Basal insulin controls sugar smoothly, and patients with diabetes benefit a lot

*Only for medical professionals to read and refer to an effective and stable insulin plan to help patients achieve high-quality blood glucose management
.

 In recent decades, the prevalence of diabetes in China has been increasing year by year, and it is showing a younger trend, which has seriously endangered people's health [1]
.

In clinical treatment, similar problems are often faced.
Due to various reasons, patients' blood sugar remains high and blood glucose fluctuates greatly.
Among them, hypoglycemia caused by the application of hypoglycemic drugs is also one of the inducements of increased blood glucose fluctuations, such as insulin Secretagogues or insulin will increase the risk of hypoglycemia in patients, and may increase blood glucose fluctuations [2]
.

 Clinically, compared to persistent hyperglycemia, fluctuating hyperglycemia can more promote the occurrence and development of chronic complications of diabetes [2]
.

Therefore, it is urgent to find an effective and stable high-quality hypoglycemic program
.

Following guidelines, timely application of basal insulin As diabetes progresses, pancreatic β-cell function gradually declines [3], insulin therapy has become an important means for managing hyperglycemia in patients with type 2 diabetes (T2DM)
.

In patients with T2DM, when oral hypoglycemic drugs are not effective or contraindicated, insulin should be used to control hyperglycemia and reduce the risk of diabetes complications.
In some cases, insulin therapy may be the most important or even necessary Sugar control measures[4]
.

 "China Type 2 Diabetes Prevention Guidelines (2020 Edition)" (hereinafter referred to as "CDS Guidelines") [4] pointed out in the timing of initiating insulin therapy: if newly diagnosed T2DM patients have obvious symptoms of hyperglycemia, ketosis or diabetic ketones For DKA, insulin therapy is the first choice; in the course of diabetes (including newly diagnosed T2DM patients), there is a significant weight loss without obvious cause, and insulin therapy should also be used as soon as possible; adequate oral hypoglycemic drugs after 3 months of treatment If the glycosylated hemoglobin (HbA1c) is still ≥7.
0%, you can consider starting an insulin treatment plan, usually choosing basal insulin
.

 Insulin has been discovered for a whole hundred years, and it has been updated and iterated, and there are many types
.

The ideal insulin treatment plan is to mimic the physiological insulin release and mode of action as much as possible
.

In the non-fed state, the continuous insulin secretion of pancreatic β-cells is called basal insulin secretion, which accounts for about 50% of the total insulin secretion throughout the day.
Basal insulin regulates liver glycogen decomposition and gluconeogenesis in the liver, as well as peripheral tissues.
The utilization of glucose maintains the steady state of blood sugar and regulates the life activities related to glucose metabolism [5]
.

 In the treatment of patients with T2DM, insulin therapy can be initiated if the life>
.

 For hundreds of years, in order to better simulate physiological basal insulin secretion, basal insulin preparations have been continuously improved, from the initial neutral protamine zinc insulin (NPH) to the first generation of basal insulin analogues, including insulin glargine U100 and insulin detemir , The PK curve of basal insulin is flattened, and the duration of action is further prolonged, but some patients still have the risk of hypoglycemia in clinical practice, which drives the development of new basal insulin analogues-insulin deglubber and insulin glargine U300[ 6]
.

 Compared with traditional basal insulin, these two have a longer action time, can cover blood sugar control 24 hours a day, and have a more stable drug effect
.

Insulin degludec has a half-life of 25h and an action time of 42h.
The daytime variability of its antidiabetic efficacy is only 1/4 of that of insulin glargine U100[4,7]
.

The half-life of insulin glargine U300 is 19h and the action time is 36h.
Studies have shown that its release after injection is more stable and slower than that of insulin glargine U100[4,8]
.

At the same time, the risk of hypoglycemia of the two is lower than that of traditional basal insulin
.

