Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
BMJ 2024; 384 doi: https://doi.org/10.1136/bmj-2023-076410 (Published 29 January 2024) Cite this as: BMJ 2024;384:e076410
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Dear Editor
Thanks to the research for its thought-provoking and landmark article. Glucagon-like peptide-1 receptor agonists (GLP-1Ras) are the most effective drug for glycaemic control and weight loss in treating type 2 diabetes by reducing haemoglobin A1c and fasting plasma glucose concentrations (1); Science has named GLP-1 drugs the Breakthrough of the Year, which shed weight, cure diabetes and heart failure as well as kidney disease (2). The Chinese idiom "heart wide body obesity"; The inhibition of GPR75 may provide a therapeutic strategy for obesity and highland barley-based functional foods with anti-diabetes and anti-obesity (3,4). It is very necessary to clarify the coevolutionary mechanism of disease resistance genes and human functional foods (barley and rice) as well as GLP-1Ras.
We think that the major scientific basis for whole grains similar GLP-1Ras control chronic diseases: Human chronic disease outbreak owes its origin to consumption of brown rice and barley for staple diet, whereas white rice and wheat white flour today. This view has been verified by authoritative global data that low intake of whole grains contributes most to human chronic diseases (5). Whole rice can be used to prevent diabetes and its related complications in humans, especially the health benefits for RS1> RS3> RS5> RS4> RS2 (6).
Barley plays an important role in health and civilization of human migration hunger from Africa to Asia and Eurasia, major components of barley similar GLP-1Ras control chronic diseases are -glucan, resistant starch, polyphenols, dietary fiber, arabinoxylan, saponarin, tocols, GABA, SOD, and phytosterols. Barley is a feed for lean pigs, especially 25 kinds of high quality ham in Yunnan (Ninglang black pig ham) are related to barley functional forage; barley grains and grass combat more than 20 chronic diseases and the hunger-longevity theory (7). We need to do a lot of research, such as provide a glimpse of the way forward.
This work provided a new way of regular consumption of functional foods (functional rice and highland barley) is mainly supplemented by GLP-1Ras therapy to help us overcome chronic diseases. However, the similarities and differences between the molecular mechanisms of functional food and GLP-1Ras have broad prospects in future research and development for prevention and treatment of chronic diseases.
References
1. https://www.bmj.com/content/384/bmj-2023-076410
2. https://www.science.org/content/article/breakthrough-of-the-year-2023#se...
3. Yawen Zeng, Hafiz Ghulam Muhu-Din Ahmed. Barley functional foods and human genes affect obesity. Science, 2021,373(6550): https://www.science.org/doi/10.1126/science.abf8683
4. Yawen Zeng, Xiaomeng Yang, Xia Li, Xiaoying Pu,Li'E Yang,Jiazhen Yang. Barley functional foods control human type I diabetes. Science, 2021,373(6554): https://www.science.org/doi/10.1126/science.abg4502
5. https://www.thelancet.com/article/S0140-6736(19)30041-8/fulltext#sec1
6. https://www.tandfonline.com/doi/full/10.1080/87559129.2021.2024221
7. https://www.science.org/doi/10.1126/science.ade1662
Competing interests: No competing interests
Accurate comparison of the efficacy of GLP-1RAs: Incorporating time effects and population stratification
Dear Editor
Yao and his colleagues conducted a systematic review and network meta-analysis to compare the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in blood glucose control, weight management, and lipid profiles in type 2 diabetes (T2D) .[1] This review is extensive and meticulous, but there are still some aspects that could be improved.
The forest plot in this review does not specify time points while evaluating glycaemic control, body weight, and lipid profile. The intervention duration spanning from 12 to 78 weeks is excessively broad, making it challenging to accurately compare efficacy. This limitation is inherent in traditional network meta-analysis methods. Up until December 2023, several head-to-head studies [2 3] and meta-analysis [4 5] have provided evidence of the favorable impact of tirzepatide on blood glucose control and weight management. Nevertheless, it remains unclear whether tirzepatide consistently sustains its efficacy over different treatment durations, specifically at week 4, 8, 16, and 32. Both this review and prior research currently lack information on this aspect. In order to better guide physicians in providing individualized clinical treatment for patients, the time-varying drug effect of GLP-1RAs should also be taken into account.
This review exclusively focused on patients with T2D, thereby limiting its applicability to non-diabetic individuals seeking to utilize GLP-1RAs for weight loss. We consider it somewhat biased to solely demonstrate the weight-reducing efficacy of GLP-1RAs in patients with T2D. As of the publication date of this review, liraglutide, semaglutide, and tirzepatide have been approved by the Food and Drug Administration (FDA) for weight reduction, and several randomized clinical trials have been conducted or are currently in progress to explore their efficacy in promoting weight loss among overweight or obese individuals without diabetes. [6 7] To promote a broader use of GLP-1RAs for weight reduction, it is essential to expand population coverage, such as including individuals who are overweight or obese without diabetes.
When assessing the potential baseline effects on the primary outcomes, this review appears to be inadequate, despite taking into account patient age, diabetes duration, and background treatment, with meta-regression analysis. The meta-regression analysis should ideally be conducted on population groups with comparable baseline characteristics. For instance, considering that there is a weight difference of approximately 20 kg between Asians and Caucasians, [2 8] it becomes apparent that direct application of regression analysis would not be appropriate. So, should the efficacy differences between different regions or ethnicities be discussed separately?
In conclusion, the precision of predicting the clinical efficacy of GLP-1RAs would be enhanced, with a further investigation into the temporal dynamics of drug effects, and an expansion of the study population with categorization.
1. Yao H, Zhang A, Li D, et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. Bmj 2024;384:e076410. doi: 10.1136/bmj-2023-076410 [published Online First: 2024/01/30]
2. Gao L, Lee BW, Chawla M, et al. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nat Med 2023;29(6):1500-10. doi: 10.1038/s41591-023-02344-1 [published Online First: 2023/05/26]
3. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-16. doi: 10.1056/NEJMoa2206038 [published Online First: 2022/06/04]
4. Shi Q, Nong K, Vandvik PO, et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. Bmj 2023;381:e074068. doi: 10.1136/bmj-2022-074068 [published Online First: 2023/04/07]
5. Alkhezi OS, Alahmed AA, Alfayez OM, et al. Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. Obes Rev 2023;24(3):e13543. doi: 10.1111/obr.13543 [published Online First: 2022/12/30]
6. Wharton S, Batterham RL, Bhatta M, et al. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring) 2023;31(3):703-15. doi: 10.1002/oby.23673 [published Online First: 2023/01/20]
7. Wharton S, Blevins T, Connery L, et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med 2023;389(10):877-88. doi: 10.1056/NEJMoa2302392 [published Online First: 2023/06/23]
8. Aroda VR, Aberle J, Bardtrum L, et al. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. Lancet 2023;402(10403):693-704. doi: 10.1016/s0140-6736(23)01127-3 [published Online First: 2023/06/30]
Competing interests: No competing interests