The elderly population is rapidly increasing worldwide; South Korea especially is among the countries expected to see life expectancy increase significantly [1]. As of 2024, those aged 65 years and older accounted for 19.2% of the country’s total population [2]. The speed of this aging is the fastest in the world. While Korea’s aging population reflects significant social progress, being due to medical advancements and improved living standards, it also brings to the forefront various public health issues, such as the increasing burden of chronic diseases, including type 2 diabetes mellitus (T2DM); this burden has become a major concern globally. Diabetes in particular is a significant cause of death, accounting for an estimated 11.3% of deaths worldwide in 2019 [3]. As of 2020, 5.27 million Korean adults over 30 years of age were diagnosed with diabetes; 3 million of those patients are over 60 years of age, making up more than half of the total diabetes population [4]. Looked at from the other direction, the prevalence of diabetes among Korean seniors over 65 years of age is 30.1% [4]; moreover, the prevalence of pre-diabetes in this age group is alarmingly high at 50.4%. Given the rising trend in obesity among the elderly, it is anticipated that the risk of diabetes in this population will continue to increase in the foreseeable future [5]. The increasing trend of diabetes prevalence in the elderly varies by region and race; prevalences are relatively low in European countries, but particularly pronounced in high-income East Asian countries like Korea. This strong increase is attributed to changes in lifestyle habits, including diet, and to rapid changes in socio-economical factors in East Asia, in addition to pathophysiological characteristics [6].

The dual burden of T2DM and geriatric-specific syndromes in the elderly leads to these patients having multifaceted needs, which a comprehensive approach is needed to address [7]. Current management strategies are still largely based on evidence from younger populations; more tailored approaches for elderly T2DM are currently lacking and emphatically required. Nonetheless, establishing an optimal management strategy for elderly diabetes is challenging for several reasons. Disease expression in the elderly is often ambiguous, complicating diagnosis and management; in particular, unlike younger adults, elderly adults with T2DM exhibit considerable variability due to factors such as age-related physiological changes, multiple chronic diseases, and varying levels of functional, cognitive, and mobility abilities [8]. Elderly individuals also have a high incidence of cardiovascular diseases and cancer, which conditions significantly increase the risk of death. Acute complications of diabetes that are particularly dangerous in the elderly include hyperglycemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), severe hypoglycemia, and severe acute infections, which also elevate mortality risk [9]. Even non-lifethreatening microvascular complications can lead to declines in function and quality of life, potentially resulting in loss of independence. Neurocognitive impairment is also more frequent in patients with diabetes, and constrains their ability to manage glycemic levels and respond to hyperglycemia and hypoglycemia [10]. Moreover, recent socioeconomic changes have led to an increase in obesity, which, in addition to being often seen in younger diabetes, is now also appearing as sarcopenic obesity in elderly T2DM [11]. Finally, polypharmacy is common among the elderly, and increases the risk of drug interactions and side effects [12]. Given all of these complicating factors, it is necessary to develop an integrated strategy for diabetes care in the elderly that reflects the complex and heterogeneous individual characteristics of this age group and takes into account their distinctive lifestyle habits, socioeconomic factors, and support systems.

In this review, we will explore the multifaceted characteristics of T2DM in the elderly and approaches to its treatment. By enumerating these factors, we aim to highlight the importance of individualized treatment and the need for treatment strategies that can address the diverse needs of elderly patients with T2DM.

T2DM in the elderly involves complex age-related changes in numerous physiological processes associated with glucose and insulin metabolism. Although the action of insulin does not itself change significantly, insulin secretion from β-cells is reduced and insulin sensitivity in peripheral tissues is decreased as part of the aging process [13]. Reduction of the rate of insulin secretion in response to glucose is particularly pronounced in lean elderly individuals [14]. Generally, aging is associated with decreased skeletal muscle mass and function; this is accompanied by an increase in abdominal visceral fat, another major factor leading to increased insulin resistance [15]. Notably, in Korea, the prevalence of obesity among individuals over 60 years of age is 40% as of 2021, with the abdominal obesity rate exceeding 30% [5]. In the very elderly, those over 70 and even 80 years of age, the abdominal obesity rate is as high as 38%. Other factors contributing to increased insulin resistance in elderly T2DM include decreased physical activity, increased fat accumulation in muscles and liver, dysfunction of muscle mitochondria, and an increased inflammatory response. A sedentary lifestyle leads to increased obesity and insulin resistance; obesity increases low-grade inflammation, which can inhibit the insulin signaling system and lead to hyperglycemia [16,17].

