Ideas and Opinions
Individualizing Glycemic Targets in Type 2 Diabetes Mellitus:
Implications of Recent Clinical Trials
Faramarz Ismail-Beigi, MD, PhD; Etie Moghissi, MD; Margaret Tiktin, NP; Irl B. Hirsch, MD; Silvio E. Inzucchi, MD; and Saul Genuth, MD
One of the first steps in the management of patients with type 2
diabetes mellitus is setting glycemic goals. Professional organiza-
tions advise setting specific hemoglobin A1c (HbA1c) targets for
patients, and individualization of these goals has more recently
been emphasized. However, the operational meaning of glycemic
goals, and specific methods for individualizing them, have not been
well-described. Choosing a specific HbA1c target range for a given
patient requires taking several factors into consideration, including
an assessment of the patient’s risk for hyperglycemia-related com-
plications versus the risks of therapy, all in the context of the overall
clinical setting. Comorbid conditions, psychological status, capacity
for self-care, economic considerations, and family and social sup-
port systems also play a key role in the intensity of therapy. The
individualization of HbA1c targets has gained more traction after
recent clinical trials in older patients with established type 2 diabetes
P atients with type 2 diabetes mellitus are well-known to
have an increased risk for atherosclerotic cardiovascular
disease (CVD) and microvascular complications. The re-
sults of recent large multicenter trials in patients with es-
tablished type 2 diabetes mellitus (1–3) have confounded
the optimization of therapeutic approaches to prevent these
sequelae. Our purpose is to present a framework for setting
a glycemic target range for an individual patient in the
outpatient setting. This article represents our perspective
and should not be taken as the view of any entity or
organization.
Table 1 (4 –7) summarizes the major outcomes of 4
large trials conducted in patients with type 2 diabetes mel-
litus. The UKPDS (United Kingdom Prospective Diabetes
Study) (4) tested the effect of more versus less intensive
glycemic control in middle-aged patients (mean age, 53
years) with newly diagnosed type 2 diabetes mellitus. The
results, similar to those of the DCCT (Diabetes Control
and Complications Trial) (8) in patients with type 1 dia-
betes mellitus, demonstrated that intensive therapy delayed
the onset and reduced the progression of albuminuria and
retinopathy but did not decrease the risk for myocardial
infarction (MI). A 10-year observational follow-up of the
DCCT (9) found a reduced rate of MI, despite hemoglo-
bin A1c (HbA1c) values that converged at approximately
8.0% after 2 years.
See also:
Web-Only
Conversion of graphics into slides
554 © 2011 American College of Physicians
Annals of Internal Medicine
mellitus failed to show a benefit from intensive glucose-lowering
therapy on cardiovascular disease (CVD) outcomes. The limited
available evidence suggests that near-normal glycemic targets
should be the standard for younger patients with relatively recent
onset of type 2 diabetes mellitus and little or no micro- or macro-
vascular complications, with the aim of preventing complications
over the many years of life. However, somewhat higher targets
should be considered for older patients with long-standing type 2
diabetes mellitus and evidence of CVD (or multiple CVD risk fac-
tors). This review explores these issues further and proposes a
framework for considering an appropriate and safe HbA1c target
range for each patient.
Ann Intern Med. 2011;154:554-559. www.annals.org
For author affiliations, see end of text.
The findings of the UKPDS contrast with epidemio-
logic data (10) that show an exponential increase in CVD
events as a function of increasing HbA1c. Three large, mul-
ticenter trials (1–3), conducted in older patients (aged 60
to 66 years) with well-established type 2 diabetes mellitus
and either multiple risk factors or a previous CVD event,
tested whether even more intensive glucose control would
reduce CVD risk. The ACCORD (Action to Control Car-
diovascular Risk in Diabetes) trial (1) tested the effect of
intensive versus standard glycemic control (HbA1c ⬍6.0%
vs. 7.0% to 7.9%) on CVD events. The intensive glycemic
control in this 5-year trial was stopped after an average of
3.5 years of follow-up because of increased all-cause and
CVD-related mortality with no reduction in the primary
outcome (a composite of nonfatal myocardial infarction,
nonfatal stroke, and CVD death). The ADVANCE (Ac-
tion in Diabetes and Vascular Disease: Preterax and Dia-
micron Modified-release Control Evaluation) trial (2) as-
sessed the effect of decreasing HbA1c to 6.5% or less on
vascular outcomes. The VADT (Veterans Affairs Diabetes
Trial) (3) enrolled participants (97% men) with poorly
controlled type 2 diabetes mellitus. It assessed CVD out-
comes from reducing HbA1c to less than 6.0% versus 8%
to 9%. Although the ADVANCE trial and the VADT
found no increase in mortality, they also reported no ben-
eficial effect of intensive glucose control on their composite
macrovascular outcomes. In addition, weight gain and 2-
to 3-fold higher rates of severe hypoglycemia occurred with
intensive glycemic treatment. In contrast with the CVD
findings, all 4 trials reported that intensive glycemic con-
trol had positive effects on various microvascular out-
comes, with prevention of albuminuria being common to
all. More intensive control also improved retinopathy and
 Setting Glycemic Targets in Type 2 Diabetes Mellitus Ideas and Opinions

