Can J Diabetes 40 (2016) 66–72

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Review

Review of Hypoglycemia in the Older Adult: Clinical Implications

and Management
Mousumi Sircar MD a,c, Ashmeet Bhatia MD a,c, Medha Munshi MD a,b,c,*
a Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
b
Joslin Diabetes Center, Boston, Massachusetts, USA
c
Harvard Medical School, Boston, Massachusetts, USA

a r t i c l e i n f o a b s t r a c t

Article history: The aging of the population is a worldwide phenomenon. The prevalence of diabetes rises with increas-
Received 7 August 2015
ing age, so the personal and financial costs of diabetes in the aging population have become significant
Received in revised form
burdens. In 2012, 104 billion (59%) of the estimated $176 billion in United States healthcare expendi-
15 October 2015
Accepted 16 October 2015 tures attributable to diabetes were utilized by patients older than 65 years of age [American Diabetes
Association (1)]. With improvement in diabetes management and better glycemic control in the general
population, there is an increase in the prevalence of hypoglycemia, which is the complication of the treat-
Keywords:
diabetes ment of diabetes. Older adults with diabetes have a higher risk for hypoglycemia due to altered adap-
geriatric tive physiologic responses to low glucose levels. These patients also have comorbidities, such as cognitive
hypoglycemia and functional loss, that interfere with prompt identification and/or appropriate treatment of hypogly-
older adult cemia. Older adults who suffer from hypoglycemia also have increased risk for falls, fall-related frac-
patient safety tures, seizures and comas and exacerbation of chronic conditions, such as cognitive dysfunction and cardiac
events. Thus, hypoglycemia in the older adult must be proactively avoided to decrease significant mor-
bidity and mortality. Education of the patients and caregivers is important in prevention and treatment
of hypoglycemia. In this article, we discuss the important aspects and unique challenges pertaining to
hypoglycemia in older population. We also highlight the risks, consequences and prevention and man-
agement strategies for hypoglycemia that can be used by healthcare providers caring for older populations.
© 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

r é s u m é
Mots clés :
Le vieillissement de la population constitue un phénomène mondial. La prévalence du diabète augmente
diabète
gériatrique
en fonction de l’âge, de sorte que les coûts personnels et financiers du diabète liés à la population vieillissante
hypoglycémie sont devenus d’importants fardeaux. En 2012, les 104 milliards de dollars (G$) (59%) en soins de santé
personne âgée attribuables au diabète que les É.–U. ont dépensés par rapport à l’estimation prévue de 176 G$ ont servi
sécurité des patients aux patients de plus de 65 ans [American Diabetes Association (1)]. En raison de l’amélioration de la prise
en charge du diabète et de la meilleure régulation de la glycémie de la population générale, on observe
une augmentation de la prévalence de l’hypoglycémie, qui est la complication liée au traitement du diabète.
Les personnes âgées souffrant de diabète sont exposées à un risque plus élevé d’hypoglycémie en raison
de l’altération des réponses physiologiques adaptatives aux faibles taux de glycémie. Ces patients ont
également des comorbidités comme des pertes cognitives et fonctionnelles qui interfèrent avec
l’identification prompte et/ou le traitement approprié de l’hypoglycémie. Les personnes âgées qui souffrent
d’hypoglycémie sont également exposées à l’augmentation du risque de chutes, de fractures liées aux chutes,
de crises épileptiques et de comas et à l’exacerbation de maladies chroniques comme le dysfonctionnement
cognitif et les événements cardiaques. Par conséquent, l’hypoglycémie chez la personne âgée doit être
évitée de manière proactive pour diminuer significativement la morbidité et la mortalité. L’éducation des
patients et la formation des soignants sont importantes pour la prévention et le traitement de l’hypoglycémie.
Dans le présent article, nous traitons des aspects importants et des défis particuliers de l’hypoglycémie

* Address for correspondence: Medha Munshi, MD, 110 Francis Street, LMOB 1B, Boston, Massachusetts 02215, USA.
