One, two, three, four, five, five steps to slimming brought by the latest "diet pills"!

*Only for medical professionals to read for reference for 7 years! It's finally here! Since 2014, the FDA has approved a new drug for chronic weight management for the first time
.

This article summarizes obesity in China: More drugs are needed to curb the epidemic.
Step by step: Five thousand people work together to lose weight.
It is expected: The fifth step is not the end of the study.
On June 4, 2021, the US Food and Drug Administration (FDA) approved the division.
Semaglutid injection (2.
4mg/week) is used for chronic weight management [1] As a supplement to reduce calorie diet and increase exercise to lose weight, this drug is suitable for obese adults (BMI≥30kg/m2) Or overweight adults (BMI≥27kg/m2) with at least one complication (hypertension, type 2 diabetes, or hypercholesterolemia)
.

Figure 1 FDA approved smegaglutide for chronic weight management 1.
Obesity in China: more drugs are needed to curb the epidemic.
Obesity, as a chronic non-communicable disease, can lead to insulin resistance, high blood pressure, dyslipidemia, type 2 diabetes, A series of complications such as cardiovascular disease and non-alcoholic fat shorten people's life expectancy
.

The whole world is suffering from the obesity pandemic, and the Chinese are no exception[2-4]
.

Over the past 40 years, the prevalence of overweight and obesity in China has been increasing.
The overweight and obesity rates of children under 6 years old are 6.
8% and 3.
6%, respectively, and the overweight and obesity rates of children and adolescents aged 6-17 have further increased to 11.
1%.
And 7.
9%, the overweight rate among adults is more than 1/3, reaching 34.
3%, and the obesity rate is also as high as 16.
4% [2]
.

The obesity pandemic has forced us to answer questions of treatment and management [3]
.

Changing life>
.

At the same time, people's acceptance of bariatric surgery is relatively low, and it is not everyone's first choice to make a cut to lose weight
.

Drugs have become a transitional option between life>
.

Table 1 Approved weight-loss drugs are very limited, especially in China.
Recently, the FDA approved smegaglutide for chronic weight management
.

This drug is the first drug approved for weight management in chronic obese or overweight adults since 2014
.

This approval is mainly based on a series of studies on the treatment effect of smeglutide on obese patients (STEP), and its weight loss effect is considered to be almost comparable to that of bariatric surgery
.

2.
Step by step: Five thousand people work hard together to lose weight.
The STEP series of research is worthy of the name.
It takes nearly 5000 participants to lose weight collectively, one step at a time
.

This series of research includes five steps, STEP 1 (weight management), STEP 2 (weight management for patients with type 2 diabetes), STEP 3 (weight management + intensive behavioral intervention), STEP 4 (weight maintenance management) and STEP 5 ( Long-term weight management) [5]
.

At present, the results of STEP 1-4 have all been announced, and four articles have been published in three top medical journals, NEJM, Lancet, and JAMA [6-9]
.

Next, let us follow this road to see how amazing this diet pill is! Figure 3 The STEP 1 study was published in the NEJMSTEP 1 study (NCT03548935) led by Feinberg School of Medicine at Northwestern University.
It mainly confirmed whether obese adults can be achieved through life>
.

This study included 1961 participants with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with obesity-related diseases, but diabetics were excluded.
1306 received 2.
4 mg of smeglutide once a week and 655 received Placebo treatment, supplemented by life>
.

Figure 4 The STEP 1 study design first answered the question of whether to lose weight.
The results showed that the average body weight change of the smeglutide group at 68 weeks was -14.
9%, while the placebo was -2.
4%.
The difference between the two groups was- 12.
4%; the average weight change of simegliutide group was -15.
3kg, and the placebo group was -2.
6kg, the difference between the two groups was -12.
7kg, the weight loss effect of simegliutide was outstanding
.

The proportion of smeglutide group that lost more than 5%, more than 10%, and more than 15% was also higher
.

Figure 5 Simeglutide can make people lean.
The STEP 1 study shows that 2.
4 mg of smeglutide + life>
.

However, since patients with type 2 diabetes were excluded from the study, the effect of this intervention on overweight and obese patients with type 2 diabetes is unclear
.