Table 1. Selected Characteristics and Outcomes of the UKPDS, ACCORD Trial, ADVANCE Trial, and VADT

Variable UKPDS ACCORD Trial ADVANCE Trial VADT References

Duration of study, y 11 3.5 5 5.6 1–4

Goal 1–4
Intensive therapy FPG ⬍6.0 mmol/L HbA1c ⬍6.0% HbA1c ⱕ6.5% HbA1c ⬍6.0%
(⬍108.1 mg/dL)
Standard therapy FPG ⬍15.0 mmol/L HbA1c, 7.0%–7.9% Standard HbA1c values HbA1c, 8.0%–9.0%
(⬍270.3 mg/dL)

HbA1c achieved, % 1–4

Intensive therapy 7.0 6.4 6.4 6.9
Standard therapy 7.9 7.5 7.0 8.5

Change in achieved HbA1c, % 0.9 1.1 0.6 1.6 1–4

Annual event rates per 100 patients

Severe hypoglycemia* 1–4
Intensive therapy 0.71† 4.6† 0.56† 12.0†
Standard therapy 0.20 1.5 0.30 4.0
Primary outcome‡ 1–4
Intensive therapy 4.09† 2.11 3.62† 4.39
Standard therapy 4.60 2.29 4.00 4.89
All-cause mortality 5
Intensive therapy 0.13 1.41† 1.86 2.22
Standard therapy 0.25 1.14 1.99 2.06
Cardiovascular mortality 5
Intensive therapy 0.53 0.79† 0.95 0.83
Standard therapy 0.52 0.56 1.08 0.63
Retinopathy§ 1–4, 6
Intensive therapy 0.79† 1.83† 6.0 4.0
Standard therapy 1.10 2.60 6.3 5.7
Visual deterioration㛳 1–4, 6
Intensive therapy 3.44† 4.84 10.9 3.03
Standard therapy 4.16 5.05 10.8 3.95
Neuropathy¶ 1–4, 7
Intensive therapy 2.33† 2.51† 8.44 6.86
Standard therapy 2.77 2.84 8.30 7.14
Renal failure** 1–4, 7
Intensive therapy 0.08 0.57 0.4 2.0
Standard therapy 0.08 0.59 0.6 1.8
Renal failure and retinopathy†† 4, 7
Intensive therapy 0.86† 2.35 – –
Standard therapy 1.14 2.35
Microalbuminuria‡‡ 1, 3, 4, 7
Intensive therapy 2.13† 3.38† 4.74† 1.73
Standard therapy 2.82 4.14 5.14 2.35
Macroalbuminuria‡‡ 1, 3, 4, 7
Intensive therapy 0.49† 0.73† 0.58† 0.52†
Standard therapy 0.72 1.05 0.82 0.91