In the elderly, not only are the mechanisms that regulate hyperglycemia compromised, but also those that protect against hypoglycemia [14,18]. There is a diminished response of glucose counter-regulatory hormones, such as glucagon and catecholamines, which are normally secreted in response to declining blood glucose levels. Additionally, in the elderly, the hypoglycemia-associated autonomic function involved in the detection and response to hypoglycemia are impaired. Functional impairments, cognitive decline, and mobility problems commonly associated with geriatric syndromes further impede the ability to recognize and respond to recurrent hypoglycemic events, increasing the risk of severe hypoglycemic episodes [19].

Sarcopenia is defined as progressive loss of skeletal muscle mass and function. In the elderly, it is caused by decreased metabolic rate due to aging, inhibition of protein synthesis, and impairment of muscle repair and regeneration capabilities. Muscle mass typically decreases at a rate of 1% to 2% per year starting at age 50, increasing to 3% per year after age 60, and then accelerating rapidly after age 75 [20,21]. In men, sarcopenia may correlate with a decrease in testosterone levels. As age increases, changes in the balance of hormone axes linked to the adrenal glands, sex hormones, insulin-like growth factor-1 (IGF-1), or IGF receptors can further contribute to muscle strength loss [22].

In elderly T2DM, multiple mechanisms cause skeletal muscle mass to be lost at a faster rate than in healthy elderly individuals [21]. Accordingly, the risk of developing sarcopenia is two to three times higher compared to those without T2DM [21,23]. The prevalence of sarcopenia in diabetes varies across studies, with meta-analyses reporting rates ranging from 5% to 50% [24]. Mechanistically, insulin resistance in T2DM results in inefficient utilization of glucose and amino acids, leading to nutritional deficiencies that cause muscle weakness and sarcopenia. Meanwhile, hyperglycemia leads to accumulation of advanced glycation end-products in muscle tissue, which weakens muscle contractility. Additionally, the decrease in activity of antioxidant enzymes and increase in reactive oxygen species associated with diabetes damage muscle mitochondria, resulting in abnormal mitochondrial function. This is linked to altered lipid oxidation, elevated lipid levels in muscle cells, and insulin resistance, all of which contribute to sarcopenia [25]. The chronic systemic pro-inflammatory state common in diabetes, characterized by increased levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 5 (IL-5), interleukin 6 (IL-6), and C-reactive protein and decreased levels of anti-inflammatory cytokines, may promote muscle damage and breakdown [26]. Finally, sarcopenia itself interferes with metabolic processes and negatively impacts glucose metabolism, further worsening the progression of diabetes and its complications, contributing to additional muscle loss and dysfunction, and ultimately leading to a vicious cycle that increases the risk of frailty. Some medications related to diabetes treatment may also affect muscle mass and performance in elderly patients with T2DM [27].

Frailty, characterized by decreased physiological and homeostatic reserves and increased vulnerability to stressors, is closely linked to the onset and progression of T2DM in the elderly. Fried’s frailty criteria are often used as a clinical phenotype and definition of frailty. According to this rubric, an elderly person can be diagnosed with frailty if they exhibit three or more of the following: (1) weakness or poor handgrip strength, (2) slow gait speed, (3) low physical activity, (4) exhaustion, and (5) unintentional weight loss [28]. When frailty coexists with T2DM in elderly individuals, the risk of hospitalization and mortality increases, and the prognosis upon hospitalization is generally worse [29]. Lack of physical activity, loss of appetite, and reduced food intake are major contributing factors to frailty, and diabetes itself can also be a risk factor for the progression of frailty. Notably, in elderly individuals with diabetes, it has been observed that frailty increases with both lower and higher blood glucose levels, suggesting a U-shaped relationship with glycemic control. Therefore, it is crucial to avoid significant fluctuations that can lead to either hypoglycemia or hyperglycemia [30].