Compared with insulin glargine U100, when the blood glucose control situation is similar, patients who use insulin glargine U300 have a 21% reduction in nighttime confirmation and the incidence of severe hypoglycemia [9], while the number of hypoglycemia events in patients who use insulin degluargine decreases by 30 %[10]
.

 Whether in the past or now, insulin is of great significance for the treatment of diabetes, and the clinical application of new insulin preparations can better help patients control blood sugar, help delay the occurrence and development of complications, and improve the quality of life of diabetic patients [11 ]
.

The 2020 edition of the "CDS Guidelines" [4] includes these two new basal insulin analogs, which have a longer action time and stable and no peak compared with traditional basal insulin [5], which can better mimic the effect of physiological basal insulin.
, Steady control of sugar
.

However, if the two are compared, they are also different
.

Low variability and stable glucose control helps TIR reach the standard.
In order to further understand the stability of the two insulins, a randomized, double-blind, crossover study [12] conducted a normal glucose clamp experiment on 57 cases of type 1 diabetes (T1DM).
The variability of insulin deglubber and insulin glargine U300 at steady state was evaluated
.

The results showed that insulin glargine U300 was 30% lower than insulin degludec in reducing blood sugar (P<0.
0001)
.

At the same time, the day-to-day variability of the hypoglycemic effect of insulin degludec is 1/4 of that of insulin glargine U300 (P<0.
0001), and the intra-day variability is 37% lower than that of insulin glargine U300 (P<0.
0001)
.

It can be seen that insulin degludec can achieve a continuous and stable effect on blood sugar throughout the day, and help blood sugar to reach the standard smoothly
.

 The "Expert Consensus on the Management of Blood Sugar Fluctuations in Diabetic Patients" [13] pointed out that the occurrence of chronic complications of diabetes is closely related to the development of blood glucose fluctuations
.

Therefore, in the treatment of clinical diabetes, attention should be paid to reducing the volatility of blood sugar
.

The international consensus released in 2019 recommends that the blood glucose within the target range (TIR) ​​control target of T1DM and T2DM patients is >70%[14]
.

And thanks to the stable PK/PD, insulin degludec can also help patients reduce blood glucose fluctuations and help TIR reach the standard
.

In an 8-week study of 24 patients with T2DM, the patients randomly received insulin degludec or other insulin treatments.
The blood glucose control status was monitored with an instant scanning blood glucose meter.
The results showed that insulin deglucol treatment was effective in controlling glucose.
The target range, TIR is as high as 77.
3%[15]
.

Effectively lowering blood sugar and optimizing basic insulin regimens Optimizing blood sugar lowering strategies to benefit more diabetic patients is an important task of clinical treatment
.

For this reason, the hypoglycemic effects of insulin deglubber and insulin glargine U300 have also received attention
.

 The first head-to-head study of insulin deglubber and insulin glargine U300-the BRIGHT study [16] is a multi-center, open-label, positive control, two-arm, 24-week non-inferiority study, including poor control of oral hypoglycemic drugs The patients with T2DM were randomly divided into insulin glargine U300 and insulin degluargine groups.
After 24 weeks of treatment, it was found that when the HbA1c control of the two was equivalent, the fasting blood glucose (FPG) improved better in the insulin degluargine group, and the decrease was better than that of insulin glargine U300 The group had a high 0.
43mmol/L (Figure 1), and the amount of insulin was reduced by 20% compared with the insulin glargine U300 group (0.
43U vs.
0.
54U).
At the same time, the risk of hypoglycemia was similar between the two groups
.

It suggests that insulin degludec can achieve better FPG control at a lower dose without increasing the risk of hypoglycemia
.

