FormalPara Key Points

Neither sulfonylureas nor alpha-glucosidase and dipeptidyl‐peptidase-4 inhibitors showed an association with frailty or diabetic complications.

Older adults with hypoglycemia and prefrailty, impaired instrumental activities of daily living, and diabetes mellitus received glinides, thiazolidinedione, and biguanide and glucagon-like peptide-1 receptor agonists, respectively.

Sodium-glucose cotransporter 2 inhibitors were administered to people with high frailty scores despite a high body mass index; therefore, attention should be paid to frailty development and sodium-glucose cotransporter 2 inhibitor side effects.

Many older adults with frailty, diabetic complications, and hypoglycemia are treated with insulin, warranting more careful management.

1 Introduction

Frailty is a condition that specifically affects older adults [1] and requires comprehensive management on a global scale [2, 3]. Globally, approximately 13.7% of adults aged >65 years show frailty [4]. In Japan, 8.7% of people aged ≥65 years are considered frailty [5].

The life expectancy of people with diabetes mellitus has been increasing, and the population is aging [6, 7]. As a result, individuals with diabetes, who can now live as long as those without diabetes, face greater challenges associated with frailty [8, 9]. In Japan, one in five people aged ≥65 years is suspected to have diabetes, including 23.2% of men and 16.8% of women aged ≥70 years [10]. Individuals with diabetes are more likely to develop frailty [11] than those without diabetes, with an odds ratio of 1.48 [12]. In addition, activities of daily living (ADLs) tend to decline before physical functions in older adults with diabetes [13, 14]. Therefore, it is necessary to identify frailty as early as possible and implement diabetes care based on the characteristics of older adults with diabetes by assessing multiple domains of physical, psychological, functional, and social status.

We previously investigated frailty-related factors in older adults with diabetes [14]. The results showed that the frequency of developing frailty was high among individuals with diabetes aged >60 years even with independent ADLs. The risk factors for developing frailty include comorbidities, inappropriate diet, lifestyle, and health behaviors, and they differ between men and women. In women, the Kihon Checklist (KCL) is significantly associated with living alone and skeletal muscle percentage; prefrailty, with peripheral neuropathy; and sarcopenia, with diabetes duration, low-density lipoprotein cholesterol level, diet score, and irregular lifestyle. In men, the KCL score is significantly associated with peripheral neuropathy, diet score, and coronary artery diseases (CAD); frailty, with CAD and inoccupation; prefrailty, with diet score; and sarcopenia, with living alone. These sex differences in the risk factors of frailty should be considered when selecting preventive strategies for older adults with type 2 diabetes early in the prefrailty stage. Particularly, it is important to evaluate social participation and diet therapy in men and skeletal muscle mass and psychosocial function in women.

Altogether, numerous and complex factors need to be considered to maintain the health of older adults with diabetes. Particularly, the relationship between pharmacotherapy and frailty must not be neglected. Therefore, in diabetic pharmacologic therapy, it is important to select drugs that consider not only glycemic control and hypoglycemia, but also age and frailty [8, 9]. Diabetes treatment is evolving and can be tailored to the characteristics of patients with diabetes [15, 16]. With the advent of several diabetes drugs, glycemic control in patients with diabetes has gradually improved, and the progression of diabetic complications has been controlled [17]. In diabetic pharmacologic therapy, it is also important to tailor treatment to the characteristics of older adults with diabetes [18]. Comorbidities, such as frailty, sarcopenia, and dementia, as well as health status and drugs that are likely to induce hypoglycemia, should be considered when selecting therapeutic agents.

The Japan Diabetes Society divides patients into three categories (I, II, and III) according to cognitive function, the degree of instrumental and basic ADLs, and the presence or absence of comorbidities. Further, it sets the target value of glycated hemoglobin (HbA1c) to <7.0–8.0%, a wider range than the conventional standard. In patients taking insulin, sulfonylureas (SUs), or other drugs that may cause severe hypoglycemia, the target is set even higher at HbA1c <7.5–8.5%, with a lower limit (6.5–7.5%) applied in each case [19]. According to the Standards of Care in Diabetes 2024, older adults who are otherwise healthy, with few coexisting chronic illnesses and intact cognitive function and functional status, should have lower glycemic goals (e.g., HbA1c <7.0%–7.5% [53–58 mmol/mol]), while those with multiple coexisting chronic illnesses, cognitive impairment, or functional dependence should have less stringent glycemic goals (e.g., HbA1c <8.0% [64 mmol/mol]) [20].

