Overweight or obesity is an important factor leading to type 2 diabetes. For patients who still have poor blood sugar control through healthy diet, active exercise, and medication, a breakthrough treatment option is expected.
On March 2, "The Lancet" published an important study of semaglutide in patients with type 2 diabetes. In the STEP-2 trial, medication once a week can help overweight or obese type 2 diabetic patients lose an average of nearly 10 kg in weight, and more than a quarter of the patients lose more than 15%, which is much higher than the existing drugs in diabetic patients. At the same time, this also significantly improves overall health conditions including blood sugar, blood pressure, and blood lipids.
This is also the third time that the STEP series of semaglutide has won the top medical academic journal in one month. In the STEP-1 trial published in the New England Journal of Medicine (NEJM) and the STEP-3 trial published in the Journal of the American Medical Association (JAMA), for people without diabetes but overweight and obesity, a 68-week semaglutide treatment combined with diet and exercise intervention can reduce body weight by 15kg-17kg.
"These results are exciting and are similar to the effects we have observed in invasive (metabolic) surgery. This represents a new era in weight management for patients with type 2 diabetes, and marks a shift in the treatment model for obesity." Professor Melanie Davies, lead author of the paper and co-director of the Diabetes Center at the University of Leicester .
This global multicenter trial was conducted in 149 clinical centers in 12 countries and regions in North America, Europe, South America, the Middle East, South Africa and Asia, and included 1,210 patients with type 2 diabetes. The average course of type 2 diabetes in these patients is as long as 8 years. Under the current treatment, the blood sugar control is poor (glycated hemoglobin [HbA1c] 7%-10%), and the body mass index (BMI) exceeds the standard (≥27 kg/m2), and the average weight 99.8 kg, with an average BMI of 35.7 kg/m2.
Patients were divided into groups of 1:1:1 to receive semaglutide 2.4 mg (a trial dose for weight management), semaglutide 1.0 mg (a dose approved for the treatment of type 2 diabetes), or placebo. Semaglutide is injected subcutaneously once a week for 68 weeks. The patients also received lifestyle interventions. They were required to eat 500 calories less than before the test, exercise 150 minutes a week, and receive consultation visits every four weeks.
Patient compliance is good. In fact, 87% of patients completed the treatment and 96% completed all the trial links. 24 patients received obesity salvage treatment (4 patients in the semaglutide 2.4 mg group, 7 patients in the semaglutide 1.0 mg group, and 13 patients in the placebo group), and 1 patient in the placebo group underwent bariatric surgery .
The results at 68 weeks showed that the average weight loss effect of semaglutide 2.4 mg was more significant than that of semaglutide 1.0 mg or placebo, which was statistically significant.
According to the treatment allocation, the weight of patients in the semaglutide 2.4 mg group, semaglutide 1.0 mg group, and placebo group was reduced by 9.6%, 7.0%, and 3.4%, respectively.
According to actual treatment, the weight of patients in the semaglutide 2.4 mg group, semaglutide 1.0 mg group and placebo group was reduced by 10.6%, 7.6%, and 3.1%, respectively.
▲The average weight change of each group during the A-trial period (assigned by the treatment group, regardless of whether the treatment was stopped or received other interventions) and B-the actual treatment period (receiving the trial treatment). (Image source: Reference [1])
In terms of treatment allocation, more than two-thirds of patients in the semaglutide 2.4 mg group lost ≥5% of their weight, which was higher than the other two groups (68.8% vs 57.1% vs 28.5%). The odds of ≥5% weight loss following 2.4 mg of somalutide were 1.62 times higher than those receiving 1.0 mg of somalutide and 4.88 times higher than those receiving placebo. This data reached the primary endpoint of the trial.
Similarly, more than 45%, 25%, and 10% of patients in the semaglutide 2.4 mg group lost at least 10%, 15%, and 20% respectively, which was also higher than the other two groups.
▲5%, 10%, 15%, and 20% weight loss in each group during the A-trial period (assigned by the treatment group, regardless of whether the treatment was stopped or received other interventions) and B-the actual treatment period (receiving the trial treatment). (Image source: Reference [1])
The Somalutide 2.4 mg group also had more significant improvements in waist circumference (-9.4 cm vs -6.7 cm vs -4.5 cm), systolic blood pressure (-3.9 mm Hg vs -2.9 mm Hg vs -0.5 mm Hg), multiple blood lipid indexes, and a range of inflammatory markers.
▲Improvement of waist circumference (A) and systolic blood pressure (B) in the three groups (Image source: Reference [1])
The blood sugar control of the two semaglutide treatment groups was significantly better. The HbA1c of the semaglutide 2.4 mg group, the semaglutide 1.0 mg group, and the placebo group were reduced by 1.6%, 1.5%, and 0.4% respectively, and fasting blood glucose was reduced by 2.1%, 1.8%, and 0.1% respectively. 28.6%, 25.1%, and 7.1% of the patients in the three groups reported that they took a reduction in the amount of hypoglycemic drugs (dose reduction, dressing change or withdrawal).
▲Improvement of blood glucose control in the three groups, including HbA1c fasting blood glucose (Image source: Reference [1])
Compared with placebo, Semaglutide 2.4 mg also brought greater improvement in physical function scores.
In terms of safety, 87.6% of patients in the semaglutide 2.4 mg group reported adverse events, and the proportions of the semaglutide 1.0 mg group and the placebo group were 81.8% and 76.9%. The most common gastrointestinal events, such as nausea, vomiting, diarrhea, and constipation, are mostly short-lived, mild to moderate, and recoverable. Most patients do not stop their medication.
Based on these data, the research team pointed out that for adult patients with overweight or obesity and type 2 diabetes, on the basis of lifestyle intervention, semaglutide 2.4 mg once a week can bring about clinically significant weight loss.
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References:
[1] Melanie Davies, et al., (2021). Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet, DOI: 10.1016/S0140-6736(21)00213-0
[2] Weight loss drug hope for patients with type 2 diabetes. Retrieved March 3, 2021, from https://www.eurekalert.org/pub_releases/2021-03/uol-wld030221.php
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