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Original article

Therapeutic choices in elderly diabetic patients

Lyse Bordier a,∗ , Jean Doucet b , Bernard Bauduceau a
a
Service d’Endocrinologie, Hôpital Bégin, avenue de Paris, 94160 Saint-Mandé, France
b
Service de Médecine Interne Polyvalente, Université de Normandie, CHU de Rouen, 76031 Rouen cedex, France

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

Keywords: The care of elderly diabetic patients has now become a real public health issue due to the increase in the
Diabetes number of patients. In this population, complications are more serious and are intertwined with more
Elderly specifically gerontological issues. Treatment goals should be individualized based on the patient’s clinical
Malnutrition
presentation. New therapeutic drug classes are particularly interesting because of their effectiveness in
Hypoglycemia
terms of cardiovascular and renal protection, but the risk/benefit ratio needs to be well assessed on an
Cognitive disorder
Treatment individual basis. Insulin therapy is often necessary, either in case of failure of oral antidiabetics or because
of comorbidities, particularly in the event of renal failure. Educating the patient and family early in the
course of the disease is one of the keys to effective and safe treatment. The management of elderly diabetic
patients must avoid both too much laxity in those who have successfully aged and unreasonable activism
in fragile subjects because of the risk of hypoglycemia.
© 2023 Elsevier Masson SAS. All rights reserved.

1. Introduction
The treatment of type-2 diabetes has become more effective but
also more complex in recent years due to evolution of management
and the introduction of new drug classes. The therapeutic objec-
tives have changed, adapting to the person and no longer solely
focused on blood sugar level.
While it remains important to obtain good glycemic balance, it
is also essential to take cardiac and renal risks into account, using
molecules which have demonstrated their protective effect.
These new therapeutic classes are now unavoidable, multiply-
ing but complicating prescriber choice, particularly in the elderly,
the number of which increasing. A quarter of the diabetic popula-
tion is now over 75 years old, due to the increase in the prevalence
of diabetes and improvement in life expectancy thanks to improved
quality of care. However, the elderly and diabetic population is not
homogeneous, and these patients accumulate the complications of
diabetes and those related to age [1]. The geriatric complications
are often overlooked or underestimated, even though they have a
direct impact on treatment options. Finally, few studies focused on
this particular population, to which it is not possible to extrapolate
results obtained in younger patients. This is why choice of treat-
ment requires good assessment of the clinical situation of elderly
diabetic patients.
This text was presented at the “42nd Nicolas Guérité Days”, held
in Paris on November 18, 2022.
2. Definition of elderly persons
The definition of elderly, according to the WHO, is currently
65 years for patients with comorbidities and 75 years for subjects
who have aged well. This is why age in itself is not the only parame-
ter to be taken into account, which led the French Health Authority
(HAS) to distinguish three categories of elderly people [2]:
• “vigorous”: in good health, independent and well-integrated
socially, autonomous in decision-making and functionally, com-
parable to younger adults;
• “frail”: in an intermediate state of health and at risk of falling into
the “sick” category. They are a vulnerable population, with func-
tional, motor and cognitive limitations and decline in adaptive
capacity;
• “sick”: dependent, in poor health due to advanced chronic mul-
tiple pathology generating disabilities and social isolation.
3. Epidemiology

The prevalence of type-2 diabetes in France was 5.3% of the

general population in 2020, whereas it was only 4.6% in 2012 [3].
∗ Corresponding author. Prevalence increases to a peak between 70 and 85 years of age
E-mail address: bordierlyse@gmail.com (L. Bordier). in men and between 75 and 85 years in women. In 2016, 1 in 5

https://doi.org/10.1016/j.ando.2023.04.003
0003-4266/© 2023 Elsevier Masson SAS. All rights reserved.

Please cite this article as: Bordier L, et al, Therapeutic choices in elderly diabetic patients, Ann Endocrinol (Paris),
https://doi.org/10.1016/j.ando.2023.04.003
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men aged 70 to 85 and 1 in 7 women aged 75 to 85 were treated
pharmacologically for diabetes [4].
The incidence of complications of diabetes tends to stabilize, but
they remain frequent in the elderly. Mean age at hospitalization is
69.5 years for myocardial infarction, 75 years for stroke, 72.6 years
for lower limb wounds, 71.3 years for amputation and 69.9 years
for dialysis or kidney transplantation [4].