ACCORD ⫽ Action to Control Cardiovascular Risk in Diabetes; ADVANCE ⫽ Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-release Control
Evaluation; FPG ⫽ fasting plasma glucose; HbA1c ⫽ hemoglobin A1c; UKPDS ⫽ United Kingdom Prospective Diabetes Study; VADT ⫽ Veterans Affairs Diabetes Trial.
* An episode that requires third-party assistance.
† P ⬍ 0.05 compared with standard glycemic therapy.
‡ An aggregate end point of any diabetes-related end point (UKPDS); a composite of nonfatal myocardial infarction, nonfatal stroke, and fatal myocardial infarction and
stroke (ACCORD); combined microvascular and macrovascular disease (ADVANCE); and time to occurrence of a composite of major cardiovascular events (VADT).
§ Nine-year results (UKPDS), worsening of ⱖ3 steps in fundus photographs (ACCORD), new or worsening retinopathy (defined as development of proliferative retinopathy,
macular edema, or photocoagulation therapy or diabetes-related blindness) (ADVANCE), or progression to proliferative retinopathy (VADT).
㛳 Two-line (UKPDS, ADVANCE, and VADT) or 3-line (ACCORD) change in visual acuity.
¶ Nine-year results (UKPDS), loss of sensation to light touch (10-g monofilament) (ACCORD), new or worsening neuropathy (ADVANCE), or peripheral neuropathy
(VADT).
** Dialysis or plasma creatinine level ⬎250 ␮mol/L (⬎2.8 mg/dL) not related to acute intercurrent illness (UKPDS); initiation of dialysis, end-stage renal disease, renal
transplantation, or increase in serum creatinine level to ⬎292 ␮mol/L (⬎3.3 mg/dL) in the absence of an acute reversible cause (ACCORD); need for renal replacement
therapy or death from renal causes (ADVANCE); or creatinine level ⬎265 ␮mol/L (⬎3.0 mg/dL) (VADT).
†† A composite of retinopathy, photocoagulation, vitreous hemorrhage, and fatal or nonfatal renal failure (UKPDS and ACCORD).
‡‡ Nine-year results (UKPDS).

