The perspectives of physicians regarding antidiabetic therapy de‐intensification and factors affecting their treatment choices—A cross‐sectional study

Comprehensive diabetes management may include treatment intensification or the administration of antidiabetic combination therapy. However, this may be associated with an increased risk of adverse events and death. The aim of this study was to understand physicians' perspectives regarding treatment de‐intensification, HbA1c goals individualisation, and factors affecting their treatment choice for patients with type 2 diabetes mellitus (T2DM).


| INTRODUC TI ON
The worldwide prevalence of diabetes mellitus (DM) in 2019, was 9.3%, while in Saudi Arabia a higher prevalence rate was reported (15.8%) putting an immense burden on the healthcare system. Direct expenses on diabetes in Saudi Arabia exceeded 13.9% of the total health expenditure. 1 Unless a patient-centred, comprehensive multidisciplinary approach is enforced for the management of DM, the disease burden on Saudi Arabia will continue to escalate to an alarming level. 2 Comprehensive diabetes management includes an appropriate dietary plan, exercise, and antidiabetic medications. Nevertheless, the target glycaemic control is not always achieved using single antidiabetic medication and many patients may need to start treatment intensification to prevent the development of microvascular and macrovascular complications. [3][4][5] Treatment intensification can be done either through increasing the dose of the single antidiabetic agent or by the administration of antidiabetic combination therapy. 6 Treatment guidelines recommend the use of intensive antidiabetic therapy for patients with uncontrolled DM. 7-10 A previous large randomised controlled trial (RCT) reported that intensive antidiabetic therapy is associated with marked reduction in the risk of developing microvascular and macrovascular complications among type 2 diabetes mellitus patients (T2DM). 11 Another large database study found that delay in treatment intensification is associated with multiple life-threatening complications such as myocardial infarction, stroke and heart failure. 12 There are different variables that are reported to be associated with the need to treatment intensification in patients with DM such as high HbA1c value (8.0% and above), long duration of the disease and presence of other comorbidities. 13 However, aggressive pharmacological treatment to achieve HbA1c targets may not be advisable or even practical and one size-fit all approach is not recently recommended. An enlightened patient-centred approach that determines individualised goals for each patient with ongoing follow up is recommended, however, weighting the risk and benefits is challenging. 14 Intensive antidiabetic therapy should be used carefully as it is associated with an increased risk of adverse events and death. 15 One of the leading adverse events associated with intensive antidiabetic therapy is hypoglycaemia. [16][17][18] Hypoglycaemia has been a major concern for of many researches recently, with some of the post-hoc analysis of RCTs have demonstrated an increased risk of death and cardiac complications with hypoglycaemia. 19,20 There are limited studies that addressed antidiabetic treatment de-intensification in order to decrease the clinical and economic burden of the associated hypoglycaemic episodes and to achieve the optimal HbA1c level. 21,22 The excessive burden of DM, and the high prevalence of intensive antidiabetic therapy or as it is called "diabetes over-treatment," increased the importance of exploring how physicians perceive this approach. This study aimed to understand physicians' perspectives regarding anti-diabetic treatment de-intensification and factors affecting their treatment choices for patients with type 2 DM.

| Study design and study population
A cross-sectional survey study was conducted using two previously validated questionnaires. Genere and colleagues' questionnaire, which was developed to understand physicians' awareness of, agreement with and their practices of individualising HbA1c goals and antidiabetic treatment de-intensification. In addition, it has been used to identify HbA1c level at which physicians start treatment deintensification and what important patient factors that motivate them to consider such practice. 23 In addition, Grant and colleagues' questionnaire, which was used to assess factors affecting physicians' treatment choice when prescribing antidiabetic treatment for patients with type 2 DM has been used. 24

| Sampling and recruitment
Physicians from any related speciality, whether general practitioners, internists, or endocrinologists were invited to participate in the study. The inclusion criteria were any physician who currently practising his job and treating patients with type 2 DM.
A convenience sample of all eligible physicians who are registered in the Ministry of Health of Saudi Arabia was invited to participate in the study. Physicians were invited to participate in the study either by email or through sharing the online questionnaire link to them through social media websites such as twitter.

What's known
• Treatment guidelines recommend the use of intensive antidiabetic therapy for patients with uncontrolled DM.
• Intensive antidiabetic therapy should be used carefully as it is associated with an increased risk of adverse events and death.
• Aggressive pharmacological treatment to achieve HbA1c targets may not be advisable or even practical and one size-fit all approach is not recently recommended.

