"Expert Guidance Opinions on the Initiation Adjustment Period of Basic Insulin for Adults with Type 2 Diabetes" has been released!

*Only for medical professionals to read for reference.
Pay attention to safety, clear goals, start adequately, and actively adjust
.

At present, the level of glucose control in patients with type 2 diabetes (T2DM) is generally deviated, and the application of insulin is not standardized
.

The "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2020 Edition)" pointed out that patients with T2DM should start insulin therapy as soon as possible (3 months) if their blood sugar still does not reach the control target based on the combination of life>
.

Among them, basal insulin is one of the initial insulin treatment options recommended by the guidelines
.

However, according to the ORBIT study, the current status of the use of basal insulin in Chinese diabetic patients is not optimistic: more than half of the patients have clinical inertness during the treatment process, which is manifested as late initial treatment of basal insulin or low initial treatment dose of basal insulin [2]
.

 Therefore, experts in the field of internal secretion and metabolic diseases jointly formulated the "Expert Guidance Opinions on the Initial Adjustment Period of Basic Insulin for Adults with Type 2 Diabetes" [3] (hereinafter referred to as the "Opinions"), which was officially released on October 25, 2021.
To help clinicians better use basal insulin and improve the management of T2DM patients
.

 Initial adjustment period-laying a good foundation is very important! According to the "Opinions", the initial insulin dose adjustment period is 8 to 12 weeks after the initiation of insulin treatment.
It is the period during which most insulin hypoglycemic clinical studies aim to achieve the goal of blood glucose control and actively adjust the insulin dose
.

In the insulin maintenance period after the initial dose adjustment period, usually only a small adjustment of the insulin dose is required to maintain the blood glucose target and avoid the occurrence of hypoglycemia [3]
.

 The initial dose adjustment period is also the period when blood glucose control improves the most
.

Studies have shown that: patients with T2DM started insulin glargine treatment for 24 weeks and adjusted the effective dose.
The decrease in HbA1c during the initial dose adjustment period accounted for 80% of the overall decrease in 24 weeks [4]; 3 before the initial insulin treatment If the monthly HbA1c does not meet the standard, the risk of HbA1c not meeting the standard (HbA1c>7.
0%) after 24 months increases by 2.
7 times [5]
.

It can be seen that laying a good foundation at this stage to achieve effective blood sugar control and reduce the risk of hypoglycemia is very important to achieve long-term blood sugar control, and it can even be said to be the key to the success of long-term insulin therapy
.

 However, the initial dose adjustment period is relatively prone to hypoglycemia, which hinders dose adjustment and leads to drug withdrawal
.

Real-world studies have shown that if hypoglycemia occurs in the first 3 months after the initiation of basal insulin therapy, the risk of hypoglycemia in the following 24 months increases by nearly 5 times [5]
.

 Therefore, it is important to choose a basal insulin with a low risk of hypoglycemia
.

At present, basic insulins in clinical application in China mainly include intermediate-acting insulin (NPH, neutral protamine zinc insulin), long-acting human insulin analogs (insulin detemir, insulin glargine U100), and ultra-long-acting human insulin analogs ( Insulin glargine U300, insulin deglubber) [3] (Table 1)
.

 Table 1 Types and basic characteristics of basal insulins.
As can be seen from the table, ultra-long-acting insulin analogues not only act longer, but are stable without peaks.
They can effectively avoid blood glucose fluctuations and are closer to the physiological insulin secretion pattern, so the risk of hypoglycemia is significantly lower than Other basal insulin
.

According to the BRIGHT study, comparing insulin glargine U300 in the ultra-long-acting insulin analogue with insulin degluargine, after 24 weeks of treatment with insulin degluargine and insulin glargine U300, the improvement of HbA1c was similar and the overall incidence of hypoglycemia was similar.
, But the risk of hypoglycemia is relatively lower in the insulin glargine U300 treatment group during the initial dose adjustment period (0-12 weeks) [6]
.

 The "Opinion" reminds that when hypoglycemia is suspected, the blood glucose level should be measured immediately to confirm the diagnosis.
If the blood sugar cannot be measured, it can be treated as hypoglycemia
.

Diabetes patients with blood sugar ≤3.
9mmol/L, that is, they need to supplement glucose or carbohydrate-containing foods.
Severe hypoglycemia needs to be treated and monitored according to the patient's awareness and blood sugar status [3]
.

Individuation of glucose control goals and strategies for dose adjustment.
According to the "Opinions", three principles should be followed for a successful insulin initiation treatment plan: clear goals, adequate initiation, and active adjustments
.

Of course, for people at high risk of hypoglycemia, the three principles need to be adjusted to appropriately adjust the target, start with a small dose, and adjust the amount carefully
.

 After selecting the appropriate basal insulin, the next step is to determine the appropriate glucose control target
.

The "Opinions" suggest that the goal of glucose control should be fasting blood glucose (FPG), based on the principle of individualization, comprehensively considering the patient's age, course of disease, life expectancy, concomitant diseases, hypoglycemic treatment plan, patient wishes, etc.
[3]
.

 For most non-pregnant adult T2DM patients, reasonable blood glucose control goals are HbA1c<7%, FPG 4.
4~6.
1mmol/L; for patients with a short course of disease, long life expectancy, no serious complications or low risk of hypoglycemia, More stringent blood glucose control goals can be set, such as HbA1c<6.
5%, FPG 4.
4~5.
6mmol/L; for patients with a history of severe hypoglycemia, short life expectancy, and serious diseases, blood glucose control goals can be more relaxed.
Such as HbA1c<8.
0%, FPG≤7.
0mmol/L or higher[3]
.

After the basal insulin program determines the glucose control goal, it is necessary to pay attention to the start of sufficient amount
.