neuropathy outcomes in both the UKPDS and the AC-
CORD trial (4, 6, 7).
These findings have clinicians pondering the clinical
implications of these trials, the role of intensive glucose
control in prevention of complications, how to balance the
potential benefits of intensive glycemic control against its
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risks in an individual patient, and how to arrive at an
appropriate glucose target for a specific patient. These
questions are posed in the context of published guidelines
from professional groups with different HbA1c goals,
which are largely based on the results of older clinical trials
and epidemiologic data. Each organization discusses the
19 April 2011 Annals of Internal Medicine Volume 154 • Number 8 555
Ideas and Opinions Setting Glycemic Targets in Type 2 Diabetes Mellitus
importance of individualizing glycemic goals but provides
little guidance on how this should be done.
Establishing an individualized goal requires the con-
sideration of 2 sets of variables, clinical characteristics and
the psychosocioeconomic setting— both of which are spe-
cific to each patient. Although we discuss clinical charac-
teristics first, the psychosocioeconomic setting often plays a
determining role in setting glycemic targets (11, 12). Of
note, some of our recommendations are based on clinical
judgment, rather than strong evidence; these may be
viewed as being overly conservative, but we prefer to err on
the side of safety.
CLINICAL CHARACTERISTICS
Comorbid Conditions
Significant comorbid conditions may limit survival or
be debilitating, and they may also interfere with the imple-
mentation of glycemic control strategies. In addition, a
greater disease burden may increase the number of medi-
cations that a patient receives. This can lead to confusion,
errors, poor adherence, increased side effects and cost,
drug– drug interactions, and frustration. Patients with
other medical conditions that are expected to reduce life
expectancy, and thereby shorten the period in which dia-
betic complications can develop, should be targeted to a
higher glycemic range.
Age
Patient age is also an important consideration. The
younger the age at the onset of diabetes mellitus, the
greater the cumulative exposure to hyperglycemia and sub-
sequent risk for complications; the older the age at onset,
the higher the probability of existing comorbid conditions
and the shorter the expected life span. These issues are
increasing in importance, because more patients develop
diabetes mellitus at a younger age and older patients live
longer.
The ACCORD trial reported a trend toward lower
all-cause mortality among participants younger than 65
years at baseline who were randomly assigned to receive
standard treatment (13), whereas the ADVANCE trial re-
ported lower rates of combined major macro- and micro-
vascular events in younger participants in the intensive-
therapy group (2); however, neither finding was statistically
significant. In a VADT substudy (14), younger patients
(aged 57 vs. 64 years) with lower coronary calcium scores
(by computed tomography) at baseline had fewer CVD
events with intensive control. No trial data on patients
younger than 45 years with newly diagnosed type 2 diabe-
tes mellitus are available. However, a near-normal HbA1c
target range seems appropriate for younger patients, who
are unlikely to have established atherosclerosis.
Duration of Diabetes Mellitus
Participants in the UKPDS had newly diagnosed type
2 diabetes mellitus, whereas those in the ACCORD and
556 19 April 2011 Annals of Internal Medicine Volume 154 • Number 8
ADVANCE trials and the VADT had type 2 diabetes mel-
litus for 8.0 to 11.5 years. The long-term follow-up of the
UKPDS showed fewer micro- and macrovascular events as
a result of previous intensive control (9). Participants in
the VADT with established CVD had type 2 diabetes mel-
litus for 2 years longer than those without established
CVD (3). These findings imply (but do not prove) that
intensive treatment is more likely to have benefits the ear-
lier it is begun. This may be especially true in patients with
a family history of premature coronary artery disease.
Presence of Cardiovascular (Macrovascular) Disease
Patients with type 2 diabetes mellitus and a history of
myocardial infarction are at high risk for recurrent events
(15). Among the participants enrolled in the 3 recent trials,
32% to 40% had a history of a CVD event; these partici-
pants had greater mortality. However, intensive treatment
led to no reduction in new CVD events or mortality (1–3).
In the VADT substudy (14), patients with higher coronary
calcium scores (associated with more advanced CVD)
showed no reduction in CVD events with intensive glyce-
mic treatment. These findings imply that a higher HbA1c
target may be more appropriate for such patients.
Presence of Microvascular Disease
The Kumamoto study (16) tested the effect of multi-
ple daily insulin injections versus standard insulin therapy
in Japanese patients with type 2 diabetes mellitus. The
investigators reported that intensive glycemic control de-
creased the progression of albuminuria and retinopathy
that were present at enrollment (secondary prevention).
The recent trials showed modest reductions in progression
of albuminuria (Table 1), and the ACCORD trial found
that intensive control decreased the progression of retino-
pathy (6) and neuropathy but not the composite outcome
of advanced microvascular disease (7). A microvascular
complication in an organ often suggests that other micro-
vascular (and macrovascular) complications may be present
or evolving; more aggressive glycemic control may there-
fore be considered in the presence of microalbuminuria
without elevated serum creatinine levels or in patients with
early retinopathy (6, 7, 16). However, few data indicate
that strict glucose control alters the progression of renal
disease once serum creatinine level is elevated (⬎221
␮mol/L [⬎2.5 mg/dL]). Special precautions are advised in
patients with autonomic neuropathy, who are predisposed
to hypoglycemia unawareness and have increased cardiac
mortality.
History of Severe Hypoglycemia
The biggest impediment to achieving near-normal gly-
cemic control is the increased occurrence of severe hypo-
glycemia (that requiring third-party assistance). Severe hy-
poglycemia occurred approximately 2 to 3 times more
often with intensive therapy in the trials (Table 1) and is
more common in persons with low cognitive function
(17). In older patients with type 2 diabetes mellitus, de-
mentia is associated with episodes of severe hypoglycemia
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 Setting Glycemic Targets in Type 2 Diabetes Mellitus Ideas and Opinions

(18), and such episodes in patients with CVD may also

Figure. Framework to assist in determining glycemic
lead to myocardial ischemia or arrhythmia (19). The
treatment targets in patients with type 2 diabetes.
ACCORD and ADVANCE trials both reported higher
mortality rates in participants with 1 or more episodes of
Most Intensive Less Intensive Least Intensive
severe hypoglycemia (20, 21), although no direct cause-
6.0% 7.0% 8.0%
and-effect relationship was established. For these and other
pragmatic reasons, less intensive HbA1c targets are widely Psychosocioeconomic considerations
accepted as appropriate for patients with recent severe Highly motivated, adherent, Less motivated, nonadherent,
knowledgeable, excellent limited insight, poor self-care
hypoglycemia. self-care capacities, and capacities, and weak
comprehensive support systems support systems