What's new
• Majority of physicians were familiar with the concept of HbA1c goals individualisation.
• Only 66.3% of physicians reported that they apply treatment de-intensification and dose adjustment in their practice.
• Physicians showed higher consideration to objective patient clinical data and their assessment of patient's health status, with minor consideration to patientrelated factors.

| Study instrument
Genere's questionnaire was developed by a panel of internal medicine physicians and specialist in health sciences research and diabetes affiliated with the National Institute of Health-funded Chicago Centre for Diabetes Transaction Research. 25 The questionnaire has identified the concept of individualising HbA1c as "choosing an HbA1C goal for each patient based on their characteristics." Physicians were asked whether they are familiar with this concept, using yes/no question format, and their agreement with this concept was measured using a 5-point Likert scale; ranged from strongly agree to strongly disagree. The frequency of the physicia's practice of HbA1c goals individualisation was also measured using a 5-point Likert scale; ranged from always to rarely. Physicians were asked to choose between three choices regarding the degree of importance of each variable ("major consideration," "minor consideration," or "not a consideration").

| Ethical approval
Permission and approval for the use of the study questionnaires was sought from the corresponding authors. Participants were informed that by completing the online questionnaire, this would be considered written consent and agreement to participate in the study.

The study has been approved by the Ministry of Health-Ethical
Committee-Saudi Arabia.

| Statistical analysis
Data were analysed using the SPSS software, version 25. The descriptive analysis was reported as mean (µ) ± SD for normally distributed quantitative variables and as median (Interquartile range (IQR)) for non-normally distributed variables. Descriptive statistics was used to describe the respondents' basic information. Categorical data were reported as percentages and frequencies. Logistic regression analysis and Chi-squared test were used to assess the relationship between physicians' demographics and their awareness of, agreement with, and practice of HbA1c individualisation and antidiabetic treatment de-intensification. In addition, it was used to compare the response of physicians from different specialties. Physicians and practices covariates were dichotomised at the median (because of the skewness of the data), where years of experience were classified as equal to or more than 3 years and less than 3 years, size of practice as equal to or less than 1000 patients and more than 1000 patients, percentage of patients aged above 18 years or 65 years as equal to or less than 40% and more than 40%. A confidence interval of 95% (P < .05) was applied to represent the statistical significance of the results and the level of significance was assigned as 5%.  Table 1 shows the details of physicians and practices characteristics.

| HbA1c goals individualisation
The majority of physicians (n = 183, 89.3%) reported that they were familiar with the concept of HbA1c goals individualisation. The vast majority (n = 170, 83%) of those who are familiar with the concept of HbA1c goals individualisation agreed with it. However, only 66.3% of them (n = 136) reported that they apply this concept in their daily practices most of the time or in all cases ( Table 2).
Physicians' familiarity with the concept of HbA1c goals individualisation was significantly associated with their years of experience

| Physicians consideration of antidiabetic medication choice
When selecting the antidiabetic therapy for patients, physicians showed a higher consideration to last measured HbA1C level  When a patient has symptoms that could be from their medications

(64.8)
When a patient is at risk for polypharmacy

(43.7)
When a patient raises concerns about the costs of medications

(25.4)
When a patient may not be taking the medicine as prescribed and do not discuss physical activities and lifestyle with them. [36][37][38][39][40] The process of initiating antidiabetic therapy adjustment conversations is restricted by the limited time spent in clinical practice during the provision of healthcare to patients, as such conversation requires a thorough discussion of the risks and benefits related to antidiabetic therapy de-intensification. 23 In this study, almost one third (34.6%) of the physicians reported that they would initiate a conversation about antidiabetic therapy de-intensification with patients who maintained stable for one year.
Pre-defined HbA1c levels were used by many physicians as a cut-off The current study found that physicians have various considerations when prescribing antidiabetic therapy for their patients. However, we expect that this is minimal, since around 9.3% of the participants reported that they are not familiar with such concept.
In addition, the use of the questionnaire in this study could limit the options to the physicians in some aspects and restrict their answers to what were already identified, for example, the subjective patient factors that affect the physicians' choice of treatment.
This research addressed the "over-treatment" problem among patients with type 2 diabetes in the country. The study has also revealed the attitudes and perspectives of physicians towards treatment de-intensification and dose adjustment. This would help policy makers to interpret the importance of such issue and propose guidelines for the management of type 2 diabetes in the region, particularly addressing the importance of treatment optimisation. In addition, this would help in reducing adverse events and mortality rates in this group of patients, and improve the economic and health outcomes.
Physicians should educate their patients after implementing this approach to monitor their blood glucose levels on a continuous basis to have a better control, and to decrease the probability of experiencing any potential drug adverse events. Continuous education programmes to healthcare professionals should focus more on updating physicians' knowledge about contemporary practices and highlight the importance of revising patients' therapy on continuous basis to implement any necessary treatment de-intensification. This would decrease the possibility of unintended overtreatment of patients that might increase their potential harm because of adverse drug events.
As there is a scarcity of studies examining physicians' perspectives regarding treatment de-intensification in type 2 diabetes in the Middle East, it will be interesting to conduct more studies using different methods eg, interviews or focus groups. This will ensure the exploration of all factors that could affect the perspectives of physicians regarding this issue, and hence, drawing a broader picture about the management of such growing disease in the area. This will assist in designing the appropriate protocols and guidelines for the management of type 2 diabetes.

| CON CLUS IONS
The findings of this study showed that antidiabetic therapy adjust-

ACK N OWLED G EM ENTS
This study was supported by Isra University (Amman, Jordan) and Najran University and Cancer Society in Najran, Saudi Arabia.

D I SCLOS U R E S
The authors declare that they have no competing interests.