E-mail address: mmunshi@bidmc.harvard.edu

1499-2671 © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcjd.2015.10.004
 M. Sircar et al. / Can J Diabetes 40 (2016) 66–72 67

dans la population âgée. Nous mettons également l’accent sur les risques, les conséquences et les stratégies
de prévention et de prise en charge de l’hypoglycémie que les prestataires de soins de santé peuvent utiliser
pour intervenir auprès des populations âgées.
© 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Definition and Classification of Hypoglycemia hormone are also released, but these are less critical in terms of
adaptive responses to hypoglycemia.
It is difficult to know the exact prevalence of hypoglycemia
(usually defined as blood glucose levels less than 70 mg/dL or
Age-Related Compromise of the Adaptive Responsive to
3.9 mmol/L) because many different classifications have been used
Hypoglycemia
in studies over the years. In addition, developments in new tech-
nologic methods over the past decades have made changes in how
The responses of a healthy adult to hypoglycemia are lost to
hypoglycemia is determined. Traditionally, hypoglycemia was defined
varying degrees in the adult patient with diabetes and are criti-
as the presence of the Whipple triad, which included 1) low blood
cally lost in the older population (3,4). Increased duration of
glucose; 2) symptoms and signs associated with low blood glucose
diabetes, as well as the effect of aging on the endocrine, neuro-
levels; and 3) resolution of these symptoms and signs by carbohy-
logic and cardiovascular systems is additive to the consequences
drate ingestion. Some studies categorize hypoglycemia as major or
of hypoglycemia in older patients.
minor episodes. Major hypoglycemia typically suggests life-
Aging has an impact on counter-regulation (5,6). In healthy older
threatening levels requiring third-party assistance. Minor hypo-
adults without diabetes, glucose counter-regulation by glucagon as
glycemia, presenting with symptoms such as tachycardia, sweating
well as growth hormone and epinephrine responses to hypogly-
and dizziness can be treated with simple sugars. Minor hypogly-
cemia are impaired through the physiology of aging, effectively
cemic episodes frequently go unrecognized in older adults because
muting the autonomic process, which would have produced symp-
they may present with nonspecific symptoms such as brief epi-
toms in the patient (3,5). Glucose is not properly secreted when its
sodes of lightheadedness or vertigo. However, in frail older patients,
levels fall, which represents loss in pancreatic, renal and hepatic
they can lead to dangerous falls with fractures, decline in quality
processes. This is additive with the autonomic compromise present
of life and increased mortality. Symptomatic vs. silent are other ways
in all patients with diabetes. The brain depends upon renal, hepatic
of classifying hypoglycemia (2). Hypoglycemic unawareness is a
and endocrine regulation of glucose levels and becomes an unfor-
common cause of silent hypoglycemia and is highly prevalent in
tunate victim of dysregulation. When deprived of glucose, which
older adults. Thus, it is important to look carefully for the possi-
is its primary fuel, the particular tasks that are lost are those requir-
bility of unrecognized hypoglycemia in older patients.
ing quick response, multitasking and sustained attention. Even in
a cognitively intact patient, an hour may elapse after hypoglycemia
resolves before the brain is restored to full function (4).
Physiologic Responses to Hypoglycemia
Last, aging physiology also changes the pharmacokinetics of oral
medications and insulin, particularly in regard to drug absorption
In healthy adults, when blood glucose levels fall (usually below
and distribution as well as renal elimination (2). These changes are
70 mg/dL or 3.9 mmol/L), multiple responses are triggered, and
not necessarily predictable due to the differing spectra of renal-
euglycemia is quickly restored. In response to hypoglycemia, insulin
function losses with the physiology of aging, in addition to differ-
secretion from the pancreas will first decrease as the initial response.
ences in body fat and gender.