4. Geriatric complications need to be taken into account in
the choice of treatment
In the elderly, the complications of diabetes and aging mutually
aggravate each other, inducing loss of autonomy; geriatric com-
plications should not be ignored. Malnutrition, cognitive disorder
often associated with depression and hypoglycemia worsen and are
inter-related with the consequences of diabetes.
Gerontological assessment is therefore essential to detect
complications related to aging that may be overlooked or under-
estimated. This evaluation allows better understanding of the
patient’s clinical presentation, specifying the degree of frailty so as
to individualize glycemic targets and choose the most appropriate
treatment.
4.1. Frailty
A patient is considered frail according to the definition of the
French Society for Geriatric Medicine and Gerontology (Société
française de gériatrie et de gérontologie) when they prove to be
medically and socially vulnerable. Several definitions and criteria
of frailty can be used [5]. The most common definition is based
on clinical parameters defined by Fried et al., with 5 criteria [6]:
weight loss > 4.5 kg (or > 5% of initial weight) in 1 year, exhaustion,
slowed walking speed, decreased muscle strength, and sedentary
lifestyle. A person is considered frail if more than 3 of these criteria
are present. The definition by Rockwood et al. is broader, compris-
ing cognition, mood, motivation, motor skills, balance, activities
of daily living, nutrition, social condition and comorbidities [7].
Finally, the Short Emergency Geriatric Assessment (SEGA) scale,
which is easy to assess, allows fairly complete assessment of frailty
by all those who work with patients.
4.2. Malnutrition
The HAS health authority recently updated criteria for malnu-
trition in subjects over 70 years of age, defined by the association
of phenotypic data and an etiological criterion [8]:
• the phenotypic criteria are weight loss ≥ 5% in 1 month or ≥ 10%
in 6 months compared to usual weight, and/or BMI < 22 kg/m2 ,
and/or confirmed sarcopenia. A single phenotypic criterion is
enough. To calculate BMI, the HAS recommends systematically
using the height gauge. Sarcopenia, according to the 2019 EWG-
SOP European consensus, is defined by the combination of 2
parameters: reduction in strength and reduction in muscle mass
[9];
• the etiological criterion is > 50% in food intake for more than
1 week or reduction in intake compared to usual consumption
or to theoretical protein-energy requirements for more than
2 weeks.
Severity of malnutrition is defined by any of the follow-
ing criteria: BMI < 20 kg/m2 and/or weight loss ≥ 10% in 1 month
or ≥ 15% in 6 months, and/or albuminemia ≤ 30 g/L. Evaluation of
oral condition and chewing and swallowing capacities complete
the screening for malnutrition and condition the success of adapted
food management.
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Annales d’Endocrinologie xxx (xxxx) xxx–xxx
Quality control of nutritional status must be regular and atten-
tive, since an obese person can also be malnourished. Diagnosis is
then more difficult and is based on a single phenotypic criterion:
weight loss ≥ 5% in 1 month or ≥ 10% in 6 months and/or confirmed
sarcopenia.
4.3. Cognitive disorder
According to most of the literature, diabetes increases the
risk of cognitive decline 1.2–1.7-fold, depending on the type of
assessment, while risk of dementia is multiplied by 1.6 [10]. A meta-
analysis of 28 studies confirmed a 73% increased risk of developing
any type of dementia, 56% for Alzheimer’s disease and 127% for
vascular dementia [11].
Mild cognitive impairment, with no impact on daily life, is com-
mon and affects 19% of patients over 65 years old.
Nearly half of these subjects develop true dementia over time,
and diabetes promotes this harmful development [12].
In France, the GERODIAB study, a prospective multicenter
observational cohort follow-up study, assessed the link between
glycemic control and 5-year morbidity and mortality in 987 peo-
ple with type-2 diabetes aged 70 years and over [13]. The study
confirmed under-evaluation of cognitive disorder by physicians in
everyday practice; health practitioners reported that 11% of their
patients had cognitive disorder, while 28.8% had a Mini-Mental
State Examination (MMSE) score < 25. These results suggest that
a superficial assessment of cognitive status is often insufficient and
that an evaluation test is necessary in case of the slightest doubt.
Screening for cognitive impairment must be regularly repeated,
because a tendency for aggravation of geriatric complications, such
as those of diabetes, is very common [14]. Memory problems can
induce errors in drug intake or insulin injection and food intake
disorder.
