Practice Update: Endocrinology | Volume 1. Number 2. 2016

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JOURNAL SCAN
Teenage girls with type 1 diabetes have poorer metabolic control than boys
and face more complications in early adulthood
Journal of Diabetes and Its Complications
Take-home message
• The goal of this study was to evaluate differences in metabolic control
between adolescent males and females with type 1 diabetes. Investigators
categorised HbA1c values into three groups: < 7.4% (57 mmol/mol); 7.4% to
9.3% (57–78 mmol/mol); and > 9.3% (78 mmol/mol). Females were over-
represented in the highest HbA1c group (51.7% vs 46.2% expected) and
underrepresented in the lowest HbA1c group (34.2%; P < 0.001). As young
adults, females were more likely to have retinopathy (P < 0.05). Increased
HbA1c values in females compared with males were seen at diagnosis (11.2%
vs 10.9%) and in adolescence (8.5% vs 8.2%), but not as young adults.
• Adolescent females with type 1 diabetes have worse glycaemic control than
males with type 1 diabetes. This difference resolves in young adulthood, but
young adult females have higher rates of retinopathy.
AIMS To compare metabolic control
between males and females with type
1 diabetes during adolescence and as
young adults, and relate it to microvas-
cular complications.
METHODSData concerning 4000 adoles-
cents with type 1 diabetes registered in
the Swedish paediatric diabetes quality
registry, and above the age of 18 years
in the Swedish National Diabetes Reg-
istry was used.
RESULTS When dividing HbA1c values
in three groups; < 7.4% (57 mmol/mol),
7.4–9.3% (57–78 mmol/mol) and >9.3%
(78 mmol/mol), there was a higher
proportion of females in the highest
group during adolescence. In the group
with the highest HbA1c values during
adolescence and as adults, 51.7% were
females, expected value 46.2%; in the
group with low HbA1c values in both reg-
istries, 34.2% were females, P < 0.001.
As adults, more females had retin-
opathy, P < 0.05. Females had higher
mean HbA1c values at diagnosis, 11.2 vs
10.9% (99 vs 96 mmol/mol), P < 0.03,
during adolescence, 8.5 vs 8.2% (69 vs
66 mmol/mol) P < 0.01, but not as young
adults.
CONCLUSIONS Worse glycaemic control
was found in adolescent females, and
they had a higher frequency of mi-
crovascular complications. Improved
paediatric diabetes care is of great im-
portance for increasing the likelihood of
lower mortality and morbidity later in life.
Teenage girls with type 1 diabetes
have poorer metabolic control than
boys and face more complications in
early adulthood. J Diabetes Compli-
cat 2016;30:917–922, Samuelsson U,
Anderzén J, Gudbjörnsdottir S, et al.
EDITORIAL
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EMED081601
EXPERT OPINION
FDA revises recommendation for metformin
use in patients with chronic kidney disease
Dr Silvio Inzucchi, Professor of Medicine at the Yale University School of Medicine in New Haven, Connecticut, discusses
the recent change to the package label for metformin relating to its use in patients with chronic kidney disease.
The US Food and Drug Administration just
recently decided to change the package
label for metformin as related to use in
chronic kidney disease (CKD) patients.1,2 This
was in response to two citizen petitions that
were filed with the agency in 2013, one from our
group. The prior label restricted its use to men
with serum creatinine <1.5 mg/dL and women
with serum creatinine <1.4 mg/dL.
Evidence has emerged over the past 20 years
that the prior guidelines for those with impaired
renal function were overly restrictive and pre-
vented the use of this important, effective, and
cheap medication in hundreds of thousands of
patients in the US. Although lactic acidosis is
a serious and potentially life-threatening condi-
tion, it is actually no more common in patients
prescribed metformin. Moreover, surveys showed
high rates of metformin use in patients with mild
to moderate chronic kidney disease, despite the
earlier FDA guidelines in place since drug ap-
proval in 1995. Despite this fact, lactic acidosis
rates were not observed to have increased. In fact,
when a metformin-treated patient develops lactic
acidosis, it is almost always due to some other
event, such as a major cardiac event or sepsis. So,
metformin is felt to be an “innocent bystander”
in these cases.
