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DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Drug Trends
New incretin agents offer opportunity to improve care for type 2
diabetes
T
he best partner to metformin and lifestyle
changes in the early treatment of type 2
diabetes is an incretin analogue or a DPP-4
inhibitor. Prof Stephan Jacob, director of the
Institute for Cardiometabolic Medicine, Vil-
lingen, West Germany, presented this view at a
recent symposium sponsored by Astrazeneca.
In support of his views, he referred to
two large studies on treatment for type 2
diabetes in general practice. The UK General
Practice study, with 15 years of follow up of
some 91 000 patients with type 2 diabetes,
investigated the risk of myocardial infarction,
congestive heart failure and all-cause mortal-
ity associated with the prescription of oral anti-
diabetes drugs.
1
Metformin monotherapy as the advocated
first-line therapy for type 2 diabetes was used
as the comparator to the other oral agents.
‘The findings of a significant excess risk with
both first- and second-generation sulphonyl-
ureas (24–61%) raises questions about our
current approaches’, Dr Jacob noted.
Another example of how poorly we are
doing, and indicating opportunities to do
better is highlighted in another general practice
study,
2
which covers some 22 years of observa-
tions with 50 000 type 2 diabetes patients. Dr
Jacob pointed out that this retrospective study
related HbA
1c
levels in patients to survival,
based on concerns about the safety of aiming
for lower levels of HbA
1c
in the ACCORD study.
This study compared two cohorts of
patients. One, where therapy was intensified
from monotherapy to combination therapy
(chiefly sulphonylureas) (28 000 patients), was
compared with the other, whose subjects had
changed to regimens that included insulin
(20 000 patients). All-cause mortality, adjusted
for age, gender, smoking status, cholesterol,
cardiovascular risk and general morbidity, was
the primary outcome.
The results of the combined cohorts showed
a U-shaped association, with the lowest HbA
1c
levels at about 7.5%. Both lower and higher
HbA
1c
levels had higher hazard ratios, associ-
ated with increased all-cause mortality and car-
diac events. Insulin-based regimens had a 50%
higher incidence of mortality after correction
for other factors.
‘So, therapy directed safely to lower-
ing HbA
1c
levels is not necessarily improving
outcomes. Clearly, the incretins offer a very
exciting way to lower glucose without caus-
ing hypoglycaemic events – the occurrence of
which is also associated with higher mortality’,
Dr Jacobs noted.
These new agents offer a number of other
advantages, such as reduced weight gain, or
weight loss, and no interaction with lifestyle
interventions. ‘While we do not yet have out-
come data for these agents, we know that in
the case of saxagliptin, safety data are solid’,
Dr Jacob concluded.
J Aalbers, Special Assignments Editor
1.
Tzoulaki,
et al
. Risk of CV disease and all-cause
mortality among patients with type 2 diabetes
prescribed oral antidiabetes drugs.
Br Med J
2009;
e-pub doi:10.1136/bmjb4731.
2.
Currie CJ,
et al
. Survival as a function of HbA
1c
in
people with type 2 diabetes: a retrospective cohort
study.
Lancet
2010;
375
(9713) 481–489.
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