Don't be afraid, let's ask what the STEP 2 research says! Figure 6 The STEP 2 study was published in the LancetSTEP 2 study (NCT03552757), led by the University of Texas Southwestern Medical Center, focusing on 2.
4 mg smeglutide, 1.
0 mg simegliutide, and comfort once a week.
Efficacy and safety of the drug for the management of overweight or obese adult body weight and type 2 diabetes
.

This study included 1210 patients with BMI ≥ 27kg/m2 and type 2 diabetes with HbA1c levels between 7% and 10%.
Among them, 404 received semaglutide 2.
4 mg treatment, and 403 received simedex Glutide 1.
0 mg was treated, and 403 people received placebo treatment
.

1.
0 mg of smeglutide subcutaneously injected twice a week has been approved for the treatment of type 2 diabetes
.

All participants received life>
.

Figure 7 The STEP 2 study design accepts patients with type 2 diabetes.
The results show that the body weight of patients in the smeglutide 2.
4mg group lost 9.
6%, while the placebo group lost 3.
4%, and the weight loss effect of the smeglutide 2.
4mg group was better.
Obvious (-6.
2%; P<0.
0001)
.

The proportion of patients in the 2.
4 mg smeglutide group who lost at least 5% weight at the end of the study was significantly higher than that in the placebo group (68.
8% vs 28.
5%; OR 4.
88; P<0.
0001)
.

The incidence of adverse reactions in the 2.
4 mg smeglutide group (87.
6%) and the 1.
0 mg smeglutide group (81.
8%) was higher than that in the placebo group (76.
9%), mainly gastrointestinal adverse reactions
.

Figure 8 Smeglutide can also make diabetic patients thinner than 90% of type 2 diabetic patients who are overweight or obese, and more than 20% of obese patients also have type 2 diabetes
.

Some drugs used to treat type 2 diabetes are associated with weight gain, exacerbating this diabetes + obesity situation
.

The STEP 2 study shows that smeglutide 2.
4mg is as easy to use for overweight and obese type 2 diabetic patients.
Not only does it not gain weight, but it can also lose weight! However, smeglutide alone is not enough.
Intensified life>Let's move on to the STEP 3 study! Figure 9 The STEP 3 study was published in the JAMASTEP 3 study (NCT03611582), led by the Perelman School of Medicine at the University of Pennsylvania.
It mainly compared 2.
4 mg of smeglutide or placebo once a week as an overweight or obese adult initial The effect of low-calorie diet intensified behavioral therapy aid
.

This study included 611 overweight or obese adults without diabetes.
Participants' BMI ≥ 27kg/m2 and obesity-related diseases also had 1 comorbidity.
Among them, 407 received 2.
4 mg of Simei once a week.
Glutide treatment, while 204 people received placebo treatment
.

Figure 10 The STEP 3 study design attempts to explore the weight loss effect of "strong cooperation".
The results showed that the average body weight of the smeglutide group was reduced by 16.
0% compared with the beginning, while the placebo group was reduced by 5.
7%.
The difference between them reached -10.
3% (P<0.
001)
.

The proportion of smeglutide group with a weight loss of more than 5% was higher (86.
6% vs 47.
6%; P<0.
001), and the proportion of weight loss of more than 10% and 15% was also higher (75.
3% vs 27.
0%, P<0.
001; 55.
8% vs 13.
2%, P<0.
001)
.

However, there were more gastrointestinal adverse reactions in the smegliutide group (82.
8% vs 63.
2%), and 3.
4% of the smegliutide group discontinued the study
.

In fact, a total of 567 patients completed the study, and 505 were still receiving treatment at the end of the study
.

Figure 11 Simeglutide + intensive life>However, further research is needed to assess whether this effect can be maintained
.

This requires a look at the results of the STEP 4 study! Figure 12 The STEP 4 study was also published in the JAMASTEP 4 study (NCT03548987) led by the Weight Management Center in Washington, USA.
It mainly compared overweight or obese adults receiving life>
.

This study included 902 participants with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with obesity-related diseases, but excluded diabetes patients
.

Participants tried to reach a tolerated dose of 2.
4 mg of smegliutide once a week in the first 20 weeks.
Then, of the 803 participants who reached the 2.
4 mg dose, 535 continued to receive smegliutide treatment, 268 People switched to placebos
.

All participants received life>
.

Figure 13 The STEP 4 study design had an operation result showing that the participants who successfully reached the tolerated dose of 2.
4 mg of smeglutide once a week in the first 20 weeks lost an average of 10.
6% in body weight
.