4.4. Depressive state
Depression is common in older people with diabetes: preva-
lence is almost twice as high as in the rest of the population, and
this figure is twice as high again in women. Undetected, untreated
or undertreated depression affects an individual’s ability to suc-
cessfully manage their diabetes, impedes adherence to treatment,
undermines caregiver-patient relationships, and impairs progno-
sis, increasing mortality 1.2–2.6-fold [15].
4.5. Hypoglycemia
Hypoglycemia is particularly common and severe in elderly
patients. Risk factors comprise history of hypoglycemia, over-
ambitious glycemic goals, sulfonylurea, glinide or insulin treat-
ments, co-morbidity and cognitive disorder [16].
At inclusion in the GERODIAB study, 33.6% of patients had
experienced one or more hypoglycemia episodes in the previous
6 months. Hypoglycemia was minor in 29.7% of cases and severe
in 3.3%, and accompanied by coma in 0.6% [13]. In an American
retrospective study conducted from 2009 to 2014, the risk of rehos-
pitalization after a first admission for an episode of hypoglycemia
was 10% [16]. The main factors determining hospitalization for
hypoglycemia comprised age, treatment with insulin or sulfony-
lurea, complications of diabetes, co-morbidity and polypharmacy.
A recent meta-analysis of 44 studies attested to the serious-
ness of hypoglycemia in seniors [17]. In this survey, covering a
global population of more than 2.5 million patients, hypoglycemia
was accompanied by a doubling of the number of deaths, essen-
tially in the first 90 days after the event. Hypoglycemia is also
associated with cardiovascular mortality, dementia, micro- and
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macro-angiopathic complications, falls and fractures, multiplying
the incidence of these events by a factor of 1.5–2.
In an English study, 5-year mortality was compared between
diabetic patients with or without history of severe hypoglycemia.
After adjustment, the excess risk of mortality was 21% in patients
over 60 with history of severe hypoglycemia. This result shows that
hypoglycemia is a marker of mortality risk, requiring therapeutic
choices to avoid these accidents [18].
5. Therapeutic modalities
In the elderly, non-drug and drug therapy do not differ from
those in younger patients. However, these therapeutic options
must be adapted to the clinical presentation of the patient, taking
account of frailty, diabetes and geriatric complications and hypo-
glycemic risk [19].
5.1. Non-drug treatment
5.1.1. Dietary therapy
Like in young people, diet is fundamental in the management
of elderly patients living with diabetes [20]. However, in seniors,
the fight against malnutrition is essential and requires screening
for taboos or preconceived ideas that are too often anchored in the
imagination and habits [21]. To avoid onset or aggravation of sar-
copenia, diet must combine sufficient energy and protein intake
[22]. Contrary to popular belief, energy needs decrease little in
elderly subjects and are even, for comparable effort, 20% higher
than in young adults.
In the elderly, diet no longer aims at reducing excess weight but
rather at limiting the risk of malnutrition. It is advisable to proscribe
any excessive food restriction resulting in caloric intake < 1500
calories per day. Without being lax, the pleasure of meals is to be
respected, because frustration is both badly experienced and gener-
ally useless. A reasonable consumption of sugar at the end of a meal
may be authorized of this approach. The recommended daily dis-
tribution is 3 meals, avoiding skipping food intake in order to limit
the risk of hypoglycemia, especially in case of treatment involving
sulfonylureas, glinide or insulin.
During hospitalization, the risk of malnutrition is particularly
high and requires great vigilance on the part of the staff and in
particular of the dieticians.
5.1.2. Physical activity
The practice of physical activity must also take into account the
clinical state of the elderly person with diabetes. Benefits relate to
the quality of glycemic balance, muscle trophicity and socialization
and the strengthening of self-esteem. Regular walking should be
encouraged, along with endurance and resistance training when
possible. Physiotherapy allows frail subjects to maintain muscle
mass.
5.2. Medication
5.2.1. Metformin
Metformin is by consensus the first-line treatment, including in
the elderly. It improves insulin resistance, does not induce hypo-
glycemia and has a weight-neutral effect. Its digestive side effects
can be limited by incremental dosing, during or at the end of meals.
