Type 2 Diabetes in Older Persons

Introduction

Hypoglycaemia

Glucose targets

Specific Treatments

Oral agents

Injectable agents

Hypertension

Dyslipidemia

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(See Strength of Recommendations Taxonomy (SORT) for explanation of Grade A-C)

SEMDSA 2017 Recommendations
A holistic individualised care plan for older individuals, with the aim of maintaining independence should be sought	C
Prevention of hypoglycaemia should take priority over attainment of glycaemic targets	C
The healthy older adult who has a life expectancy that exceeds the duration of randomised controlled trials showing benefit, should generally receive diabetes care with goals and targets similar to those for younger adults	C
Patients older than 65 years should be screened annually for cognitive impairment, dementia and depression because these impact on diabetes management decisions	B
Metformin is the initial drug of choice for older adults unless contra-indicated or not tolerated	B
Sulphonylureas should be used with caution as the risk of hypoglycaemia increases exponentially with age. They should be avoided in older adults at particularly high risk for hypoglycaemia or its consequences	B
Thiazolidinediones should be used with caution due to the risk of fractures and heart failure	C
DPP-4 inhibitors have excellent tolerability profiles, very low risk of hypoglycaemia and is the preferred second drug for the older person with comorbidities	B
If insulin mixture is used, premixed solutions and prefilled pens should be used to reduce dosing error	B
The clock drawing test may be used when assessing capability of a patient to administer insulin	C

INTRODUCTION 

There is no general agreement on the age at which a person becomes old. The common use of chronological age to mark the threshold of old age assumes equivalence with biological age, yet these two are not necessarily synonymous. There is no universally accepted age that defines the older person; the United Nations, World Health Organisation and Statistics South Africa accept age 60+ as being older, while many developed countries use age 65+ (the pensionable age). 

This chapter will use age 60+ as a basis to define the age at which a progressive decline in health and functional status is more likely to occur, and co-morbidities are likely to be common enough to justify some generalisations about diabetes management. Ageism (discrimination based only on age) is unacceptable. The aim of this chapter is to improve the care of the older person, not to deny care based only on the age of the person.

Ageing is regarded as a major contributor to the diabetes epidemic. The percentage of the South African population aged 60 years and above rose from 7.1% (2.8 million) in 1996 to 8.0% (4.1 million) in 2011.¹ Estimates show that the older population will continue to increase, and it is estimated that by 2030 there will be ~7 million older persons in South Africa^.1 The national prevalence of diabetes, hypertension, dyslipidaemia and obesity in 2012 is shown in The South African National Health and Nutrition Examination Survey-1 (SANHANES-1). 

For the population older than 65 yrs, 40% have abnormal glucose regulation and 50% have dyslipidaemia.² Diabetes in older adults is linked to higher mortality, yet they are often excluded from randomised controlled trials of diabetes.^3,4 The care of older persons with diabetes impacts on the whole family, and this must be taken into account.

Diabetes in older persons is unique and may be complicated by a non-specific clinical presentation with vague symptoms. Age-related insulin resistance (IR) coupled with age-related declines of pancreatic beta-cell function both contribute^.5,16 A small increase in fasting plasma glucose (FPG) and a significant increase in post-prandial or 2 hours post oral glucose tolerance test (OGTT) are usually seen. It has also been shown that the renal threshold for glucose increases with age and therefore may not demonstrate glycosuria despite elevated blood glucose.⁷ 

The recommended diagnostic criteria for diabetes remains the same. Caution needs to prevail with the interpretation of the HbA_1c as it may be altered by co-existing conditions. These biological differences have important therapeutic relevance to this patient population.

HYPOGLYCAEMIA

Impaired liver and renal function due to ageing, with or without coexisting disease leads to decreased gluconeogenesis. This can be compounded by the reduced clearance of medications such as insulin and sulphonylureas, and may put patients at higher risk of hypoglycaemia. The normal (autonomic) defences against hypoglycaemia may be impaired and can lead to hypoglycaemic unawareness.^8,9,10 In addition; hypoglycaemia is hazardous in the older person as it predisposes to falls, cognitive impairment and may precipitate cardiac adverse events.¹¹ The avoidance of hypoglycaemia should therefore be a priority.

