News & Analysis
Medical News & Perspectives
For Patients With Type 2 Diabetes,
What’s the Best Target Hemoglobin A1C?
Jennifer Abbasi
M
edical organizations are at odds
over new guidance that recom-
mends easing hemoglobin A1C
(HbA1c) targets for patients with type 2 dia-
betes. The updated guidance statement
from the American College of Physicians
(ACP), which focuses on glycemic control
with medications, says clinicians should per-
sonalize goals and aim to achieve an HbA1c
level of between 7% and 8% for most pa-
tients with type 2 diabetes.
The ACP set its target higher than rec-
ommended by other prominent health
groups. The American Diabetes Associa-
tion (ADA) generally recommends an HbA1C
goal of less than 7%, while the American As-
sociation of Clinical Endocrinologists (AACE)
advises even tighter control of 6.5% or lower
if it can be achieved safely.
The HbA1c test provides an estimate of
the blood glucose level over the prior 2 to 3
months and is widely used in clinics. A nor-
mal HbA1c level in people without diabetes
is less than 5.7%.
In evaluating the clinical trial evidence for
intensive HbA1c targets with pharmacologi-
cal therapy, the ACP committee weighed ben-
efits of reducing the risk of microvascular and
macrovascular complications against ad-
verse effects, treatment burdens, and costs
before issuing its controversial guidance.
Amir Qaseem, MD, PhD, vice president
for clinical policy at the ACP, said the orga-
nization created the new guidance state-
ment to help its members sort through con-
flicting HbA1c targets advised by different
professional groups. With 152 000 mem-
bers, the ACP is the largest US medical spe-
cialty organization and is composed mainly
of primary care internists, who regularly see
patients with diabetes.
The ACP’s guidance statement, pub-
lished in the Annals of Internal Medicine, is a
quality analysis of 6 existing guidelines from
other US and European health organiza-
tions and a summary of the 5 “treat to tar-
get” clinical trials and follow-up studies fre-
quently cited in them. The statement’s 6
authors each independently reviewed and
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scored the guidelines using an established
evaluation instrument that takes into ac-
count factors including rigor of develop-
ment, stakeholder involvement, and edi-
torial independence.
The highest scoring US guideline, from
the Department of Veterans Affairs and the
Department of Defense, emphasizes shared
decision making and suggests target ranges
rather than a fixed target level. The AACE
guideline scored lowest, with none of the 6
ACP panelists saying they would recom-
mend its use, and the ADA guideline came
in second from last.
Withindaysofthenewguidancebeingre-
leased, the ADA and AACE, along with the
American Association of Diabetes Educators
and the Endocrine Society, said they “strongly
disagree” with the higher targets in a joint
press release. The groups also disagree with
the ACP’s new guidance to deintensify phar-
macological treatment for patients whose
HbA1c value is persistently less than 6.5%.
“Ourbiggestconcernisthatifwegointhis
direction,we’rereallysendingthewrongmes-
sage,” AACE President Jonathan Leffert, MD,
Am
er
ic
an
C oll
ege o f
c i at i o n o f C l i
A sso nic
an
ic
er
Am
told JAMA. “We really should be trying to be
more aggressive about what we do for people
who have diabetes, not less aggressive.”
A Fine Balance
Critics of the ACP’s new recommendations
worry that the benefits of tight glycemic con-
trol could be lost with relaxed targets. In the
UK Prospective Diabetes Study (UKPDS), the
Action in Diabetes and Vascular Disease:
Preterax and Diamicron MR Controlled
Evaluation (ADVANCE) trial, and the Action
to Control Cardiovascular Risk in Diabetes
(ACCORD) Eye Study, tighter blood glucose
targets were associated with reduced
microvascular complications, and follow-
up studies demonstrated that the benefits
of previous intensive targets can persist
through a “legacy effect.”
But according to the ACP’s analysis, the
main benefit of intensive glycemic control in
people with type 2 diabetes is small abso-
lute reductions in the risk of surrogate mi-
crovascular events “such as retinopathy
detected on ophthalmologic screening
or nephropathy defined by development or
ns
ia
s ic
Phy
al
En
do
cr
Am
ino
er
log
ic
an
ists
Di
ab on
etes at i
Associ
(Reprinted) JAMA Published online May 30, 2018 E1
 News & Analysis

progression of albuminuria.” Although it’s cial and financial support. “We have to be tients,” Cefalu said. “We agree that there are
possible that improvements in these end very mindful about the trade-offs in the ben- certain patients at high risk [for hypoglyce-
points may translate to fewer serious clini- efits versus the harms on quality of life,” mia], for which you have to relax control and
cal outcomes down the road, like blind- Lipska said. individualize therapy. Our association has
ness, kidney failure, or amputations, there is In the not-so-distant future, however, been saying that for years. We just don’t
uncertainty around this, according to Kasia newer diabetes drugs and devices could shift agree that this is most patients.”