Since frailty is a multifaceted syndrome influenced by various physiological, psychological, and social factors, multifactorial intervention is crucial in delaying its progression. However, evidence supporting this approach is still limited [31,32]. The Sarcopenia and Physical Frailty IN older people: multicomponent Treatment strategies (SPRINTT) project was a clinical study conducted to determine the effectiveness of multifactorial intervention therapy on 1,519 community residents aged 70 or older with frailty and sarcopenia. In that study, the intervention therapy consisted of personalized moderate-intensity physical activity, customized nutritional counseling, and technological support. After a 3-year follow-up, the customized intervention was found to significantly improve mobility [33].

As individuals age, the impact of single diseases such as diabetes on the risk of death decreases. However, diabetes is networked with the onset and progression of numerous major diseases, and in the elderly, it often coexists with multiple chronic conditions; the interaction between diabetes and these conditions then increases risk of death. The diversity of potential multi-morbidities highlights the complex heterogeneity of diabetes in the elderly population. Managing diabetes requires an individualized treatment approach tailored to the characteristics of major comorbidities and maintaining quality of life.

Concerning the specifics of multimorbidity, it has been reported that as many as 50% to 90% of elderly people with diabetes have at least one additional chronic disease [34], and that 40% have four or more comorbidities [35]. Both comorbidities and the medications used to treat them can affect insulin secretion and sensitivity. For example, steroids used in the treatment of many combined diseases facilitate hyperglycemia by promoting hepatic glucose production and contribute to insulin resistance by increasing visceral fat, breaking down proteins and fats, producing free fatty acids, and causing hepatic fat accumulation [36]. When conditions such as depression and arthritis co-occur with diabetes complications, they lead to decreased physical activity, increased disability, lower quality of life, and significantly higher use of medical services [37]. Diabetes patients are subject to greatly increased risk of severe major comorbidities such as heart failure, renal and liver diseases, and dementia. These diseases increase glycemic variability, reduce exercise ability, and impair cognitive function, making glucose management difficult and hindering the achievement of treatment goals. As a result, elderly diabetes patients with these comorbidities face greater risk of hyperglycemic crises or severe hypoglycemia and of mortality [38,39].

In diabetes patients, the incidence of hypoglycemia increases with age. In 2019, we reported that compared to patients in their 30s, Korean diabetes patients in their 70s had 1.4 times higher risk of hypoglycemia, and patients in their 80s, 1.9 times higher risk [40]. Fortunately, this shows a trend of decreasing risk of hypoglycemia in the elderly compared to 10 years prior. In addition to age itself, hypoglycemia risk is increased by aging-related factors such as decreased renal function, changes in the pharmacokinetics of insulin or insulin secretagogues, cognitive decline, and low body weight [41,42]. As mentioned earlier, a defective glucose counter-regulatory system, hypoglycemia-associated autonomic dysfunction, and diminished awareness of hypoglycemia in the elderly all contribute to the frequent occurrence of hypoglycemia; thus, in a vicious cycle, frequent experiences of hypoglycemia further impair the ability to recognize and respond to low blood glucose levels, thereby increasing the risk of severe hypoglycemic events [43]. Notably, the glycemic range at which adrenergic and cholinergic symptoms appear before neuroglycopenic symptoms (which can lead to decreased consciousness) is narrower in elderly individuals than in young adults [18,44]. Moreover, the symptoms of hypoglycemia in the elderly are often atypical, leading to unclear and delayed diagnosis. Elderly patients may also have poor physical performance, making it difficult to manage hypoglycemia even if they know how to respond, particularly for individuals living alone. Severe hypoglycemia, which often manifests as decreased consciousness, can result in falls, fractures, cognitive impairment, cardiovascular disease, malignant arrhythmias, renal dysfunction, dementia, and even death [41].

Hyperglycemia-related complications in elderly individuals can also be fatal. Particularly, HHS or DKA with uncontrolled diabetes have demonstrated higher mortality, and commonly co-occur with severe infection in elderly T2DM. With the recent increase in use of sodium glucose co-transporter 2 (SGLT2) inhibitors, there is especially a need for caution regarding development of DKA. Euglycemic DKA occurs even without an absolute deficiency of insulin and is caused by excess glucosuria from SGLT2 inhibitor use, dehydration from polyuria, and excessive use of ketones as an alternative energy source due to glucose starvation. In the elderly, impaired insulin secretion, decreased renal function, and mitigated glucose control, along with acute conditions such as nutritional deficiencies, disorders of the thirst center, concurrent use of diuretics, and infections, can all be risk factors for euglycemic DKA, significantly increasing the vulnerability of this population [45]. Fig. 1 summarizes the various factors contributing to the onset and progression of diabetes in the elderly.

