Burden of Current Insulin Therapy and Expectations for Future Insulin Therapy: Results from INBEING, a Web-Based Survey in Japan

Abstract

Introduction

This survey assessed the perspectives of physicians, people with diabetes (PWD), and caregivers in Japan regarding initiation barriers and treatment burden associated with insulin therapy, and expectations for new insulin therapies.

Methods

An online survey, conducted May–June 2023, was completed by physicians (n = 411), PWD (type 1 diabetes, n = 108; type 2 diabetes [T2D]: insulin-naive, n = 114; insulin-treated, n = 108), and caregivers (family members, n = 107; nurses, n = 117; care workers, n = 104). Agreement with statements regarding initiation barriers, current feelings, and burden of insulin therapy was assessed. Physicians’ views on ideal glycated hemoglobin (HbA_1c) levels and actual levels in PWD at insulin initiation were captured.

Results

Most PWD agreed with the statements “I don’t want to be bothered with doing injections” (77.8–92.1%) and “I don’t want to inject myself for the rest of my life” (78.7–91.2%). Physicians also considered these factors to be of high importance for PWD; however, physician and PWD (insulin-naive T2D) responses were significantly different for 11 statements. The greatest underestimation by physicians was for the statement “my family will be worried” (41.8% vs. 66.7%), whereas social factors (e.g., “my friendships may suffer,” “if I take insulin I will be discriminated against”) were overestimated by physicians (49.1% vs. 33.3% and 46.5% vs. 24.6%, respectively). Although > 70% of physicians considered HbA_1c < 9.0% (< 75 mmol/mol) ideal for insulin initiation, only ~ 30% of PWD started insulin at HbA_1c < 9.0% (< 75 mmol/mol). Nurses rated the burden of assisting with insulin injections significantly lower than family members or care workers. Respondents agreed the need for less frequent injections and improved glycemic control were important attributes expected from future insulin therapies.

Conclusion

Differences in perceptions between physicians and PWD in Japan regarding insulin therapy persist, but this gap may be narrowing. Both groups agreed that future insulin therapies should be simpler and provide better glycemic control.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13300-024-01664-w.

Key Summary Points

Why carry out this study?

Japanese clinical practice guidelines recommend that insulin therapy be initiated in people with type 2 diabetes who have inadequate glycemic control despite the use of lifestyle interventions and treatment with non-insulin glucose-lowering medications; however, despite the clear benefits of timely insulin initiation, this process is often delayed owing to physician- and/or individual-related factors, such as physician reluctance, concerns regarding adherence, fear of injections, interference with daily activities, and social stigma.

Widespread reluctance among healthcare professionals and people with diabetes (PWD) towards insulin initiation has been reported in Japan; consequently, there is a need for an up-to-date understanding of the barriers to insulin treatment and expectations of future insulin therapies.

The INBEING study aimed to examine the treatment burden and realities associated with insulin therapy in Japan from the perspectives of physicians, PWD, and caregivers, and to explore the expectations of these groups regarding new insulin therapies.

What was learned from the study?

Although the perspectives of physician and PWD were aligned for several factors influencing resistance to insulin initiation, they were statistically significantly different for 11 factors; this gap needs to be addressed to improve person-centered diabetes management.

Although more than 70% of physicians considered glycated hemoglobin (HbA1c) levels under 9.0% (75 mmol/mol) to be ideal for insulin initiation, only approximately 30% of PWD started insulin at HbA1c under 9.0% (75 mmol/mol).

Regarding new insulin therapies, physicians, PWD, and caregivers agreed that the need for less frequent injections, simpler treatments and injection preparations, further improvement in glycemic control, and a lower risk of hypoglycemia were all important attributes expected from future insulin therapies (regardless of whether PWD would start insulin for the first time or switch from an existing insulin therapy).

Introduction

Japanese clinical practice guidelines recommend starting insulin therapy in people with type 2 diabetes (T2D) who have inadequate glycemic control despite the use of lifestyle interventions and treatment with non-insulin glucose-lowering agents [1, 2]. Timely initiation of insulin is critical for T2D management and has distinct clinical benefits, including improved glycemic control and long-term outcomes [3, 4]. However, this process is often delayed owing to physician- and/or individual-related factors, including physician reluctance, physician experience (e.g., specialists may favor starting intensive insulin regimens more than general physicians), concerns regarding adherence, concerns regarding undesired outcomes (e.g., weight gain and hypoglycemia), fear of injections, interference with daily activities, social stigma, and feelings of personal failure [5–8]. Demographic characteristics (e.g., age, duration of diabetes, cultural beliefs, and family environment) may also influence individuals’ perceptions towards insulin therapy [9–11].