Following the publication of the above guidelines, the selection of diabetic drugs that consider the characteristics of older adults is becoming more widespread in clinical practice. Particularly, diabetes specialists should select diabetic drugs to extend the patients’ healthy life expectancy and improve their quality of life and well-being. However, it remains unclear how diabetologists are applying treatment guidelines to select drug therapy for older adults with diabetes in practice. Therefore, this study investigated the relationship between the use of diabetes medications and frailty among older adults with diabetes at diabetes-specific medical institutions nationwide in Japan.

2 Methods

2.1 Study Design and Participants

This cross-sectional study was conducted as part of the frailty prevention program for older adults with diabetes (i.e., the f-PPOD study). The inclusion criteria were as follows: type 2 diabetes, age 60–80 years, treatment with any diabetic pharmacologic therapy for >2 years, and having unimpaired basic ADL (defined as Barthel index ≥85). The exclusion criteria were as follows: certification for long-term care/support needs; cerebrovascular disease and peripheral artery disease; paralysis in any part of the body; severe diabetes complications, including microvascular disease and CAD; comorbidities (e.g., heart failure, liver and renal disorders, anemia, malignancy, dementia); and depression or other psychiatric problems.

Study participants were recruited between 21 March, 2017 and 7 February, 2020 from eight outpatient diabetes clinics in Japan. As this was a multi-purpose exploratory study of frailty in older adults with diabetes, the sample size was designed to include 10% of outpatients (approximately 400 individuals) who met the eligibility criteria at each outpatient clinic. After screening by trained assessors (certified diabetes educators, certified nurses in diabetes nursing, and a diabetologist) using medical records, all eligible participants were sequentially recruited on arrival at outpatient visits.

The study protocol was approved by the Kyoto University Graduate School and Faculty of Medicine Ethics Committee (R1373) and by the ethics committee of each participating institution. The study was compliant with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment.

2.2 Data Collection and Instruments

Participants were enrolled in the study on the day of their outpatient visit to the diabetologist, and information from their medical records and blood tests conducted on the same day was collected. The latest status of diabetic complications was collected from medical records, based on examinations performed at least once a year according to the guidelines. Self-reported questionnaires were completed by patients on the day of participation in the study. All data were collected by trained nurses (certified diabetes educators and certified nurses in the field of diabetes).

2.2.1 Participants’ Demographic Characteristics

Demographic characteristics, including age, sex, academic background, family structure, work status, irregular lifestyle (irregular bedtimes and/or irregular eating habits), drinking habits, smoking habits, and diabetes medications, were obtained from medical records and via a self-reported general questionnaire. Body composition was measured using the bioelectrical impedance method (HBF-375; OMRON Healthcare Co., Ltd., Kyoto, Japan).

2.2.2 Diabetes-Related Factors

Diabetes duration, treatment, complications, and blood test results were obtained from the medical records. Hypoglycemia was confirmed by reviewing self-monitored blood glucose records or hypoglycemic episodes via self-reported questionnaire over the last 3 months. Hypoglycemia was defined as a blood glucose level <70 mg/dL [21] or the presence of hypoglycemic symptoms with symptom improvement following carbohydrate intake. Severe hypoglycemia was defined as a blood glucose level <54 mg/dL [21] or a severe event characterized by altered mental and/or physical status requiring assistance for treatment of hypoglycemia, irrespective of the glucose level [21]. Diabetes self-management performance was measured using the Summary of Diabetes Self-Care Activities Measure [22]. The higher the mean subscale score, the higher the level of self-care practice.

2.2.3 Frailty

Frailty was evaluated using the KCL, developed and validated by the Japanese Ministry of Health, Labour, and Welfare and widely used in Japan [23]. Recently, the KCL has been translated into other languages and used in various countries [24]. This comprehensive questionnaire is used to assess multiple domains, including the physical, psychological, functional, and social statuses, of older adults without disabilities. A higher score in each KCL domain indicates a higher risk of requiring support or care. Kihon Checklist scores of ≥8 and ≥4 points were defined as frailty and prefrailty, respectively [23].

