As the general population continues to age, we must be
prepared to manage more patients having diabetes as the number
of adults 65 years or older affected by diabetes is also going
to increase proportionately. This is a heterogeneous group and
the management need to be more patient centered prioritizing
general well-being and quality of life. Co-existing
morbidities are to be considered and the patient’s ability to
manage the disease must be assessed along with the social
support system available to them. The decisions are to be
taken considering specifically the functional status (ADLs and
FADLs), cognitive dysfunction and risk of hypoglycemia.
Key words: diabetes, GLP-1 receptor agonists, DPP-4
inhibitors, SGLT2 inhibitors, insulin
Management of diabetes in elderly
Treatment related complications are very likely to occur in
this group, hence treatment should be simplified. We have to
individualize glycemic goals. Older adults with no other
co morbidities or intact functional status, we can go for a
good glycemic control with an A1c <7.0%. But on those with
multiple co-morbidities having functional disability, goal
should be relaxed to < 8.0 - 8.5% [1]. Dietary advice must
be reinforced focusing on healthy eating. Optimize and
encourage exercise depending on the functional status,
addressing the problems related to sarcopenia and risk of
falls. Multidisciplinary approach incorporating and
constituting social support system helps to provide a better
care. Devices and technologies may not suit most, but may play
a big role in care as in the case of self-monitoring of blood
glucose for timely recognition of hypoglycemia. The treatment
strategies and algorithms are more or less the same
incorporating the special needs of this group.
Special challenges to be addressed when choosing a drug for
diabetes in elderly
1. Hypoglycemia
Hypoglycemia vulnerability, recognition, and challenges in
prompt intervention are major concerns in managing diabetes in
elderly. When choosing a treatment in elderly, priority will
be to avoid hypoglycemia and always the glycemic goals will be
set keeping this in mind. Training and retraining of
hypoglycemia recognition and management should be given to
patient on sulphonylurea, glinides or insulin and also to
their care takers. At risk population for hypoglycemia in
elderly must be identified and drug selection should be
focused to avoid hypos.
At risk or vulnerable group include patients having:
• Longer duration of diabetes
• Target organ damage
• Visual problems, hearing impaired
• Dementia
• Autonomic neuropathy with risk for cardiac autonomic
dysfunction
• Living alone - It may not be possible to get external
assistance in severe hypos.
• History of falls
• Hypoglycemia unawareness or previous history of severe
hypoglycemic episodes
• Polypharmacy
• Depression
• Disability, functional limitations, urinary incontinence
2. Initiation of injectable - Insulin or GLP 1 analogues
It is always a challenge in elderly and every effort should be
made to avoid medication errors. This could be wrong injection
technique, dose calculation errors, forgetfulness and missing
or repeat injections.
3. Affordability should also be assessed before
planning a treatment in elderly and the cost must suit to
their pocket.
Newer drugs for diabetes management in elderly
There are many newer oral drugs introduced for treating type 2
diabetes. They act without causing hypoglycaemia and that is
the major attraction to these classes of drugs when chosen for
elderly.
When we look at the older classes of drugs, Metformin is still
the first oral anti diabetic (OAD) drug to be considered in
all type 2 diabetic patients after incorporating diet and life
style modification. It may be used safely in patients
with estimated glomerular filtration rate ≥30 mL/min/ 1.73 m
2.
However, it is contraindicated in patients with advanced renal
insufficiency, hepatic dysfunction or congestive heart failure
because of the increased risk of lactic acidosis. Metformin
may be temporarily discontinued before radiological
interventions, and during hospitalizations. Insulin
secretagogues such as Sulfonylureas should be used with
caution because of the risk of hypoglycaemia. When cost
is a major concern we can consider using a sulfonylurea
especially a glimeperide, glipizide or gliclazide as they do
not oppose ischaemic preconditioning [2]. Glyburide or
glibenclamide should never be used in elderly diabetic
patients because of its longer duration of action and the risk
of prolonged hypoglycaemia.
