VOLUME 10 NUMBER 4 • NOVEMBER 2013
147
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REPORT
and GLP-1A. An ADA/EASD/IDF statement
released 28 June 2013 found that there is
insufficient information to modify current
treatment recommendations for GLP-1A.
Initiating insulin in the world of
incretins: when is the right time?
Prof Stefano Del Prato, Department of
Endocrinology and Metabolism, University
of Pisa, Italy
Insulin, if used in the proper manner, should
allow for best HbA
1c
control in hypothetical
situations; yet defining the right time to ini-
tiate insulin therapy poses great difficulty.
Prof Del Prato questioned whether insulin
therapy is already inappropriately delayed.
Clinical inertia is a major contributor to this
delay, due to an unbalanced assessment
of hypoglycaemia, weight gain, chronic
hyperinsulinaemia and limited understand-
ing of the role functional beta-cell mass
loss plays in disease progression. Another
confounding factor is physician concerns
and underestimation of the patient’s toler-
ance for regular testing and injections.
Translating these considerations into the
real-world setting, Prof Del Prato presented
results from the A
1
chieve study. This global
cohort of more than 66 000 participants
saw approximately 45 000 patients initiated
on insulin during the course of the study.
In terms of glycaemic efficacy, a reduction
in HbA
1c
level of 2.1% was seen from base-
line to 24 weeks, with 30–35% of patients
achieving target at 24 weeks.
There was no significant difference in
hypoglycaemia between baseline and 24
weeks, and a weight gain of 100 g was
seen over this period. Weight gain was
dependant on the type of insulin used.
Insulin detemir was equated with an
increased weight-loss trend, whereas the
other insulin formulations were associated
with weight gain. In terms of self-assessed
quality of life, a significant improvement
was reported over the study period.
Prof Del Prato considered criteria for
selection of insulin or a GLP-1A as poten-
tial treatment in the patient failing met-
formin. Insulin is the therapy of choice in
those with high HbA
1c
levels; in the patient
with a focus on body weight reduction, a
GLP-1A is more appropriate. There may,
however, be some logic in combining the
two agents, as there are many synergies
between the function of insulin and the
GLP-1 receptor agonists. The primary effect
of decreased fasting glucose is gained from
both agents.
Decreased inter-prandial glucose is seen
with basal insulin; and GLP-1A use effects
decreased fasting glucose. Mechanisms
of action shared by both agents include
decreased hepatic glucose production and
decreased glucagon secretion. Other mech-
anisms of basal insulin are increased insulin
concentration and increased non-glucose-
dependant endogenous insulin; whereas
GLP-1A has the benefit of increased glucose-
dependant insulin secretion and increased
satiety, with decreased food intake and
delayed gastric emptying.
In his closing statements, some indi-
cations for initiation of insulin were con-
sidered. ‘If the patient is symptomatic at
the time of diagnosis, initiate with insulin
therapy. When HbA
1c
level is under control,
with improved well-being of the patient,
halt the insulin and introduce a different
agent. Then, as disease progression occurs,
insulin can be reinitiated in the patient with
improved expectations and experience.’
Minimising adverse treatment out-
comes: weight, hypoglycaemia and
treatment adherence
Prof Stefano Del Prato, Department of
Endocrinology and Metabolism, University
of Pisa, Italy
Prof Del Prato opened his second presen-
tation with the thought that a conserva-
tive approach to management of diabetes
leads to clinical inertia. In support of this
statement, he illustrated a typical timeline
of the diabetic patient between diagno-
sis and pro-active HbA
1c
control: diet and
exercise are therapy of choice for the ini-
tial two-and-a-half years. During this time,
the HbA
1c
level increases and the patient is
initiated on an oral agent as monotherapy.
Glycaemic control worsens and the oral
agent dose is up- titrated, until the addi-
tion of a second oral agent is required in
combination therapy. Upon failure of com-
bination therapy, basal insulin is added to
the regimen.
The average time period between diag-
nosis and insulin initiation is eight years,
representing an eight-year period of avoid-
able glycaemic burden. Furthermore, insulin
initiation at this late stage of disease pro-
gression generally has a high rate of com-
plications, with 30% of patients displaying
prior cardiovascular disease by this stage.
A proactive approach to diabetes man-
agement is recommended by Prof Del Prato,
whereby individual targets are set at diag-
nosis and reacted to if not achieved. In this
manner, long-term outcomes are improved,
with fewer complications. Insulin should be
considered an interventional option through-
out the timeline of diabetes disease progres-
sion, and Prof Del Prato questioned why it is
not being more commonly used. Concerns
surrounding insulin use are hypoglycaemia,
weight gain and adherence to therapy.
In terms of hypoglycaemia, the peak
plasma concentration of insulin detemir is
preferable to that of NPH insulin, with the
advantage of fewer overall and nocturnal
hypoglycaemic events. ‘Weight worry’ is a
common psychological barrier preventing
initiation of insulin therapy. It has been pos-
tulated that with insulin use, a 1% decrease
in HbA
1c
level equates to a weight gain of
2 kg. Insulin glargine has a neutral effect on
body weight. Insulin detemir activates cere-
brocortical
β
-activity in overweight humans
and may therefore have some potential to
condition appetite.
Data from A
1
chieve suggest that switch-
ing to insulin detemir from NPH insulin or
glargine is associated with a greater reduc-
tion in HbA
1c
level, as well as a greater
proportion of patients achieving target.
The switch to detemir also resulted in
small weight loss. Adherence is a consid-
erable problem in the management of
type 2 diabetes, with approximately two-
thirds of patients taking < 80% of doses.
It is postulated that a 10% improvement
in adherence translates to an additional
0.15% reduction in HbA
1c
level. Minimising
hypoglycaemia and weight gain are effec-
tive measures to improve adherence.
Hypoglycaemia: diving, driving and
flying
Dr Angela Murphy, endocrinologist
Presenting existing data on the effects of
hypoglycaemia on driving, diving and flying,
Dr Murphy drew the following conclusions.
Hypoglycaemia does affect driving
performance, with a trend that diabetic
patients have increased risk for motor vehi-
cle accidents, but accidents caused directly
by diabetics are rare. Generally, there are no
restrictions placed on the driving of private
vehicles. However, requirements for com-
mercial driving include a 24-month review
to establish that no hypoglycaemia has