Here are the essential changes (very similar to
those in use in the UK):
• Base assessment on eGFR, not serum
creatinine.
• Obtain eGFR before starting metformin and
annually; more frequently in those at risk for
renal impairment (eg, the elderly).
• Metformin can be used when the eGFR is
<60 mL/min but remains contraindicated in
patients with an eGFR <30.
• Don’t start metformin in patients with an eGFR
in the 30–45 range.
• If the eGFR falls <45 in someone on metform-
in, assess the overall benefits and risks before
continuing treatment. Stop metformin if the
eGFR falls <30.
• Hold metformin before iodinated contrast pro-
cedures if the eGFR is 30–60; also if there is
any liver disease, alcoholism, or heart failure;
or if intra-arterial contrast is used. Recheck
the eGFR 48 hours after the procedure; restart
metformin if renal function is stable.
The recent FDA communication certainly does
not mean that the drug can be used in those with
advanced renal disease. It remains a drug abso-
lutely contraindicated when the eGFR is <30.
My only criticism of the new guidelines is that
they do not include recommendations for dose
adjustment in those with an eGFR 30–45. This is
what our group had recommended in two reviews
published on this topic.3,4 Therein we advised that
the dose be cut in half when an eGFR of 45 was
reached to minimise any chance of getting to a
toxic level in patients with that degree of kidney
disease. I’d also caution not to use the drug if
renal function is or expected to become unstable.
This FDA decision is a very important one
for those of us managing patients with type 2
diabetes. It has been estimated that somewhere
around 800,000 to 1.6 million patients will now
be eligible for metformin in the US. Indeed, how
often do we wish we could continue metformin
in someone who’s developed mild CKD? The al-
ternative often is a more expensive and/or riskier
medication. So, I and many of my colleagues are
very enthusiastic about this change.
References
1. Food and Drug Administration. Metformin-containing
drugs: drug safety communication – revised warnings for
certain patients with reduced kidney function. Available
at: www.fda.gov/Safety/MedWatch/SafetyInformation/
SafetyAlertsforHumanMedicalProducts/ucm494829.
htm. Accessed on April 12, 2016.
2. Food and Drug Administration. FDA drug safety com-
munication: FDA revises warnings regarding use of the
diabetes medicine metformin in certain patients with re-
duced kidney function. Available at: www.fda.gov/Drugs/
DrugSafety/ ucm493244.htm. Accessed on April 12, 2016.
3. Lipska KJ, Bailey CJ, Inzucchi SE. Diabetes Care
2011;34:1431-1437.
4. Inzucchi SE, Lipska KJ, Mayo H, et al. JAMA 2014;
312:2668-2675.
Dr Silvio Inzucchi is Professor of
Medicine (Endocrinology); Clinical
Director, Section of Endocrinology;
Director, Yale Diabetes Center;
Director, Endocrinology and
Metabolism Fellowship, Yale
School of Medicine, New
Haven, Connecticut.
EXPERT COMMENTARY
By Prof Sof Andrikopoulos
The FDA’s decision to change the package
label for metformin for its use in patients
with eGFR <60 mL/min (but >30 mL/
min) is a positive one. It’s important to note
that there is no evidence suggesting that using
metformin when eGFR <60 but >30 is harmful
as long as the dose of metformin is titrated, the
patient is closely monitored and the patient’s
kidney function is measured annually. If these
measures are taken, as most endocrinologists
would, then it’s very useful to use metformin.
It’s an effective drug and we know it’s a safe
drug.
I’ve had discussions with the Therapeutic
Goods Administration about changing the pack-
age label of metformin in Australia, in line with
that in the US, and the TGA is currently review-
ing this.
Prof Sof Andrikopoulos is President of the
Australian Diabetes Society, Head of the
Islet Biology and Metabolism Research
Group at the Department of Medicine,
University of Melbourne, Editor-in-Chief
of the Journal of Endocrinology and
Journal of Molecular Endocrinology.
DIABETES
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