Lipska, MD, an endocrinologist at the Yale the balance of benefits and harms. But most patients with type 2 diabetes
School of Medicine and a clinical investiga- “Today, we have a lot of tools—medica- aren’tyoungandhealthy,Qaseemargues.Only
tor at the Yale–New Haven Hospital Center tions and monitoring, including continuous around 3 million of the estimated 23 million
for Outcomes Research and Evaluation. glucose monitoring devices—which are much adults with diagnosed diabetes are younger
“A lot of these studies show that albu- more able to increase the intensification and than 45 years, and 10 million are 65 years or
min levels in the urine go down or the ap- decrease the risks,” Leffert said. older. More than half of people with diabetes
pearance of the [retina] improves on the eye According to William T. Cefalu, MD, the have at least 1 other chronic condition.
exam, but it’s very hard to find evidence that ADA’s chief scientific, medical, and mission Above all, Qaseem said, the ACP guid-
you reduce the risk of dialysis or reduce the officer, glucose-lowering sodium-glucose ance emphasizes personalized goals. He said
risk of blindness,” said Lipska, who was not cotransporter 2 inhibitors and glucagon- HbA1c targets lower than 7% may be appro-
involved with the ACP guidance statement. like peptide-1 receptor agonists have been priate in a small number of healthy patients
At the same time, intensive glycemic shown in recent trials to reduce cardiovas- who are expected to live at least 15 more years
control can pose serious risks. The best ex- cular risk and mortality and are associated and “who understand and [are] willing to take
ample of this comes from the ACCORD trial, with a low risk of hypoglycemia and favor- the risk of significant harms for possible small
which compared the effects of standard and able effects on weight. benefits of pharmacological treatment.” Pa-
intensive therapy on cardiovascular events “We feel that an individual who has dia- tients who can achieve tight glycemic con-
in patients with type 2 diabetes. betes can benefit from one of these agents trol with diet and lifestyle modifications alone
One year in, the intensive therapy if they have underlying cardiovascular dis- should be encouraged to do so, he added.
group achieved a median HbA 1c level of ease,” Cefalu said. “The [ACP] guidance did Yet Leffert fears that physicians and pa-
6.4% compared with 7.5% in the standard not really account for the newer medica- tients will settle for less based on the new
therapy group. At the 3.5-year mark, pa- tions and that’s one of the concerns.” recommendations. “What will happen is that
tients receiving intensive therapy fared no The ADA has already incorporated these we’ll get this lack of intensification in pa-
better in terms of major cardiovascular newer medication classes into their diabe- tients who already have poor control over
tes standards of diabetes,” he said. “My sense is that when the
care but, accord- patients get to 8.5 or 8.3 or 8.2 and we have
ing to Qaseem, this target of between 7 and 8, then the phy-
“Perhaps the fact that these guidelines
the ACP com- sician and the patient will stop there.”
disagree is actually good for the mittee did not To Schneider, however, the ACP’s guid-
discourse and for clinicians to realize factor them in to ance doesn’t feel like a major shift from the
its analysis be- ADA’s advice, which says less intensive
there is no one right answer,” cause they have therapy may be appropriate in some pa-
Kasia Lipska, MD yet to be evalu- tients, such as those with a history of severe
atedintrialswith hypoglycemia, extensive comorbidities, or
events but had an increased risk of severe treat-to-target strategies. The ACP’s guid- limitedlifeexpectancy.Alloftheavailableclini-
hypoglycemia and higher cardiovascular and ance could be updated in the future if clear cal guidance statements, he points out, rec-
all-cause mortality, leading the investiga- evidence of benefits outweighing harms at in- ommend individualized HbA1c goals.
tors to end the trial early. tensive targets emerges for these drugs, Experts agree that the best HbA1c tar-
“Overtreatment is real,” said Benjamin which are also more expensive than older get for a patient with diabetes is a person-
Schneider, MD, an assistant professor of fam- treatments, Qaseem said. alized one.
ily medicine at Oregon Health and Science “What we’re really arguing about is a
University who did not work on the ACP Personalization Is Key small change in the approach,” Schneider
guidance statement. Although he has wit- Patients with new-onset diabetes who are said. “Having arguments about it between
nessed the consequences of long-standing on the younger side and otherwise healthy different specialty societies is hard on pa-
hyperglycemia in his patients, he has also may be most likely to benefit from early, tight tients and hard on physicians that are hav-
seen many patients struggle with the con- glycemic control. It’s this group of patients ing these conversations on a daily basis.”
sequences of hypoglycemia. that the ADA and AACE are most con- Lipska sees some benefit to the de-
The efforts to reach an HbA1c of less than cerned about in terms of relaxed targets, es- bate: “Perhaps the fact that these guide-
7% can also result in overburdened pa- pecially with a projected increase of new- lines disagree is actually good for the dis-
tients with a poor quality of life, Lipska said. onset type 2 diabetes and increasing course and for clinicians to realize there is no
This can be especially true for patients who incidence in younger age groups. one right answer.”
are managing multiple chronic conditions “Our concern is that relaxing the guide- Note: Source references are available through
and medications, sometimes with limited so- lines may not be appropriate in most pa- embedded hyperlinks in the article text online.

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