2.2.4 Physical Functions

In our previous study, walking speed, one-leg balance stand time, grip strength, timed up-and-go time, BMI, and body composition were assessed [14]. An 11-m walkway was used to measure the usual walking speed, which was calculated over a 5-m distance between the 3-m and 8-m marks. The one-leg balance standing time was measured by asking each participant to stand for as long as possible, up to 120 s, with their eyes open. Grip strength was measured using a digital hand dynamometer (T.K.K.5401; Takei Scientific Instruments Co., Ltd., Niigata Prefecture, Japan). Measurements were taken with the participant in an upright position, holding the grip dynamometer so that the second joint of the index finger was at 90°. The timed up-and-go test shows the time required in a sequence of actions to stand from an armless chair, walk 3 m, turn, walk back, and sit down in a chair. Of these measured parameters, grip strength, BMI, and body composition were markers of frailty and sarcopenia. Therefore, we assessed three items in this study.

2.3 Statistical Analysis

Data are expressed as the mean ± standard deviation for continuous variables and as the number (percentage) for categorical variables, unless otherwise noted. The normality of numerical variables was assessed using Q–Q (quantile–quantile) plots. The Student’s t-test was used to compare continuous variables, while the chi-square and Fisher’s exact tests were used to compare the categorized variables depending on the presence and absence of each diabetes drug (SU, glinides, alpha-glucosidase inhibitors [αGIs], biguanides [BGs], thiazolidinedione [TZDs], dipeptidyl peptidase 4 inhibitors [DPP4is], sodium-glucose cotransporter 2 inhibitors [SGLT2is], glucagon-like polypeptide receptor agonists [GLP-1RAs], and insulin preparations), respectively. Logistic regression analyses were performed to evaluate the association of each diabetes drug with diabetes complications and frailty after adjusting for age, sex, and diabetes duration. Multiple linear regression analyses were performed to evaluate the association of each diabetes drug with body composition, grip strength, and KCL score after adjusting for age, sex, and diabetes duration. Statistical significance was set at p < 0.05. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 28.0 (IBM Corp., Tokyo, Japan).

3 Results

3.1 Participant Characteristics

Of the 421 eligible participants, 417 participants were enrolled in this study. Among them, four participants were excluded because of certification of long-term care needs (n = 2), withdrawal of consent (n = 1), or incomplete data (n = 1) (Fig. 1). The mean participant ages of the participants, diabetes duration, BMI, HbA1c level, serum albumin level (Alb), serum creatinine level (CRE), and estimated glomerular filtration rate (eGFR) were as follows: 70.1 ± 5.4 years, 15.0 ± 10.9 years, 24.5 ± 3.8 kg/m2, 7.2 ± 1.0%, 0.85 ± 0.30 mg/dL, and 65.6 ± 18.0 mL/min/1.73 m2, respectively (Table 1). The diabetes medications used were as follows: SUs (33.8%); glinides (8.2%); αGI (9.1%); BG (32.6%); TZD (5.3%); DPP4i (65.9%); SGLT2i (10.8%); GLP-1 RA (7.4%); and insulin (29.0%) (Table 1). Regarding diabetic complications, nephropathy, retinopathy, peripheral neuropathy, and CAD were 15.6%, 23.0%, 16.8%, and 15.1%, respectively. Meanwhile, hypoglycemia and serious hypoglycemia were prevalent in 23.7% and 2.9%, respectively (Table 1).

Fig. 1
figure 1

Study flow chart

Full size image
Table 1 Participant characteristics
Full size table

3.2 Clinical Characteristics of People with Type 2 Diabetes by Diabetic Drug

All drugs were used more frequently in the prefrailty condition; the average KCL score was >4 points (Table 2). Patients taking SUs had a longer duration of diabetes (17.2 ± 10.4 years) and slightly higher HbA1c levels (7.5 ± 0.9%) (Table 2). Patients taking glinides had higher medication control scores (better medication adherence; 6.9 ± 0.4) on the Summary of Diabetes Self-Care Activities Measure (Table 2), but they also had a higher frequency of diabetic retinopathy (38.2%), lower grip strength (24.9 ± 8.1 kg), and higher KCL scores (6.5 ± 4.3), indicating a tendency to be frail. Patients taking ɑGI had a longer duration of diabetes (20.7 ± 9.5 years), lower Alb levels (4.09 ± 0.35 mg/dL), and lower renal function (CRE: 0.97 ± 0.39 mg/dL, eGFR: 57.1 ± 15.3) (Table 2). In addition, they had a higher frequency of hypoglycemia (36.8%) and lower physical activity level (1.7 ± 1.5), but nutritional status (0.2 ± 0.4) and cognitive function (0.4 ± 0.5) were better (Table 2).

