"The Lancet" is heavy!

▎Editor of WuXi AppTec's content team Hyperglycemia is an important clinical sign of type 2 diabetes (T2DM), and blood glucose control has also been proven to be an important principle for improving type 2 diabetes and its complications
.

It is currently believed that the first priority in the treatment of type 2 diabetes is to prevent and treat metabolic disorders such as hyperglycemia and hyperlipidemia, promote the normal metabolism of sugar, protein and fat, and prevent complications
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However, chapter 4 international diabetes experts led by Professor Ildiko Lingvay of the Department of Internal Medicine of the University of Texas Southwestern Medical Center published a paper in the famous medical journal "The Lancet" and jointly pointed out: The concept of treatment needs to undergo an important change.
We need to control weight as the primary treatment goal (most patients with type 2 diabetes need to lose ≥15% weight), followed by blood glucose control
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After the publication of this paper, the concept of “treating sugar before obesity” has quickly become a topic of high concern in the international diabetes field.
Experts from international diabetes organizations such as the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have also actively discussed this.
, The concept of diabetes management is likely to usher in an important update in the future! Screenshot source: THE LANCET obesity and type 2 diabetes obesity is closely related to the increase in morbidity and mortality of many diseases, including type 2 diabetes
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Type 2 diabetes is one of the most important metabolic complications of obesity, and obesity will also promote the progression of type 2 diabetes
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For insulin-resistant type 2 diabetic patients, their adipose tissue will release more non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other important components that cause the development of insulin resistance, so this part of the patients will lose weight.
Significant benefits from heavy intervention; for patients with β-cell dysfunction and type 2 diabetes, weight loss will greatly reduce the body's demand for insulin, thereby improving metabolism and blood sugar control and minimizing the overall treatment burden
.

It should be pointed out that although not all patients with type 2 diabetes suffer from obesity, the vast majority of patients with type 2 diabetes have "abnormal fats", and these "abnormal fats" are closely related to the pathogenesis of type 2 diabetes
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Based on the important link between obesity and diabetes in the key pathophysiological mechanism, more and more studies have shown in recent years that compared with controlling blood sugar to reduce the complications of type 2 diabetes, weight control is more directly at the root of the disease and provides Opportunity to reverse the disease
.

The primary treatment goal: weight loss by 15%, weight loss, age, duration of diabetes, and insulin application are important prognostic indicators for remission of type 2 diabetes (without drug treatment for fasting blood glucose <5.
6 mmol/L)
.

One of the authors of the current paper, Professor Lingvay from the University of Texas Southwestern Medical Center, pointed out that the results of large-scale phase 3 clinical studies such as the DiRECT study and the Look AHEAD study strongly indicate that weight control can improve patients with type 2 diabetes.
Control blood sugar levels, and reverse potential metabolic abnormalities of type 2 diabetes and obesity-related complications (such as fatty liver, obstructive sleep apnea, osteoarthritis, hypertension, and elevated blood lipids, etc.
)
.

In general, the benefits of weight control for some people with type 2 diabetes (such as reducing risk factors for cardiometabolic diseases, improving quality of life, etc.
) exceed the benefits of simply controlling blood sugar
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Therefore, it is necessary for us to change our concept and regard weight control as the primary treatment goal for type 2 diabetes
.

Ideally, if the body weight of obesity-related type 2 diabetes patients is reduced by 15% or more and maintained for a long time, the overall condition of the disease will have an improvement effect that is difficult to achieve by other glucose-lowering interventions
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For some patients, it may be difficult to achieve the "15%" goal, but the closer to this goal, the greater the benefit for patients
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In view of different disease phenotypes, the paper recommends that patients with type 2 diabetes be divided into three subgroups: Patients with obesity-related diseases: approximately 40%-70% of all patients with type 2 diabetes
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The main pathological driving factor is insulin resistance, which is the main target group of weight loss intervention, and the secondary treatment target is to improve blood sugar, blood pressure, and blood lipids
.

Patients with cardiovascular disease as the main comorbidity: about 1/3 of all patients with type 2 diabetes
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The main pathological driving factors are atherosclerosis and inflammation, the main treatment goal is cardiovascular protection, and the secondary treatment goal is to improve body weight, blood sugar, blood pressure, blood lipids, and blood coagulation
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Patients with isolated hyperglycemia: about 10%-20% of all type 2 diabetes patients
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The main pathological driving factor is β-cell dysfunction, and the main treatment goal is HbA1c<7%, but it can also benefit from weight loss
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People at different stages of the disease can also benefit from weight loss
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For obese patients who have not yet experienced blood glucose abnormalities, early weight intervention is expected to improve the metabolic syndrome caused by obesity and prevent the occurrence of diabetes; for patients with type 2 diabetes, weight intervention is expected to improve metabolic abnormalities and improve the effect of diabetes treatment , Prevent or even reverse the occurrence of diabetes complications
.