Hypoglycemia risk
PSYCHOSOCIOECONOMIC CONTEXT Low Moderate High
Patient-specific psychological, social, and economic Patient age, y
conditions and underlying capacities for self-management 40 45 50 55 60 65 70 75
play a critical role in setting targets. These issues can be Disease duration, y
explored during a structured and detailed interview with 5 10 15 20

the patient and discussion with family members, as appro-
priate (22). Although many of the topics we discuss seem
self-evident, health care providers who are pressed for time
may not address these critical issues properly. These topics
are not all-inclusive and often overlap. It is important to
remember that the patient must implement the strategy,
and their full understanding and acceptance of the means
of controlling their blood glucose level safely is critical
(22–24).
Safety Concerns and Support Systems
Safety is of paramount importance with the use of any
glycemic control strategy, particularly when drugs with a
higher risk for severe hypoglycemia are being used. Safety
is often related to living conditions and family support
systems (25); for example, a highly intensive target would
be inappropriate for an insulin-treated patient who lives
alone and has no routine daily check made by family,
friends, or neighbors. Patient education and health coach-
ing may also have positive effects on patient empower-
ment, self-care, and outcomes (23, 24).
Adverse Effects of Medications
Adverse effects can include weight gain and hypogly-
cemia associated with the use of insulin or sulfonylureas;
weight gain, edema, heart failure, and fractures associated
with thiazolidinediones; or gastrointestinal side effects of
metformin and certain incretin-based drugs. Drug reac-
tions increase in frequency with the use of multiple medi-
cations. Because intensive glycemic targets usually require
polypharmacy, the risk– benefit ratio of adding another
medication to reduce blood glucose level requires careful
consideration.
Psychological and Cognitive Status
Diabetes mellitus is a chronic disease that requires life-
long lifestyle modification and ongoing medical manage-
ment. Depression, which is often present in patients with
type 2 diabetes mellitus, limits the successful attainment of
goals (26). Loss of cognitive function is amplified in pa-
tients with type 2 diabetes mellitus who have mild clinical
or subclinical cerebrovascular disease or concomitant Alz-
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Other comorbid conditions
None Few or mild Multiple or severe
Established vascular complications
None Cardiovascular disease
None Early microvascular Advanced microvascular
Glycemic goals and treatment intensities are shown in terms of increas-
ing severity or magnitude of clinical variables, as well as with limitations
set by the psychosocioeconomic context. Greater height of a triangle
indicates increased clinical concern about the considered variable. If a
patient’s position on the various triangles is widely disparate, the treat-
ment target should be determined by the farthest-right position. As al-
ways, sound clinical judgment should prevail in these circumstances. The
location of the triangles in the figure is not meant to represent their
relative importance in setting glycemic targets. The depicted targets as-
sume stable outpatient treatment protocols. Depending on the set glyce-
mic target range for any given patient, the target range may have to be
decreased (for example, for a patient in the intensive care unit with an
acute infection) or increased (for example, for a patient admitted for
acute renal injury) for various periods. Note that although hemoglobin
A1c and mean blood glucose levels have a strong positive correlation in
populations, this relationship varies substantially at an individual level
and across certain populations (for various medical, nonmedical, and
unknown reasons) among both glucose levels at a given hemoglobin A1c
value and hemoglobin A1c values at a given average blood glucose level
(30). A hemoglobin A1c value represents the mean effect of glycation
reaction on hemoglobin over 2 to 3 months, whereas blood glucose levels
obtained by fingersticks give a more accurate picture of glycemic control
on a day-to-day basis.
heimer disease. A Mini-Mental Status Examination to as-
sess cognitive function may be an important component of
the clinical evaluation of patients with type 2 diabetes
mellitus (27).
Economic Considerations
The cost of certain treatment methods, especially
newly marketed medications and glucose test strips, may be
prohibitive for many patients. Glycemic control can often
be achieved with older, commonly available, and less ex-
pensive medications, but patients may feel that they are
receiving inferior treatment. In addition, all-cause mortal-
ity rates for patients with type 2 diabetes mellitus are
higher among lower socioeconomic groups (28). A careful
discussion of this psychologically and socially sensitive is-
sue is important before finalizing goals.
19 April 2011 Annals of Internal Medicine Volume 154 • Number 8 557
Ideas and Opinions Setting Glycemic Targets in Type 2 Diabetes Mellitus