Table 2 Characteristics of the participants with type 2 diabetes by diabetes treatment
Full size table

Patients taking were younger (68.2 ± 5.0 years) and had higher body weight (64.6 ± 11.6 kg) and BMI (25.3 ± 4.3 kg/m2) (Table 2). They also had lower dietary scores (4.5 ± 1.6) and higher HbA1c levels (7.4 ± 1.0%) but also had better renal function (CRE: 0.77 ± 0.21 mg/dL, eGFR: 70.0 ± 17.1), albeit higher Alb levels (4.29 ± 0.33 mg/dL) (Table 2). Patients taking TZD were more likely to be smokers (36.4%) and had lower dietary scores (4.2 ± 1.7) and higher Alb levels (4.41 ± 0.44 mg/dL) (Table 2). None of the patients on TZD had diabetic nephropathy (0.0%), but they had lower instrumental ADL (0.9 ± 1.1) (Table 2). Patients takingDPP4is had drinking habits (38.5%) and higher exercise scores (3.7 ± 2.4) (Table 2). Patients taking SGLT2is were younger (67.9 ± 6.2 years) and had higher body weight (67.6 ± 12.7 kg), higher BMI (25.8 ± 4.1), lower dietary scores (3.9 ± 1.8), and higher HbA1c levels (7.8 ± 1.0%) (Table 2). Diabetic retinopathy was also more common (40.0%), and KCL scores were higher (6.0 ± 3.4) (Table 2).

Patients taking GLP-1RAs had a higher body weight (70.8 ± 13.5 kg), higher BMI (26.5 ± 4.5), and longer duration of diabetes (20.8 ± 11.8 years) (Table 2). They also had lower diet (4.2 ± 1.4) and exercise (2.6 ± 2.2) scores, higher HbA1c level (7.6 ± 1.1%), higher CRE level (1.00 ± 0.41 mg/dL), and more cardiovascular complications (29.0%) (Table 2). Patients taking insulin had a longer duration of diabetes (20.4 ± 11.0 years), higher HbA1c level (7.7 ± 1.0%), poorer renal function (CRE: 0.94 ± 0.39 mg/dL, eGFR: 60.5 ± 18.7), and lower Alb levels (4.09 ± 0.31 mg/dL) (Table 2). Hypoglycemia (44.6%), severe hypoglycemia (6.6%), diabetic nephropathy (27.6%), diabetic retinopathy (38.0%), diabetic peripheral neuropathy (25.6%), and cardiovascular disease (25.6%) were also common. In addition, they had lower grip strength (26.2 ± 7.8 kg), a higher frequency of frailty (28.9%), higher KCL scores (5.8 ± 3.7), and lower social ADL (1.0 ± 1.0) and physical activity (1.6 ± 1.3) (Table 2).

3.3 Relationship Between Each Diabetic Drug and Diabetic Complications

The relationship of each diabetes drug with hypoglycemia, severe hypoglycemia, and microvascular and macrovascular damage is shown in Table 3. The frequency of hypoglycemia was not higher in patients taking SUs. There was also no relationship between ɑGI, BG, TZD, DPP4i, or GLP-1RA and hypoglycemia or diabetic complications. Patients taking glinides experienced severe hypoglycemia (5.715 [1.309–24.947], p = 0.020). In contrast, hypoglycemia showed a significant association with insulin use (4.160 [2.497–6.931], p < 0.001); however, severe hypoglycemia did not show a relationship. The concomitant medications for SU, SGLT2i, and αGI are shown in the Electronic Supplementary Material (ESM). Retinopathy was associated with the use of glinides (2.443 [1.113–5.363], p = 0.026), SGLT2i (2.758 [1.352–5.627], p = 0.005), and insulin (2.138 [1.269–3.601], p = 0.004). Nephropathy, peripheral neuropathy, CAD, and CAD and arteriosclerosis obliterans were significantly associated with insulin use (2.519 [1.409–4.502], p = 0.002; 1.946 [1.103–3.433], p = 0.022; 2.274 [1.265–4.086], p = 0.006; and 2.035 [1.181–3.508], p = 0.011, respectively).