The Global Attitudes of Patients and Physicians study surveyed people with diabetes (PWD) and physicians across China, France, Germany, Japan, Spain, Turkey, the UK, and the USA. Both groups reported negative perceptions towards insulin therapy, particularly regarding the restrictive nature of insulin regimens; the most commonly expressed challenges were adherence to the prescribed insulin dosing time and frequency [12]. Adherence and dissatisfaction levels statistically significantly varied across countries: PWD in Japan reported the highest rate of insulin nonadherence (43.8%), and physicians in Japan expressed the second highest treatment dissatisfaction rate (21.5%), closely after Turkey (22.5%) [12]. The Diabetes Attitudes, Wishes and Needs (DAWN) study surveyed more than 5000 PWD and almost 4000 healthcare professionals (HCPs) from 13 countries across Asia, Australia, Europe, and the USA [13–15]. The survey revealed substantial widespread reluctance among HCPs and PWD to start insulin therapy, and identified statistically significant differences in attitudes towards insulin therapy across countries [13, 14]. For example, US HCPs were statistically significantly more likely to delay insulin initiation than their counterparts in all countries, except India and Japan. Additionally, PWD perceived insulin therapy as less effective and had higher self-blame for requiring insulin in the USA than in other countries [13, 14]. In the DAWN Japan study, a distinction was made between Japanese physicians’ perceived PWD concerns and the actual concerns reported by Japanese PWD [16, 17]; however, DAWN Japan utilized data from 2004, and the diabetes treatment landscape in Japan has evolved substantially since then [2, 18, 19]. Attitudes towards insulin therapy may have shifted since the completion of the DAWN Japan study, so it is necessary to reassess the barriers to current insulin treatment and expectations of future insulin therapies.

The INsulin Burden and Expectation in people with dIabetes, physiciaNs and careGivers (INBEING) survey examined the treatment burden and realities associated with insulin therapy in Japan from the perspectives of physicians, PWD, and caregivers, and explored their expectations for new insulin therapies.

Methods

Study Design and Participants

An online survey conducted from May to June 2023 was completed by physicians, PWD, and caregivers in Japan. Physicians were recruited from a validated panel of over 60,000 healthcare professionals (maintained by PLAMED Inc.), whilst PWD, and caregivers were recruited from a panel of approximately 4,200,000 research consumers (maintained by INTAGE Healthcare Inc.). Individuals who met the inclusion criteria were invited to complete the survey via a web-based platform (developed by INTAGE Healthcare Inc.). Survey inclusion criteria varied for each group of participants: physicians (diabetologists [including endocrinologists] or general internists) needed experience starting insulin in, and be actively managing, PWD; PWD had to be at least 18 years old, with diagnosed type 1 diabetes (T1D) or T2D, and treated with or without insulin therapy (T2D only); caregivers were family members, nurses, or care workers assisting insulin-treated adults with T1D or T2D. The surveyed physicians and caregivers were not necessarily treating or caring for the surveyed PWD.

Three questionnaires were designed by INTAGE Healthcare Inc., one for each group of participants (physicians, PWD, and caregivers), and were based on the findings from a targeted literature review and questions used in previous, similar surveys [12, 16, 17, 20–22]. Each questionnaire was validated and refined by conducting web-based cognitive interviews in 16 individuals (two from each of the eight target subgroups: diabetologists, general internists, people with T1D, insulin-naive people with T2D, insulin-treated people with T2D, family members, nurses, and care workers). Participants were expected to complete the questionnaire in approximately 15 min.

After sociodemographic characteristics were captured for all subgroups, participants were asked about their attitudes, perspectives, and realities regarding insulin therapy. The extent of agreement with statements regarding the causes of resistance or barriers to starting insulin (physicians and PWD), barriers to assisting insulin injection (caregivers), and feelings towards insulin therapy (PWD) was measured with a 6-point Likert scale (“completely agree,” “mostly agree,” “slightly agree,” “mostly disagree,” “completely disagree,” and “don’t know”). This format was adapted to measure the extent of difficulty that insulin-treated PWD experience when using insulin injections, and adapted further to measure the extent of burden that caregivers experience when assisting with or preparing insulin injections. Physicians were asked for their views regarding the glycated hemoglobin (HbA_1c) level at which they would consider starting insulin if they themselves had T2D; these views were contrasted with actual HbA_1c levels at the time of insulin initiation reported by insulin-treated people with T2D. Physicians, PWD, and caregivers were asked separately to select expected attributes of new insulin therapies when starting treatment or when switching from an existing insulin (multiple selection was allowed). Physician views on criteria to consider when starting insulin therapy (including ideal HbA_1c level), PWD reasons for starting insulin therapy, HbA_1c target determination details in PWD, time spent by caregivers when assisting with insulin injections, and family member reactions when PWD have a sick day were also captured.