Incretin-based therapies
Incretin-based therapies (glucagon-like peptide-1 receptor
agonists [GLP-1RAs] and dipeptidyl peptidase-4 [DPP-4]
inhibitors) act by increasing glucose-dependent insulin
secretion in response to nutrient intake, and hence do not
cause hypoglycaemia.
Gliptins are oral dipeptidyl peptidase 4 inhibitors and are
considered a preferred choice after Metformin because of no
risk of hypoglycemia by itself. It is safer in elderly though
cost may be a barrier. DPP-4 inhibitors are CV neutral and do
not increase major adverse cardiovascular outcomes [3]. DPP4
inhibitors could be considered as the second option after
Metformin or as the third drug in triple therapy in elderly
because of no risk of hypoglycaemia. They are administered
orally and also weight neutral. The important side effects are
headache, nasopharyngitis, upper respiratory tract infection
and acute pancreatitis. Some of them in this class may need a
dose adjustment based on eGFR reduction. Sitagliptin was the
first agent introduced in this class in 2006.
Sitagliptin Dose 100 mg daily and the dose adjustment is to be
made as:
{eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary,
eGFR ≥30 to <45 mL/minute/1.73 m2: 50 mg once daily, eGFR
<30 mL/minute/1.73 m2: 25 mg once daily; ESRD requiring
hemodialysis or peritoneal dialysis: 25 mg once daily;
administer without regard to timing of hemodialysis}
Others in the same class are Vildagliptin, Saxagliptin,
Linagliptin, Teneligliptin. Omarigliptin is a long-acting
DPP-4 inhibitor for once weekly dosing that is presently
approved in Japan. Except for linagliptin, which is eliminated
via a biliary route, all other DPP-4 inhibitors are excreted
in the urine and requires dosage adjustment in renal
impairment. Gliptins are considered CV neutral however
saxagliptin treatment showed a significantly increased risk of
heart failure-related hospital admissions and a post hoc
analysis showed a non-significant increased risk of
hospitalization for heart failure among alogliptin - treated
patient [4].
GLP-1 receptor agonists are injectables except oral
semaglutide which is not yet currently available for use in
India. GLP-1 receptor agonists (daily to weekly injections)
liraglutide, semaglutide and dulaglutide comes in this class.
Important limitations are available only as injection,
frequent GI side effects like nausea, vomiting, abdominal
discomfort, cost is a barrier, and weight loss may not be
acceptable to all. Gastrointestinal (GI) adverse events may
lead to premature treatment discontinuations and this may be
more in elderly because of a difference in GI tolerability in
older individuals [5]. They are not preferred in the elderly
with weight loss and loss of appetite. This class of drugs is
proven beneficial in patients with established CVD and
potentially for those at high risk for CVD (reduction in major
adverse cardiovascular events - liraglutide, semaglutide,
dulaglutide) [6]. Injectable Semaglutide had a comparable
efficacy and safety profile in non-elderly and elderly
patients with type 2 diabetes across the SUSTAIN 1-5 trials
especially with the benefit of low risk of severe
hypoglycaemia in elderly [1]. Weight loss is an added
advantage in obese people.
SGLT2 inhibitors
SGLT2 inhibitors reduce HbA1c by 0.5% -1.0% and have shown
favorable effects on body weight, blood pressure, lipid
profile, arterial stiffness and endothelial function, having
documented cardio protective and renoprotective effects [1].
This class of drugs exerts their glucose-lowering effect by
increasing renal excretion of glucose by inhibiting glucose
reabsorption by inhibiting SGLT2 receptors in the proximal
renal tubules.
This class includes canagliflozin, dapagliflozin,
empagliflozin, and ertugliflozin. Weight loss may be
beneficial side effect especially in obese, reduction in
systolic blood pressure, reduced cardiovascular mortality in
patients with established CVD, improved renal outcomes in
patients with nephropathy [7]. For the treatment and
management of heart failure in elderly patients with diabetes,
early initiation of SGLT2 inhibitor therapy appears to be
effective [8].