Figure 1 Compared with insulin glargine U300, insulin degluargine group has a higher FPG reduction.
Real-world study——CONFIRM study [17], 4056 T2DM patients started treatment with insulin degluargine or insulin glargine U300 for 180 days, the results showed that the same Compared with insulin glargine U300, the HbA1c improvement of patients in the insulin degludec group was significantly better (treatment difference: 0.
27%, P=0.
03), and the risk of hypoglycemia was reduced by 30% (RR: 0.
70; 95% CI: 0.
49-0.
99), The daily dose of insulin degludec was 10% less (40.
8U/d vs.
42.
3U/d, RR: 0.
91, P=0.
038)
.

 Another real-world study, the ReFLeCT study [18], showed that when T2DM patients switched from other basal insulin (59.
1% insulin glargine U100/U300) to insulin deglubber for 12 months, the patients’ HbA1c and FPG got significantly Improved (P<0.
001), and the overall risk of hypoglycemia was significantly reduced (RR: 0.
46; 95% CI: 0.
38-0.
56)
.

  Summary Clinically, patients often face problems such as persistently high blood sugar and large blood sugar fluctuations, and there is an urgent need for an effective and stable ideal hypoglycemic program to bring high-quality blood sugar management to patients
.

As the disease progresses, patients with T2DM have a progressive decline in their own insulin secretion function and usually require insulin therapy
.

The 2020 version of the "CDS Guidelines" pointed out that the initial insulin therapy is usually basal insulin
.

Among the new generation of basal insulin analogues, insulin degludec has significant advantages in effective glucose control, stable glucose control, and low risk of hypoglycemia.
It can help patients achieve higher-quality blood glucose management and improve the long-term outcome of patients
.

Expert profile Professor Li Yan, deputy director of the Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University • Member of Diabetes Branch of Chinese Medical Association (Deputy Leader of Obesity Group) • Standing Committee of Endocrinology and Metabolism Branch of Chinese Medical Doctor Association • Standing Committee of Endocrinology and Metabolism Branch of Chinese Society of Geriatrics • China Vice Chairman of the Diabetes Branch of the Geriatric Health Care Association • Vice Chairman of the Diabetes Branch of the Chinese Research Hospital Association • Deputy Chairman of the Diabetes Branch of the Guangdong Medical Association • Honorary Chairman of the Endocrine and Metabolism Expert Committee of the Guangdong Pharmaceutical Association • Standing Member of the Endocrinology and Metabolism Branch of the Guangdong Medical Association • Reviewer of the English edition of Chinese Medical Journal and Chinese Pharmacology Bulletin • Chinese Journal of Endocrinology and Metabolism, Chinese Journal of Diabetes, and Chinese Journal of Practical Internal Medicine • Chinese Journal of Medical Frontiers, Drug Evaluation, and International Diabetes "Editorial reference: [1] Cao Xinxi, Xu Chenjie, Hou Yabing, etc.
China Chronic Disease Prevention and Control.
2020;28(1):14-19.
[2]Wang Ping, Shan Zhongyan, Jiang Yaqiu.
Journal of China Medical University.
2017;46(3):244-247.
[3]Gao Z, et al.
Diabetes Metab Res Rev.
2021;37(2): e3364.
[4] Diabetes Branch of Chinese Medical Association.
Chinese Journal of Diabetes.
2021;13(4): 315-409.
[5] Ran Xingwu, Mu Yiming, Zhu Dalong, et al.
Chinese Journal of Diabetes.
2020; 28( 10):721-728.
[6] Yang Wenying.
Drug Evaluation.
2019;16(21):11-12.
[7]Heise T, et al.
Diabetes Obes Metab.
2012;14(9):859-64.
[8]Becker RH, et al.
Diabetes Care.
2015 Apr;38(4):637-43.
[9]Linong Ji, et al.
Poster presented at: IDF 2019 P-0519.
[10]Wysham C, et al.
JAMA.
2017 Jul 4;318(1):45-56.
[11]Li Yan.
Chinese Journal of Frontier Medicine (Electronic Edition).
2021;13(6):9-15.
[12]Heise T, et al.
Diabetes Obes Metab.
2017;