This Guidelines summary of Diabetes and frailty: an expert consensus statement on the management of older adults with type 2 diabetes includes key recommendations for primary care practitioners.
The authors’ aim was to provide prescriptive guidance for glycaemic management in older adults with diabetes according to frailty, including frailty-specific glycaemic targets, and to encourage appropriate revision of therapy according to individual need and frailty status.
Reflecting on your Learnings
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Degrees of Frailty and Treatment Goals in Older Adults with Type 2 Diabetes
- There are several ways to assess frailty, but tools like the Electronic Frailty Index, Rockwood scale, and Timed Up and Go test can be used to confirm clinical suspicion
- Prognoses, and hence appropriate diabetes treatment goals, for older adults with diabetes vary greatly according to frailty, and therefore need to be individualised
- Frailty, rather than comorbidity, underpins target setting, recommended interventions, and treatment goals in older adults with diabetes (see Table 1)
- It is important to remember that frailty is a dynamic process; a person’s frailty categorisation may change, hence the need for regular reassessment, particularly following a change in circumstances, such as moving to a care home, hospitalisation, increased adherence to medications, or weight loss due to decreased appetite
- Re-evaluation of frailty should occur, as a minimum, at the annual diabetes review, but earlier if there has been a change in health status, and 3 months after any intervention (escalation or de-escalation)
- Targets may need to be re-evaluated based on the development and diagnosis of coexisting chronic illnesses and/or changes in cognitive function and functional status
- Individuals should be assessed for any signs of change in physical or mental status, or in vision or cardiovascular (CV) status.
Table 1: Target Setting, Recommended Interventions, and Treatment Goals According to Frailty in Older Adults with Diabetes
|Level of frailty||Status||Treatment goals||Recommended interventions||Recommended targets|
|© Strain D et al 2021. Reproduced with permission.A significant part of clinical decision making in older people with diabetes involves consideration of their frailty status, but this will vary in importance depending on the presence of other factors including severe comorbidity, vascular complications, and cognitive impairment.|
BP=blood pressure; FPG=fasting plasma glucose; HbA1c=haemoglobin A1c; QoL=quality of life
Diet and Exercise
- The management of diabetes in older people should focus on diet and exercise
- Any resulting weight loss from lifestyle intervention in frail older people with diabetes or overweight should be modest (for example, 5–7%)
- Optimal nutrition with adequate protein intake is recommended for maintaining muscle volume in such patients. However, it should be noted that there are potential disadvantages associated with high protein intake: for example, red meat intake may increase the risk of end-stage renal disease. Therefore, maintaining a daily protein intake of 0.8 g protein/kg is recommended for both healthy individuals and those with diabetes and chronic kidney disease
- It is important that older adults with type 2 diabetes are encouraged to exercise regularly, if such activities can be carried out safely. These exercises include weight-bearing activity, aerobic activity, and/or resistance training.
Hypoglycaemia in Older Adults with Diabetes
- The avoidance of hypoglycaemia must be a paramount concern in the diabetes management of the frail older adult, and it cannot be assumed that regimens previously well tolerated in this respect will remain so
- The treatments for type 2 diabetes with the greatest propensity for causing hypoglycaemia are insulin and the insulin secretagogues: sulfonylureas (SUs) and glinides.
Review of Available Antihyperglycaemic Therapies
- Table 2 summarises the pros and cons of the various drug classes of antihyperglycaemic therapies as they pertain to older adults; further detail is provided in the full guideline.
Table 2: Pros and Cons of Antihyperglycaemic Therapies for the Treatment of Type 2 Diabetes in Older Adults
|Metformin—alters mitochondrial cell energetics to inhibit gluconeogenesis, oppose the action of glucagon and increase insulin sensitivity|
|SUs and glinides—stimulate pancreatic insulin secretion regardless of blood glucose concentration|
|DPP-4 inhibitors— inhibit breakdown of endogenous GLP-1, which glucose-dependently stimulates insulin secretion and inhibits glucagon secretion|
|SGLT2i inhibit reabsorption of glucose (from renal tubules), leading to increased urinary glucose output and osmotic diuresis|
|GLP-1 RAs—stimulate insulin secretion, inhibit glucagon secretion and also reduce appetite; GLP-1 RAs work in a glucose-dependent manner|
|TZDs—increase cellular expression of glucose transporters, thereby increasing insulin sensitivity and peripheral glucose uptake|
|Exogenous basal insulin—binds to insulin receptors in liver to inhibit glycogenolysis and gluconeogenesis, and binds to peripheral insulin receptors (muscle, adipose) to stimulate glucose uptake||—||—|
|First-generation basal insulin analogues—insulin glargine, insulin detemir|
|Ultra-long-acting insulin analogues—insulin degludec, insulin glargine U300|
|© Strain D et al 2021. Reproduced with permission.ASCVD=Atherosclerotic; CV=cardiovascular; CVD=cardiovascular disease; CVOT=cardiovascular outcome trial; DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1; GLP-1 RA=glucagon-like peptide-1 receptor agonist; MACE=major adverse cardiovascular events; MI=myocardial infarction; NPH=neutral protamine Hagedorn; SGLT2i=sodium-glucose cotransporter-2 inhibitor; SU=sulfonylureas; TZD=thiazolidinedione|
Glycaemic Management in Older Adults with Diabetes, According to Frailty
- It is suggested that fit older adults aged under 75 years should follow an algorithm based on the American Diabetes Association/European Association for the Study of Diabetes consensus statement. The only potential exception is that of the use of thiazolidinediones (TZDs) for the management of diabetes in patients for whom hypoglycaemia should be avoided; this class of oral antihyperglycaemic drugs is relegated to a reserve position due to their impact on osteoporosis and risk of heart failure
- The choice of agents for the management of diabetes in older adults should be based on frailty status and the extent of coexisting chronic illness and cognitive and functional status
- Clinicians are recommended to follow the simple glycaemic management algorithm depicted in Algorithm 1 for older adults with type 2 diabetes, according to their level of frailty
- When escalating therapy, the risk of hypoglycaemia should be considered for those on insulin or SUs. It is not necessary to automatically discontinue an SU if there is no evidence of hypoglycaemia, although the dose should be reduced in the short term. For people on neutral protamine Hagedorn (NPH) or premix insulin, switching to a basal insulin analogue (glargine, detemir, or degludec) with a dipeptidyl peptidase-4 inhibitor can be considered.
