[acb-diabetics] interesting study

Thu Sep 9 23:40:00 GMT 2010

This article originally posted 

02 September, 2010

 and appeared in  

Medication, 

Type 2 Diabetes, 

Issue 537

Intensive Glucose Lowering Therapy -- Weighing the Evidence

A review of two intensive therapies to lower blood glucose levels in newly
diagnosed Type 2 patients.

Advertisement 

A study by Lingvay 

et al. has compared two intensive therapies to lower blood glucose levels in
patients with newly diagnosed Type 2 diabetes. The findings reveal the
efficacy

and safety of both insulin and triple oral therapy. 

To achieve optimal glycemic control is of prime importance in the prevention
of long-term cardiovascular complications of Type 2 diabetes, but the level

of control required and the methods used to achieve this control are
controversial. Insulin therapy is mostly advised for patients with
inadequate glycemic

control after treatment with oral antidiabetic agents. Adverse effects, such
as weight gain and hypoglycemic episodes, however, are a great concern,
which

frequently delays the start of this treatment. Insulin therapy is at present
not advocated for patients with newly diagnosed Type 2 diabetes, and
treatment

algorithms currently recommend diet and exercise in combination with or
without administration of metformin. A new study by Lingvay et al. examines
two

regimens of intensive therapy -- insulin and triple oral therapy -- in
patients with newly diagnosed Type 2 diabetes. Insulin therapy was as safe
and as

effective as oral therapy in the achievement of glycemic control, treatment
compliance, treatment satisfaction and quality of life improvement. The
investigators

suggest, therefore, that insulin should be considered as a first-line
treatment for Type 2 diabetes.

The study was a randomized, open-label trial designed to compare treatment
of 58 drug-naive patients with newly diagnosed Type 2 diabetes with either
insulin

plus metformin or with triple oral therapy. The improvement in glycemic
control seen in this trial was marked: HbA

1c

 levels dropped from 10.8% to 5.9% in the 3-month lead-in period, during
which time all participants received insulin plus metformin. After the
lead-in

period, patients either continued treatment with insulin plus metformin or
were switched to triple oral therapy, which consisted of glibenclamide,
metformin

and pioglitazone. Glycemic control was maintained at around 6% in both
treatment groups throughout the 3 years of the trial. Treatment with triple
oral

therapy did not alter HbA

1c

 levels compared with insulin plus metformin treatment and no progressive
deterioration of glycemic control could be detected in either group. The
investigators

attribute this finding to a reduction in glucose toxicity as a result of the
initial insulin treatment. Furthermore, rates of hypoglycemia were low in

both groups and comparable.

The study to some extent is comparable to the 3-year data from the United
Kingdom Prospective Diabetes Study (UKPDS). The UKPDS also showed that good
glycemic

control can be achieved and maintained with insulin or oral agents in the
first years after treatment is initiated. Notably, glycemic control
eventually

deteriorated in both treatment groups. This result was attributed to
progressive β-cell failure, which is recognized as part of the natural
progression

of Type 2 diabetes. The maintenance or improvement of β-cell function is
desirable in the treatment of Type 2 diabetes, and to date no treatment
regime

has been associated with long-term β-cell preservation. Further follow-up of
the study will hopefully assess β-cell function in both treatment groups,

and preservation of β-cell function in response to either treatment will be
of great interest.

The benefits of tight glycemic control are increasingly controversial, and
although long-term cardiovascular benefits have been demonstrated in the
UKPDS,

none have been found in the short term. The UKPDS follow-up has shown
cardiovascular morbidity and mortality benefits 10 years after completion of
the

study,

 whereas three studies of shorter duration, ACCORD

, ADVANCE, and VADT, did not show any benefit of tight glycemic control on
cardiovascular outcomes. Notably, the ACCORD trial was stopped prematurely
because

of increased mortality in the intensive treatment group of the study. This
finding has led to some anxiety about intensive therapies for Type 2
diabetes

and the possible effects of hypoglycemia, weight gain and medication on
mortality. Analysis of the VADT has shown that the greatest benefit on
cardiovascular

outcomes was seen in patients with diabetes of shorter duration, which
suggests that intensive treatment early on in the disease might be
desirable.