Important adverse effects are genitourinary tract infections,
diabetic ketoacidosis (could be euglycemic) and orthostatic
hypotension [9]. Long-term safety needs to be established and
other concerns raised are Fournier gangrene, bone fractures,
lower limb amputations and acute kidney injury. Side effects
such as volume depletion may be more common in elderly and may
need special attention because of the added risks of
orthostatic hypotension, confusion and falls.
Initiation of Insulin therapy
Once-daily basal insulin injection therapy is associated with
minimal side effects and may be a reasonable option as the
best staring insulin in many older patients. Basal insulin
analogues are preferred considering lesser hypoglycaemia with
longer duration of action needing single daily injection. As
the duration of diabetes increases; some of them may require
meal time insulin dose and multiple injections. Education and
training along with simplification of regimen is always a
challenge. Meal time insulin options are regular human insulin
or insulin analogues. Meal timings, quantity and quality of
food taken also may vary in elderly. Insulin analogues may be
preferred as the injection can be given just before or after
the meal considering the faster onset and short duration of
action.
Newer Insulins
a) Bolus or meal time Insulin Analogues
As the duration of diabetes increases, some of them may
require meal time insulin dose and multiple injections.
Insulin analogues include Insulin Aspart, Insulin Lispro,
Insulin Glulisine and Faster Insulin Aspart. Faster Aspart and
Insulin Aspart were well-tolerated in both elderly and younger
adults with type 1 diabetes, hence Faster Aspart may be
considered in selected patients to safeguard hypoglycaemic
episodes although more clinical data are needed to confirm
this [10].
b) Basal Insulin analogues
Basal Insulin analogues are shown to achieve similar glycemic
control with lesser hypoglycemic episodes. In an observational
study, the addition of Glargine-100 to oral antidiabetic
therapy resulted in a significant and clinically relevant
improvement in glycemic control with low rates of hypoglycemia
across all age groups, including those aged ≥75 years, though
symptomatic hypoglycemia incidence was more common in the
≥75-year-old group [11]. Glargine-300 and Insulin Degludec-100
provided similar glycemic control improvements with relatively
low hypoglycemia risk [12]. In a pre-planned meta-analysis in
elderly patients with diabetes demonstrated a significant
reduction in hypoglycaemic events including nocturnal
confirmed hypoglycaemia with Insulin Degludec relative to
Insulin Glargine [13]. In a retrospective new-user cohort
study of female Medicare beneficiaries aged ≥65 years
initiating glargine, detemir or NPH, Glargine use was
not associated with an increased risk of breast cancer
compared with NPH or detemir [14].
Premixed verses co formulation
Predominaant premixed insulin analogues have the advantage of
faster onset of action compared to human premixed insulins. A
soluble co-formulation of basal insulin with bolus insulin in
a single injection is available as Ryzodeg 70/30 (Insulin
degludec and insulin aspart). This premixed/co-formulation
simplifies Insulin regimen and with less risk of
hypoglycaemia. Cost is definitely higher with newer insulins.
Other currently available basal insulin analogues Insulin
glargine and insulin detemir cannot be combined with
rapid-acting analogues.
Co-formulations of basal analogue and GLP-1 analogue
The available options are:
• Insulin degludec/liraglutide (IDegLira)
• Insulin glargine/lixisenatide (IGlarLixi)
In selected obese elderly patients with type 2 diabetes this
may be considered as an option.
Conclusions
Diabetes in elderly is more challenging and management plan
should always consider the functional status and life
expectancy of the person. The quality of life is more
important in these people and treatment must be simplified.
Hypoglycemia is a major limiting factor and goals should be
individualized. Newer drugs address hypoglycaemia better and
appear cardiac neutral or favouring better. The
management must be comprehensive addressing all the
co-morbidities. If the patient is healthy and has good
functional status, the care must be at par with any other
young patient with diabetes. Hence elderly as a group
must be assessed individually and the care must be designed to
suit the patient. Preference should be given to drugs with low
risk of hypoglycaemia and with less complex regimen. Life
expectancy, disability and other co morbidities must be
considered in individualising care. Cost of therapy and ease
of availability must be addressed in every case to have
compliance to treatment.
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