Treatment Escalation and Simplification/De-escalation Algorithms
Algorithm 1: Treatment Escalation and Simplification/De-escalation Plan for Older Adults Living with Type 2 Diabetes and with No or Mild Frailty
Algorithm 2: Treatment Escalation and Simplification/De-escalation Plan for Older Adults Living with Type 2 Diabetes and with Moderate Frailty
Algorithm 3: Treatment Escalation and Simplification/De-escalation Plan for Older Adults Living with Type 2 Diabetes and with Severe Frailty
Treatment Simplification/De-escalation Guidance in the Glycaemic Management of Older Adults with Diabetes
- When contemplating modification of a diabetes regimen, it is helpful to conduct a basic audit of the status of the person with diabetes. An individual at advanced age (for example, over 75 years), identified as being moderately or severely frail, with a glycated haemoglobin (HbA1c) value less than 53 mmol/mol (less than 7.0%), would suggest a high risk of occurrence of complications from hypoglycaemia
- Consideration should be given to de-escalation of therapies that may induce this feared complication, such as SUs or SU–insulin combinations
- It should not be assumed that treatment regimens that have been intensified historically or those that were initiated in hospitals should continue indefinitely
- For older adults with diabetes, attending medical appointments may be difficult or impractical. In such cases, teleconsultations may be a suitable alternative
- De-escalation of non-insulin glucose-lowering regimens can be achieved by either lowering the dose or discontinuing some medications. Insulin regimens can either be de-escalated by reduction of the dose or simplified by switching to more manageable regimens with lower risk of hypoglycaemia such as, for example, from premix insulins to a basal insulin analogue with or without a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitor
- Glucose monitoring in older adults with type 2 diabetes should be increased after any switch in insulin therapy, with the dosages adjusted on an individual basis and dependent on the previous insulin regimen
- It is important to be mindful that SUs and GLP-1 RAs raise endogenous insulin secretion, hence they decrease the unit-dose requirement for exogenous insulin compared with insulin monotherapy. A sensible approach would be either to reduce the dose of SU when administered in combination with insulin or to discontinue SU treatment altogether, in favour of insulin monotherapy with close metabolic monitoring during and after any change in regimen
- TZDs also increase sensitivity to insulin, so, again, compensatory dose adjustments are required when these are used in combination with insulin
- In a small proportion of individuals, stopping insulin suddenly can precipitate diabetic ketoacidosis, so insulin should be withdrawn slowly and response to each dose adjustment should be monitored, ideally within 1 month
- A single early-morning urinary C-peptide to creatinine ratio measurement can provide reassurance that there is sufficient residual pancreatic function to safely de-escalate and discontinue insulin, but this may have to be organised by secondary care teams for people living in the community
- Often during reviews of frail older adults, individuals will be identified with a low HbA1c (less than 48 mmol/mol; less than 6.5%). It should be considered that insulin resistance may have subsided sufficiently that no therapies are required. In this scenario, it is reasonable to discontinue all antihyperglycaemic agents and review control after 3 months against an individualised HbA1c goal
- Care must be taken to identify those who may be at risk of rebound hyperglycaemia if on multiple agents even if HbA1c is less than 48 mmol/mol (less than 6.5%) and, therefore, in such circumstances, a pragmatic/ sequential cessation of medication may be required. In such people, previous glycaemic control/HbA1c and medication commencement history may support rapid or slower discontinuation
- HbA1c can rise sharply after stopping an SU, even if this has been taken for many years, so it may be appropriate to restart at a lower dose in such cases
- People living with diabetes should be reviewed after each change in regimen (that is, a 3-month review programme with an HbA1c measurement after every withdrawal) to check that glycaemic control (and other risk factor management) is appropriate for their frailty category, and also to check whether frailty status has changed
- In all cases, it is important to explain to the individual (and relatives) that the reasons for de-escalation are concerned with improving symptoms, function and quality of life, frailty status and comorbidity in order to avoid the misconception that de-escalation represents ‘giving up hope’
- A regular review of medication is recommended, and considerations should be made for simplification of regimens, where possible, to reduce pill burden, including consideration of combination therapies.