After survey completion, responses were screened and considered for exclusion if the respondent’s reported sex or age differed from those registered in the panel database (differences of ≤ 2 years were considered acceptable for registered age); completion time was short (< 15 min); responses were inconsistent or repetitive (e.g., reporting a current treatment regimen that is not available, inconsistency with answers to other questions, or repetition between answers, such as always choosing the same scale level for Likert-scale questions); or if participating physicians had seen zero insulin-treated people in the preceding month (Fig. S1).

Ethical Approval

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki, which were consistent with good clinical practices and applicable laws and regulations in Japan. The study protocol and informed consent form were submitted to the Medical Corporation TOUKEIKAI Kitamachi Clinic Ethical Review Board for review/approval as a minimal-risk study, and ethical approval was granted on May 17, 2023 (NN1436-7732). Before completing the survey, all respondents provided informed consent for participation and publication of aggregated level data via a web-based platform.

Statistical Analyses

Data were collected through a web-based interface and managed using Microsoft Excel. Sociodemographic and questionnaire results were reported using descriptive statistics. The χ² test was used to evaluate statistically significant differences between groups for all respondent groups, except for caregivers, for whom Fisher’s exact test was used. Use of Fisher’s exact test ensured accuracy when items with an expected frequency of under 5% made up 20% or more of the total number of items. The significance level was set at α = 0.05. Statistical analysis was performed using R version 4.2.2. No statistical analysis was conducted for questions exploring expected treatment attributes for initiating or switching insulin therapy.

Results

Participants

Table 1 summarizes the sociodemographic characteristics for each participant group. Overall, 411 physicians completed the survey: 259 diabetologists (63.0%) and 152 general internists (37.0%), with a mean of 20 and 25 years of clinical experience, respectively. Of the 330 PWD who completed the survey, 108 (32.7%) had T1D, 108 (32.7%) had T2D and were treated with insulin, and 114 (34.5%) had T2D and were insulin-naive. Mean (standard deviation [SD]) age across all three subgroups was 61.0 (9.5) years. Overall, 328 caregivers completed the survey, comprising 107 family members (32.6%), 117 nurses (35.7%), and 104 care workers (31.7%). Participant flow is presented in Fig. S1.

Table 1.

Summary of sociodemographic characteristics of participating physicians, PWD, and caregivers

	Participant groupa
Physicians	Total	Diabetologist (including endocrinologist)	General internist
Number of respondents, n (%)	411 (100.0)	259 (100.0)	152 (100.0)
Medical specialty certifications,b n (%)
Fellow of the Japanese Society of Internal Medicine	200 (48.7)	142 (54.8)	58 (38.2)
Board-certified diabetologist of the Japan Diabetes Society	192 (46.7)	182 (70.3)	10 (6.6)
Board-certified endocrinologist by the Japan Endocrine Society	82 (20.0)	80 (30.9)	2 (1.3)
Do not hold any of the above	135 (32.8)	46 (17.8)	89 (58.6)
Clinical experience, mean (SD), years	21.6 (10.8)	19.7 (10.5)	24.9 (10.6)

PWD	Total	People with T1D	Insulin-naive people with T2D	Insulin-treated people with T2D
Number of respondents, n (%)	330 (100.0)	108 (100.0)	114 (100.0)	108 (100.0)
Sex, n (%)
Male	256 (77.6)	70 (64.8)	96 (84.2)	90 (83.3)
Female	74 (22.4)	38 (35.2)	18 (15.8)	18 (16.7)
Age, mean (SD) years	61.0 (9.5)	59.2 (10.0)	61.7 (9.1)	62.0 (9.4)