GLUCOSE TARGETS  

Hyperglycaemia is associated with chronic (micro and macrovascular) complications and acute metabolic complications. The general recommendation is to aim for an HbA_1c <7.0% based on the results of the UK Prospective Diabetes Study (UKPDS). The UKPDS showed a reduction in microvascular complications with glycaemic control, but mostly excluded people >65 years.¹² The Veterans Affair Diabetes trial (VADT) included older patients and did show a benefit with a decreased risk of nephropathy with good control. 

However, like the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, it failed to show any cardiovascular benefit.¹³ Other trials like the ACCORD (average duration of diabetes 10 years with average age 64 years) found a higher overall mortality in intensively-treated (HbA_1c target < 6%) patients.¹⁴

The most reasonable interpretation of the existing evidence is that safe, effective prevention of cardiovascular disease includes the intensive glycaemic control that begins early in the course of diabetes, and that aggressive intensive control in older persons with high cardiovascular risk, may be harmful.¹⁵

When deciding on a treatment plan, it is important to appreciate the heterogeneity of this population and understand the disparities that may exist between individuals of the same chronological age. The principles to be followed in choosing individualised glycaemic targets, including older persons, is discussed in Glycaemic Targets. 

Healthy older persons should be treated to achieve similar glucose, blood pressure and lipid targets as their younger counterparts.¹⁶ The UKPDS showed benefit of intensive glycaemic control over 10 years, so it is reasonable to aim for intensive control in healthy older persons with a life expectancy greater than 10 years. For older persons with limited life expectancy, cognitive impairment, frailty, high fall risk or multiple comorbidities (e.g. cardiac, renal, respiratory, neurological diseases), less stringent targets (HbA_1c up to 8.5% and fasting glucose up to 12 mmol/L) may be acceptable. The prevention of hypoglycaemia should always take priority in these latter patients.

SPECIFIC TREATMENTS

When individualising therapy it is important to contemplate all the potential benefits and harms. Generally medication with the least risk of hypoglycaemia is preferred. Lifestyle modification is still advised and if no contraindication exists, exercise should form part of the treatment plan.

ORAL AGENTS 

• Metformin

Has evidence of benefits. The dose should be adjusted for renal function. Additional precautions might be necessary at times of severe illness such as dehydration or the use of contrast agents etc.^17,18 Metformin may be associated with biochemical vitamin B₁₂ deficiency in older patients with diabetes mellitus.¹⁹ Its significance is not known but it should be treated. It may also cause undesirable weight loss/cachexia in normal weight individuals; treatment will need to be changed if this occurs.

• Sulphonylureas

Sulphonylureas with active metabolites (glibenclamide and glimepiride), generally have a higher risk of hypoglycaemia. Gliclazide MR is the preferred sulphonylurea as it has the lowest risk of hypoglycaemia (Refer to: Glucose Control : Non-Insulin Therapies for a detailed review). The mean age of patients in the European GUIDE study was 60 yrs and gliclazide MR was 2.5 times less likely to cause significant hypoglycaemia than glimepiride (3.7% vs. 8.9% of patients)^.22 The WHO Comparative Safety and Efficacy of Glibenclamide in the Elderly report analysed comparative evidence for safety and efficacy of glibenclamide, glimepiride, glipizide and gliclazide. The evidence showed that glibenclamide was not a safe medication for use in older persons (patients older than 60 years of age).

Recommendations: Glibenclamide must not be used in older persons.²³ Gliclazide MR had a superior safety profile for hypoglycaemia than glimepiride, in a group of patients that included older persons. Initial doses of sulphonylureas should be at half the dose used for adult patients and doses should be increased more gradually.^20,21,22 When prescribing sulphonylureas in older persons it is best to start at the lowest dose and slowly titrate to the individualised target while monitoring for hypoglycaemia. For older individuals at particularly high risk of hypoglycaemia (e.g. HbA_1c target <6.5%, renal impairment, erratic food intake, cognitive impairment, hypoglycaemia unawareness) or its consequences (frailty, high fall risk, inability to respond rapidly to symptoms, severe cardiovascular disease, autonomic neuropathy) it is best to avoid the sulphonylureas as a class.