Next, the pancreas will increase glucagon production as counter-
The age-related compromise in response is detailed in Table 1.
regulation. The liver then detects the decrease in insulin and the
Considering the age-related changes on the neurologic, endo-
increase in glucagon and responds by increasing both glycogenolysis
crine, cardiac, renal and hepatic responses to hypoglycemia, it is clear
and gluconeogenesis. The adrenal glands next produce epinephrine,
that signs and symptoms may not be relied upon in these patients.
which acts on muscle, fat and kidney to decrease glucose clear-
Therefore, a warning may not be provided before a sentinel event
ance. Should glucagon be deficient, this epinephrine response
such as a fall.
becomes particularly significant. The adrenals, along with the periph-
eral nervous system, which detects hypoglycemia, then mediate an
autonomic response via neurotransmitters. Acetylcholine triggers Consequences of Hypoglycemia in Older Adults
hunger and diaphoresis while norepinephrine triggers arousal with
tremor and palpitations. These are the primary life-saving responses Consequences of hypoglycemia in older adults can be cata-
to hypoglycemia. As secondary responses, cortisol and growth strophic. Hypoglycemia can increase the risk for cardiovascular

Table 1
Age-related compromise of the adaptive response to blood glucose <70 mg/dL (3.9 mmol/L)

Normal physiologic response Age-related changes

Glucagon Increased release triggers hepatic increase in Decreased secretion

Neurologic/autonomic
glucose level 50-70 mg/dL
(2.8-3.9 mmol/L)
Glucose level <50 mg/dL (2.8 mmol/L)
Vascular
ACh, acetylcholine; NE, norepinephrine.
glycogenolysis and gluconeogenesis
Adrenal release of epinephrine, peripheral nervous
system-mediated increase in acetylcholine producing
hunger and norepinephrine producing tremor/
diaphoresis and arousal
Increase in arterial elasticity resulting in adaptive cardiac
perfusion during diastole
Decreased epinephrine secretion, decreased ACh/NE release,
possible loss of hunger, tremor, diaphoresis/arousal
Decreased ability to recognize and/or treat hypoglycemic
symptoms
Relatively increased epinephrine secretion
Loss of arterial elasticity, resulting in compromise of perfusion
to both cardiac and neurologic tissue (possibly resulting
emiplegia/coma)
68 M. Sircar et al. / Can J Diabetes 40 (2016) 66–72
events (4). Acute hypoglycemia in patients can promote QT
prolongation, which can predispose patients to life threatening
ventricular arrhythmias. There is also a potentially maladaptive vagal
response, which only increases the chances for ventricular ectopy
(4). It is likely that hypoglycemia is a marker of frailty as well as
multiple comorbidities (7,8).
There is a bidirectional relationship between hypoglycemia and
dementia (9). Hypoglycemia may increase the risk for dementia;
both vascular and Alzheimer disease. On the other hand, patients
with cognitive dysfunction can have difficulty with tasks such as
identification and treatment of low glucose levels and medication
self-administration. In a study of 497,900 veterans older than
65 years of age, dementia and cognitive impairment were inde-
pendently associated with increased risk for hypoglycemia, with
significant odds ratios of 2.42 for dementia and 1.72 for cognitive
impairment (10). Psychomotor retardation co-occurring with cog-
nitive impairment also needs to be considered in those with hypo-
glycemia because this may require caregiver intervention (11). In
addition, some older patients who are cognitively intact may develop
delirium (temporary neurological decline) following acute ill-
nesses, infections or hospitalization, which may put them at risk
for medication errors and hypoglycemia.
Nocturnal hypoglycemia, found in half of overnight blood glucose
profiles in adults (4), can be particularly problematic in older adult
populations. This is particularly the case because these episodes can
be missed by the patients, caregivers and providers. Older adults
frequently suffer from nocturia as well as poor vision, with pos-
sible balance and gait abnormalities. Patients who are already at
risk for falling at night from these factors are placed in further danger
from reduced or absent hypoglycemic awareness.
Other factors that can contribute to hypoglycemia in the elderly
can be alcohol ingestion, exercise, weight loss, renal or liver disease,
fasting or missing meals, as well as multiple daily insulin dosing.
It is commonly noted that the elderly patients often take incor-
rect or higher doses, which may cause hypoglycemia, especially with
insulin. The patients need special individualized education ses-
sions focusing on drug dosing and administration. Care givers also
benefit with such sessions. Patients seem to do better with fewer
medications and easy dosing schedules.
