Postponing the Addition of Insulin

Summarized by Robert W. Griffith, MD
May 17, 2007

Summary

A study of the times at which type 2 diabetic patients add insulin to a sulfonylurea-metformin drug combination shows maximal doses of medications are often not used, and starting insulin therapy is often delayed for long periods, both of which add to the risk of diabetic complications.

Introduction

Type 2 diabetes is a progressive disease, so that it normally requires some escalation of medication to keep it under control. The benefits of good control are well proven, and as soon as lifestyle modifications fail to maintain this control, either a sulfonylurea or metformin are prescribed. When a single drug fails, the other one is usually added, so that many type 2 diabetics are maintained on a combination of a sulfonylurea, such a glyburide, and metformin. Unfortunately this combination, too, is likely to fail after a time, in spite of dosage escalation.

Despite inadequate glucose control, many patients (and their physicians) are often reluctant to escalate to insulin injections. This means they may have long periods of unnecessarily high HbA1c levels, or an increased 'glycemic burden'.¹ The magnitude of this problem has been investigated by Kaiser Permanente researchers, and their results are published in the Journal of General Internal Medicine.

What was done

The data for the study came from the Kaiser Permanente Northwest health maintenance organization. Type 2 diabetes patients who started on a sulfonylurea-metformin combination treatment between 1996 and 2000 were enrolled. They were followed until insulin was added to their treatment, or until they left the health plan, or died.

During the time of the study, the guidelines in place for treating type 2 diabetes recommended sulfonylurea as first line treatment, followed by metformin when necessary, and then insulin when the HbA1c exceeded 8%. For this analysis, patients who left the health plan before they had received the sulfa-metformin combination treatment for 6 months were excluded, as were those given a third oral antidiabetic agent before getting insulin, or who didn't have HbA1c determinations during the critical periods. These restrictions left 3,891 patients' information for analysis.

Using an HbA1c level of 8% as the goal of treatment, three measures of 'failure' were made: 1. the number of months subjects spent above the goal before starting insulin (or follow-up ended); 2. the level the HbA1c reached before insulin was started; 3. the glycemic burden, expressed by the HbA1c level above 8% x the months over 8% (thus one month at 9% would be equal to 10 months at 8.1%).

Patients were classified into 3 groups: 1. those who reached and maintained their HbA1c goal; 2. those who reached but failed to maintain their goal; 3. those who never reached their goal.

What was found

The average age of the subjects was 60; the average follow-up was 4½ years. Almost one-fifth of the subjects (18%) failed to reach their HbA1c goal; they were, on average, younger than the rest (54 years). A quarter (24%) reached and maintained their goal; their last observed dose levels of both metformin and sulfa drugs were lower than in the two classes who failed to maintain their goal HbA1c.

The majority of subjects - 2,241 or 57% - reached but failed to maintain their goal. On average, these patients continued on combined sulfa-metformin medication for nearly 3 years, accruing a glycemic burden equivalent to 32 months of an HbA1c of 9%. And the 18% of subjects who never attained their goal continued with the combination therapy for an average of 30 months, reaching HbA1c levels of 10%.

For those who attained but failed to maintain 8% HbA1c levels it took about 5 years for half of them to start insulin; for those who never reached the 8% goal it took 2 years before half of them had started insulin.

Less than half the patients were taking them maximum doses of either their sulfonylurea or metformin medication, suggesting that dose adjustments might have improved glycemic control.

What these findings mean

The study shows that over 80% of the type 2 diabetics included achieved the goal of an HbA1c of 8% or below, but most of them were unable to maintain that goal; they continued on the oral meds combination for an average of 3 years before adding insulin, in spite of the guidelines in existence. This means they were exposed to a risk of potentially avoidable serious diabetic complications.

Of course, there are other options when a sulfa-metformin combination fails - the addition of another oral agent, such as a thiazolidinedione (e.g. rosiglitazone, pioglitazone). This particular study did not include an analysis of this approach, as there were few cases. It's generally considered that, in spite of such options for alternative oral medications, many patients will eventually require insulin; it's the nature of this progressive disease.

This study shows that patients with type 2 diabetes are often not treated with maximal doses of effective oral medications and that the institution of insulin therapy is often delayed for quite long periods. Improved patient and physician education, as well as improved communications between both parties, should result in improved glycemic control, and, therefore, fewer complications of the disease.

Source

• Delay of insulin addition to oral combination therapy despite inadequate glycemic control. GA. Nichols, YH. Koo, SN. Shah , J Gen Intern Med , 2007, pp. 453--458

Footnotes
1. HbA1c is shorthand for a type of hemoglobin, the oxygen-carrying element in red blood cells. (Hb stands for hemoglobin, and A1c is the designation of the subtype.) It's important because glucose binds to HbA1c and is only released very slowly, so that the HbA1c represents the average blood glucose level over the previous 4 weeks. It's a better measure of the degree of diabetes than isolated blood sugar determinations.

Related Links
American Family Physician: Insulin for Type 2 Diabetes
UK National Health Service: Insulin in Type 2 Diabetes
Mayo Clinic: Treatment of Diabetes

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