Section 1

Marianne is 71 years old, lives with her husband and has had type 2 diabetes for 7 years. Her general health remains good; she plays golf regularly, is an active member of the local bridge club and is a driver.

Glycaemic control has slowly deteriorated in recent years, with a recent HbA_1c measurement of 68 mmol/mol despite continued use of metformin 1000 mg twice daily. Her lipid profile is well controlled on simvastatin 40 mg at night. Other readings include: eGFR 68 mL/min/1.73 m²; FBC, LFT and TFT normal; ACR 6.3 mg/mmol; BP 142/68 mmHg on ramipril 10 mg once daily; BMI 27.3 kg/m². Marianne has background diabetic retinopathy.

What factors might you consider in agreeing an HbA_1c target with Marianne?

Section 2

An individualised approach is essential when approaching glycaemic control in the elderly.^1–4 Short life expectancy would remove the necessity for tight glycaemic control. With increasing duration of diabetes the benefit of tight glycaemic control lessens,⁵ especially if a drug with the potential to cause hypoglycaemia needs to be used. There is an association between both poor and tight levels of glycaemic control and increased mortality in elderly people with diabetes, and also an adverse effect from a high degree of glycaemic variability.⁶

Avoidance of hypoglycaemia is of paramount importance in the elderly/frail; not only are they at increased risk of experiencing hypoglycaemia, but the consequences may be more profound. Declining renal and hepatic function may increase the risk of drug toxicity (including an increased risk of hypoglycaemia), as can polypharmacy; many older people are on complex drug regimens for which the likelihood of drug interaction is high.

Clearly, managing diabetes in the elderly requires a holistic approach. In addition to reviewing biochemistry, medication and risk of hypoglycaemia, assessments of comorbidities, lifestyle, mood, cognitive status and social support are required to achieve a true functional status (rather than relying on age), which in turn can help decide target HbA_1c.^1–4

Assessment of frailty, specifically, is important in directing management. Frailty is characterised by diminished strength and endurance that increases vulnerability for developing dependency and/or death.⁷ Sarcopenia (loss of muscle strength) is a central feature of frailty. Tools are available to quantify frailty, and thus help agree appropriate glycaemic targets.

When Marianne is seen at the surgery, it is clear that she has good physical and mental health. There is no evidence of frailty, depression, dementia or cognitive decline. She is well able to manage activities of daily living, and has good support from her husband. She has little in the way of comorbidities. It seems quite probable that she will live into her eighties. Provided we can avoid the risk of medication-induced hypoglycaemia, it would seem reasonable to aim for an HbA_1c in the range of 53–59 mmol/mol.⁷

Why is hypoglycaemia such an important issue in choosing medication in the elderly?

Section 3

With increasing age and duration of diabetes, the adrenalin response to falling glucose levels becomes blunted, with accompanying loss of the autonomic warning symptoms of hypoglycaemia (tremor, sweating, palpitations and nausea).⁸ Under these circumstances, the danger is of progression to very low blood glucose levels and the more serious problem of neuroglycopaenia (confusion, behavioural change, speech difficulty, blurred vision, drowsiness and, ultimately, convulsions and coma). The gravity of this situation may be exacerbated by a sluggish response of glucagon (which stimulates release of glucose from the liver). Cognitive decline exacerbates the problem of hypoglycaemic awareness.

Thus, in the elderly, the combined effects of a deficient adrenalin response and glucagon inadequacy can result in an absence of warning symptoms, with rapid descent to severe hypoglycaemia by which time cognitive dysfunction has taken hold. Under these circumstances there is a risk of serious injury, including fractures and head injuries, and also of cardiac arrhythmias and cardiovascular events.⁹ Severe hypoglycaemia is likely to result in hospital admission.¹⁰

What would you consider as the next option to improve glycaemic control for Marianne? What diabetes medications are most useful in the elderly?