• DPP-4 inhibitors

These oral agents are dosed once-daily. They are weight neutral, have excellent tolerability profiles and pose no risk of hypoglycaemia. As such, they are attractive agents in older persons. They lower HbA_1c levels by only 0.6% and are mostly used as add on agents. Not all drugs in this class have the same adverse event profile, and all available agents in South Africa must be adjusted for renal impairment.^24,25,26 (See: Glucose Control : Non-Insulin Therapies for details). Their excellent tolerability profiles, low risk of hypoglycaemia, and once-daily dosing make this drug class suitable for the frail and debilitated older persons. Studies by Schweizer et al²⁷ in populations aged over 75 years and by Strain et al²⁸ in patients aged over 70 years conclude that vildagliptin is safe in the elderly, and HbA_1c targets for control can be achieved safely.

• Thiazoledinediones

The use of pioglitazone in older adults needs to be carefully weighed with the risks of fluid retention, weight gain, and increased risks of heart failure, fracture and possibly bladder cancer.²⁹ The use of TZDs in patients over the age of 75 is not recommended at primary care level.

• SGLT2 Inhibitors

At the time of publication, these drugs were not yet registered in South Africa. Refer to Glucose Control : Non-Insulin Therapies for a more detailed review. These drugs cause glycosuria resulting in fluid and caloric loss. They do not cause hypoglycaemia. They can result in weight loss, dehydration, hypotension, acute kidney injury and fungal genital infections, and should be avoided in the frail older person. Canagliflozin has been associated with bone fractures and toe amputations. Empagliflozin was associated with reductions in cardiovascular outcomes, death and heart failure in a secondary prevention study, particularly in older people. Patient selection will be important in determining treatment success with this class.

INJECTABLE AGENTS

• Insulin

Prior to initiating insulin it is important to evaluate whether or not the patient is capable of using an insulin pen or drawing up and administering the correct dose. The patient and caregivers should be able to monitor and interpret blood glucose levels. The prescribed insulin regimen should be simple, individualized and have the least risk of hypoglycaemia. The clock drawing test is a screening tool commonly used when screening for dementia. It can accurately be used to predict which older subjects are likely to have problems with insulin therapy.^30,31,32 Premixed and prefilled insulin pens as alternatives to mixing and conventional syringes are preferred as these have been shown to minimize errors in this group.³³ Detemir and glargine may be used to lower the frequency of hypoglycaemic events.^34,35 The same principles of initiating insulin in general apply, but conservative doses with more conservative glycaemic targets should be used in older persons. (See section on insulin)

• GLP-1 agonists 

These are not contra-indicated in overweight older persons but should be used with caution in normal weight older persons because of undesirable weight loss, which may affect muscle bulk strength (sarcopaenia). (See section on non-insulin therapy). Their weight-reducing effect and gastrointestinal side effects may be detrimental for the frail older patients with poor caloric intake and poor nutrition.³⁶These drugs should be used with caution in older patients with unintentional weight loss, are malnourished or at high risk for malnutrition.³⁷ Liraglutide was beneficial in lowering adverse cardiovascular outcomes compared to standard therapies in patients with pre-existing cardiovascular disease in the LEADER trial.³⁸

HYPERTENSION

More intensive control of BP (systolic <140 vs. <120) does not improve outcomes and results in more side effects.²⁹ The target BP for older persons is <140/90 mmHg (see section on hypertension). Drugs with proven benefit in older persons include thiazide-like diuretics (indapamide), ACE-inhbitors and angiotensin receptor blockers and calcium channel blockers, although amlodipine may increase the risk of heart failure.⁴⁰

DYSLIPIDEMIA

The treatment of dyslipidaemia with statins for both primary and secondary prevention of CV events has been shown to reduce CV morbidity and mortality in older people with diabetes. The data on the use of fibrates in this patient population are equivocal.²⁸Combination statin and fibrate therapy in older persons should only be prescribed under specialist supervision. (Refer to: Cardiovascular Risk and Dylipidaemia.)

Author: Sophia Rauff
Editors: Aslam Amod and Zaheer Bayat

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