Table 2. Proposed Approximate HbA1c Targets Determined by Clinical Characteristics (in the Absence of Severe Hypoglycemia)*

Age Duration of Diabetes Complications Treatment Intensity

Mellitus (HbA1c Target)†
Macrovascular Microvascular
⬍45 y Any None and None or early Most intensive (ⱕ6.5%)
Any Established and/or Advanced Less intensive (⬃7.0%)
45–65 y Short‡ None and None or early Intensive (6.5%–7.0%)
Long§ None and None or early Less intensive (⬃7.0%)
Any Established and/or Advanced Not intensive (7.0%–8.0%)
⬎65 y Short‡ None and None or early Less intensive (⬃7.0%)
Long§ None and None or early Not intensive (7.0%–8.0%)
Any Established and/or Advanced Moderated (⬃8.0%)㛳
⬎75 y or infirm at any age Any Any and/or Any Moderated (⬃8.0%)㛳

HbA1c ⫽ hemoglobin A1c.

* This is a summarized and highly simplified version of the text, with each of the depicted categories encompassing large segments of the population with type 2 diabetes
mellitus. Patient characteristics should be considered sequentially from left to right. For example, for a person aged 43 years who has had diabetes for 6 years and had a
myocardial infarction 3 years ago, we recommend a less intensive target of approximately 7%, regardless of microvascular complications. Alternatively, the same patient with
no history of cardiovascular disease and few or no microvascular complications could be treated most intensively, if it was otherwise safe. Some of the proposed glycemic
targets, especially the HbA1c target ⱕ6.5%, should be viewed as suggestions and are not based on direct evidence from randomized, controlled trials. “Treatment intensity”
should be applied after consideration of all clinical characteristics and the psychosocioeconomic context, as discussed. Not all patients fit precisely in these categories, and
clinical judgment must be exercised in setting an appropriate glycemic target range for each patient.
† Target blood glucose level should be increased immediately after a severe hypoglycemic episode. In the absence of evidence from controlled trials, we recommend relaxation
of targets by an average of 2.5–3.3 mmol/L (45– 60 mg/dL), or approximately 1.5% to 2.0% of HbA1c, for at least several weeks. A more prolonged relaxation of goals is
indicated after 2 or more episodes, especially if the episodes occur within weeks of each other. The presence of hypoglycemia unawareness necessitates further relaxation of
targets for more prolonged periods, and perhaps permanently. Other serious diseases also necessitate reassessment of the optimal glucose levels. Note that the relationship
between average blood glucose level and HbA1c varies (30).
‡ Approximately 5 to 10 years or less. Numbers are inexact because of the uncertainty of onset of type 2 diabetes mellitus. Our choice of a 5-year threshold is somewhat
arbitrary and is meant to express disease of relatively short duration.
§ Approximately 10 to 20 years or more. Numbers are inexact because of uncertainty of onset of type 2 diabetes mellitus. We chose the 10-year threshold because the average
known duration of type 2 diabetes mellitus among participants in the 3 large, recent trials was approximately 10 years.
㛳 The goal is to lessen the risk for hypoglycemia while reducing the possibility of large glycosuria, water and electrolyte loss, infections, and nonketotic hyperosmolar coma.
We suggest this target because it represents a mean blood glucose level of approximately 10.0 mmol/L (180 mg/dL), at which point, most patients will not be consistently
or significantly glycosuric (30).