Caregivers	Total	Family members	Nurses	Care workers
Number of respondents, n (%)	328 (100.0)	107 (100.0)	117 (100.0)	104 (100.0)
Sex, n (%)
Male	144 (43.9)	68 (63.6)	16 (13.7)	60 (57.7)
Female	180 (54.9)	37 (34.6)	100 (85.5)	43 (41.3)
Other/decline to answer	4 (1.2)	2 (1.9)	1 (0.9)	1 (1.0)
Age, mean (SD), years	50.6 (11.0)	55.5 (11.8)	46.0 (9.5)	50.8 (9.6)
Age of family member with diabetes, mean (SD), years	65.3 (14.5)	65.3 (14.5)	–	–

PWD people with diabetes, SD standard deviation, T1D type 1 diabetes, T2D type 2 diabetes

^aFor the diabetologist and general internist subgroups, the target numbers of questionnaire completions were 250 and 150, respectively; for all remaining subgroups, the target was 100 questionnaire completions

^bFor multiple-choice questions, the sum of the answers may exceed 100% owing to respondents selecting more than one answer

Causes of Resistance to Insulin Initiation Among PWD: Physicians and Insulin-Naive People with T2D

Figure 1 shows the proportions of physicians and insulin-naive people with T2D who agreed with each statement in the negative image of injections, social effects/interpersonal effects, feelings of guilt regarding diabetes self-management, and negative image towards insulin therapy categories. Overall, physicians perceived the most common reasons for PWD resistance to insulin initiation to be “I don’t want to inject myself every day” (89.3%), “I don’t want to be bothered with doing injections” (86.9%), and “I don’t want to inject myself multiple times a day” (86.4%). Similarly, the most common reason for resistance reported by insulin-naive people with T2D was “I don’t want to be bothered with doing injections” (92.1%) (Fig. 1).

Fig. 1.

Causes of resistance to insulin initiation among PWD based on responses from physicians and insulin-naive people with T2D. The figure shows the percentage of physicians who responded “a major cause of resistance” or “a little cause of resistance,” and of PWD who responded “completely agree,” “mostly agree,” or “slightly agree” to each statement. *Statistically significant differences (p < 0.05 [χ²]) between physician and PWD responses. PWD people with diabetes, T2D type 2 diabetes

Regarding the proposed statements describing potential causes of resistance to insulin initiation, the beliefs of physicians and those of insulin-naive people with T2D differed statistically significantly (p < 0.05) for 11 statements (Fig. 1). The statements with the largest discrepancies were “my family will be worried” (24.9%-point difference), “I’m on insulin because I didn’t do what I was supposed to” (24.4%-point difference), and “people would think it is my fault that I need to take insulin” (21.4%-point difference).

Causes of Resistance to Insulin Initiation Among PWD: Comparison Between PWD Subgroups

Causes of resistance to insulin initiation among PWD were analyzed by diabetes subgroup to identify any differences in opinions between people with T1D, insulin-naive people with T2D, or insulin-treated people with T2D (Fig. 2). In the negative image of injections category, compared with insulin-treated people with T2D, a statistically significantly higher proportion of insulin-naive people with T2D agreed with each of the proposed statements describing potential barriers to insulin initiation (Fig. 2). The largest differences were for the statements “using injectors is difficult” (47.5%-point difference), “injections are scary” (34.6%-point difference), and “I don’t want to inject myself every day” (28.4%-point difference). Statistically significant differences were also observed between people with T1D and insulin-naive people with T2D for five items in this category (Fig. 2).

Fig. 2.

Current feelings towards insulin therapy based on responses from people with T1D, insulin-treated people with T2D, and insulin-naive people with T2D. The figure shows the percentage of PWD who responded “completely agree,” “mostly agree,” or “slightly agree” to each statement. Asterisks highlight statistically significant differences (*p < 0.05 [χ²]) between subgroups. N/A not applicable, PWD people with diabetes, T1D type 1 diabetes, T2D type 2 diabetes

In the social/interpersonal effects category, the proportion of respondents who agreed that “people would think it is my fault that I need to take insulin” was statistically significantly higher (p < 0.05) for insulin-treated and insulin-naive people with T2D (67.6% and 66.7%, respectively) than for people with T1D (50.9%). The level of agreement for the statement “injecting insulin in the presence of others is embarrassing” was consistent in people with T1D and insulin-treated people with T2D (64.8% for both).

In the feelings of guilt regarding diabetes self-management category, a statistically significant difference was observed between the proportion of insulin-naive people with T2D and insulin-treated people with T2D who agreed that “using insulin means my disease is worsening” (71.1% vs. 57.4%, respectively; p < 0.05). Agreement with the statement “I’m on insulin because I didn’t do what I was supposed to do” statistically significantly differed between people with T1D and those with T2D (insulin-naive or insulin-treated) (Fig. 2).