Participants who continued to receive smeglutide treatment after 20 weeks lost 7.
9% of their body weight, while those who were secretly switched to placebo rebounded by 6.
9%.
The difference between the two groups reached -14.
8% (P<0.
001)
.

At the same time, participants in the smeglutide group had a thinner waist (-9.
7cm; P<0.
001), a lower systolic blood pressure (-3.
9mmHg; P<0.
001), and a higher physical function score (2.
5; P<0.
001)
.

Participants in the smeglutide group had a higher incidence of gastrointestinal adverse events (49.
1% vs 26.
1%), but the rate of discontinuation of medication due to adverse events was similar (2.
4% vs 2.
2%)
.

Figure 14 The weight of simegliutide will rebound.
The STEP 4 study not only shows that receiving simegliutide treatment can lose weight, but also through the trick of changing the day, it further proves that participants will rebound if they do not have simegliutide
.

This "sinister and cunning" research design makes people more convinced that smegaglutide has the ability to maintain continuous weight loss
.

3.
It is expectant: The fifth step is not the end point of the study
.
The results of the STEP 5 study (NCT03693430) have not yet been announced .

The total design time of 104 weeks of STEP 5 research is a whole year faster than the previous four projects of 68 weeks
.

During the 104-week study, participants’ long-term weight loss effects and safety will be tested
.

Dr.
John Sharretts, director of the Diabetes, Lipid Disorders and Obesity Division of the FDA's Center for Drug Evaluation and Research, pointed out that the approval of this drug provides a beneficial new treatment option for obese or overweight adults and can be included in a weight management plan [1] In addition to its use in chronic weight management, smeglutide was also approved by the FDA for the treatment of type 2 diabetes in 2017
.

Figure 15 The STEP 5 study design lasted 104 weeks.
At present, the National Medical Products Administration (NMPA) of China has also approved the marketing application of smeglutide 0.
5mg/1.
0mg injection in China, which is suitable for the treatment of type 2 diabetes [10 ]
.

However, there is still uncertainty about when smeglutide 2.
4mg injection will be approved for the market in China for weight management [3]
.

However, the STEP 5 study is not the end of this series of studies, and the next step is to focus on whether smeglutide is useful for Chinese people! In fact, the STEP 6 study (NCT03811574) focused on the effectiveness and safety of smeglutide in overweight or obese East Asian adults, and the STEP 7 study (NCT04251156) is planning to specifically explore smegel among Chinese.
The effectiveness and safety of glutide, the next STEP 8 study (NCT04074161) even wants to further increase the dose of smeglutide to 3.
0mg once a week
.

Figure 16 The STEP 5 study has been completed, but it is far from the end point.
The effect of smeglutide in different populations has also attracted attention.
For example, the STEP TEENS study (NCT04102189) will evaluate the application of this drug in adolescents, STEP-HfpEF The study (NCT04788511) focused on the effect of smeglutide in obese patients with heart failure, and the STEP-HfpEF-DM study (NCT04916470) further subdivided the population into type 2 diabetes patients with heart failure and obesity
.

In addition, the study on the effect of smeglutide on the cardiovascular outcome of overweight or obese patients (SELECT; NCT03574597) is also underway, aiming to explore the effect of smeglutide on obesity or previous cardiovascular disease.
The impact of cardiovascular event risk in overweight patients
.

So much research is on the way, and it seems that our "chasing fan" road will continue! References: [1] FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014.
June 04, 2021.
Accessed via https:// -drug-treatment-chronic-weight-management-first-2014 on 2021-06-09.
[2] Pan XF, Wang L, Pan A.
Epidemiology and determinants of obesity in China.
Lancet Diabetes Endocrinol.
2021 Jun;9( 6):373-392.
doi: 10.
1016/S2213-8587(21)00045-0.
PMID: 34022156.
[3] Zeng Q, Li N, Pan XF, Chen L, Pan A.
Clinical management and treatment of obesity in China.
Lancet Diabetes Endocrinol.
2021 Jun;9(6):393-405.
doi: 10.
1016/S2213-8587(21)00047-4.
PMID: 34022157.
[4] Wang Y, Zhao L, Gao L, Pan A , Xue H.
Health policy and public health implications of obesity in China.
Lancet Diabetes Endocrinol.
2021 Jun 4:S2213-8587(21)00118-2.
doi: 10.