Dataset Information

Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis.

ABSTRACT:

Aims

To explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults.

Methods

Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multivariate meta-analysis.

Results

A total of 31 double-blind randomized controlled trials with 22,948 participants were included in the meta-analysis. The MD and 95% CI of the pooled GLP1-RA-induced change in the glycated hemoglobin level was -0.78% (-0.97%, -0.60%) in the random-effects model and -0.45% (-0.47%, -0.44%) in the fixed-effect model, with a high heterogeneity (I2 = 97%). The pooled body weight reduction was -4.05 kg (-5.02 kg, -3.09 kg) in the random-effects model and -2.04 kg (-2.16 kg, -1.92 kg) in the fixed-effect model (I2 = 98%). The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. A negative correlation between glycemic control and weight reduction was obtained.

Conclusion

Long-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults.

SUBMITTER: Yeh TL

PROVIDER: S-EPMC9876280 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis.

Yeh Tzu-Lin TL Tsai Ming-Chieh MC Tsai Wen-Hsuan WH Tu Yu-Kang YK Chien Kuo-Liong KL

PloS one 20230125 1

<h4>Aims</h4>To explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults.<h4>Methods</h4>Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multi ...[more]

PMID: 36696429

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Project description:ObjectiveTo synthesize current evidence of the impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on hypoglycemia, treatment discontinuation and glycemic level in patients with type 2 diabetes.DesignSystematic review and network meta-analysis.Data sourcesLiterature search (Medline, Embase, the Cochrane library), website of clinical trial, bibliographies of published systematic reviews.Eligibility criteriaRandomized controlled trials with available data comparing GLP-1 RAs with placebo or traditional anti-diabetic drugs in patients with type 2 diabetes.Data synthesisTraditional pairwise meta-analyses within DerSimonian-Laird random effects model and network meta-analysis within a Bayesian framework were performed to calculate odds ratios for the incidence of hypoglycemia, treatment discontinuation, HbA1c<7.0% and HbA1c<6.5%. Ranking probabilities for all treatments were estimated to obtain a treatment hierarchy using the surface under the cumulative ranking curve (SUCRA) and mean ranks.Results78 trials with 13 treatments were included. Overall, all GLP-1 RAs except for albiglutide increased the risk of hypoglycemia when compared to placebo. Reduction in the incidence of hypoglycemia was found for all GLP-1 RAs versus insulin (except for dulaglutide) and sulphonylureas. For the incidence of treatment discontinuation, increase was found for exenatide, liraglutide, lixisenatide and taspoglutide versus placebo, insulin and sitagliptin. For glycemic level, decrease was found for all GLP-1 RAs versus placebo. Dulaglutide, exenatide long-acting release (exe_lar), liraglutide and taspoglutide had significant lowering effect when compared with sitagliptin (HbA1c<7.0%) and insulin (HbA1c<6.5%). Finally, according to SUCRAs, placebo, thiazolidinediones and albiglutide had the best decrease effect on hypoglycemia; sulphanylureas, sitagliptin and insulin decrease the incidence of treatment discontinuation most; exe_lar and dulaglutide had the highest impact on glycemic level among 13 treatments.ConclusionsAmong 13 treatments, GLP-1 RAs had a significant reduction with glycemic level but a slight increase effect on hypoglycemia and treatment discontinuation. While albiglutide had the best decrease effect on hypoglycemia and treatment discontinuation among all GLP-1 RAs. However, further evidence is necessary for more conclusive inferences on mechanisms underlying the rise in hypoglycemia.

Project description:ObjectiveMetabolic Syndrome, which can be induced or exacerbated by current antipsychotic drugs (APDs), is highly prevalent in schizophrenia patients. Recent preclinical and clinical evidence suggest that agonists at trace amine-associated receptor 1 (TAAR1) have potential as a new treatment option for schizophrenia. Intriguingly, preclinical tudies have also identified TAAR1 as a novel regulator of metabolic control. Here we evaluated the effects of three TAAR1 agonists, including the clinical development candidate ulotaront, on body weight, metabolic parameters and modulation of neurocircuits implicated in homeostatic and hedonic feeding.MethodsEffects of TAAR1 agonists (ulotaront, RO5166017 and/or RO5263397) on body weight, food intake and/or metabolic parameters were investigated in rats fed a high-fat diet (HFD) and in a mouse model of diet-induced obesity (DIO). Body weight effects were also determined in a rat and mouse model of olanzapine-, and corticosterone-induced body weight gain, respectively. Glucose tolerance was assessed in lean and diabetic db/db mice and fasting plasma glucose and insulin examined in DIO mice. Effects on gastric emptying were evaluated in lean mice and rats. Drug-induced neurocircuit modulation was evaluated in mice using whole-brain imaging of c-fos protein expression.ResultsTAAR1 agonists improved oral glucose tolerance by inhibiting gastric emptying. Sub-chronic administration of ulotaront in rats fed a HFD produced a dose-dependent reduction in body weight, food intake and liver triglycerides compared to vehicle controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in HFD rats switched to ulotaront or RO5263397 treatment compared to those switched to vehicle. Chronic ulotaront administration also reduced body weight and improved glycemic control in DIO mice, and normalized corticosterone-induced body weight gain in mice. TAAR1 activation increased neuronal activity in discrete homeostatic and hedonic feeding centers located in the dorsal vagal complex and hypothalamus with concurrent activation of several limbic structures.ConclusionThe current data demonstrate that TAAR1 agonists, as a class, not only lack APD-induced metabolic liabilities but can reduce body weight and improve glycemic control in rodent models. The underlying mechanisms likely include TAAR1-mediated peripheral effects on glucose homeostasis and gastric emptying as well as central regulation of energy balance and food intake.

Dataset Information

Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis.

Aims

Methods

Results

Conclusion

Publications

Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis.

Similar Datasets

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