A Step Ahead Towards
Better Health
Beginning Insulin Treatment of Obese Patients
with Evening 70/30 Insulin plus
Glimepiride versus Insulin Alone

This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued Glimepiride with insulin alone.

Research designs and methods:
This was a multi-center ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulphonylureas who took Glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180–300 mg/dl (10–16.7 mmol/l) on this treatment were randomized to placebo + insulin (PI) or glimepiride + insulin (GI) for 24 weeks. A dosage of
70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120
mg/dl (6.7 mmol/l), equivalent to F.P.G 140 mg/dl (7.8 mmol/l). Outcome measures included
FPG, HbA1 c, insulin dosage, weight, serum insulin and lipids, and adverse events.

FPG and HbA1 c were equivalent at baseline:
261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24 weeks, the FPG (fasting plasma glucose) target was achieved in both groups (136 vs.138 mg/dl, 7.6 vs. 7.6 mmol/l), and HbA1 c values were equal (7.7 vs. 7.6%). However, with GI,control improved faster and fewer subjects dropped out (3 vs. 15%, P 0.01), and less insulin was needed (49 vs. 78 U/d, P 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia.

Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.

Sulfonylurea + Insulin:
Sulfonylurea treatment of type 2 diabetes undergoes secondary failure at rate between 5 and 20% yearly (1,2). Consequently, initially effective treatment with a sulfonylurea commonly fails within 5 years. Early results of the U.K. Prospective Study of treatments of type 2 diabetes show that secondary failure is not limited to sulfonylureas,but occurs at similar rates with diet and metformin as well. Thus, type 2 diabetes is progressive combinations of treatments are routinely needed, and insulin often becomes necessary when oral agents fail.
Unfortunately, beginning insulin may be considered problematic for obese patients with type 2 diabetes, and marked hyperglycemia may be permitted before insulin is started.
The present study examined whether this way of starting insulin can be applied to the situation in which most patients with type 2 diabetes actually are treated. Instead of using a fixed dose of insulin or titrating the dose to the point of hypoglycemia, physicians more often start with a low dose and increase it gradually, seeking moderate control.

In this study, insulin was started at 10 U/day and increased 5 or 10 U weekly based on the subjects daily FBG tests until the target value of 120 mg/dl was reached.
The study’s design was a balance of simplicity, simulating conditions of clinical practice, and allowing enough glucose testing (twice daily) and contact with study personnel (weekly phone contact and monthly visits) to permit evaluation of both the adverse effects and the effectiveness of these tactics.
The subjects selected were likely to have relatively difficult-to-control diabetes, being quite obese and with very high FPGs on glimepiride alone.

The effectiveness of combining an evening injection of insulin with a sulfonylurea when sulfonylurea a monotherapy fails has been documented previously. A study of mildly obese subjects found that adding a fixed dose of 20 U NPH insulin at bedtime while continuing 20 mg glipizide twice daily reduced FPG to 144 mg/dl (8 mmol/l) and HbA1 c to 7.6% (7).
This HbA1 c value was 2.1% lower than that obtained with the same dose of insulin plus placebo. In the same study, increasing the insulin dosage as much as possible without hypoglycemia reduced FPG to 113 mg/dl (6.3 mmol/l) and HbA1 c to 7.1%, 1.2% lower than with insulin alone.

In summary:
The efficacy of evening-insulin therapy in a common clinical situation. It demonstrated that, for obese patients not
responding to full doses of glimepiride, slowly titrating suppertime 70/30 insulin based on patient-measured FBG safely
restores acceptable glycemic control either in combination with continued glimepiride or by itself.
"Combined therapy restored glycemic control more rapidly and with lower doses of insulin".
Combined therapy with glimepiride plus suppertime 70/30 insulin is a safe effective treatment for obese patients with type 2 diabetes not well controlled by a sulfonylurea alone.



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