Section 4

A second oral agent would be appropriate for Marianne.⁴ Before making this choice, we should check whether Marianne has any symptoms or signs of cardiovascular disease or heart failure, and assess renal function and cardiovascular risk. A further urinary ACR should be undertaken to confirm albuminuria.

An SGLT2 inhibitor would be an alternative option, carrying a low risk of hypoglycaemia while having the benefits of weight loss, renoprotection and cardiovascular protection (Marianne’s albuminuria would suggest diabetic nephropathy, a situation of increased cardiovascular risk). Problems with SGLT2i use include an increased risk of genital thrush, increased micturition, and a small risk of diabetic ketoacidosis and Fournier’s gangrene.

The DPP-4 inhibitors are a safe, well-tolerated, weight-neutral option with a low risk of hypoglycaemia. They can be used down to end-stage renal failure per appropriate dosing, and cardiovascular safety has been demonstrated.^11–13

Sulfonylureas (SUs) would be a more problematic choice for glycaemic control (as would the meglitinides, such as repaglinide) in a woman of Marianne’s age, because of the associated risk of hypoglycaemia, and particularly so as Marianne drives. If these agents were to be used, then initiation of glucose monitoring would be necessary. Pioglitazone is not contraindicated and is not prone to causing hypoglycaemia, but there is always the concern of inducing heart failure in the elderly, and further concerns about the possible association with fracture risk and bladder cancer.¹⁴ Both SUs and pioglitazone may lead to weight gain. Neither of these agents look to be a favourable option for Marianne.

GLP-1 receptor agonists may, in the right context, be useful agents in the older person, particularly where obesity is present. Once-weekly injectable preparations could be advantageous, especially if there is a requirement for another person to administer treatment. The GLP-1 RAs achieve impressive improvements in glycaemic control together with weight loss, can provide cardiovascular protection and possibly renoprotection, and can be used safely in chronic kidney disease down to low eGFR values. The most troublesome side-effects are gastrointestinal.

Where possible, insulin is better avoided in the elderly because of the risk of hypoglycaemia and the complexity of administration. If an individual’s high HbA_1c makes insulin therapy necessary, then a full education package (including advice on avoidance, recognition and treatment of hypoglycaemia; blood glucose monitoring and interpretation; and advice on driving) will be essential.

After discussion of benefits and risks, Marianne opted for an SGLT2i, which can provide renoprotection and cardioprotection. Dapagliflozin 10 mg once daily was commenced alongside her metformin.¹⁵

Section 5

Mike is 78 years old and has had type 2 diabetes for 19 years. Six years ago, he suffered a myocardial infarction. He has osteoarthritis of his hip that requires the use of a stick to walk and has had a stairlift installed. Mike is able to wash, dress and cook for himself. In the past, he has received input from the physiotherapist and occupational therapist. Mike lives alone, but his daughter lives nearby and helps with his shopping and housework. She helps organise his medications. Mike has friends who drop in to see him, and he enjoys time in the garden and watching sport on TV. He is helped out to visit the local park and attend home matches of his local football team.

Medication list: metformin 1000 mg twice daily; gliclazide 80 mg twice daily; alogliptin 25 mg once daily; aspirin 75 mg once daily; atorvastatin 80 mg once daily; bisoprolol 2.5 mg once daily; lisinopril 20 mg once daily; bendroflumethiazide 2.5 mg once daily; doxazosin 8 mg daily; sertraline 50 mg once daily; co-codamol 8/500 taken as needed.

Mike is reviewed because he has been experiencing episodes of shakiness and sweating after a long time spent gardening, and dizziness that appears to be associated with standing. He also reports a generalised muscle ache.

Cognition appears intact from a mini-mental test score, and screening questions would suggest Mike is not significantly depressed. BP is 117/58 mmHg, with postural drop on standing. BMI is 31.2 kg/m².