A limitation of the study that needs to be taken into consideration is the
fact that the population of patients analyzed by Lingvay et al. was not
typical

of the majority of newly diagnosed patients seen in clinical practice. The
trial enrolled obese (mean BMI 36 kg/m

2

), young patients (mean age 45 years) with very poor diabetic control at
diagnosis (mean HbA

1c

 levels 10.8%). These patients could represent a highly motivated group of
participants who showed symptoms of Type 2 diabetes at an early stage. These

characteristics do not, however, apply to the majority of newly diagnosed
patients, who are largely asymptomatic in the early years of their illness.
Some

doubts, therefore, remain as to whether the results of Lingvay et al. could
be extrapolated to all patients with Type 2 diabetes.

In clinical practice, to convince patients with Type 2 diabetes to start
daily insulin injections remains one of the greatest challenges. Compliance
and

treatment satisfaction rates were high in both treatment groups in this
study and these levels were maintained over 3 years. Previous studies have
shown

that initiation of insulin therapy is often delayed because of patient
apprehension. In conclusion, thisstudy is a small trial of relatively short
duration

that shows insulin therapy to be a safe and effective treatment for newly
diagnosed Type 2 diabetes and comparable to triple oral therapy. Currently,
neither

of these treatment regimens is recommended for initial treatment of Type 2
diabetes, and although the findings revealed good compliance and
satisfaction

with insulin therapy, caution should be used in the recommendation of
aggressive glucose-lowering strategies. Follow-up of current outcome studies
should

answer some of the important questions on intensive therapies and glycemic
control that remain. How early should we treat? Which agents should we use?

Which patients should be targeted? Is β-cell function preserved by early
intensive treatment? Until these issues have been elucidated, insulin should
remain

an alternative option rather than the preferred first-line treatment in the
management of newly diagnosed Type 2 diabetes mellitus.

Practice Pearls:

Insulin treatment could be as safe and as effective as triple oral therapy
in patients with newly diagnosed Type 2 diabetes mellitus. 

Insulin therapy should be considered as an option rather than the preferred
first-line treatment for newly diagnosed Type 2 diabetes mellitus. 

The benefits of tight glycemic control in Type 2 diabetes mellitus remain
controversial, however, and intensive strategies might be associated with
increased

morbidity and mortality. 

Nat Rev Endocrinol. 2010;6(1):9-10

Publisher's Commentary:

The study concludes that intensive therapy with insulin is effective for
newly diagnosed Type 2's and so is intensive therapy with three oral agents.

Notably, glycemic control eventually deteriorated in both treatment groups.
This result was attributed to progressive β-cell failure, which is
recognized

as part of the natural progression of Type 2 diabetes. The maintenance or
improvement of β-cell function is desirable in the treatment of Type 2
diabetes

mellitus, and to date no treatment regimen has been associated with
long-term β-cell preservation.

Glucose toxicity occurs when blood sugars are above normal. So the question
that comes into play is, "What is normal?" According to many studies, a
normal

A1c is below what we determine as the definition of pre-diabetes which is
from 5.6 to 6.4%. So would an A1c of 5.3% be considered normal without
glucotoxicity?

If we look at young people without diabetes, who are not overweight, the
norm is below 5%, probably about 4.3 to 4.5%.   If betacell failure occurs
when

blood sugars are above normal, which would be most likely below 5%, then
could we prevent betacell failure if we were able to lower blood sugars
below

5%? No studies have been done to aggressively lower A1c's into the normal
range of below 5%. Is it possible that if we remove the glucotoxicity by
having

normal blood sugars that betacells could possibly regain their effectiveness
and requirements for insulin would improve?

Why haven't we seen any studies where the goal is to get to normal blood
sugars? Is it due to the fact that the only way that is possible today is
with

the use of insulin (or major weight loss) and that we have a fear that if we
try to lower the A1c below 6% that hypoglycemia and weight gain might occur?