Management of Diabetes in Older Adults with a Focus on
Prevention of Hypoglycemia
Establish appropriate glycemic goals
From clinicians’ perspectives, studies from the 1990s pushed the
physician community toward tighter glycemic control by demon-
strating reduction in long-term complications (12,13). This prac-
tice has led to increased use of insulin earlier in the course of the
disease and to increased risk for hypoglycemia. A recent national
survey of the older adult population in the United States showed
that between 1999 and 2011, the hospital admission rates for hyper-
glycemia decreased by 55%, while those for hypoglycemia decreased
by 9%. So now there are significantly more older adults being admit-
ted to the hospital for hypoglycemia rather than hyperglycemia (14).
These results suggest that the risks and benefits of tight glycemic
control need to be carefully balanced, considering the inherent risks
of treatment in this age group. Hypoglycemia was shown to be more
frequent, of longer duration and more likely to be missed when patients
with glycated hemoglobin (A1C) levels <7% underwent continuous
glucose monitoring (CGM) (15). In a large observational study of more
than 9000 older adults in the United States, severe hypoglycemia requir-
ing third-party intervention was shown to be more frequent when
A1C levels were <42 mmol/mol (<6%) or >75 mmol/mol (>9%) (16).
Mortality was used as an outcome in a longitudinal 22-year study of
adults older than 50 years of age in the United Kingdom. The results
showed that all-cause mortality increased with both low and high
A1C values, showing a U-shaped relationship between A1C values
and the risk for mortality (17). This phenomenon is also supported
by the results of the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) study (7). The higher mortality with low A1C levels is
thought to be secondary to increased risk for hypoglycemia. There-
fore, either continuous glucose monitoring or careful daily logs are
recommended in this population in addition to A1C monitoring.
Most expert opinions and guidelines suggest liberal glycemic
goals based on overall health and life expectancy (11,18). In a recent
consensus report supported by the American Diabetes Association
and the American Geriatrics Society (19), it is recommended that
the glycemic goals should be established based on assessment of
severe comorbidities, cognitive function and functional abilities. In
older adults with few comorbidities and normal cognitive and func-
tional status, A1C <7.5% is recommended. On the other hand, in
patients with end-stage chronic diseases, such as those in long-
term care facilities or moderate-to-severe cognitive dysfunction or
dependency in more than 2 activities of daily living (ADLs), a goal
of A1C levels <8.5% is recommended. For the group of patients with
intermediate health (multiple chronic diseases, mild to moderate
cognitive dysfunction or dependency in more than 2 instrumental
activities of daily living [IADLs]), A1C goals of <8% are recom-
mended. In general, it is important to avoid glucose levels that are
too high or too low in this population. A similar theme is seen in
the guidelines by the Canadian Diabetes Association. In these guide-
lines, A1C levels ≤8.5% are recommended for the older patients with
diabetes who have limited life expectancy, experience episodes of
hypoglycemia and are dependent in their functional capacities. The
Canadian Diabetes Association guidelines also recommend assess-
ment of cognitive function and suggest less stringent A1C level
targets for those with cognitive impairment (20).
It is important to remember that simply liberating the goal of
A1C levels does not protect older patients against the risk for hypo-
glycemia. Testing for A1C levels has several significant limitations
despite its being used as the gold standard for measuring glyce-
mic control. The test is dependent on the normal lifespan of red
blood cells’ being 3 months and reflects average glucose levels over
that time period. However, many common comorbidities in older
adults, such as blood transfusion, anemia/bleeding, renal disease,
erythropoietin deficiency/uremia/acidosis or infections may prolong
or shorten the life spans of red blood cells and can thus affect A1C
levels (21). In these patients, A1C levels may not reflect true gly-
cemia, and if the treatment changes are made based on only A1C
levels, they may lead to overtreatment and hypoglycemia. It is also
important to remember that A1C levels simply reflect mean glucose
levels over the past 90 days, and measurement of A1C levels misses
critical excursions in glucose that occur on a daily basis. A small
study evaluated 40 patients >70 years of age with A1C levels >8%,
with CGM during a 3-day period (22). The results showed that 65%
had at least 1 episode of hypoglycemia, as defined by glucose levels
lower than 70 mg/dL (3.9 mmol/L). In addition, 54% of patients with
hypoglycemic episodes had A1C levels between 8% and 9%, whereas
46% had A1C levels >9%. Most concerning was the fact that glucose
levels dropped to below 50 mg/dL (2.8 mmol/L) in 46% (of a total
of 102 hypoglycemic events). Thus, A1C levels should not be used
as the sole parameter for assessing glycemic control in the elderly.
