Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with and without overweight/obesity: meta-analysis of randomized controlled trials

Fang, Zhang; Tang, Lei; Zhang, Yuwei; Lu, Qiongshi; Tong, Nanwei

doi:10.1038/s41598-017-16018-9

Cited by 16 publications

(16 citation statements)

References 41 publications

(147 reference statements)

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“…Our findings are in good agreement with a pooled analysis including 16 randomized controlled trials demonstrating similar efficacy of exenatide treatment between obese and non‐obese patients with T2D, except that the patients in that pooled analysis were divided into more BMI groups (≥20 to <25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m 2 ) . A recent meta‐analysis focusing on Asian patients with T2D also found that patients with and without overweight/obesity can benefit from GLP‐1RAs . Another study conducted in obese Korean patients with T2D who were treated with 22‐week exenatide twice daily in combination with both metformin and sulfonylurea also found that baseline body weight and weight reduction during the intervention could not predict the HbA1c reduction in this population, although the median disease duration for patients in that study was 8 years and the median BMI was 30.78 kg/m 2 …”

Section: Discussionsupporting

confidence: 88%

Effect of baseline body mass index on glycemic control and weight change with exenatide monotherapy in Chinese drug‐naïve type 2 diabetic patients

Deng

Lin

Yang

et al. 2019

Journal of Diabetes

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Highlights• This study demonstrates that glycemic control with exenatide monotherapy is similar among normal-weight, overweight, and obese Chinese patients with newly diagnosed type 2 diabetes (T2D). Body weight decreased by 3.7%, 5.5%, and 5.7% in normal-weight, overweight, and obese patients, respectively. • Hence, normal-weight patients with T2D would benefit from exenatide as much as overweight or obese patients on glucose control, without an increased risk of excess weight loss. AbstractBackground: The weight-reducing effect of exenatide has been proved, but too much weight loss in normal-weight patients may concern physicians. This study evaluated the effects of exenatide monotherapy on glycemic control and weight change in normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes (T2D). Methods: In this multicenter prospective study, 29 normal-weight, 54 overweight, and 27 obese newly diagnosed and drug-naïve patients with T2D were treated with exenatide for 48 weeks. The primary efficacy endpoint was the effect of baseline body mass index (BMI) on glycemic control, measured as the change in HbA1c from baseline to Week 48 compared among different BMI groups. Other endpoints included comparisons of the effects of exenatide on fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body weight, and other metabolic indices.Results: After 48-week treatment, the estimated mean changes in HbA1c in normalweight, overweight, and obese patients were −1.9%, −1.8%, and −1.5%, respectively (P = 0.290 among groups after adjustment for baseline values). There were similar declines in FPG and 0.5-and 2-hour PPG among groups. There were nonsignificant trends from normal-weight to overweight to obese patients for increased weight reduction (decreases of 2.2, 3.9, and 4.0 kg, respectively; P = 0.104) and changes in waist circumference (decreases of 2.2, 3.2, and 5.6 cm, respectively; P = 0.078). Conclusions: Baseline BMI had no effect on glycemic control, weight change, or other metabolic indices with exenatide monotherapy. Normal-weight patients with Hongrong Deng and Shuo Lin contributed equally to this work.

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Section: Discussionsupporting

confidence: 88%

Effect of baseline body mass index on glycemic control and weight change with exenatide monotherapy in Chinese drug‐naïve type 2 diabetic patients

Deng

Lin

Yang

et al. 2019

Journal of Diabetes

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“…The selected RCTs were published between 2008 and 2021. Besides, in the included studies, 23 RCTs reported weight loss 7 8 9 10 11 12 13 16 17 18 19 20 21 22 23 24 25 26 27 28 37 , 20 RCTs provided BMI and WC as efficacy parameters 5 6 7 8 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 , 14 RCTs showed total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) 7 8 9 10 12 13 16 17 21 23 24 26 27 28 , 15 RCTs displayed high density lipid-cholesterol (HDL-C) 8 9 10 11 12 13…”