Could it be that when using industrial doses of insulin the results can be
very unpredictable? Counting carbohydrates is not an accurate science: even
the

manufacturers can be off by 20%. What if just a couple of units of insulin
could be used to control blood sugar levels? The risk for hypoglycemia would

be considerably lower. How can a patient use just a few units of insulin? If
they reduced their intake of carbohydrates their requirements for insulin

would be reduced. This would allow for more predictability in insulin dosing
and for reduction of A1c levels closer to normal without the risk of
hypoglycemia.

Send me your comments at 

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This article originally posted 02 September, 2010 and appeared in  

Medication, 

Type 2 Diabetes, 

Issue 537

Intensive Glucose Lowering Therapy -- Weighing the Evidence

A review of two intensive therapies to lower blood glucose levels in newly
diagnosed Type 2 patients.

Advertisement 

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News and Information for Medical Professionals 

Sign up for our 

complimentary

weekly e-journal  

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Search Diabetes In Control 

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All Articles This Week | 

Next 

This article originally posted 

02 September, 2010

 and appeared in  

Medication, 

Type 2 Diabetes, 

Issue 537

Intensive Glucose Lowering Therapy -- Weighing the Evidence

A review of two intensive therapies to lower blood glucose levels in newly
diagnosed Type 2 patients.

Advertisement 

A study by Lingvay 

et al. has compared two intensive therapies to lower blood glucose levels in
patients with newly diagnosed Type 2 diabetes. The findings reveal the
efficacy

and safety of both insulin and triple oral therapy. 

To achieve optimal glycemic control is of prime importance in the prevention
of long-term cardiovascular complications of Type 2 diabetes, but the level

of control required and the methods used to achieve this control are
controversial. Insulin therapy is mostly advised for patients with
inadequate glycemic

control after treatment with oral antidiabetic agents. Adverse effects, such
as weight gain and hypoglycemic episodes, however, are a great concern,
which

frequently delays the start of this treatment. Insulin therapy is at present
not advocated for patients with newly diagnosed Type 2 diabetes, and
treatment

algorithms currently recommend diet and exercise in combination with or
without administration of metformin. A new study by Lingvay et al. examines
two

regimens of intensive therapy -- insulin and triple oral therapy -- in
patients with newly diagnosed Type 2 diabetes. Insulin therapy was as safe
and as

effective as oral therapy in the achievement of glycemic control, treatment
compliance, treatment satisfaction and quality of life improvement. The
investigators

suggest, therefore, that insulin should be considered as a first-line
treatment for Type 2 diabetes.

The study was a randomized, open-label trial designed to compare treatment
of 58 drug-naive patients with newly diagnosed Type 2 diabetes with either
insulin

plus metformin or with triple oral therapy. The improvement in glycemic
control seen in this trial was marked: HbA

1c

 levels dropped from 10.8% to 5.9% in the 3-month lead-in period, during
which time all participants received insulin plus metformin. After the
lead-in

period, patients either continued treatment with insulin plus metformin or
were switched to triple oral therapy, which consisted of glibenclamide,
metformin

and pioglitazone. Glycemic control was maintained at around 6% in both
treatment groups throughout the 3 years of the trial. Treatment with triple
oral

therapy did not alter HbA

1c

 levels compared with insulin plus metformin treatment and no progressive
deterioration of glycemic control could be detected in either group. The
investigators

attribute this finding to a reduction in glucose toxicity as a result of the
initial insulin treatment. Furthermore, rates of hypoglycemia were low in

both groups and comparable.

The study to some extent is comparable to the 3-year data from the United
Kingdom Prospective Diabetes Study (UKPDS). The UKPDS also showed that good
glycemic

control can be achieved and maintained with insulin or oral agents in the
first years after treatment is initiated. Notably, glycemic control
eventually

deteriorated in both treatment groups. This result was attributed to
progressive β-cell failure, which is recognized as part of the natural
progression

of Type 2 diabetes. The maintenance or improvement of β-cell function is
desirable in the treatment of Type 2 diabetes, and to date no treatment
regime

has been associated with long-term β-cell preservation. Further follow-up of
the study will hopefully assess β-cell function in both treatment groups,

and preservation of β-cell function in response to either treatment will be
of great interest.