Investigations are arranged that show: HbA_1c 51 mmol/mol; eGFR 55 mL/min/1.73 m²; LFTs normal; TSH 3.2 mIU/L; cholesterol 3.4 mmol/mol, non-HDL cholesterol 2.1 mmol/mol; Hb 132 g/L.

What do you think might be the cause of Mike’s shakiness and dizziness?

Section 6

The cause of Mike’s dizziness may be multifactorial, but postural hypotension would certainly seem to be a significant contributor. Although Mike has not been monitoring capillary glucose levels very regularly (despite encouragement to do so), he is aware that readings have been running <10 mmol/L and, on occasion, falling below 4 mmol/L. This information, together with the low HbA_1c and use of gliclazide, suggest that his symptoms may be due to hypoglycaemia.

What changes in medication might you now make?

Section 7

The problem of polypharmacy in the elderly is well documented. De-intensification and simplification of medication regimens should always be attempted, where possible. Overtreatment of hyperglycaemia in older people needs to be avoided, not least because the benefits accrued from intensive glycaemic control can take years to become apparent.¹⁶

As an elderly person living alone with comorbidities and a degree of frailty, Mike is vulnerable to hypoglycaemia and its consequences. Tight glycaemic control is inappropriate under these circumstances, and an HbA_1c up to 64 mmol/mol would be acceptable. Mike’s gliclazide was, therefore, discontinued. Empagliflozin was commenced because it can provide cardiovascular protection in those who, like Mike, have established cardiovascular disease.¹³ It also offers improvement in glycaemic control with a low risk of hypoglycaemia.

There may be concern that Mike’s beta-blocker could attenuate the adrenalin response to hypoglycaemia, although, at this stage, it was felt better to continue with his bisoprolol for its cardiovascular benefits.

Mike’s BP is unnecessarily low and, as doxazosin would be particularly implicated with his postural hypotension, this treatment was stopped. If symptoms of dizziness did not clear and BP remained on the low side, then consideration could be given to withdrawing his thiazide diuretic.

Finally, the symptoms of myalgia that Mike reports may relate to his high dose of atorvastatin, and could contribute to his mobility problems. Accordingly, the dose of atorvastatin was reduced to 20 mg daily, a creatinine kinase (CK) level was requested, and a follow-up appointment arranged for a month’s time.

Factors that can direct agreement of an appropriate HbA_1c in an elderly person are summarised in Section 13 at the end of this module, and frailty assessment is central to this process.⁷

Section 8

Claire is 81 years old and lives in a care home permanently. She has Alzheimer’s disease and long-standing type 2 diabetes. Four years previously, she suffered a right-sided stroke that left her with residual weakness. She has frequent lower urinary tract infections that have, on occasion, led to hospital admission, and has episodes of urinary incontinence. Claire uses a frame to mobilise and a wheelchair when outside. She needs some assistance with dressing, toileting and bathing.

The care home staff report that, since commencing fluoxetine 3 months ago, Claire’s appetite, sleep and mood have improved, and she is engaging more with them and the other residents. She remains rather drowsy in the morning, but picks up as the day progresses.

You are asked to review her diabetes. Blood tests ahead of her review show: HbA_1c 87 mmol/mol; eGFR 37 mL/min/1.73 m², with a raised urea level; cholesterol 4.7 mmol/L; normal FBC, LFT and TFT.

Capillary glucose readings are typically between 9 and 14 mmol/L in the morning, with readings up to 20 mmol/L later in the day. BP is 143/66 mmHg.

Medication: clopidogrel 75 mg once daily; omeprazole 20 mg once daily; atorvastatin 20 mg once daily; ramipril 5 mg once daily; amlodipine 5 mg once daily; metformin 500 mg twice daily; insulin Lantus 22 units at night; donepezil 5 mg once daily; fluoxetine 5 mg once daily; trimethoprim 100 mg at night; amitriptyline 25 mg; solifenacin 10 mg once daily; calcium/vitamin D supplements.

