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Ultra-long-acting basal insulin reduces blood glucose variability and hypoglycaemia risk in the elderly

Dr. Jenny Lee
Specialist in Geriatrics Medicine
Hong Kong
12 Mar 2020

Hypoglycaemia and large fluctuations in blood glucose levels impact elderly patients with diabetes to a greater extent and more adversely than younger adult patients. In addition, age-related conditions and other comorbidities make diabetes management in the elderly even more challenging. A new-generation ultra-long-acting basal insulin analogue allows once-daily dosing and flexible timing of administration without compromising glycaemic control. In an interview with MIMS Doctor, Dr Jenny Lee, Specialist in Geriatrics Medicine in Hong Kong, discussed the value of these features in the management of elderly patients with type 2 diabetes mellitus (T2DM). 

Impacts of hypoglycaemia and glycaemic variability in the elderly

“The prevalence of T2DM in Hong Kong is 12.5 percent and about 50 percent of individuals with diabetes are over 65 years of age,” said Lee. 

“For older adults, especially those with a longer history of diabetes, good glycaemic control entails not only the prevention of hyperglycaemia, but also the avoidance of hypoglycaemia. While glucose peaks and glycaemic variability are associated with risks of dementia and major adverse cardiovascular [CV] events, glucose levels that are too low may cause damage to glucose-dependent vital organs such as the brain and the heart,” she noted. (Figure 1) [Diabetes Care 2017;40:879-886; Diabetologia 2018;61:48-57]

According to Lee, cognitive impairment, functional decline and disability, as well as depression – on top of the usual complications of diabetes – make the task of glycaemic control even more challenging in the elderly who have a reduced ability to manage their condition and are often dependent on caregivers. “In the elderly, food intake and appetite are affected by health status and mood, their limited dietary choices, and resistance to dietary changes. Poor drug compliance and poor diet control associated with these age-related conditions contribute significantly to hypoglycaemia in T2DM,” Lee explained.

“Among older adults with T2DM, there is increasing evidence of a bidirectional relationship between hypoglycaemia and dementia. Hypoglycaemia commonly occurs in older patients with T2DM and may negatively influence cognitive performance, which in turn compromises T2DM management, leading to hypoglycaemia,” she noted. [JAMA Intern Med 2013;173:1300-1306]

“Hypoglycaemia in the elderly patients with diabetes is associated with increased morbidity and mortality. For instance, comorbidities and concomitant medications, lower blood glucose thresholds for hypoglycaemic symptoms, and reduced awareness of hypoglycaemia coupled with defective counter-regulatory mechanisms put the elderly at increased risk of falls and consequently fractures, especially hip fractures, which are associated with high 1-year mortality rates. The elderly are also at higher risk of cardiac arrhythmias, which are often linked to deaths as a result of nocturnal hypoglycaemia,” Lee continued.

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T2DM treatment goals in the elderly

The latest American Diabetes Association (ADA) guidelines have specifically addressed the management of diabetes in older adults (aged ≥65 years), recommending that treatment and target HbA1c levels for elderly patients be individualized according to their frailty status, which is broadly classified into three categories based on a consensus framework. [Diabetes Care 2018;41(Suppl 1):S119-S125; Diabet Med 2018;35:838-845]

Older adults in a robust state of health with good cognitive and functional status may be managed using treatments and goals similar to those in diabetic adults below 65 years of age, with HbA1c levels controlled at <7.5 percent and fasting blood glucose levels at 5.0–7.2 mmol/L.

“Those with mild-to-moderate cognitive or physical impairments and life-limiting concomitant diseases fall into the prefrail or intermediate category. These patients are less likely to reap the benefits of tight long-term glycaemic control and more likely to suffer serious adverse effects from hypoglycaemia. Therefore, the HbA1c target is relaxed to <8.0 percent and the upper limit of fasting blood glucose is raised to 8.3 mmol/L,” Lee advised.