In devising treatment strategies, it is crucial to both target factors related to the pathophysiological pathways of diabetes and address risk factors that can significantly impact the patient’s ability to manage their condition effectively. This approach includes the development of tools that synthesize the characteristics of the heterogeneous elderly population-based on the main risk factors for diabetes in this group. Additionally, there is a need to reorganize existing diabetes management approaches for the general adult population to consider the individual overall health status of elderly patients, particularly those in high-risk health groups. However, evidence supporting treatment strategies for elderly patients with diabetes who are highly vulnerable to complications remains limited.

Despite ongoing research efforts, many challenges remain in solving elderly diabetes in the elderly. First, to fully understand the status of diabetes in the elderly, it is necessary to conduct a sufficiently large-scale, population-based status analysis using available health and medical big data. In addition to prevalence, awareness rate, and control rate, this analysis should include factors such as body composition indicators (e.g., sarcopenia, sarcopenic obesity, and underweight), cognitive function, mental health, physical function, lifestyle habits, income level, the status of socio-economically vulnerable subjects, excessive medical use including polypharmacy, and major concomitant diseases. Second, a tool is needed to classify the heterogeneous characteristics of elderly diabetes patients into appropriate subgroups (Fig. 2). This classification should consider frailty status, disease severity, residual pancreatic function, cardiorenal risk, cognitive function, medication use, and socioeconomic factors. However, no large-scale, comprehensive dataset measuring all these variables currently exists. An integrated healthcare big data platform utilizing linked data from the Korea Disease Control and Prevention Agency, Statistics Korea, Health Insurance Review and Assessment Service, National Health Insurance Service, and individual hospitals can be used to develop a health risk score that objectifies the vulnerability of the elderly. If a more advanced dataset can be built in the future, it can be used to strengthen the health risk prediction and classification system. For elderly patients with advanced diabetes, the intensity of drug treatment should be gradually reduced, and treatment focus should shift to caregiving to improve quality of life for the remainder of their time. It is important to determine the optimal ranges of blood glucose, blood pressure, and lipid levels that maintain function and quality of life while minimizing damage from hyperglycemia and hypoglycemia. Moreover, risks and functional vulnerabilities for cardiovascular and renal disease must be identified, and optimal metabolic control goals and drug use strategies tailored to those conditions must be established. Quality of life can be further improved by reducing polypharmacy as much as possible and simplifying overly complex treatment regimens. Elderly diabetes patients with multiple comorbidities are at very high-risk of frequent hospitalizations due to acute illnesses. Individualized strategies for inpatient and aftercare are needed for these patients, focusing on glycemic management, polypharmacy, delirium, and fall prevention. In addition, there is a need to develop multifactorial interventions tailored to overcoming frailty, such as exercise, nutrition, and support interventions. Lastly, although many Western research results have been published, these findings cannot be directly applied to Koreans due to racial, regional, and social differences. Therefore, efforts will be needed to establish and analyze data on diabetes in the elderly in Korea to determine optimal management strategies for this population.

The increasing prevalence of elderly T2DM highlights increases in risk factors such as previous obesity and inactivity, as well as improvements in general healthcare that extend life expectancy. The diverse phenotypes of T2DM in the elderly are often accompanied by frailty, necessitating a highly individualized management approach. Comorbidities prevalent in this population may limit treatment options, and drug contraindications must be carefully considered. As a result, treatment goals for the elderly are often less stringent, intended to prevent hypoglycemia and minimize lifestyle changes that may not provide significant benefit within the expected lifespan. The presence of frailty, sarcopenia, severe life-limiting conditions, cognitive decline, and functional impairment greatly influences management strategies. Therefore, individualized treatment plans must balance the benefits and risks of intensive glycemic control with the goal of preventing complications of hyperglycemia and hypoglycemia while maintaining quality of life. Additionally, developing effective and tailored exercise and nutritional interventions is essential to combat frailty in this population. Lastly, it is important to build and analyze data tailored to the Korean population to optimize diabetes management strategies for the specific needs of the country’s elderly population.