What might be on your checklist when reviewing Claire’s diabetes care?

Section 9

A holistic approach to diabetes care is essential in the frail elderly person.⁴ Maintaining safety and focusing on quality of life are important principles. Diabetes has an adverse impact on physical and mental health. Thus, for example, the risk of falling is increased around three-fold in people with diabetes.¹⁷ There is evidence of an association between diabetes and Alzheimer’s disease and cerebrovascular dementia,¹⁸ and the relationship between diabetes and depression appears to be bi-directional in causality.¹⁹ Good care can help avoid hospital admission, bearing in mind that approximately one in six people occupying hospital beds has diabetes, with the vast majority being over 65 years old.²⁰

Areas to be considered at review include:

• Mental health, depression
• Cognitive skills, dementia
• Vision, hearing
• Mobility, balance, risk of falls
• Activities of daily living
• Comorbidities
• Medication review, polypharmacy, drug side-effects and interactions
• Appropriate glycaemic control, avoidance of hypoglycaemia
• Cardiovascular risk, hypertension, hyperlipidaemia
• Dentition

What issues arise from this review for Claire?

Section 10

Poorly controlled glycaemia, over-zealous BP control, morning drowsiness, urinary incontinence and recurrent urinary tract infections are issues that will need addressing.

What do you think about Claire’s current level of glycaemic control? What would you recommend as a target HbA_1c?

Section 11

Whilst intensive glycaemic control is not appropriate for Claire, given her degree of frailty, a reasonable target for HbA_1c would be <70 mmol/mol, to ensure she remains asymptomatic from hyperglycaemia without risking hypoglycaemia;⁷ see further detail in Section 13. The degree of hyperglycaemia she is currently experiencing will generate glycosuria that predisposes to urinary tract infection, and an osmotic diuresis that may trigger urinary incontinence. Her elevated urea level points toward dehydration.

What changes might you make to her medication?

Section 12

In considering treatments for hyperglycaemia, Claire’s metformin cannot safely be increased further given her current eGFR measurement. There is the option of uptitrating the dose of Lantus, which will improve fasting glucose levels, although first we should check injection sites and ensure that site rotation of injections, new needle for each injection and correct needle length are all in place. Addressing rises in post-prandial glucose requires an additional agent. Intensification of her insulin regimen to incorporate a fast-acting prandial insulin would risk hypoglycaemia, require more intensive glucose monitoring and be logistically more difficult to establish. The safest option would be a DPP-4 inhibitor, which would be compatible with Claire’s renal failure and minimise the risk of hypoglycaemia (see discussion of options in Section 4).

A urine dipstick reveals glycosuria, but not indicators of infection. There is no evidence of bladder prolapse. A foot examination reveals the build-up of callus on the heels and under the metatarsal heads, and Claire is referred to a podiatrist.

Claire is prescribed linagliptin 5 mg once daily. Her dose of Lantus is increased by 2 units to 24 units daily, aiming for morning blood glucose readings in the range 6­–10 mmol/L. Further 2-unit increases of Lantus could be made at weekly intervals until fasting glucose readings are within target range.

Claire’s burden of anticholinergic medication is high. Amitriptyline and solifenacin both contribute to this and, having excluded morning (fasting) hypoglycaemia, may well account for Claire’s morning drowsiness. In view of this, and as Claire is now sleeping better, her amitriptyline is stopped.

It is possible that as glycaemic control improves and the osmotic diuresis eases off, solifenacin can be discontinued. Indeed, if urinary tract infections are avoided, her prophylactic trimethoprim may not be necessary. Staff are advised to encourage Claire to maintain a good fluid intake.

Section 13. Setting glycaemic targets in the elderly

In agreeing an appropriate HbA_1c target in the elderly, key elements are functional status, life expectancy and risk of hypoglycaemia.⁷

A useful review of managing diabetes in older adults can be found in the ADA standards of care document.³