The full text of the 2020 CDS Guide is released, let’s take a look at how to recommend insulin!

*Only for medical professionals to read and reference the hot "Chinese Type 2 Diabetes Prevention and Control Guide 2020 Edition" is freshly released! Type 2 diabetes (T2DM) is a chronic progressive disease.
As the course of the disease progresses, the patient's β-cell function declines and the difficulty in controlling glucose increases.
Insulin therapy is a common and effective way to control glucose, and it is also a high control method for most patients.
The only way for blood sugar, when oral hypoglycemic drugs are not effective, patients need to start insulin therapy in time to control hyperglycemia and reduce the risk of diabetes complications [1].

When using insulin, when to start, which type of insulin to choose, how to titrate the dose, and how to reduce the risk of hypoglycemia have become compulsory courses for endocrinologists.

 The newly released "China Type 2 Diabetes Prevention Guidelines 2020 Edition" (hereinafter referred to as the 2020 "CDS Guidelines") issued by the Diabetes Branch of the Chinese Medical Association (CDS) has been updated compared to the 2017 version.
What are the specific updates? The main points can help us better use insulin, a hypoglycemic weapon, to help more patients reach their blood sugar standards? Let's take a good inventory.

Update points 1 T2DM treatment route update initial insulin treatment preferred basal insulin First of all, the 2020 "CDS Guidelines" recommends the timing of the initial treatment of insulin and the choice of insulin type: in terms of treatment pathways, T2DM patients' life>
Previously, for patients who need to initiate insulin therapy, the 2017 CDS Guidelines only pointed out the choice of basal insulin or premixed insulin, and did not make clear recommendations for the type of insulin in the T2DM treatment route [2].

 Figure 1.
Simple path of hyperglycemia treatment for type 2 diabetes patients From the evidence-based evidence, basal insulin therapy does have certain advantages compared to premixed insulin.

A meta-analysis by scholars such as Przemyslaw showed that although the two types of glycosylated hemoglobin (HbA1c) have similar control conditions, compared with the premixed insulin regimen, patients who use insulin glargine combined with oral hypoglycemic agents have overall and symptomatic hypoglycemia The risk is lower, the weight gain is less, and the number of serious adverse events during the treatment of patients can be reduced.
At the same time, compared with the baseline data, it can improve the quality of life of patients in the group [3].

 Update point 2 Guide to the new generation of ultra-long-acting insulin analogues There are many types of basal insulin, how should I choose? The "CDS Guidelines" include many innovative hypoglycemic drugs that have been marketed in China in recent years, as well as two new ultra-long-acting insulin analogues-insulin glargine U300 and insulin degludec.

Compared with traditional basal insulin, the two have a longer action time and a more stable PK/PD, which can reduce the risk of hypoglycemia and help patients to control glucose for a long time and steadily.

 The world's first head-to-head trial of insulin glargine U300 and insulin degluargine-the BRIGHT study shows that insulin glargine U300 and insulin degluargine are similar in terms of HbA1c reduction and overall risk of hypoglycemia.

After 24 weeks of treatment, HbA1c decreased by 1.
64% (insulin glargine U300) and 1.
59% (insulin degludec) [4].

It is suggested that two ultra-long-acting basal insulin analogs can help patients achieve HbA1c standards [4].

In addition, in a glucose clamp test close to the real world, after 3 months of treatment with insulin glargine U300 and insulin deglu, a 24-hour glucose clamp test was performed according to the patient's individualized insulin dosage, and the PK of the two groups were compared.
/PD curve found that insulin glargine U300 reduced the relative intraday variability by 23% compared with insulin degluargine (Figure 2) [5], suggesting that insulin glargine U300 can control blood glucose more steadily throughout the day.  Figure 2.
Insulin glargine U300 has a 23% reduction in relative intraday variability compared with insulin deglubber.
Update point 3 Do not adjust the dose of basal insulin in this way.
Do not be ambiguous.
At present, some of the T2DM patients who initiate basal insulin therapy in my country have a low initial dose and Insufficient dosage adjustment after the initial treatment and other problems, resulting in its unsatisfactory blood glucose control after insulin treatment [6], so it is very important to standardize the clinical application of basal insulin.

 In this regard, the "CDS Guidelines" also updated the application method of basal insulin, proposing that the initial dose is 0.
1 to 0.
2 U/kg/day, and the maximum dose is 0.
5 to 0.
6 U/kg/day.

For patients with HbA1c>8.
0%, starting at 0.
2~0.
3U/kg/day can be considered; for patients with BMI≥25kg/m2, starting at 0.
3U/kg/day can be considered when starting basal insulin.

After that, the doctor needs to adjust the insulin dosage according to the patient's fasting blood sugar level, usually every 3 to 5 days, and adjust 1 to 4 U at a time according to the blood sugar level until the fasting blood sugar reaches the target.

When using insulin glargine U300, the patient can also adjust the dose by 1U every day.
In this way, the patient's HbA1c reduction and the hypoglycemic event rate are equivalent to the amount under the doctor's guidance [7].

 Update point 4 In addition to the "gold standard", there are new standards.
TIR reflects blood glucose fluctuations.
HbA1c is clinically used as the "gold standard" for evaluating long-term blood glucose control status, and it is also an important basis for clinical decisions on whether treatment needs to be adjusted.

However, because HbA1c cannot reflect immediate blood glucose levels, nor can it reflect blood glucose fluctuations, this "CDS Guidelines" incorporates glucose target range time (TIR), glucose above target range time (TAR), and glucose below target range time (TBR) and other parameters that reflect blood glucose fluctuations are used to evaluate blood glucose control, thereby optimizing blood glucose management, and can also help doctors and patients choose more ideal hypoglycemic drugs [1].