Weight intervention strategies Current weight control strategies for type 2 diabetes include life>
.

Life>
.

Not only that, through life>
.

However, most patients gradually reach a plateau or rebound in weight within 1 to 3 years.
Therefore, it is difficult to achieve long-term sustained weight loss in patients with type 2 diabetes through life>
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Bariatric surgery: Bariatric surgery such as Roux-en-Y gastric bypass surgery can reduce the weight of patients with type 2 diabetes by an average of 22% to 37%; sleeve gastrectomy can reduce the weight of patients by an average of 19%
.

As an effective treatment for obese patients, bariatric surgery can make 75% of type 2 diabetes patients short to medium term (up to 5 years) and 37% to 51% of type 2 diabetes patients long-term (up to 20 years).
Effective relief
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A number of randomized trials have compared bariatric surgery with the best medical treatment and found that bariatric surgery can bring higher remission rates and improve long-term blood glucose control for patients with type 2 diabetes
.

In addition, bariatric surgery can also improve other obesity-related metabolic complications, such as abnormal blood pressure, triglycerides, LDL-C, and HDL-C levels
.

It should be pointed out that bariatric surgery has strict indications due to its own related contraindications and possible risks, so it is not suitable for all obese patients with type 2 diabetes
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Drug therapy: Drug therapy provides another option for patients to control their weight for a long time
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Currently approved drugs for chronic weight management are: orlistat (gastrointestinal lipase inhibitor) phentermine-topiramate (acting on the central nervous system to stimulate the release of norepinephrine) naltrexone-an Fepropone (inhibits norepinephrine and dopamine reabsorption, antagonizes opioid receptors) Liraglutide (3.
0mg) (GLP1R agonist) Semagglutide (2.
4mg) (GLP1R agonist) ▲ Type 2 diabetes Obesity treatment drugs and efficacy (picture source: reference [1]) Among them, phentermine is also approved for short-term weight control.
In addition to the above drugs, hypoglycemic drugs such as SGLT2 inhibitors, GLP1R agonists, and biguanides Drugs (metformin) and amylin analogs (pramlintide) have also been proven to promote weight loss
.

Related meta-analysis results show that smeglutide has the most prominent effect in weight control (an average weight loss of 11.
41% in all dose groups), followed by phentermine-topiramate (an average weight loss of 7.
97% in all dose groups), and this The overall risk of adverse events for the two drugs is similar
.

The challenges faced by weight control strategies and the opportunities brought by innovative drugs are based on the large amount of supporting research evidence of weight control in the management of type 2 diabetes.
Many patients with type 2 diabetes may benefit from weight-centered diabetes treatment
.

However, under the existing intervention methods, achieving the primary treatment goal of type 2 diabetes-weight loss is still facing considerable challenges
.

Only a small number of patients can achieve substantial weight loss and maintenance by life>
.

In addition, with the help of existing weight management drugs and enhanced life>
.

More innovative drugs, such as dual/triple agonists currently under development: GIP (glucose-dependent insulinotropic polypeptide)/GLP-1 (glucagon-like peptide 1) receptor dual agonists, GLP-1/GCGR (Glucagon receptor) dual agonists, and modified amylin agonists, etc.
will bring more drug treatment options and opportunities for long-term weight control of type 2 diabetic patients
.

Related reading "The Lancet" sub-journal depth: These innovative therapies are expected to change the future of the treatment of type 2 diabetes.
Two "The Lancet": once a week, better than insulin! New drugs with dual mechanisms for type 2 diabetes have a wide range of metabolic benefits.
The Lancet and NEJM are published together! The treatment of type 2 diabetes may usher in the "new era", and the new dual-mechanism drug has an eye-catching effect on reducing blood sugar and weight loss.
: Type 2 diabetes can be "relieved" with drug withdrawal! What does "relief" mean to patients? Reference [1] Ildiko Lingvay, et al.
, (2021).
Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation.
THE LANCET, DOI:https://doi.
org/10.
1016/S0140 -6736(21)01919-X[2] Primary Goal in T2D Should Be Weight Loss, Diabetologists Say.
Retrieved October 22, 2021, https:// Disclaimer: WuXi AppTec Content Team Focus on introducing global biomedical health research progress
.

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.

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.