Can Diet and Monotherapy Maintain Fasting Blood Glucose and HbA1c at Levels Recommended by Mthe ADA?
Abstract & Commentary
Synoposis: After nine years, only 25% of the patients in the UKPDS 49 could maintain blood glucose and HbA1c levels recommended by the American Diabetes Association.
Source: Turner RC, et al. JAMA 1999;281:2005-2012.
The united kingdom prospective diabetes study (UKPDS 33) has previously confirmed that improved blood glucose control will delay the progress of microvascular complications in patients with type 2 diabetes mellitus.1 The objective of UKPDS 49 was to assess how often various monotherapies and diet alone can achieve the glycemic control targets set by the American Diabetes Association (ADA). (HbA1c levels < 7% and fasting blood glucose [FBG] levels < 140 mg/dL.)
A total of 4075 patients newly diagnosed as having type 2 diabetes mellitus ranging from 25-65 years in age, with a median FBG concentration of 207 mg/dL and a HbA1c level of 9.1%, and who had a mean body mass index of 29 constituted the study group.
After three months on a high carbohydrate, high-fiber diet patients were randomized to therapy with diet alone, insulin, sulfonylureas, or metformin. Each therapeutic agent as monotherapy increased two- to three-fold the proportion of patients who attained a Hba1c level below 7% compared to diet alone. However, the progression of deterioration was such that after three years, approximately 50% of patients could attain this goal with monotherapy, and after nine years this declined to 25%. The majority of the patients need multiple therapies to attain these target levels in the longer term.
Comment by Ralph R. HalL, MD, FACP
It is now deemed important to reach the goals recommended by the ADA since attaining these goals is associated with a marked reduction of microvascular disease. Until now, physicians have avoided multiple drugs hoping to enhance compliance and quality of life. Their patients, however, had HbA1c levels far above the recommended goals.
The situation becomes even more complicated if the patients have hypertension and elevated blood lipids. UKPDS 392 demonstrated that if recommended levels of blood pressure were to be attained, three drugs would be necessary in at least 29% of the patients. Another recent study has shown that only 66% of the patients reach recommended goals for blood lipids when two drugs are used in maximum dosages.3
What is the solution? UKPDS 33 also demonstrated that insulin was not harmful. Perhaps we should use insulin with one other oral drug. Insulin has been shown to work well with metformin. However, metformin usually requires two or more tablets per day when the long-acting sulfonylureas require only one tablet per day. We should strive to use the most powerful of the statin drugs for management of blood lipids and try to increase exercise intensity to a greater degree than we have in the past. Exercise has been successful in lowering both blood glucose and blood lipids and, if used 4-5 times per week, to be effective in weight reduction, which has its own benefits.
There are both short-term quality of life issues (the inconvenience of taking multiple drugs) and long-term quality of life issues, such as the development of microvascular disease and macrovascular disease, to consider.
Until we have better drugs or can have better compliance with weight reduction and exercise, we will need to spend more time with our patients working on both short- and long-term quality of life issues.
References
1. UKPDS 33. Lancet 1998;352:837-853.
2. UKPDS 39. Br Med J 1998;317:713-720.
3. Kanters SDJM. Diabet Med 1999;16:500-508.
After three years, what percent of the patients in the UKPDS study were controlled on monotherapy?
a. 75%
b. 50%
c. 25%
d. 85%
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