Regarding the calculation of the starting dose, the "Opinions" gives precise guidance: The starting dose of basal insulin can be calculated based on body weight, usually 0.
1~0.
3U/(kg·d); for HbA1c>8.
0%, 0.
2~0.
3 can be considered U/(kg·d) start; when the body mass index (BMI) ≥25kg/m2 starts insulin glargine U100 treatment, 0.
3 U/(kg·d) can be considered to start [3]
.

After a sufficient amount is started, the basal insulin dose is not static, but needs to be dynamically adjusted according to the actual situation
.

According to the "Opinions", in the basal insulin regimen, when the basal insulin dose does not reach 0.
5 to 0.
6 U/(kg·d), if the FPG does not meet the standard and there is no significant hypoglycemia, the basal insulin dose can be adjusted to optimize blood glucose.
, Without changing the treatment plan
.

Before reaching the set blood glucose target value, it is recommended that patients, under the guidance of a doctor, adjust 2~6U per week according to FPG until the FPG reaches the standard [3]
.

 For patients who have the ability to monitor blood glucose, sense hypoglycemia, and have self-management capabilities, doctors can guide them to make simple self-insulin dosage adjustments
.

For example, for insulin glargine, patients can adjust 1U every day until the FPG reaches the standard [3]
.

 The "Opinions" recommends that patients on insulin therapy should monitor their blood glucose according to the insulin treatment plan, and adjust the dose of basal insulin before going to bed according to FPG to promote blood glucose to reach the standard [3]
.

When ≥1 kinds of oral hypoglycemic agents (OADs) have not reached the standard after 3 months of standard treatment, basic insulin therapy can be initiated to improve blood sugar control: HbA1c>9.
0% or FPG>11.
1mmol/L, with or For newly diagnosed T2DM patients without obvious symptoms of hyperglycemia, if hyperglycemia needs to be corrected in a short time, consider starting basal insulin combined with prandial insulin therapy [3]
.

 Regarding the basal-meal insulin regimen, the "Opinions" also gives clear recommendations: basal insulin combined with OADs and/or glucagon-like peptide 1 receptor agonist (GLP-1RA) standard treatment after 3 months, FPG For patients who meet the standard, but HbA1c still does not meet the standard, on the basis of basal insulin therapy, add meal insulin 4~6U before the main meal/breakfast; adjust the meal insulin 1~2 times per week according to the blood glucose level before the next meal , Adjust 1~2U or 10%~15% each time until the pre-meal blood sugar of the next meal reaches the standard; according to the need of blood sugar control, it will gradually increase to 2~3 times/d prandial insulin therapy[3]
.

Special populations specialize and use insulin to benefit patients.
Special populations in T2DM patients, such as the elderly and people with diabetes mellitus with impaired vital organs, should not only follow the basic principles in insulin therapy, but also consider some special recommendations
.

The "Opinions" pointed out that on the basis of life>
.

Basal insulin is convenient and highly compliant, and is suitable for most elderly patients.
Therefore, basal insulin is the first choice when starting insulin therapy, and preparations with lower risk of hypoglycemia are selected [3]
.

 People with diabetes mellitus with impaired vital organs mainly include people with chronic kidney disease (CKD) and people with impaired liver function
.

For CKD patients, it is recommended to choose insulin analogues that have low risk of hypoglycemia and are conducive to patient self-management
.

Patients with renal insufficiency should start with a small dose and increase the dose to avoid hypoglycemia
.

Patients with T2DM with severe liver dysfunction may consider insulin therapy [3]
.

 The previously mentioned ultra-long-acting insulin analogue insulin glargine U300, in elderly patients and patients with renal insufficiency, can effectively control glucose without increasing the risk of hypoglycemia, helping patients with special diabetes to control their blood glucose stably (Figure 1) [ 7, 8]
.

 Figure 1 Insulin glargine U300 is more effective in lowering blood sugar in the elderly (left) and patients with renal insufficiency (right).
Summary There is a general deviation in the glucose control level of T2DM patients in China.
The current situation of basal insulin use is not optimistic, and a more standardized basal insulin is urgently needed Guidelines for initial treatment; a good foundation for the initial insulin dose adjustment period will help achieve long-term blood sugar control, but attention should be paid to the selection of basal insulin that is not prone to hypoglycemia; ultra-long-acting insulin analogs have a longer action time, stable and no peaks, The risk of hypoglycemia is significantly lower than that of other basal insulins; insulin treatment plans need to follow three principles: clear goals, start with adequate amounts, and actively adjust
.

References: [1] Diabetes Branch of Chinese Medical Association.
Guidelines for Prevention and Treatment of Type 2 Diabetes in China (2020 Edition) [J].
Chinese Journal of Diabetes, 2021, 13(4): 315-409.
DOI: 10.
3760/cma.
j.
cn115791-20210221-00095.
[2] Gao L, Zhang P, Weng J, et al.
J Diabetes.
2020.
DOI: 10.
1111/1753-0407.
13046.
[3] Chinese Medical Association Diabetes Branch.
Adult Type 2 Diabetes Basal Insulin Expert guidance on initial adjustment period[J].
Chinese Journal of Diabetes, 2021, 29(10).
[4] Owens DR, et al.
Diabetes Res Clin Pract.
2014;106:264-274.
[5] Mauricio D , et al.
Diabetes Obes Metab.
2017;19:1155–64.
[6] Rosenstock J, et al.
Diabetes Care 2018;41:2147–54.
[7] Bernard Charbonnel, et al.
Presented at: American Diabetes Association Scientific Sessions 2019,131-LB.
[8] Haluzík M, et al.
Diabetes Obes Metab 2020,22(8):1369-1377.
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