Why do pills tend to fail in the end and do they all fail at the same rate?
Pills for type 2 diabetes tend to fail after a period of time because the severity of the diabetes tends to progress. Diabetes is a disorder associated with aging, reduction in physical activity, and increasing body weight. Since all of these things tend to progress with time, it is not surprising that the severity of the diabetes tends to progress and the response to pills that were previously effective tends to be diminished.
Not only this, but there appears to be a normal aging-related decline in the ability of the pancreas to make insulin that is steeper in those with diabetes. Since one is presently unable to prevent this or prevent aging from occurring, the only factors that are controllable to prevent progression of the diabetes are weight and exercise, and these are notoriously difficult to manage with consistent success. Therefore, it is not surprising that many people with type 2 diabetes tend to require more and higher doses of pills over time and that many eventually fail to be controlled on pills alone.
The pills do not all tend to fail at the same rate. The sulfonylurea drugs and metformin (see Questions 41 and 52 for a description) tend to fail at a rate of about 5% of patients who were previously controlled on them per year. Thus, after 10 years, half of the patients taking these drugs initially successfully will no longer be controlled on them. However, there is encouraging news from some of the newer types of pills for diabetes.
It appears as if the medications of the TZD class and possibly the DPP-IV inhibitor class (see Questions 41 and 52 for a description) may actually modify the course of the diabetes itself and slow its progression. The TZD type of drugs acts to improve the body’s response to the insulin it produces, while the DPP-IV inhibitor class may act to restore the health of the insulin-producing cells of the pancreas.
Whether these types of drugs are able to achieve these improvements in a long-term manner, such that patients on them will not require insulin or other drugs by injection at all, remains to be shown by long-term studies.