“In very frail older patients, especially those with multiple long-term chronic diseases or terminal illnesses who have short life-expectancy, high rates of hospital admission and a high risk of mortality, diet and glycaemic control becomes even more difficult. For these patients, glycaemic goals are even less stringent, with an HbA1c target of <8.5 percent and a fasting blood glucose target of 5.6–10.0 mmol/L as a guide. In patients who are dying from terminal malignancies or advanced chronic diseases, glycaemic monitoring during end-of-life care could be omitted,” Lee added.

Appropriate therapy for elderly T2DM patients

“Vulnerability to hypoglycaemia, physical and cognitive impairments, dependence on caregivers for diet and drug management, and the presence of comorbidities limit treatment options for elderly patients with T2DM,” noted Lee.

Ultra-long-acting basal insulin (eg, insulin degludec [IDeg]) is an optimal treatment option for elderly patients with T2DM requiring insulin therapy because of its ease of use, once-daily dosing, and the reduced within-day and day-to-day variability in glucose-lowering effect, which reduces the risk of hypoglycaemia. (Figure 2) In addition, this type of insulin offers flexible timing of administration (ie, no need to be given at the same time every day), which is more convenient for both the patients and the caregivers. [Diabetes Obes Metab 2012;14:859-864; Diabetes Res Clin Pract 2015;109:19-31]

“Ultra-long-acting basal insulin is particularly suitable for elderly patients with a history of hospitalization due to hypoglycaemia or those with frequent episodes of severe hypoglycaemia with other insulins or antidiabetic agents, regardless of their financial means, because avoiding the higher cost of hospitalization would justify the use of ultra-long-acting basal insulin,” noted Lee. “It is also a suitable and safer option for the prefrail and frail groups of patients and those who have irregular meals for whatever reason.”

“For those who depend on community nurses or caregivers for insulin injections and those who are unable to administer insulin injections at the same time daily due to unpredictable work schedules, ultra-long-acting insulin is a convenient and safe option, as long as the interval between injections is over 8 hours apart,” she noted.

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Starting and switching insulin therapy in elderly patients

“It would be advantageous to use ultra-long-acting basal insulin as the initial insulin therapy in elderly patients, especially those who are frail and have a variable appetite. Those already on other types of insulin but have frequent hypoglycaemia and hyperglycaemia may benefit from the use of a long-acting or an ultra-long-acting insulin. To switch over, I would first assess whether the existing control is too tight or too loose and then adjust the dose accordingly, preferring to err on the side of caution and to allow higher glucose levels at the beginning of drug switching, and to then gradually increase the dose as needed,” advised Lee.

“For those with large blood glucose fluctuations [eg, morning fasting levels <5 mmol/L and postprandial levels >20 mmol/L], and very often, a high HbA1c level, I would reduce the current total dose by about 20 percent when switching over to ultra-long-acting basal insulin. This may result in higher blood glucose levels in the beginning, but with careful titration, HbA1c levels may actually improve over the long term with maintenance of stable blood glucose levels. Afterall, for elderly patients with competing comorbidities or those with established diabetes complications such as kidney disease, their shorter life expectancy renders them much less likely to benefit from good HbA1C control, but hypoglycaemic episodes can be very dangerous,” she added.   

The randomized, double-blind, treat-to-target crossover SWITCH 2 trial, which comprised two 32-week treatment periods, demonstrated significantly lower rates of both overall symptomatic hypoglycaemia (219.9 vs 275.1 episodes per 100 patient-years of exposure [PYE]; estimated rate ratio [ERR], 0.77; 95 percent confidence interval [CI], 0.70 to 0.85; p<0.001; rate difference, -19.4 percent) and  nocturnal symptomatic hypoglycaemia (72.0 vs 88.4 episodes per 100 PYE; ERR, 0.75; 95 percent CI, 0.64 to 0.89; p<0.001; rate difference, -4.4) with IDeg vs insulin glargine U100 in T2DM patients for the full treatment period. (Figure 3) [JAMA 2017;318:45-56]

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Summary

“In summary, T2DM management and treatment goals for the elderly should not be the same as those for young adults. Instead, these should be individualized according to the patient’s frailty status, with the prevention of hypoglycaemia being a priority,” concluded Lee.

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