It is recommended to start insulin therapy if glycemic goals are not met on oral antidiabetic drugs alone, and a “basal first” approach is recommended in most cases. |
Despite having a higher rate of increase in the prevalence of diabetes over the past few years, the use of insulin in Asia has not increased to a large extent, and nearly half of the insulin users from Asia fail to achieve glycemic targets. |
Although guideline recommendations for insulin initiation and titration exist, clinically, physicians and patients do not employ the guideline-recommended titration algorithms because they consider them to be very burdensome. |
The current article summarizes the consensus recommendations related to insulin initiation and titration, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with type 2 diabetes mellitus. |
A practical and actionable consensus would facilitate insulin initiation and optimization in Asia. |
Introduction
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To understand the experts’ approach to their clinical practice
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To assess what experts would give as guidance for primary care physicians
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Development of practical and actionable consensus to facilitate insulin initiation and optimization in Asia
Methods
Results
Discussion
Self-Monitoring of Blood Glucose
Box 1 Consensus Statements on SMBG
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Initiation of SMBG should be considered as soon as T2DM has been diagnosed as it can improve compliance and help in dose adjustments of antidiabetic medications, especially insulin.
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SMBG is generally recommended while initiating insulin. The frequency and type of the glucose monitoring device depend on the patient’s convenience and physician’s advice.
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For basal insulin initiation/titration, a daily fasting glucose measurement is the optimal recommendation.
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In resource-constrained settings, simplified SMBG could be FPG measurement 1–3 times/week.
Delay in Insulin Initiation
Current Options for Insulin Initiation and Dosing
International guidelines | Guideline recommendations |
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ADA [21] | The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when HbA1c levels (> 10% [86 mmol/mol]) or blood glucose levels (≥ 300 mg/dL [16.7 mmol/L]) are very high Basal insulin alone is the most convenient initial insulin regimen and can be added to metformin and other oral agents. Starting doses can be estimated on the basis of the body weight (0.1–0.2 U/kg/day) and the degree of hyperglycemia, with individualized titration over days to weeks as needed Glucagon-like peptide 1 receptor agonists with or without metformin based on glycemic needs are the first-line injectable therapy for individuals with type 2 diabetes with or at high risk for atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease |
IDF [17] | Consider starting insulin alone or in combination with other glucose-lowering drugs when people with T2DM are unstable, with symptoms and signs of acute decompensation Basal insulin should be preferred, and it can be temporary |
Local Asian guidelines | Guideline recommendations |
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Vietnam [38] | The first Vietnam national guidelines for type 2 diabetes diagnosis and treatment were issued by the Ministry of Health in 2017 and the second one in 2020 (available only in Vietnamese). Initiation of basal insulin or premixed insulin (once or twice daily) is recommended by the current guidelines. However, glucagon-like peptide 1 receptor agonists are preferred to insulin in these cases. The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when HbA1c levels (≥ 9%) or blood glucose levels (≥ 300 mg/dL [16.7 mmol/L]) are very high |
Pakistan [39] | If metformin is contraindicated, sulfonylureas, dipeptidyl peptidase IV inhibitors, or insulin can be used as an alternative |
Thailand has its own guidelines for diabetes treatment (available only in Thai), endorsed by the Thai Diabetes Association, the Endocrine Society of Thailand, and the Ministry of Public Health. The guidelines are updated every 3–4 years and the latest version was published in 2020 The essential diabetes drug list includes insulin, metformin, and other glucose-lowering drugs | |
Philippines [42] | People with T2DM who are on noninsulin regimens should be initiated only with basal insulin, which can be combined with meal-time rapid-acting insulin injections |
Malaysia [43] | Insulin/OAD in combination with metformin if HbA1c ≥ 7.5. Basal insulin/premixed insulin + combination therapy or intensive insulin therapy + OAD if HbA1c > 10.0 |
Indonesia [44] | Basal insulin can be initiated in combination with dual/triple OADs if HbA1c is ≥ 7.5% to < 9% with long-standing diabetes. Start basal insulin with 10 U/day or 0.2 U/kg/day. Basal insulin dose titration is needed to achieve FPG 80–130 mg/dL: > 180 mg/dL: increase 4 U 130–180 mg/dL: increase 2 U < 130 mg/dL: maintain the dose |
Singapore [45] | Insulin should be initiated if glycemic goals are not met with OADs alone. Basal insulin such as intermediate- or long-acting insulin should be used for initiation. The use of concomitant OADs should be reviewed while initiating insulin therapy, and metformin ± SGLT2 inhibitors to be continued, if appropriate. Insulin is to be initiated at 0.1–0.2 U/kg/day depending on age, comorbidities, and blood glucose levels. Dosage should be adjusted by 2–4 U once or twice weekly, or as clinically indicated, until the FPG target is reached |
RSSDI [46] | Basal insulin dosage is estimated on the basis of weight and is normally initiated at 10 U or 0.1–0.2 U/kg/day and then uptitrated on the basis of glycemic value, with typical doses ranging from 0.2 to 1.0 U/kg/day |
Box 2: Consensus Statements on Insulin Initiation and Dosing
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Younger age and high HbA1c should trigger early insulin initiation in the Asian population, but fear of hypoglycemia and lack of education are the main barriers to insulin initiation in the region.