The benefits of tight glycemic control are increasingly controversial, and
although long-term cardiovascular benefits have been demonstrated in the
UKPDS,

none have been found in the short term. The UKPDS follow-up has shown
cardiovascular morbidity and mortality benefits 10 years after completion of
the

study,

 whereas three studies of shorter duration, ACCORD

, ADVANCE, and VADT, did not show any benefit of tight glycemic control on
cardiovascular outcomes. Notably, the ACCORD trial was stopped prematurely
because

of increased mortality in the intensive treatment group of the study. This
finding has led to some anxiety about intensive therapies for Type 2
diabetes

and the possible effects of hypoglycemia, weight gain and medication on
mortality. Analysis of the VADT has shown that the greatest benefit on
cardiovascular

outcomes was seen in patients with diabetes of shorter duration, which
suggests that intensive treatment early on in the disease might be
desirable.

A limitation of the study that needs to be taken into consideration is the
fact that the population of patients analyzed by Lingvay et al. was not
typical

of the majority of newly diagnosed patients seen in clinical practice. The
trial enrolled obese (mean BMI 36 kg/m

2

), young patients (mean age 45 years) with very poor diabetic control at
diagnosis (mean HbA

1c

 levels 10.8%). These patients could represent a highly motivated group of
participants who showed symptoms of Type 2 diabetes at an early stage. These

characteristics do not, however, apply to the majority of newly diagnosed
patients, who are largely asymptomatic in the early years of their illness.
Some

doubts, therefore, remain as to whether the results of Lingvay et al. could
be extrapolated to all patients with Type 2 diabetes.

In clinical practice, to convince patients with Type 2 diabetes to start
daily insulin injections remains one of the greatest challenges. Compliance
and

treatment satisfaction rates were high in both treatment groups in this
study and these levels were maintained over 3 years. Previous studies have
shown

that initiation of insulin therapy is often delayed because of patient
apprehension. In conclusion, thisstudy is a small trial of relatively short
duration

that shows insulin therapy to be a safe and effective treatment for newly
diagnosed Type 2 diabetes and comparable to triple oral therapy. Currently,
neither

of these treatment regimens is recommended for initial treatment of Type 2
diabetes, and although the findings revealed good compliance and
satisfaction

with insulin therapy, caution should be used in the recommendation of
aggressive glucose-lowering strategies. Follow-up of current outcome studies
should

answer some of the important questions on intensive therapies and glycemic
control that remain. How early should we treat? Which agents should we use?

Which patients should be targeted? Is β-cell function preserved by early
intensive treatment? Until these issues have been elucidated, insulin should
remain

an alternative option rather than the preferred first-line treatment in the
management of newly diagnosed Type 2 diabetes mellitus.

Practice Pearls:

Insulin treatment could be as safe and as effective as triple oral therapy
in patients with newly diagnosed Type 2 diabetes mellitus. 

Insulin therapy should be considered as an option rather than the preferred
first-line treatment for newly diagnosed Type 2 diabetes mellitus. 

The benefits of tight glycemic control in Type 2 diabetes mellitus remain
controversial, however, and intensive strategies might be associated with
increased

morbidity and mortality. 

Nat Rev Endocrinol. 2010;6(1):9-10

Publisher's Commentary:

The study concludes that intensive therapy with insulin is effective for
newly diagnosed Type 2's and so is intensive therapy with three oral agents.

Notably, glycemic control eventually deteriorated in both treatment groups.
This result was attributed to progressive β-cell failure, which is
recognized

as part of the natural progression of Type 2 diabetes. The maintenance or
improvement of β-cell function is desirable in the treatment of Type 2
diabetes

mellitus, and to date no treatment regimen has been associated with
long-term β-cell preservation.

Glucose toxicity occurs when blood sugars are above normal. So the question
that comes into play is, "What is normal?" According to many studies, a
normal

A1c is below what we determine as the definition of pre-diabetes which is
from 5.6 to 6.4%. So would an A1c of 5.3% be considered normal without
glucotoxicity?

If we look at young people without diabetes, who are not overweight, the
norm is below 5%, probably about 4.3 to 4.5%.   If betacell failure occurs
when

blood sugars are above normal, which would be most likely below 5%, then
could we prevent betacell failure if we were able to lower blood sugars
below