Objective: |
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.
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| Insulin: |
| 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.
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| Results: |
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.
|
| Conclusions: |
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.
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| 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.
|
|
Conclusions: |
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.
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| 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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| |
MATTHEW C. RIDDLE, MD
JILL SCHNEIDER, MD
THE GLIMEPIRIDE COMBINATION GROUP |
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