It is important to check finger-stick glucose readings as well as to
look for comorbidities that may impact A1C values.
Assessment of comorbidities and overall health
The challenge of treating older adults with diabetes without
putting them at high risk for hypoglycemia lies in identifying and
managing other medical comorbidities successfully.
 M. Sircar et al. / Can J Diabetes 40 (2016) 66–72
Impaired cognitive function can increase the risk for hypogly-
cemia in several different ways (23). Patients with cognitive dys-
function may not have the mental capacity to identify or respond
appropriately to symptoms of hypoglycemia. In such cases, diabetic
education would be futile. Therefore, therapy needs to be tailored
appropriately after some type of cognitive evaluation. Cognitive defi-
cits may not be evident during patient interviews without testing
of higher order tasks such as insulin adjustment based on carbo-
hydrate intake. Family members accompanying patients may also
never have seen the patients attempt higher order tasks or may have
developed the habit of caring for the patients and may not be aware
of the true level of cognitive deficiency (4). Short screening tools
to assess cognitive function include the Montreal Cognitive Assess-
ment (MOCA) or the Minicog (24). The clock drawing test is quicker
and can be used to predict difficulty in insulin management if there
is difficulty in administering the MOCA (24). Depression is associ-
ated with difficulty in performing self-care, leading to difficulty in
managing diabetes (25). Although depression may not be directly
associated with risk for hypoglycemia, it may increase the risk if
depressed patients do not eat properly or omit medications from
time to time.
Because self-care is an integral part of diabetes management,
it is important to understand the functional abilities of older patients
before developing treatment plans (2). Functional status may be elu-
cidated by asking patients and caregivers about the patients’ levels
of independence in ADLs and IADLs, which can be characterized
better by using the Barthel Index. If patients are suffering falls in
their current living arrangements, it is quite possible that epi-
sodes of hypoglycemia may be responsible. Falls and their conse-
quences are especially concerning in older populations because they
have direct impacts on quality of life. In a retrospective observa-
tional study of adults with diabetes >65 years of age, patients with
hypoglycemic events had 70% higher odds of fall-related fractures
compared to those without hypoglycemia (26). In evaluating older
patients with diabetes, it is important to ascertain whether the
patients have fallen recently and whether causes for the falls were
found. Decline in gait speed, frailty measures (e.g. hand grip strength,
weight loss), physical activity level, or frequent complaints of exhaus-
tion could be red flags that patients may not be able to respond to
an episode of hypoglycemia in time to prevent an unfortunate
outcome.
Patients who should be considered at greater risk for hypogly-
cemia also include those who have recently been hospitalized or
have polypharmacy. In particular, more than 5 medications, includ-
ing the presence of beta-blockers or angiotensin converting enzyme
inhibitors increase the risk for hypoglycemia (27). These medica-
tions predispose patients to hypoglycemia by blunting the already
compromised autonomic response to falling blood glucose levels
(27). A greater level of caution should be used if these medica-
tions are used in combination with insulin. It is also important to
consider that with increasing numbers of daily medications, patients
may not have the cognitive or organizational abilities to be com-
pliant with all their medications. This may lead to errors and/or non-
compliance with insulin injections and/or glucose-lowering agents.