In the negative image towards insulin therapy category, the proportion of insulin-naive people with T2D was statistically significantly higher (all p < 0.05) than that of insulin-treated people with T2D for the statements “I don’t understand why insulin is necessary for me” (47.4% vs. 14.8%, respectively), “I’m afraid of side effects” (57.9% vs. 38.9%, respectively), and “insulin will limit my daily life activities” (68.4% vs. 42.6%, respectively). A statistically significant difference was also observed between the proportion of people with T1D and insulin-treated people with T2D for the statement “insulin will limit my daily life and activities” (61.1% vs. 42.6%, respectively; p < 0.05). The proportion of people with T1D who agreed with the statement “insulin therapy is financially burdensome” was statistically significantly higher than that of people with T2D, regardless of insulin treatment (p < 0.05; Fig. 2). Agreement with the statement “I’m afraid of hypoglycemia” was statistically significantly different between people with T1D and insulin-naive people with T2D. Agreement was consistently high across PWD groups (84.3–91.2%) for the statement “I don’t want to do insulin injections if there is another way” (Fig. 2).

Physician and Family Member Barriers to Insulin Initiation

To explore physician barriers to insulin initiation, physicians were asked about their feelings towards insulin therapy (Fig. S2a). Statements were divided into issues with doctor’s experience, burden related to explanations, considerations of burden on PWD, concerns regarding insulin therapy, and concerns regarding hypoglycemia. Physicians most frequently felt that “PWD would resist insulin therapy” (83.5%), “PWD would have to pay more for treatment” (76.6%), and that “there is a higher risk of hypoglycemia with insulin therapy than with other therapies” (70.8%). Compared with the other categories, relatively few physicians agreed with the statements in the issues with doctor’s experience category.

Family members were also asked about their feelings and possible barriers towards assisting insulin injection. Statements were divided into impact on daily life, perception regarding care, support from family, and impact on health status (Fig. S2b). Family members most frequently agreed with the statements “I am afraid of hypoglycemia” (48.6%), “assisting with insulin self-injection is important to me” (47.7%), and “it is difficult to get support from other family members for assistance with insulin self-injection” (32.7%). Agreement with all other statements was low (≤ 25.0%; Fig. S2b).

Reasons and Criteria for Initiating Insulin Therapy

When considering the initiation of insulin therapy, physicians placed the most importance on “person’s ability to inject (in terms of vision/grip strength)” (75.7%), “person’s cognitive function” (72.3%), and “HbA_1c” (72.3%) (Fig. S3). Responses were broadly similar for diabetologists and general internists, with diabetologists also emphasizing “insulin secretion capacity” (75.3% vs. 53.9%, respectively) and “person’s financial status” (41.3% vs. 24.3%, respectively) (Fig. S3). Overall, the most common PWD-reported reasons for starting insulin therapy were “recommendation from a doctor” (70.6%), “aiming for better HbA_1c and blood glucose levels” (26.4%), and “worried about progression of diabetes caused by complications” (20.6%) (Fig. S4). Similar trends were observed across PWD subgroups; however, 32.5% of insulin-naive people with T2D also answered “other”.

Ideal and Actual HbA_1c Levels at Insulin Initiation

Physicians were asked at which HbA_1c level they would ideally initiate insulin if they themselves had T2D. These results were compared with the actual HbA_1c levels reported by insulin-treated people with T2D when they started insulin treatment (Fig. 3). More than 70% of physicians (diabetologists or general internists) considered an HbA_1c level of under 9.0% (75 mmol/mol) to be ideal for insulin initiation; however, only 33.4% of insulin-treated individuals with T2D reported starting insulin treatment with an HbA_1c level of under 9.0% (75 mmol/mol) (Fig. 3). The most popular HbA_1c range to start insulin as imagined by physicians if they themselves had T2D was 8.0 to < 8.5% (64 to < 69 mmol/mol) (Fig. 3). The HbA_1c level at which physicians would recommend insulin therapy to insulin-naive people with T2D treated with oral glucose-lowering medication varied according to the individual’s age, cognitive function, and activities of daily living, with a trend for a higher ideal HbA_1c threshold as clinical background deteriorated (Fig. S5).

Fig. 3.