However, some patients do not tolerate metformin, even at low
doses. Dose adjustment is necessary when glomerular filtration
rate (GFR) is < 60 mL/min/1.73 m2 . Thus, dosage should be 2 grams
per day for GFR 45–60 mL/min/1.73 m2 and 1 gram per day for
GFR 30–45 mL/min/1.73 m2 . Below 30 mL/min/1.73 m2 , metformin
must be interrupted, as also in case of intercurrent disease or before
imaging requiring injection of iodine, to avoid lactic acidosis.
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Annales d’Endocrinologie xxx (xxxx) xxx–xxx
Metformin treatment can cause vitamin B12 deficiency, depend-
ing on dose and treatment duration. The French Society for the
Study of Diabetes (Société francophone du diabète [SFD]) and
the American Diabetes Association (ADA) guidelines highlight this
point [23,24]. Control of vitamin B12 levels should not be neglected
in patients with anemia or neuropathy, especially since this defi-
ciency is easy to treat [25].
Although there are no specific studies of metformin in the
elderly, the REACH registry study showed that, after adjusting for
confounding factors, metformin reduced mortality by 24% in sec-
ondary prevention. This benefit was also observed in subgroups in
which metformin used to be contraindicated: patients aged 65 to
80 (−23%) or with heart failure (−31%) or moderate renal failure
(−36%) [26].
5.2.2. Sulfonylureas
This therapeutic class acts by stimulating the secretion of insulin
independently of the level of glycemia, and is preferably adminis-
tered as dual therapy case of metformin inefficacy according to the
HAS guidelines [2]. This choice is essentially justified by low cost,
the decline in its use in first line, and by the habits of prescribers.
However, the side effects, with often prolonged hypoglycemia and
weight gain, mean that this drug class is now less used than new
molecules, particularly in the elderly. Its action duration is not opti-
mal, as demonstrated in the ADOPT study [27]. Dose increase must
be gradual, and glycemic self-monitoring is necessary so as not to
overlook hypoglycemia, particularly at the end of the afternoon.
New-generation sulfonylureas such as glimepiride or gliclazide
should be preferred, as a once-daily dose improves compliance and
reduces the risk of hypoglycemia compared to older sulfonylureas
such as glibenclamide [28].
An English “real-life” study was conducted between 2004 and
2012 in a cohort of 120,803 new users of oral antidiabetics, with
a mean age of 67 and follow-up of 3.7 years. As expected, the
risk of hypoglycemia was multiplied by a factor of 2.5 in sul-
fonylurea monotherapy compared to metformin alone. This risk
increased markedly when GFR was < 30 mL/min/1.73 m2 and when
high doses of sulfonylurea were used [29]. Dose adjustment, vary-
ing according to the molecules, is therefore necessary when GFR
is < 60 mL/min/1.73 m2 , and use of these drugs must be interrupted
when < 30 mL/min/1.73 m2 [23]. Poorer cardiovascular safety is
observed overall with sulfonylureas than with DPP4 inhibitors
(see below), but there is some heterogeneity in the results of the
various studies [30]. However, the CAROLINA study, comparing
linagliptin with glimepiride in patients at high cardiovascular risk
or with proven atherosclerotic disease, did not show any differ-
ences between these molecules in terms of cardiovascular side
effects. Increased hypoglycemia and modest weight gain were
found with glimepiride [31]. Results were comparable regardless
of age at study entry, 14% of patients being over 75 years of age
[32].
Repaglinide, with an effect similar to that of sulfonylureas, is
distinguished by shorter action duration, requiring several daily
doses. This molecule is more effective on postprandial glycemia and
can be used in moderate renal insufficiency. However, repaglinide
is also responsible for sometimes prolonged hypoglycemia. Finally,
for lack of studies, it is not recommended for patients over 75 years
of age.
5.2.3. Alpha-glucosidase inhibitors
Acarbose acts in particular on postprandial glycemia by reducing
the absorption of carbohydrates. This drug class does not induce
hypoglycemia, but digestive tolerance is often poor, and it can cause
flatulence or diarrhea, which frequently leads to discontinuation of
treatment. Its glycemic efficacy is limited, with a mean decrease
in HbA1c of 0.5%. Therefore, alpha-glucosidase inhibitors are not
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often used in the elderly, especially since the ACE study, in which
45% of participants were over 65, showed no cardiovascular benefit
[33].