Older patients with major coexisting medical conditions may not
be able to take oral hypoglycemic agents due to contraindications,
requiring earlier initiation of insulin regimens. The complex insulin
regimens, once again, require patients to have adequate cognitive
and functional abilities (2). It is important to note that both diabetes-
induced retinopathy and peripheral neuropathy may interfere with
self-care and increase the risk for hypoglycemia. Retinopathy can
occur along with cataracts or macular degeneration in the older adult
population. Poor vision makes it difficult for patients to see their
medications or blood glucose levels during monitoring. Further-
more, neuropathic changes may change proprioception, with loss
of balance increasing fall risk due to hypoglycemia. Generally, in
69
the geriatric population, arthritic changes may make the fine motor
control needed to self-administer insulin either difficult or impos-
sible. In the case that patients are able to complete the task, arthritic
pain may still limit compliance with physical activities. These factors
may be apparent only through dedicated functional evaluation.
Use of glucose-lowering medications
In general, older patients with diabetes should be treated with
the same principles as younger patients but with special empha-
sis on avoiding hypoglycemia and negative impacts on quality of
life. The physicians and caregivers should recognize the impor-
tance of drug interactions. Changes in drug pharmacokinetics due
to decreased kidney function are an important issue in elderly
patients because most antidiabetic drugs are excreted by the kidneys.
It is important to avoid drug dosing based on serum creatinine levels
because they are not reliable indicators of renal function in elderly
patients (28). The Cockroft-Gualt and the Modification of Diet in
Renal Disease formulas are valuable for the estimation of glomeru-
lar filtration rates in elderly patients for adjusting the dosing of the
mediations (29). Before developing the treatment plan, it is impor-
tant to identify barriers to self-care and the comorbidities that impact
them. The complexity of the treatment should match older patients’
coping abilities to avoid regimen failure and hypoglycemia.
Metformin remains the preferred first-line agent in all patients
with diabetes. However, its common side-effects of renal func-
tion, gastrointestinal symptoms and weight loss limit its use in some
older patients. The risk for lactic acidosis and decline in renal
function has been a major concern when using metformin in older
populations. However, a meta-analysis of studies over the past
2 decades have shown that metformin can be used safely in patients
with estimated glomerular function rates up to 45 (30).
Insulin and sulfonylurea are commonly used glucose-lowering
medications that result in highest risks for hypoglycemia. In some
studies, half of the older adult population was found to use
sulphonylurea drugs alone or in combination with other drugs such
as insulin (27). The sulfonylureas have the advantage of being inex-
pensive, allowing for easy daily or twice-a-day dosing and being
well tolerated. However, in patients with advanced age, poor nutri-
tion and general disability, they are associated with high risk for
hypoglycemia. In some studies, this risk for hypoglycemia is shown
to be as high as 1.8% per year (31). Some agents in this class, such
as glibenclamide and glyburide, have higher potentials to cause hypo-
glycemia, and that could be attributed to their longer durations of
action. The mechanisms of prolonged sulphonylurea action include
the decreased clearance and metabolism rates of the drug and dis-
placement of the drug from their protein-binding sites. In general,
hypoglycemia is fatal in 2% to 4% of patients with diabetes, with
1:10 sulfonylurea-related hypoglycemic incidents resulting in fatal-
ity (2). A study of Medicare recipients older than 65 years of age
indicated that severe hypoglycemia occurred in 1.2% of patients using
sulfonylureas and in 2.8% patients using insulin (2). Another study
looking at data from 3 randomized trials comparing older patients
to patients 18 to 64 years of age showed that insulin (NPH) resulted
in a higher rate of all episodes of hypoglycemia (72% vs. 60%) in older
adults, including major (5% vs. 2%), minor (56% vs. 46%) and symp-
tomatic hypoglycemic episodes (63% vs. 47%) (2). As patients age
and endogenous insulin is depleted, oral agents become ineffec-
tive, and insulin may become necessary. A large observational study
was conducted in patients using only insulin for diabetes control.
These patients were much more likely to utilize emergency-room
care than patients using oral agents. As a result, costs of emer-
gency room visits were incurred (32). Notably, this same study found
that patients older than 80 of age were 2 times more likely to expe-
rience hypoglycemia than their younger counterparts (32).