Physicians’ views on the HbA_1c level at which they would consider initiating insulin if they themselves had T2D, and actual HbA_1c levels at the time of insulin initiation reported by insulin-treated people with T2D. HbA_1c glycated hemoglobin, T2D type 2 diabetes

To explore how HbA_1c targets are defined in PWD, respondents who reported having a defined HbA_1c target were asked how their target was decided (Fig. S6). Overall, 51.5% of these PWD were involved in determining their HbA_1c target to some degree, whereas 43.9% were given a target by their physicians without consultation. This trend was observed across PWD subgroups (Fig. S6b). In the overall PWD group, 78.9% of people had an HbA_1c target of under 7.0% (53 mmol/mol) and 39.1% had an HbA_1c target of under 6.5% (48 mmol/mol) (Fig. S6c).

Difficulties with Using Insulin Injections

People with T1D or insulin-treated people with T2D were asked about difficulties in using insulin injections based on their experience. Overall, the most difficult attribute associated with insulin injections was administering “injections while away from home, traveling or on business,” with 54.6% of people with T1D and 57.4% of insulin-treated people with T2D agreeing this was “very difficult” or “somewhat difficult.” This was followed by “injecting during busy times (hours)” (44.4% and 48.1% of respondents, respectively) (Fig. 4). The proportion of respondents who agreed that “adjusting insulin doses” and “handling hypoglycemia” were difficult was statistically significantly higher for people with T1D (21.3% and 46.3%, respectively) than for insulin-treated people with T2D (11.1% and 25.9%, respectively; both p < 0.05) (Fig. 4).

Fig. 4.

Views on the difficulties in the use of insulin injections as reported by people with T1D and insulin-treated people with T2D. The bar chart shows the proportion of PWD who responded “very difficult” or “somewhat difficult” for each item. ^aFor “taking insulin with meals,” n = 91 for people with T1D and n = 55 for insulin-treated people with T2D. This item was not applicable to people who used basal insulin only. *Statistically significant differences (p < 0.05 [χ²]) between PWD subgroups. PWD people with diabetes, T1D type 1 diabetes, T2D type 2 diabetes

Degree of Burden on Caregivers

Caregivers (family members, nurses, and care workers) were asked about the burden of assisting or preparing for self-injections based on their experience (Fig. 5). In general, a smaller proportion of nurses than family members and care workers considered assisting or preparing self-injections to be burdensome. Nurses considered “instruct/reinstruct PWD and family members on how to perform injections” to be the highest burden, with 30.0% of respondents agreeing this was “somewhat burdensome” or “very burdensome.” More than one-third (37.3%) of family members reported feeling some degree of burden when assisting or preparing for insulin self-injection (Fig. S7). The highest burden for family members was associated with “check for insulin balls” (42.1%), “handling hypoglycemia (talking to PWD, wiping perspiration, taking temperature etc.)” (38.9%), and “giving assistance when injecting insulin” (35.0%) (Fig. 5). Care workers considered “handling hypoglycemia” to be the highest burden (43.6%). Statistically significant differences (all p < 0.05) were found across ten items, including “calling out (encourage insulin injections before meals etc.),” “take out the necessary tools for self-injection (injectors, alcohol swabs etc.),” and “attaching and removing needles,” between nurses and both family members and care workers (Fig. 5).

Fig. 5.

Caregivers’ views on the degree of the burden on them to assist or prepare for insulin self-injections. The bar chart shows the proportions of caregivers who responded “very burdensome” or “somewhat burdensome” for each item. *Statistically significant differences (p < 0.05 [Fisher’s exact test]) between caregiver subgroups. The numbers of respondents varied between question items in each subgroup because selection of multiple items was permitted, and not all respondents in each subgroup selected the same number of items. N/A not applicable, PWD people with diabetes

The median (minimum–maximum) time spent assisting or preparing for self-injections was 30 (0–600) min/week for family members, 30 (1–120) min/week for nurses, and 15 (0–350) min/week for care workers. Family members were also asked about their reactions when the person with diabetes they care for has a sick day: 49.5% agreed with the statement “if the person is very sick and cannot check blood glucose levels, seek medical assistance,” 27.1% agreed with “measure blood glucose more often (every 2–4 h),” 20.6% agreed with “stop taking all diabetes medications and/or using insulin,” 19.6% agreed with “try to exercise as much as possible to lower blood glucose levels,” and 16.8% agreed with “if blood glucose exceeds 270 mg/dL, take lots of drinks with no added sugar.”

