By Brenda L. Mooney
PITTSBURGH — Despite a tightly managed national formulary, the use of high-cost drugs to treat diabetes shows “substantial” variation across the VA healthcare system, according to a new research letter.
The VA-funded report, published online by the Archives of Internal Medicine, notes that the adjusted percentage of patients with diabetes receiving oral medications who used a thiazolidinedione ranged from 1.4% at the lowest-using of 139 facilities to 25.4% at the highest. In addition, the adjusted percentage of patients receiving insulin who used long-acting analogues ranged from 4% percent to 71.2% across the VA.1
Those results were surprising because, according to a research letter summary, “The Department of Veterans Affairs (VA), the largest integrated health care system in the United States, may serve as a model of efficient use of prescription drugs. It consistently ranks among the top of all US health care systems in objective ratings of quality of care for chronic diseases, and it does so with low medication costs. The VA negotiates steep price discounts with pharmaceutical manufacturers and engages in robust formulary management using a national formulary.”
The authors, led by Walid Gellad, MD, MPH, of the VA Pittsburgh Healthcare System, suggest that, while formularies “may exert powerful effects on medication choice,” they “can only go so far in standardizing healthcare delivery.”
Researchers looked at two classes of diabetes drugs — thiazolidinediones, including rosiglitazone (Avandia) and pioglitazone (Actos) and long-acting insulin analogs such as detemir (Levemir) and glargine (Lantus) — and their use in about 900,000 patients at VA clinics in 2009. Those patients received about 6.2 million prescriptions for type 2 diabetes during that time period.
“We chose these two classes because of their relatively high cost and lack of clear evidence for improved clinical outcomes relative to other DM medications,” the authors explain. At the time of the study, thiazolidinediones required prior authorization for use, while there were no restrictions on use of long-acting analogues.
According to the study, median use of thiazolidinediones was 8.2%, and median use of long-acting insulins was 40.6%.
The authors write that the variations are “likely driven by local physician norms or preferences about the use of newer drugs, which we were not able to measure.”
An invited commentary from Timothy Wilt, MD, MPH, of the Minneapolis VA, and Amir Qaseem, MD, PhD, of the American College of Physicians, says the findings show “considerable challenges” must be overcome to improve diabetes care.2
“Variability in medication prescribing is inevitable and likely warranted, thiazolidinediones and long-acting insulin analogs have a therapeutic role in some patients, given that medication risk profiles, patient characteristics, and ability to achieve glycemic targets vary,” they write.
Wilt and Qaseem also indicate that the study did not control for some confounding variables, such as HbA1c levels, and did not address local or regional restrictions on use of certain drugs.
“Despite these limitations,” they conclude, “their findings demonstrate the considerable challenges that must be overcome to improve DM care.”
For example, “Patients should also have information and be empowered to ask their physicians whether more testing and treatment and use of more expensive therapies are beneficial and what are the clinical and financial trade-offs,” Wilt and Qaseem point out in their commentary, entitled, “Implementing High-Value, Cost-Conscious Diabetes Mellitus Care Through the Use of Low-Cost Medications and Less Intensive Glycemic Control Target.”
Earlier this year, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) issued a new position statement regarding glycemic control, which aligns closely with the VA/DoD Clinical Practice Guidelines for the Management of Diabetes Mellitus.3
The VA/DoD Guidelines support an HbA1c target of less than 7% for younger patients with uncomplicated diabetes and a goal of less than 8% for those who have had the disease more than 10 years, have comorbid conditions and require a combination of medications including insulin to manage hyperglycemia. The VA/DoD guidelines recommend a range of 8%-9%, although it says aggressive glucose management is unlikely to benefit patients with advanced microvascular complications or major comorbid illness or a life expectancy of less than five years.4
Since 2006, ADA guidelines have provided an algorithm for selection of drug therapies to manage hyperglycemia, but the 2012 statement moves away from a rigidly prescriptive approach toward one that focuses not only on the patients’ pathophysiology and preferences but also on the risk/benefit profile of specific therapeutic agents.
As a result of the approval of new drugs, heightened awareness of side effects and growing uncertainty about the impact of intensive glycemic control on macrovascular complications, “glycemic management in type 2 diabetes mellitus has become increasingly complex and, to some extent, controversial,” the position statement authors note.
The more flexible guidance also reflects the realities of treatment-adherence factors: price, side effects, patient attitudes and convenience.
For cost and efficacy reasons, metformin remains the preferred first-line drug for most patients. After that, the course of treatment could vary widely.
Unless metformin is contraindicated, the ADA guidelines state that newly diagnosed patients with HbA1c:
- Below 7.5% who are also highly motivated be encouraged to implement lifestyle changes for three to six months to try to reach target levels prior to initiating pharmacotherapy, generally with metformin.
- Below 9.0% (or lower, if unmotivated to follow diet and exercise recommendations) immediately start on metformin, in most cases.* Above 9% be started on two noninsulin agents or insulin.
- Between 10% and 12% be seriously considered for insulin therapy from the outset.
- If treatment with metformin does not sufficiently reduce HbA1c after about three months, practitioners are advised to proceed to a two-drug therapy, considering the benefits, side effects and risks of each medication, which are detailed in the position statement. (If metformin is contraindicated or not tolerated, a drug from the following categories should be selected initially.) With no order of preference, a combination therapy could include:
- Thiazolidinediones (TZD)
- Oral dipeptidyl peptidase-4 (DPP-4) inhibitors
- Injectable glucagon-like peptide-1 (GLP-1) receptor agonists
- Insulin (usually basal)
- Other drugs with more modest efficacy, as appropriate in special circumstances
The addition of a second drug should lower HbA1c by an additional 1%. If no response is seen in three months and adherence is good, the second drug should be discontinued and another with a different mechanism of action should be selected. If a two-drug combination does not or no longer achieves the glycemic target, a third drug with a complementary mechanism of action could be added. At this point, however, the authors advise that insulin probably will generate the best response. If a three-drug combination without insulin is tried, it should be closely monitored to avoid hyperglycemia.
1. Gellad W, Mor M, Zhao X, Donohue J, Good C. Variation in Use of High-Cost Diabetes Mellitus Medications in the VA Healthcare System. Arch Intern Med. 2012 Oct 8:1-2. doi: 10.1001/archinternmed.2012.4482. [Epub ahead of print] PubMed PMID: 23044980.
2. Wilt TJ, Qaseem A. Implementing High-Value, Cost-Conscious Diabetes Mellitus Care Through the Use of Low-Cost Medications and Less Intensive Glycemic Control Target: Comment on “Variation in Use of High-Cost Diabetes Mellitus Medications in the VA Healthcare System.” Arch Intern Med. 2012 Oct 8:1-2. doi: 10.1001/2013.jamainternmed.203. [Epub ahead of print] PubMed PMID: 23044715.
3. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Medical management of hyperglycemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203. http://care.diabetesjournals.org/content/32/1/193.long
4. VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus. 2010. http://www.healthquality.va.gov/diabetes_mellitus.asp