70 M. Sircar et al. / Can J Diabetes 40 (2016) 66–72
Table 2
Medications that increase risk for hypoglycemia in patients taking sulfonylurea drugs
Drugs
Warfarin, salicylates, clofibrates, sulphonamides
Chloramphenicol, MAOIs, phenylbutazone
Allopurinol, probenecid, salicylates
Insulin, ethanol, beta- receptor antagonists, MAOIs
MAOIs, monoamine oxidase inhibitors; SU, sulphonylurea.
Other important factors that increase the risk for hypoglyce-
mia in patients taking sulphonylureas include longer duration of
therapy and concomitant use of certain drugs, such as insulin and
beta blockers (33,34). Some of the commonly used medications and
their interactions with the sulfonylurea class of drugs are shown
in Table 2.
Newer classes of glucose-lowering agents, both oral and inject-
able (DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibi-
tors), have much lower risks for causing hypoglycemia (34). The
DPP-4 inhibitors are oral medications with low risk for causing hypo-
glycemia, and once-a-day dosing makes them attractive for use by
older populations. They have been safely used older populations
(35) and have been included in a recent position statement for use
as a second-line therapy in selected older patient populations (36).
A recent retrospective subgroup analysis (279 patients, 65 years of
age and older) evaluating saxagliptin 5 mg daily vs. placebo dem-
onstrated the clinically relevant and significant efficacy of saxagliptin
in reducing A1C levels in older patients (37). The recently pub-
lished Saxagliptin Assessment of Vascular Outcomes Recorded in
Patients with Diabetes Mellitus (SAVOUR-TIMI) trial also supports
the use of DDP-4 inhibitors in the elderly because they are simple,
once-daily agents that incur no risk for hypoglycemia (38). However,
their use is limited in most countries due to high cost. In the future,
if these medications become more affordable, their use will decrease
the risk for hypoglycemia significantly in older adults. GLP-1 ago-
nists have higher efficacy than DPP-4 inhibitors, but they are inject-
able agents, which lowers the enthusiasm for their use in elderly
patients. A newer once-a-week formulation is attractive and can be
used with help of a caregiver. Limited data exist concerning the use
of SGLT-2 inhibitors by older adults (39). The risk for genital infec-
tion and dehydration require caution (40).
Insulin can be used safely by older adults as long as the risk for
hypoglycemia is carefully monitored. Basal insulins can be used with
other noninsulin agents in a safe manner. It is important to keep
insulin strategies simple, with the least amount of complexity pos-
sible. In a small study, a strategy of simplifying the regimen by
decreasing the number of daily insulin injections and replacing them
with basal insulin combined with noninsulin agents was found to
decrease the risk for hypoglycemia without compromising glyce-
mic control (41).
Understanding the disease and the treatment modalities is the
key to better management of diabetes. Patients should be edu-
cated about the symptoms and manifestations of hypoglycemia. It
is common to see lack of knowledge of hypoglycemia in patients
using oral and insulin therapies in the elderly (42). The older patients
with diabetes should be educated about the importance of home
glucose monitoring and recognition of lower blood sugar values and
their appropriate management. Caregivers can play important roles.
Clear instructions for hypoglycemia management should be pro-
vided. Patients with improved knowledge have shown better gly-
cemic control in some studies (31,43).
Diet and physical activity
Although loss of strength and muscle mass are expected changes
with aging, older patients with diabetes are more likely to have
Mechanism
Displacement of SU (first-generation mostly) from the protein binding sites
Reduce the hepatic metabolism of SU
Decrease urinary excretion of SU and metabolites
Possess intrinsic hypoglycemic activity
experienced accelerated functional decline (19). When compar-
ing people with diabetes to age-matched peers, it has been noted
that strength per unit of muscle mass declines with poor glycemic
control and longer duration of disease (19). These changes further
increase the risk for falls and poor outcomes in older adults with
hypoglycemia. However, physical activity has shown to improve func-
tional status in these patients. The Look Action for Health in Dia-
betes (AHEAD) study of patients 65 to 76 years of age showed
significant gains in fitness through an intensive physical-activity
intervention (19). It is important to teach patients to avoid hypo-
glycemia while exercising. Small snacks before exercises can avoid
the risk for hypoglycemia.