Expectations for Future Insulin Therapy

Physicians, PWD, and caregivers were asked for their views on expected attributes for new insulin therapies, specifically when initiating a new insulin therapy in insulin-naive PWD or when switching from an existing insulin. Figures 6, 7, and 8 show the most frequently selected attributes by respondent subgroup. Across subgroups, regardless of whether the respondent was considering insulin initiation or switching from an existing insulin therapy, “less frequent injections (e.g., daily becomes weekly),” “simpler treatment (e.g., fewer diabetes medications),” “further improved HbA_1c and blood glucose levels,” “lower risk of hypoglycemia,” and “simpler preparation for injections” were selected as the most important attributes expected from a future insulin therapy. In the nurse subgroup, “further improved HbA_1c and blood glucose levels” was not in the top five; instead, “counter measures can be taken in case of a forgotten injection or when it is not possible to inject at a prescribed time” was selected (Fig. 8). However, nurses selected “simpler preparation for injections” more often than family members (30.9%-point difference between subgroups) and care workers (21.9%-point difference between subgroups) when considering switching from existing insulin to a new insulin.

Fig. 6.

Treatment characteristics expected from a new insulin therapy when initiating insulin treatment or switching from an existing insulin to a new insulin, as reported by physicians. It was mandatory for respondents to select at least one characteristic; respondents were able to select up to five characteristics in total. HbA_1c glycated hemoglobin

Fig. 7.

Treatment characteristics expected from a new insulin therapy when initiating insulin treatment or switching from an existing insulin to a new insulin, as reported by PWD. It was mandatory for respondents to select at least one characteristic; respondents were able to select up to five characteristics in total. HbA_1c glycated hemoglobin, PWD people with diabetes, T1D type 1 diabetes, T2D type 2 diabetes

Fig. 8.

Treatment characteristics expected from a new insulin therapy when initiating insulin treatment or switching from an existing insulin to a new insulin, as reported by caregivers. It was mandatory for respondents to select at least one characteristic; respondents were able to select up to five characteristics in total. HbA_1c glycated hemoglobin

Discussion

This survey aimed to qualify the burden of insulin therapy in Japan from the perspectives of physicians, PWD, and caregivers to identify barriers to the timely initiation of insulin, attributes expected of new insulin treatments to address these barriers, and ideal and actual HbA_1c targets when starting insulin.

Resistance to insulin initiation among PWD was mostly associated with the negative impact of daily injections and the commitment to lifetime injections, the fear of hypoglycemia, the implications of disease progression, and the limiting effect of insulin on daily life. Broadly, physicians and PWD had aligned views. Perhaps unsurprisingly, insulin-naive individuals with T2D were statistically significantly more concerned about the fear, pain, difficulty, and burden associated with insulin injections than insulin-treated individuals with T2D. People with T1D and insulin-treated people with T2D found the need to inject while away from home and during busy times to be one of the most difficult aspects of their treatment. Social stigma was a concern for all PWD regardless of their experience with insulin, particularly in terms of embarrassment when injecting insulin in the presence of others (approximately 60% agreement). Furthermore, approximately 50% of insulin-naive people with T2D agreed that they did not understand why insulin was necessary for them (vs. approximately 15% in insulin-treated people with T2D). Overall, the social stigma of diabetes, the burden of daily injection regimens, and the need for early and ongoing PWD education regarding the purpose and optimization of insulin therapy remain key challenges to be addressed.

Timely insulin initiation is necessary to help to improve glycemic control and to mitigate risk for diabetes-related complications [3, 4]; therefore, concordance between clinical knowledge of appropriate HbA_1c targets for starting insulin [1–3] and real-world application of these targets is essential. Interestingly, although more than 70% of surveyed physicians considered an HbA_1c target of under 9.0% (75 mmol/mol) to be ideal for insulin initiation (should they themselves have T2D), only approximately 30% of surveyed PWD started insulin at an HbA_1c target of under 9.0% (75 mmol/mol). Moreover, only 51.5% of surveyed PWD were involved in determining their HbA_1c target to some degree, suggesting the need to improve individualized person–physician communication. Person-centered communication in T2D has indeed been shown to improve disease knowledge, self-care, metabolic control, and quality of life; therefore, it is an important factor in the management of diabetes [23].

