DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
44
VOLUME 7 NUMBER 1 • MARCH 2010
Early metformin monotherapy in type 2 diabetes reduces
drug failure: a contemporary clinical practice study
stitution of a second anti-hyperglycaemic
agent or a subsequent rise of HbA
1c
to
7.5% or more.
Primary failure of metformin therapy
occurred in 1 489 patients; a substantial
percentage of the diabetic patients. Primary
failure was regarded as having occurred if
there was evidence of a single metformin
dispensing of less than 90 days, the addi-
tion of a second anti-hyperglycaemic agent
or not reaching an HbA
1c
target of less than
7%. Despite the general efficacy and toler-
ability of metformin, clinicians should take
special note of the possibility of early met-
formin failure.
Of the 1 799 patients who reached an
HbA
1c
of less than 7% on metformin mono-
therapy, 42% experienced secondary fail-
ure within the two- to five-year follow-up
period; a rate of 17% per year. The fac-
tors of a younger age (mid-50s), a longer
duration of diabetes without therapy and
a higher HbA
1c
level at metformin initiation
were associated with a higher failure rate.
These failure rates occurred within a mean
of 17 months of metformin therapy.
Failure was least likely to occur in per-
sons who started metformin sooner and
whose HbA
1c
was lower at the time of ini-
tiating metformin therapy. These were the
only independent factors associated with a
lower rate of treatment failure.
The 42% of metformin initiators who
experienced secondary failure did so within
a mean follow-up period of 27.6 months.
This was a much higher annual failure rate
(17%) in everyday clinical practice than
that seen in clinical trials such as ADOPT (A
Diabetes Outcome Progress Trial),
2
which
was 4% annually.
The authors concluded that metformin
monotherapy might therefore be less dura-
ble in everyday clinical practice than the
recorded experience within the clinical trial
environment.
Brown JB, Conner C, Nichols GA. Secondary
1.
failure of metformin monotherapy in clinical
practice. Diabetes Care, published online 29
Dec 2009.
Kahn SE, Hafner SM, Heise MA, Herman WH,
2.
Holman RR, Jones NP, Kravitz BG,
et al
, for
the ADOPT study group. Glycemic durability
of resiglitazone, metformin, or glyburide
monotherapy.
N Engl J Med
2006;
355
:
2427–2443.
J Aalbers,
Special Assignments Editor
P
rimary metformin failure occurs com-
monlyintreatment-naïvetype2diabetes
patients. The first clinical practice study to
evaluate the benefits of immediate versus
delayed metformin therapy for type 2 dia-
betes using contemporary hyperglycaemic
targets has shown that metformin’s ben-
efits last longer if therapy is initiated within
three months of diagnosis.
1
This is in line
with guideline recommendations of early
metformin therapy and is consistent with
the hypothesis that early initiation of met-
formin preserves beta-cell function.
A finding that was not anticipated was
the high primary failure rate of metformin
where 43% of patients were not able to
reach a target HbA
1c
level of 7% and were
required to be treated with a second agent
within six months of metformin initiation.
This study was conducted in north-
west Oregon in a not-for-profit health
maintenance organisation (HMO) with
sophisticated electronic support and both
an in-house pharmacy and laboratory to
ensure optimal data capture and standa-
rised procedures in everyday clinical prac-
tice.
The 3 552 type 2 diabetic patients were
evaluated on initiated metformin mono-
therapy as their first-ever anti-hyperglycae-
mic drug. Patients were followed up for
two to five years, until they experienced
secondary failure of metformin therapy.
This was defined as the addition or sub-
Take-home message
Clinicians should initiate metformin
therapy early in type 2 diabetes and
monitor effectivity of therapy early
and regularly, with an expectation
that both primary and secondary
failure rates will be higher than those
occurring in the research and clinical
trial environment.
sibly fluvastatin enhance warfarin activ-
ity, while the effects of pravastatin are
likely to be unpredictable.
Agents that reduce the anti-
coagulant efficacy of warfarin
These include antacids (non-absorbable),
antihistamines (many), antipsychotics
(many), barbiturates, carbamazepine, chlor-
diazepoxide, cloxacillins, griseofulvin, mep-
robamate, oral contraceptives, phenytoin,
rifampins, selective oestrogen receptor
modulators, spironolactone, St John’s wort,
thiouracils, trazodone, Ubiquinone (coen-
zyme Q), vitamin C (high dosage), vitamin
K, and food items rich in vitamin K.
Sinxadi P, Blockman M. Warfarin resistance.
1.
Cardiovasc J Afr
2008;
19
: 215–217.
Warfarin: a dautingly interactional medication.
2.
Cardiovasc J Afr
2007;
18
: 397–398.
J Aalbers,
Special Assignments Editor