Quality of Life CONCLUSION

The ultimate goal of treatment is to enhance both the
short- and long-term quality of life. The variables that play
into this imprecise phrase include those previously dis-
cussed and many others, which vary from patient to pa-
tient and reflect the patient’s needs, desires, and beliefs. Of
note, type 2 diabetes mellitus is associated with a 2- to 3-
times higher prevalence of functional disabilities and co-
morbid conditions, mostly related to CVD and obesity
(29). Sensitivity to these concerns is essential to setting a
target range that is safe, acceptable, and attainable and
ensures patient satisfaction.
SETTING THE GLYCEMIC TARGET RANGE
Setting the target range is a 2-step process, in which
the clinical characteristics are considered and the range is
then amended or modified on the basis of psychosocioeco-
nomic factors. The Figure and Table 2 suggest glycemic
target ranges based on patient clinical characteristics. These
represent oversimplifications of complex medical decision-
making processes. Although most patients fit into the de-
scribed categories, not all are satisfactory matches. Some of the
proposed glycemic goals, especially the target HbA1c range of
6.5% or less, are not supported by evidence from randomized,
controlled trials. As detailed in Table 2, suggested targets
should be relaxed for the short or longer term if severe hypo-
glycemia or serious comorbid conditions are present.
558 19 April 2011 Annals of Internal Medicine Volume 154 • Number 8
On the basis of our interpretation of these landmark tri-
als, we advance the following general recommendations for
setting glycemic target ranges. First, in younger persons with
relatively recent onset of type 2 diabetes mellitus, strict glyce-
mic control aimed at a near-normal (or normal) glycemic tar-
get range should be implemented whenever safe and possible,
with the goal of preventing microvascular and macrovascular
complications over the life span (1– 4, 6, 16). Second, in older
persons with established type 2 diabetes mellitus of long du-
ration and evidence of or risk factors for CVD, a more relaxed
target range can be considered (1–3). Finally, the proposed
glycemic target range should then be adjusted on the basis of
the patient’s psychosocioeconomic context.
In summary, the glycemic target range for patients
with type 2 diabetes mellitus should be individualized ac-
cording to age; stage of disease, both in terms of duration
and presence of macro- and microvascular complications;
and propensity for hypoglycemia. In addition, careful con-
sideration must be given to each patient’s capacities, de-
sires, and values, as well as their living situation, support
systems, cognitive status, overall prognosis, and life expec-
tancy. In nearly all circumstances, the patient should be an
active participant in setting goals. Finally, glycemic targets
should not be viewed as fixed goals; they should be flexible
and be adapted to changes in the patient’s health and living
conditions.
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 Setting Glycemic Targets in Type 2 Diabetes Mellitus
From Case Western Reserve University, Cleveland, Ohio; University
of California, Los Angeles, Los Angeles, California; University of
Washington, Seattle, Washington; and Yale University, New Haven,
Connecticut.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline
.org/authors/icmje/ConflictOfInterestForms.do?msNum⫽M10-2380.
Requests for Single Reprints: Faramarz Ismail-Beigi, MD, PhD, De-
partment of Medicine, Case Western Reserve University, 10900 Euclid
Avenue, Cleveland, OH 44122-4951; e-mail, fxi2@case.edu.
Current author addresses and author contributions are available at www
.annals.org.
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19 April 2011 Annals of Internal Medicine Volume 154 • Number 8 559

Current Author Addresses: Drs. Ismail-Beigi and Genuth and Ms. Tik-
tin: Department of Medicine, Case Western Reserve University, 10900
Euclid Avenue, Cleveland, OH 44122-4951.
Dr. Moghissi: 4644 Lincoln Boulevard, Suite 409, Marina Del Rey, CA
90292.
Dr. Hirsch: University of Washington Medical Center, 1959 Northeast
Pacific Street, Seattle, WA 98915-6176.
Dr. Inzucchi: Yale University School of Medicine, 333 Cedar Street,
New Haven, CT 06520.
W-196 19 April 2011 Annals of Internal Medicine Volume 154 • Number 8
Annals of Internal Medicine
Author Contributions: Conception and design: F. Ismail-Beigi,
E. Moghissi, M. Tiktin, S.E. Inzucchi.
Analysis and interpretation of the data: F. Ismail-Beigi, E. Moghissi, I.B.
Hirsch, S.E. Inzucchi, S. Genuth.
Drafting of the article: F. Ismail-Beigi, E. Moghissi, M. Tiktin, I.B.
Hirsch, S. Genuth.
Critical revision of the article for important intellectual content:
F. Ismail-Beigi, E. Moghissi, M. Tiktin, I.B. Hirsch, S.E. Inzucchi,
S. Genuth.
Final approval of the article: F. Ismail-Beigi, E. Moghissi, M. Tiktin, I.B.
Hirsch, S.E. Inzucchi, S. Genuth.
Collection and assembly of data: F. Ismail-Beigi, E. Moghissi.
www.annals.org