Table 3 Diabetes medicines and their association with diabetes complications
Full size table

3.4 Relationship of Each Diabetes Drug with Body Composition and Frailty

The relationships of each diabetes drug to body composition and frailty were also examined (Table 4). Sulfonylurea, αGI, and DPP4i use was not associated with body composition or frailty. Glinide use was associated with lower grip strength (−2.089 [−4.038 to −0.140], p = 0.036), higher KCL score (1.424 [0.219–2.629], p = 0.021), and lower physical activity (0.442 [0.038–0.846], p = 0.032). Biguanide use was associated with higher BMI (1.235 [0.437–2.033], p = 0.003), higher body fat mass (0.999 [0.019–1.979], p = 0.046), and greater grip strength (1.251 [0.073–2.429], p = 0.037). Thiazolidinedione use was associated with lower instrumental ADL levels (0.489 [0.194–0.784]; p = 0.001). Sodium-glucose cotransporter 2 inhibitor use was associated with a higher BMI (1.579 [0.385–2.772], p = 0.010), higher KCL score (1.319 [0.233–2.404], p = 0.017), poorer oral function (0.310 [0.030–0.590], p = 0.030), and worse depressive mood (0.405 [0.034–0.777], p = 0.033). Glucagon-like polypeptide receptor agonist use was associated with higher BMI (2.206 [0.810–3.602], p = 0.002), higher body fat (2.021 [0.299–3.744], p = 0.022), and poor nutritional status (0.200 [0.021–0.379], p = 0.029). Insulin therapy was associated with lower grip strength (−1.629 [−2.870 to −0.387], p = 0.010), higher KCL score (1.021 [0.253–1.789], p = 0.009), lower social ADL (0.285 [0.080–0.490], p = 0.007), and lower physical activity (0.316 [0.059–0.574], p = 0.016). The results are summarized in the ESM.

Table 4 Diabetes medicines and their association with body composition and frailty
Full size table

4 Discussion

This study contributes to our understanding of the need for careful use of antidiabetic drugs among older adults with diabetes. Importantly, although diabetologists who prescribe antidiabetic drugs always consider the possibility of frailty, some formulations, such as SGLT2is, glinides, and insulins, are more frequently used among older adults with frailty. Although data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions with respect to some aspects of frailty [25], careful and individualized treatment of diabetes is imperative [26].

Because the use of SUs leads to a proneness to hypoglycemia, they are prescribed to patients who are less prone to hypoglycemia and do not have frailty, sarcopenia, or cognitive decline. Indeed, in our study, SU use was associated with fewer hypoglycemia episodes. This interesting finding may be explained by the fact that patients taking SUs had higher HbA1c values and were likely to be less frail. Given that SUs are avoided in more frail individuals due to the risk of hypoglycemia, we consider that SU users had a better health status and a more progressive course of diabetes. Accordingly, their hypoglycemia risk was lower, and they reported fewer hypoglycemia episodes. In contrast, glinides are mainly administered to patients with a history of severe hypoglycemia, diabetic retinopathy, weaker grip strength, and poorer physical function to achieve better glycemic control while preventing hypoglycemia and progression to frailty. The study did not follow the diagnostic criteria for sarcopenia [27], as priority was given to the assessment of various aspects of frailty. Nevertheless, the observation of low grip strength, a muscle strength-based indicator of sarcopenia, and its association with the KCL subscale, particularly the physical activity score, suggests that glinide users have reduced physical functioning.

Alpha-glucosidase inhibitors and DPP4i can be safely administered to all patients, especially those with frailty and physical or cognitive decline. Thiazolidinedione is prescribed to older adults with reduced instrumental ADLs. Particularly, TZDs are prescribed to older adults who are no longer able to clean, wash, cook, shop, manage money, or administer medications, especially to prevent hypoglycemia and improve medication management. Biguanides, SGLT2is, and GLP-1RAs are administered to patients with a high BMI. Glucagon-like polypeptide receptor agonists are prescribed to older adults who are well nourished and do not have frailty. Biguanides are especially prescribed for older adults with strong grip strength and no frailty, whereas SGLT2is are prescribed for older adults with a high BMI, diabetic retinopathy, high frailty score, oral frailty, and depressive mood. sodium-glucose cotransporter 2 inhibitor users have a particularly high incidence of frailty and diabetic complications than BG and GLP1 users.