5.2.4. Drugs with an incretin effect
The group of drugs with an incretin effect includes 2 types
of molecule used in therapy: dipeptidyl peptidase-4 inhibitors
(DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1
AR). The incretin effect is responsible for greater insulin secre-
tion after administration of glucose orally than intravenously. This
effect is due to peptide hormones secreted by the endocrine cells
of the intestine during the passage of food: glucose-dependent
insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1).
GLP-1 acts by increasing the secretion of insulin and by inhibiting
secretion of glucagon in a manner adapted to the level of glycemia,
but also by slowing gastric emptying and reducing appetite. How-
ever, these intestinal hormones have a very short half-life, being
rapidly degraded by a ubiquitous enzyme, dipeptidyl peptidase 4.
5.2.4.1. DPP-4i. DPP-4i increases the incretin effect of GLP-1, is
administered orally, does not induce hypoglycemia and has a neu-
tral weight effect. Dosage must be adapted, depending on the
molecules, according to GFR when < 50 mL/min/1.73 m2 . This class
of drug allows a decrease of 0.6–0.7% in HbA1c, depending on initial
level. Tolerance is very satisfactory, particularly at the cardiovas-
cular level, without, however, providing any particular protection,
as shown by a recent meta-analysis [34]. These drugs do not induce
digestive side effects but it is recommended, as a precaution, not
to prescribe them in case of known pancreatic disease. Finally, rare
cases of bullous pemphigoid and increased arthralgia have been
reported [35]. Thus, these molecules are particularly suitable for the
elderly and are the second-line treatment after metformin accord-
ing to the French Diabetes Society, especially in frail people after
failure of metformin, whereas the HAS recommends using sulfony-
lureas in combination with metformin [2,23].
5.2.4.2. GLP-1 AR. GLP-1 AR had initially to be injected once or
twice a day, but has been improved by delayed-release forms with
weekly effect now available on the market. These drugs have the
advantage of being more effective than oral antidiabetics, without
hypoglycemic effects, and a favorable effect on weight [36]. They
do not replace insulin, especially since there are a certain percent-
age of non-responders. The most frequent side effects are digestive
disorders, which usually improve after a few weeks [37]. The safety
of GLP-1 ARs and their beneficial cardiovascular and renal effect,
initially reported by the LEADER study with liraglutide, were con-
firmed in other studies, reviewed in a recent meta-analysis [38,39].
While this therapeutic class is very interesting in overweight type-
2 diabetic patients, it is little used in frail elderly patients because
of the risk of digestive disorder likely to aggravate malnutrition.
Moreover, data for GLP-1 AR are sparse beyond the age of 75.
However, recent reports indicated a beneficial effect in terms of
cognitive protection with, in preliminary studies, neuroprotective
and neurotrophic properties for incretins in Alzheimer dementia
and dementia of vascular origin [40].
5.2.5. Sodium-glucose co-transporter-2 inhibitors (SGLT2i)
This class of drug, now available in France for 2 years after much
delay, has an original mode of action independent of that of insulin,
by limiting renal reabsorption of glucose. It is therefore possible
to combine it with all other drugs, including insulin, with efficacy
close to that of DPP-4i. These drugs also have a favorable effect on
weight and blood pressure and do not cause hypoglycemia when
not combined with sulfonylureas or insulin. The most common side
effects are genital mycosis, especially in women. In the elderly,
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Annales d’Endocrinologie xxx (xxxx) xxx–xxx
episodes of volume depletion or hypotension may require discon-
tinuation of diuretics or modification of antihypertensive therapy.
A few cases of euglycemic ketoacidosis were reported in patients
with insulinopenia, which suggests that warning signs such as
nausea, vomiting, abdominal pain, asthenia and dyspnea should
not be overlooked. However, the CANVAS study with canagliflozin
unexpectedly showed a significant increase in the rate of minor
amputation in the feet (toe, metatarsus), particularly in patients at
risk who already had history of amputation [41]. This excess risk
was not found in the other studies or with the other molecules, but
justifies informed monitoring in patients with arteriopathy.
The remarkable results of the EMPA-REG OUTCOME study
showed, for the first time in the history of oral antidiabetics, a rapid
positive effect of empagliflozin, with 38% reduction in cardiovascu-
lar mortality and 35% reduction in hospitalization for heart failure
[42]. The efficacy of this drug class is particularly appreciable during
heart failure with reduced or conserved ejection fraction, whether
or not the patient is diabetic [43,44]. Heart failure is a complication
that is both very common – affecting 10% of subjects over 70 years of
age, half of whom live with diabetes – and frequently overlooked.