All PWD subgroups (including people with T1D) agreed that they would rather not have to perform insulin injections if there was an alternative available; although insulin therapy cannot easily be stopped once started, providing PWD with alternative, less burdensome insulin regimens may help to improve perceptions of insulin therapy for PWD. Regarding new insulin therapies, physicians, PWD, and caregivers agreed that the need for less frequent injections, simpler treatments and injection preparations, further improvement in glycemic control, and a lower risk of hypoglycemia were all important attributes expected from future insulin therapies (regardless of whether PWD would start insulin for the first time or switch from an existing insulin). The emergence and uptake of once-weekly insulin will likely help to reduce the injection burden and to mitigate, at least partly, individuals’ concerns over the difficulty of managing insulin-based treatment regimens. Indeed, once-weekly insulin analogues have been shown to improve or to sustain glycemic control while maintaining a relatively low risk of hypoglycemia compared with current once-daily basal insulin analogues, simultaneously reducing the overall number of insulin injections required [24–27].

In 2004, the DAWN Japan survey also assessed the perceptions of PWD and physicians regarding resistance to starting insulin therapy [17]. The diabetes treatment landscape has evolved since 2004, so a direct comparison between our survey and DAWN Japan cannot be easily made, but the perception gap between PWD and physicians regarding the negative impact of injections does not seem to have substantially changed. However, the gap related to the impact of social and interpersonal effects appears to have narrowed, particularly for embarrassment associated with insulin administration in the presence of others. This finding suggests that Japanese physicians may have greater empathy for PWD initiating insulin now than they did in 2004, which could be partially attributed to increased awareness of the experiences of PWD (e.g., owing to patient advocacy and social media) and the movement towards person-centered care for physicians [28].

A particular strength of this study was the large number of respondents and well-balanced distribution across overall participating physicians, PWD, and caregivers. The inclusion of people with T1D, insulin-treated T2D, and insulin-naive T2D aided generalizability of the findings for PWD; however, broader generalizability to the general population may be limited. To counteract sample bias, physicians and nurses were recruited from a large sample base; however, it was not possible to control fully for demographic characteristics (e.g., age, duration of T1D or T2D, geography, financial status, family environment, and personality traits) that may have biased the panelists. Additionally, the PWD, physicians, and caregivers who participated in this study were not linked (i.e., participating PWD were not necessarily treated by the participating physicians or caregivers); linking respondents in this way could provide additional insights in future studies.

Conclusions

Physicians and PWD hold several different views regarding the barriers and causes of resistance among PWD associated with insulin initiation. A gap exists between the ideal HbA_1c level for insulin initiation as considered by physicians and the actual HbA_1c levels at which PWD initiate insulin therapy. Physicians, PWD, and caregivers agree that improvement in glycemic control and less frequent injections are the most important characteristics expected from future insulin therapies.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Satoshi Tsuboi and Yuiko Yamamoto were involved in data collection. Yasuaki Hayashino, Satoshi Tsuboi, Yuiko Yamamoto, and Hitoshi Ishii were involved in developing the study concept and design, data analysis and interpretation, participated in critical revision and drafting of the manuscript, and approved the final manuscript for submission. All authors accept responsibility to submit the manuscript for publication.

Funding

This study and the journal’s Rapid Service Fee were funded by Novo Nordisk. Recruitment of the study participants, support with questionnaire design and fieldwork services were provided by INTAGE Healthcare Inc. and was funded by Novo Nordisk.

Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflicts of Interest

Yasuaki Hayashino reports personal fees from Boehringer Ingelheim, Daiichi Sankyo Company Ltd, Eli Lilly Japan K.K., Kowa Pharmaceuticals Inc., Merck & Co. Inc., Novo Nordisk Pharma Ltd, Ono Pharmaceutical Co. Ltd, Sanofi K.K., Sumitomo Pharma Co. Ltd and Takeda Pharmaceutical Company Ltd, outside of the submitted work. Satoshi Tsuboi and Yuiko Yamamoto are employees and shareholders of Novo Nordisk Pharma Ltd. Hitoshi Ishii received payment or honoraria for lectures from Eli Lilly Japan K.K., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Japan Pharma Ltd, Sanofi K.K. and Sumitomo Pharma Co. Ltd.

Ethics/Ethics Approval

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki, which were consistent with good clinical practices and applicable laws and regulations in Japan. The study protocol and informed consent form were submitted to the Medical Corporation TOUKEIKAI Kitamachi Clinic Ethical Review Board for review/approval as a minimal-risk study, and ethical approval was granted on May 17, 2023 (NN1436-7732). Before completing the survey, all respondents provided informed consent for participation and publication of aggregated level data via a web-based platform.