived from Gila monster saliva, was released in June 2005. By 2006, exenatide accounted for 3% (95% CI, 2%–4%) of treatment visits but with only modest increase to 4% by the fourth quarter of 2007.
Three other new classes of diabetes medications have not been widely adopted. α-Glucosidase inhibitors were noted at less than 1% of treatment visits since their first approval in 1996 and decreased to less than one-half percent by 2007. Use of the short-acting metaglinide secretagogues, available since 2000, peaked in 2002 at 3% of visits but were used in only 2% of treatment visits in 2007. Released in 2005, the injectable amylin analogue, pramlintide acetate, accounted for less than one-half percent of treatment visits in 2007.
In aggregate, combination products with 2 constituent medications have increased substantially from 9% (95% CI, 9%–9%) of treatment visits in 1994 to a peak of 21% (19%–24%) in 2004 before decreasing to 19% (17%–21%) in 2007. As a proportion of treatment visits, insulin combinations peaked in 1995 at 10% and have since decreased to 6% in 2007. Oral combinations increased rapidly after being introduced in 2000 to 15% of treatment visits in 2004 but have failed to increase further (13% in 2007). At the peak of oral and insulin combination therapy use in 2004, these combinations were the only therapy provided in 14% of treatment visits or 66% of all combination product use. By 2007, these products were less likely to be used as sole therapy (11% of treatment visits or 59% of all combination product use).
PRESCRIPTION DRUG EXPENDITURES
Drug expenditures and prescription prices increased rapidly between 2001 and 2007 according to our analysis of the IMS Health NPA data ( and ). Aggregate drug expenditures for diabetes increased by 87% from $6.7 billion in 2001 to $12.5 billion in 2007. Major contributors to this increase were glitazones and combination products, including glitazones ($1.9 billion to $4.2 billion), ultrashort-acting insulins and their combinations ($0.4 billion to $1.9 billion), and long-acting insulins ($0.1 billion to $2.0 billion). During this same period, decreases were seen in metformin and sulfonylurea expenditures. The mean price of a diabetes drug prescription increased from $56 in 2001 to $76 in 2007. This increase was due to increasing use and increasing prescription prices of glitazones ($119 in 2001 to $160 in 2007) and increased use of more costly newer drugs, including ultrashort-acting insulins ($156 in 2007), long-acting insulins ($123 in 2007), exenatide ($202 in 2007), and sitagliptin ($160 in 2007). The cost of metformin ($63 to $29) and sulfonylurea ($27 to $20) prescriptions decreased during this same period.
Figure 3 National trends in the amount spent per year on diabetes drugs, 2001 to 2007. Data are from the IMS Health National Prescription Audit and include combination products that contain these medications. “Other” includes secretagogues (eg, (more ...)
National trends in the amount spent per year on different types of insulin, 2001 to 2007. Data are from the IMS Health National Prescription Audit and include combination products that contain these medications.