This therapeutic class also shows a remarkable 38% reduction in
“hard renal events” such as doubling of serum creatinine, onset
of end-stage renal failure and death from renal causes [45]. The
excellent results on all cardiovascular and renal complications of
diabetes were confirmed in a recent meta-analysis, despite lack of
efficacy on stroke, probably due to an increase in hematocrit [45].
However, they are less effective in reducing glycemia in kidney fail-
ure, and prescription in the elderly can lead to discomfort due to
polyuria and symptoms linked to hypovolemia, inducing falls.
5.2.6. Insulin
Insulin therapy is frequently necessary in elderly diabetics. It
may be indicated temporarily during an acute episode, particularly
infectious, or during surgery. More often, definitive insulin ther-
apy is necessary due to the chronic imbalance of diabetes, signs
of insulinopenia or contraindications to oral treatment, in partic-
ular in case of severe kidney failure. Apart from in this latter case,
continuation of metformin is advised.
While elderly patients are often reluctant at first to accept
insulin treatment, this reluctance rarely resists patient explanation.
The fears of seniors come from the constraints and seriousness this
mode of treatment is reputed to involve. With a few months’ hind-
sight, the injection is more easily tolerated and the well-being that
insulin provides means that acceptance is generally acquired.
Initiation of insulin therapy requires therapeutic education,
which must aim to empower the patient. When cognitive functions
do not allow this, it is necessary to turn to the family or caregivers.
The HAS recommends starting preferably with intermediate-
duration neutral protamine hagedorn (NPH) insulin [2]. The
limitations of this type of insulin are that it does not cover the
nychthemeron and increases the risk of hypoglycemia due to its
peak of maximum activity around the fourth hour. The marketing
of slow-acting analogues and fast-acting analogues has facilitated
insulin therapy in the elderly. The prolonged duration of action and
the stability of slow analogues allow a single injection per day to be
used, while limiting the risk of hypoglycemia [46]. The availability
of slow long-acting analogues, degludec and glargine U300, further
limits the risk of hypoglycemia, particularly at night, with no real
difference between these two molecules [47,48].
In the event of insufficient treatment with an injection of basal
insulin, a switch to 2 injections of premix insulin can be suggested.
Another option is additional injection of a rapid-acting analog to
limit the rise in blood sugar after a hyperglycemic meal. Short-
acting analogues can be administered even after meals, checking
actual food intake. In certain cases, this protocol can be supple-
mented by two other preprandial injections to achieve a true basal
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bolus schema in particularly autonomous patients. On the other
hand, the prescription of a pump is a rare opportunity in very
elderly patients.
6. Glycemic targets
According to the HAS in 2013 and the SFD in 2021, with cer-
tain nuances, HbA1c targets depend on clinical presentation, which
implies at least a summary gerontological assessment [2,23].
In people over 75 who are “in good health”, well-integrated
socially and autonomous from a decision-making and functional
point of view and whose life expectancy is considered satisfactory,
the objectives are the same as those of younger subjects, with an
HbA1c target ≤ 7%.
In “frail” patients with intermediate state of health and at risk
of falling into the category of “dependent and/or very impaired
health”, an HbA1c target ≤ 8% is recommended, remaining above
7% in the event of treatment likely to cause hypoglycemia such as
sulfonylureas, glinides or insulin.
Finally, in dependent patients and/or those with “very impaired
health” due to chronic multiple pathology generating disabilities
and social isolation, the priority is to avoid acute complications
of diabetes (dehydration, hyperosmolar coma) and hypoglycemia.
The HbA1c target is 8–9%, and with preprandial capillary blood
glucose 1–2 g/L or, better still, > 1.40 g/L, in case of treatment with
sulfonylureas, glinides or insulin.
Defining a lower limit for the “frail” and dependent and/or “very
impaired health” categories when patients use treatments incur-
ring risk of hypoglycemia is precautionary, these two categories
being particularly exposed to hypoglycemic risk. Over-treatment,
often reported by surveys, can jeopardize prognosis, particularly if
it involves treatments with high hypoglycemic risk [49].