Section: Resultsmentioning

confidence: 99%

“…In addition to the weight loss effect of GLP-1A in the overweight/obesity patients with diabetes, recent studies demonstrated that GLP-1 also have an antiobesity effect in overweight/obese patients without diabetes. In 2015, Zhang et al systematically analyzed the eight randomized controlled trials (RCTs) of GLP-1RAs including liraglutide and exenatide and found that the treatment of overweight/obese patients without diabetes with GLP-1RAs can achieve –2.85 kg weight loss, significantly larger than control group 5 . Besides, in 2019, semaglutide, a recently approved novel GLP-1RA, was developed to treat overweight/obese patients without diabetes.…”

Section: Introductionmentioning

confidence: 99%

The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Patients Without Diabetes: A Systematic Review and Meta-Analysis

et al. 2022

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To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in overweight /obese patients without diabetes. All randomized controlled trials (RCTs) which reported antiobesity effect and safety of GLP-1RA in overweight/obese patients without diabetes in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. The random-effect model was used to pool data extracted from included literatures. The weighted mean difference (WMD), odds ratio (OR) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD 42020173199). The sources of intertrial heterogeneity, bias and the robustness of results were evaluated by subgroup analysis, sensitivity analysis and regression analysis, respectively. A total of 24 RCTs were recruited in the present analysis which included 5867 patients. The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo [WMD=-5.39,95%CI (-6.82, -3.96)] and metformin [WMD=-5.46,95%CI (-5.87, -5.05)]. The subgroup analysis showed that semaglutide displayed the most obvious antiobesity effect in terms of weight loss, the reduction of body mass index (BMI) and waist circumference (WC). However, GLP-1RAs treatments had more gastrointestinal adverse events (such as nausea and vomiting) than placebo and Met. The subgroup analysis also represented that semaglutide displayed the lowest risk of gastrointestinal adverse events among three kinds of GLP-1RAs. Our meta-analysis demonstrated that GLP-1RA had a superior antiobesity effect than placebo/Met in overweight/obese patients without diabetes in terms of body weight, BMI, and WC, especially for semaglutide, which had more obvious antiobesity effect and lower GI adverse events than liraglutide and exenatide.

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“…Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated important benefits in obese NAFLD patients with and without T2DM [121][122][123]. Moreover, the metabolic efficacy of these therapeutic agents seems to be similar in patients without overweight/obesity [124]. GLP-1 RAs have direct hepatic actions: They can prevent accumulation of ceramides/sphingomyelins species, inflammation, and fibrosis and also induce changes in gut microbiota [125].…”

Section: Pharmacologic Treatmentsmentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD), which approximately affects a quarter of the world’s population, has become a major public health concern. Although usually associated with excess body weight, it may also affect normal-weight individuals, a condition termed as lean/non-obese NAFLD. The prevalence of lean/non-obese NAFLD is around 20% within the NAFLD population, and 5% within the general population. Recent data suggest that individuals with lean NAFLD, despite the absence of obesity, exhibit similar cardiovascular- and cancer-related mortality compared to obese NAFLD individuals and increased all-cause mortality risk. Lean and obese NAFLD individuals share several metabolic abnormalities, but present dissimilarities in genetic predisposition, body composition, gut microbiota, and susceptibility to environmental factors. Current treatment of lean NAFLD is aimed at improving overall fitness and decreasing visceral adiposity, with weight loss strategies being the cornerstone of treatment. Moreover, several drugs including PPAR agonists, SGLT2 inhibitors, or GLP-1 receptor agonists could also be useful in the management of lean NAFLD. Although there has been an increase in research regarding lean NAFLD, there are still more questions than answers. There are several potential drugs for NAFLD therapy, but clinical trials are needed to evaluate their efficacy in lean individuals.

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Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with and without overweight/obesity: meta-analysis of randomized controlled trials

Cited by 16 publications

References 41 publications

Effect of baseline body mass index on glycemic control and weight change with exenatide monotherapy in Chinese drug‐naïve type 2 diabetic patients

Effect of baseline body mass index on glycemic control and weight change with exenatide monotherapy in Chinese drug‐naïve type 2 diabetic patients

The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Patients Without Diabetes: A Systematic Review and Meta-Analysis

Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges

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