These data can be obtained through self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM).

 TIR refers to the percentage of time that glucose is within the target range (usually 3.
9 to 10.
0 mmol/L) within 24 hours.
It is significantly related to diabetic microvascular complications, cardiovascular death and all-cause death [8, 9].
As an important indicator for evaluating blood sugar control.

According to the TIR international consensus released in 2019, the TIR control goal for patients with T1DM and T2DM is >70%[10].

 When choosing hypoglycemic drugs, the "new standard" of TIR must also be fully considered.

 A study conducted continuous blood glucose monitoring for patients with type 1 diabetes who were treated with insulin glargine U300 or insulin degluargine for 14 days, and found that compared with insulin glargine, patients treated with insulin glargine U300 had a 6.
2% higher nighttime TIR (P=0.
018) At the same time, the TAR is 7.
1% (P=0.
02) (Figure 3) [11], suggesting that compared to insulin deglu, insulin glargine U300 can help patients reduce blood sugar fluctuations and smoothly lower blood sugar.

 Figure 3.
The night TIR of patients in the insulin glargine U300 group is higher than that in the insulin deglubber group.
Update point 5 adds a hypoglycemia classification.
In insulin treatment, it is necessary to pay attention to the phenomenon of hypoglycemia in diabetic patients during the treatment.

Hypoglycemia can lead to discomfort and even life-threatening.
It is also a major obstacle to achieving blood sugar standards and should be paid special attention.

So when does it belong to hypoglycemia? This "CDS Guidelines" pointed out that as long as the blood sugar of diabetic patients receiving drug treatment is less than 3.
9mmol/L, it is considered to be hypoglycemia, and the hypoglycemia is graded to help clinicians better judge the patient's condition: Grade 1 hypoglycemia: blood sugar <3.
9mmol/L and ≥3.
0mmol/L; Grade 2 hypoglycemia: blood sugar <3.
0mmol/L; Grade 3 hypoglycemia: there is no specific blood sugar limit, accompanied by serious events with conscious and/or physical changes, requiring help from others Hypoglycemia.

At the same time, the "CDS Guidelines" pointed out that if patients undergoing insulin therapy have asymptomatic hypoglycemia or one grade 3 hypoglycemia or uninduced grade 2 hypoglycemia, blood glucose control goals should be relaxed, and hypoglycemia should be strictly avoided within a few weeks.
Partially reverse asymptomatic hypoglycemia and reduce the risk of future hypoglycemia [1].  In terms of drug selection, it is also necessary to balance the hypoglycemic effect and the risk of hypoglycemia as much as possible.
For example, the two ultra-long-acting basal insulin analogs mentioned above have the same hypoglycemic effect and the risk of hypoglycemia compared to insulin glargine U100 in the traditional basal insulin.
Lower [12, 13].

However, the BRIGHT study showed that in the first 12 weeks of treatment, that is, during the initial dose adjustment period, patients using insulin glargine U300 significantly reduced the rate of grade 1 hypoglycemia (≤3.
9 mmol/L) in the insulin degludec group by 23%.
The rate of grade 2 hypoglycemia events (<3.
0mmol/L) was significantly reduced by 43% (P=0.
038) (Figure 4) [4].

Therefore, considering the effectiveness and safety of hypoglycemia, insulin glargine U300 can be selected as the initial insulin treatment plan.

 Figure 4.
During the initial dose adjustment period, insulin glargine U300 has a lower risk of hypoglycemia than insulin degludec.
Summary The full text of the "CDS Guidelines" is freshly released, and many aspects such as the treatment path, blood glucose control goals, and hypoglycemia classification of T2DM patients have been updated.
With perfection, it can provide authoritative guidance for doctors' clinical application.

On the basis of the combined treatment of life>
In order to achieve HbA1c and TIR compliance in many ways, insulin glargine U300, a new generation of ultralong-acting insulin analogues, can be selected, which has similar hypoglycemic effects as the same new generation of ultralong-acting insulin analogues.
The low blood glucose event rate during the dose period is lower, and it has a higher night TIR.
Patients can adjust the dose by themselves.
It is an ideal choice for diabetic patients to initiate insulin therapy. References: [1] Diabetes Branch of Chinese Medical Association.
Chinese Journal of Diabetes.
2021;13(4):315-409.
[2] Jia Weiping, et al.
Chinese Journal of Diabetes.
2018;10(1):2-67.
[3]Rys P, et al.
Acta Diabetol.
2015;52(4):649-62.
[4]Julio Rosenstock, et al.
Diabetes Care.
2018;41(10):2147-2154.
[5]Lucidi P, et al.
Diabetes Care.
2021Jan;44(1):125-132.
[6]Ji L, et al.
Diabetes Obes Metab.
2017;19:822-830.
[7]Yale J, et al.
Can J Diabetes 2017,41(5):478-484.
[8]Lu J, et al.
Diabetes Care.
2018;41(11):2370-2376.
[9]Lu J, et al.
Diabetes Care.
2021; 44(2):549‑555.
[10]Battelino T, et al.
Diabetes Care.
2019;42(8):1593‑1603.
[11]I Conget, et al.
Poster on EASD 2020; 21-25 SeptemberVirtual Meeting: 670.
[12]Becker RH, et al.
Diabetes Care.
2015Apr;38(4):637-43.
[13]Vora J, et al.
Diabetes Ther.
2014Dec;5(2):435-46.
This information is for medical and scientific reference only.
Sanofi does not recommend using this product in any way that is inconsistent with the prescription information approved by your country.