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Basal insulin is the preferred insulin for initiation.
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A dose of 10 U/day as an initiation dose should be recommended for the majority of patients in the primary care setting. However, individualization is needed in certain cases, taking body weight and glycemic status into consideration, wherever feasible (0.1–0.3 U/kg/day).
Insulin Optimization and Titration
Pre-titration Requirements
Clinical Evidence on Titration Algorithms
Recommended Titration Methods
Box 3: Consensus Statements on Insulin Titration
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Titration should be ideally started at the same time or within 2 weeks of insulin initiation (the 2-week window is to assess patient comfort and allow familiarization with insulin initiation).
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In primary care settings, titration should continue till FPG goals are met. The period of such active titration should ideally be 12 weeks and may go up to 16 weeks in the real-world setting.
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Having a simple titration regimen will make it easier to follow and comply for both HCPs and patients.
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In primary care physician’s settings, basal insulin should be titrated once or twice a week (in conjunction with the SMBG readings).
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A simple up–down titration algorithm should be recommended in primary care settings, with a dose escalation of 2–4 U/week.
Physician- vs. Patient-Led Titration
Box 4: Consensus Statements on Titration Algorithm
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Patient-led titration is the preferred method of titration, and every effort must be made to achieve this goal.
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Robust patient awareness initiatives and an increase in outreach programs involving diabetes educators can help in empowering patients to titrate insulin.
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In primary care settings, both physicians and patients should drive insulin titration with more emphasis on patient-led titration.
Recommended Insulin Titration Algorithm for the Asian Population with T2DM
Insulin order for ____________________________ (Patient name/age/gender) Date:__/__/____ | |
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Glycemic status (current) | HbA1c…………% FPG …. mmol/L (or mg/dL) PPG …. mmol/L (or mg/dL) |
Glycemic goals (target) | Target HbA1c < ………% Target FPG range …. to …. mmol/L (or mg/dL) Target PPG range …. to …. mmol/L (or mg/dL) |
Insulin (type/name, starting dose and timing) | ……………….. ……(type/name) ……Units (U) ……am/pm everyday For one week□/ two weeks□ (select one) |
SMBG schedule (morning fasting) | Mon □ Tue□ Wed□ Thu□ Fri□ Sat□ Sun□ (select all that apply) |
Insulin dose-adjustment (self-titration, based on average FPG, SMBG) | Increase daily dose by …U if FPG > …. mmol/L (or mg/dL) Decrease daily dose by …U if FPG < …. mmol/L (or mg/dL) Every Mon □ Tue□ Wed□ Thu□ Fri□ Sat□ Sun□ (Titrate insulin dose once or twice a week) |
Additional instructions/remarks | Follow-up visit on ______________(date)b Free text box (other medications, special instructions, initial call or visit to set up patient led self-titration, etc.)a Contact me/nurse at __________(phone/e-mail) |
In case of emergency/hypoglycemia | In case of any medical emergency/hypoglycemia (or if blood glucose < …. mmol/L [or mg/dL]), contact the nearest hospital/ clinic for medical assistance |
Summary of Recommendations
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Regular SMBG should be recommended after diagnosis.
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Glycemic targets should be individualized, and in general, the following may be considered: HbA1c < 7%; FPG, 90–110 mg/dL (5–6 mmol/L); PPG, 160–180 mg/dL (9–10 mmol/L).
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Patient education on diabetes self-management and conversation about insulin should be started shortly after diagnosis to address common myths and set a positive context for insulin therapy.
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Start insulin therapy if glycemic goals are not met on OADs alone, and a “basal first” approach is recommended in most cases.
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An initiation dose of 10 U/day is recommended for the majority of patients in the primary care setting. Individualization is needed in certain cases, taking body weight and glycemic status into consideration, wherever feasible (0.1–0.3 U/kg/day).
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Ideally, a daily fasting glucose measurement is the optimal recommendation following insulin initiation. In resource-constrained settings, SMBG could be considered 1–3 times/week.
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Titration should be started simultaneously or within 2 weeks of insulin initiation (the 2-week window is to assess patient comfort and familiarize with insulin initiation) and should continue until FPG goals are attained. The period of such active titration should ideally be 12 weeks (up to 16 weeks in real-world settings).
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A simple up–down titration algorithm is recommended with dose escalation of 2–4 U/week. Basal insulin should be titrated once or twice a week (in conjunction with the SMBG readings).
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Both physicians and patients should drive insulin titration with more emphasis on patient-led titration. App-based titration aids could be a useful tool for primary care physicians.