Sodium-glucose cotransporter 2 inhibitors are now prescribed with consideration of the complications of chronic heart failure or renal dysfunction. They have been reported to be effective in treating heart failure and chronic kidney disease and improving physical, cognitive, or endothelial function in older adults with diabetes, heart failure, and frailty [28,29,30]. Given that diabetic complications are a risk factor for frailty [14], SGLT2is can be effective in preventing frailty by controlling blood glucose and preventing the onset and progression of complications. However, frailty encompasses not only physical aspects, but also psychological and social aspects, which can sometimes precede physical frailty [31, 32]. In the present study, frailty among SGLT2i users was characterized by oral frailty and depressed mood, which may be less readily noticed by physicians and healthcare professionals than decreased muscle strength and physical activity. These functional declines can easily lead to a vicious cycle of frailty. Oral function deterioration was found to be a cause of hypoglycemia in our previous study [14] and a risk factor for aspiration pneumonia [33]. Furthermore, depression and frailty are correlated [34], and particular attention should be paid to the development of hypoglycemia [35, 36]. Based on these studies, SGLT2is are not easily prescribed simply based on the presence of a high BMI or diabetic complications in older adults with diabetes. Thus, it is important to consider if SGLT2is are adequate for older adults with psychological and/or social aspects of frailty. At the very least, frailty should be assessed periodically during the use of SGLT2is to prevent diabetic complications and comorbidities.

In contrast, GLP-1 RA users had a high BMI and HbA1c level but exhibited good nutritional status and no frailty or complications and scored poorly on assessments related to diet and exercise. Biguanide users also had a high BMI but demonstrated high grip strength and no frailty or complications, with poor diet scores. Glucagon-like polypeptide receptor agonists are likely to cause weight loss by reducing appetite and energy intake. Therefore, it appears to be prescribed to patients who have not achieved lifestyle improvements through patient education. However, enhancing the overall lifestyle, including diet, exercise, and social activity, is important not only for glycemic control, but also for addressing frailty [37], and continuous lifestyle modification interventions may be warranted for these patients. Furthermore, the risk of frailty gradually increases even in healthy older adults as they get older. It will be necessary to monitor for weight loss, decline in nutritional status, and frailty status due to long-term use of the drug and to periodically review the drug prescription with frailty in mind [38].

Patients prescribed insulin therapy in our study were more likely to have a history of hypoglycemia and microvascular and macrovascular diseases, as well as frailty. The adults treated with insulin also often have long-standing diabetes mellitus and a reduced insulin secretory capacity, making insulin therapy essential in many cases. Diabetic complications also occur frequently. In our previous study, peripheral neuropathy and macrovascular disease were also associated with the development of frailty [14]. Therefore, hyperglycemia and poor glycemic control, rather than hypoglycemia, are implicated in the development of frailty in patients receiving insulin therapy [39]; thus, insulin therapy should be continued while carefully avoiding increased blood glucose variability.

This study had some limitations. Considering that this was a cross-sectional and not a prospective study, it was not possible to clarify whether each diabetes treatment method was a risk factor for frailty. The participants in this study had been treated with any diabetic pharmacologic therapy for more than 2 years. However, detailed information on the duration of treatment with each diabetic drug and the onset of diabetic complications and frailty was not available. Thus, the causal relationship between diabetic pharmacologic therapy and frailty remains to be explored. In addition, although we could examine the relationship between each diabetes drug and diabetic complications and frailty, we were unable to examine differences in the characteristics of frailty between patients treated with either single or multiple drugs because the number of cases was insufficient.

Furthermore, not all patients underwent routine assessments for hypoglycemia involving blood glucose or continuous glucose monitoring, potentially leading to the oversight of asymptomatic hypoglycemia. Specifically, self-monitoring of blood glucose was mainly performed by patients receiving treatment with insulin or GLP-1 RA (the use of continuous glucose monitoring was uncommon), potentially resulting in hypoglycemia being overlooked in patients receiving oral therapy. However, it has also been reported that less severe hypoglycemia can be confirmed by patient self-report [21, 40]. Therefore, in the present study, all possible hypoglycemia-related information was obtained, and information bias was minimized as much as possible by assessing both blood glucose measurement and self-report findings. Finally, this study was conducted from a preventive perspective, and the participants were relatively healthy older adults with diabetes. Therefore, our results may not be applicable to older adults with diabetes who already have functional decline or complications, highlighting the need for further research.

5 Conclusions

SGLT2is, glinides, and insulin are prescribed to patients with frailty or those at high risk of developing frailty. Therefore, these drugs should be continued with care to prevent the progression of frailty while maximizing the benefits of the therapeutic agents. In future studies, a larger number of new diabetes medications should be included to determine whether they promote or prevent frailty over a long follow-up period.