7. Therapeutic strategy
After failure of lifestyle and dietary measures, all guidelines rec-
ommend metformin treatment in the absence of contraindications
linked to impaired renal function [2,23]. In case of inefficacy of
this monotherapy, the choice is guided by the clinical state of the
patient.
7.1. Patients in good health without cardiac or renal
complications
Therapeutic options here are identical to those for younger sub-
jects. Joint medical decision, taking account of the patient’s wishes
after detailed information on the advantages and disadvantages
of each therapeutic class, leads to metformin being associated to
DPP-4i, SGLT2i or GLP-1 AR. Even in this favorable scenario, it is
preferable to avoid resort to sulfonylureas.
7.2. Patients who have aged well but who have proven
atherosclerotic cardiovascular disease
The SFD considers that a patient has proven atherosclerotic
vascular disease in case of history of vascular events (myocardial
infarction, ischemic stroke, revascularization, amputation related
to ischemia, etc.) or significant atheromatous lesion (> 50% steno-
sis of the coronary, carotid or lower limb artery, unstable angina,
silent myocardial ischemia or arteriopathy).
Elderly diabetic patients with proven atherosclerotic vascular
disease should, like young subjects, receive either SGLT2i or GLP-
1 AR in addition to metformin, regardless of HbA1c level, while
monitoring tolerance and nutritional status. These two therapeu-
tic classes are metabolically effective, improving glycemic control
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Annales d’Endocrinologie xxx (xxxx) xxx–xxx
without causing hypoglycemia, and inducing weight loss, which,
however, is not always desirable in the elderly. They have demon-
strated efficacy in reducing cardiovascular events in populations
at high or very high risk, but are likely to induce side effects
that must be known and screened for, especially in seniors. For
the SFD, after the age of 75, GLP-1 AR and SGLT2i should be
reserved for a minority of patients, ideally after consulting an
endocrinologist-diabetologist, because the risk/benefit ratio has
not been sufficiently assessed, with few studies specifically in this
population.
7.3. Patients who have aged well but have heart or kidney failure
The position statement of the SFD recommends, for healthy sub-
jects, associating metformin to SGLT2i, whatever the level of HbA1c,
because of the renal protection, which has been demonstrated on
strong criteria and its effectiveness in heart failure.
In case of contraindications to these drugs, GLP-1 AR is rec-
ommended, provided that the HbA1c does not exceed targets.
Monitoring tolerance is again essential.
7.4. In frail patients
In frail patients, the SFD advocates combining metformin to a
DPP-4i, because of the excellent tolerance of this dual therapy,
particularly regarding risk of hypoglycemia. If this treatment is
insufficient, injection of a long-acting insulin analogue is recom-
mended. The prescription of SGLT2i or GLP-1 AR can be discussed
according to clinical presentation, especially if there are signs of
cardiac or renal failure. Importantly, these molecules can then be
indicated for cardiovascular or renal protection rather than for the
normalization of blood sugar.
7.5. In patients with very poor health
As in the category of frail patients, after metformin, if not con-
traindicated, sulfonylureas or glinides should be avoided in favor of
DPP4i. In these patients, insulin therapy is often appropriate, ensur-
ing comfort by avoiding the use of multiple drugs and limiting the
risk of hypoglycemia. The risk/benefit ratio of these new classes
seems rather unfavorable, apart from the interest of SGLT2i in case
of heart failure.
8. Conclusion
Management of elderly diabetic patients is difficult because each
patient has a different profile of success in aging, so that the objec-
tives and modes of treatment cannot be standardized [50]. Vigorous
subjects should be treated like younger ones, but caution is required
for frail and dependent patients or patients with very impaired
health, in whom geriatric complications make management more
difficult. Screening for malnutrition, loss of autonomy and cognitive
disorder can guide the mode of treatment. The availability of new
therapeutic classes has brought unprecedented benefits in terms
of cardiovascular and renal protection. However, the side effects of
these drugs must be known in order to determine specific indica-
tions in elderly people.
Disclosure of interest
The authors declare that they have carried out specific interven-
tions at the request of the following pharmaceutical companies:
AstraZeneca, Boehringer, Eli Lilly, Jansen, Merck Sharp & Dohme,
Novo Nordisk, Pfizer, Servier and Sanofi.
G Model
ANDO-1511; No. of Pages 6 ARTICLE IN PRESS
L. Bordier et al.
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