In general, overly restrictive diets are discouraged in older adults
with diabetes. Weight loss and malnutrition are more common in
older adults and should be carefully avoided. Weight loss through
dieting alone (without physical activity) significantly reduces lean
muscle mass in older adults, an effect that can be allayed through
the addition of aerobic exercise (44,45). Higher risk for hypoglycemia
is seen after acute illness, anorexia and weight loss. Resultant frailty
in older adults has been associated with a 2.62-time increase in the
likelihood of a complication of diabetes (46).
Role of physicians and healthcare
It is important for physicians to inquire carefully about hypo-
glycemia and its related symptoms during each clinic visit, keeping
in mind the high prevalence of hypoglycemic unawareness.
Metformin, if tolerated, is preferred as the first-line agent because
it has potential metabolic benefits and results in fewer incidents
of hypoglycemia. It should be appropriately dosed based on renal
function. If a long-acting sulphonylurea agent is used, it should be
switched to a shorter acting option. In patients admitted to the hos-
pital, there may be decreased food intake due to acute illness, which
requires careful adjustment in medication dosage to avoid hypo-
glycemia. At the time of discharge from the hospital, careful atten-
tion should be paid to the insulin doses, and they should be clearly
specified. In cases of transition of care to nursing homes or long-
term facilities, instructions should be given for dose adjustments
based on blood sugars. Management of hypoglycemia should be
appropriately communicated. The importance of hypoglycemia and
its specific challenges in older patients should also be taught early
to the residents and house staff of both endocrinology and primary
care specialties.
Nutritionists should evaluate for dietary habits and inquire about
missing meals and weight loss. Periodical sessions with clinical
diabetic educators to assess older patients’ knowledge and under-
standing of recognition and treatment of hypoglycemia can avoid
poor outcomes. Educators can also assess medication dosing and
injecting techniques if signs of errors are detected. Additionally, care-
givers’ education becomes critical so that they can help with the
monitoring of and responses to hypoglycemic episodes. In cases in
which the caregivers are aging spouses, it may be important to con-
sider that the caregivers may have also suffered cognitive losses.
After a cognitive and functional evaluation, if patients are found to
be unable to care for their diabetes in a manner that prevents hypo-
glycemia, formal home-aide support may be utilized. Lifeline devices
 M. Sircar et al. / Can J Diabetes 40 (2016) 66–72
Table 3
Strategies for preventing hypoglycemia in older adults with diabetes
• Perform cognitive testing using short screening tools such as the Montreal Cognitive Assessment (MOCA) or MiniCog to determine whether patients are able to
self-administer their treatment regimens and monitor and respond to hypoglycemia
• Perform functional testing to determine whether patients are physically able to respond appropriately to hypoglycemia
• Identify caregivers; educate both patients and caregivers in regard to monitoring and treatment
• Simplify treatment regimen so the patients’ coping skills match the complexity of the regimen
• Do not rely upon signs and symptoms of hypoglycemia, which may be absent in this population; finger-stick glucose readings are useful; continuous glucose
monitoring can identify unrecognized and nocturnal hypoglycemic episodes.
that can summon emergency personnel may be necessary for older
patients at high risk for falling as the result of episodes of
hypoglycemia.
Some of the strategies for preventing hypoglycemia in the older
population are shown in Table 3.
Conclusions
It is challenging to manage diabetes in the elderly population
because they may have many associated comorbidities and utilize
multiple medications. All elderly patients should be managed with
individualized care and treatment plans that include early recog-
nition and management of hypoglycemia. The goals of diabetes man-
agement vary based on patients’ cognitive and functional capacities,
comorbidities and life expectancies. It is imperative to avoid hypo-
glycemia in the elderly because it may lead to a cascade of events
and to impaired quality of life.
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