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Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials.
Diabetes Obes Metab. 2014 Sep; 16(9):861-8.DO

Abstract

AIM

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels.

METHODS

Six randomized, placebo-controlled studies of lixisenatide 20 µg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression.

RESULTS

Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9 mmol/l, p < 0.001) and glucose excursion (LS mean difference vs. placebo: -4.5 mmol/l, p < 0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0 ng/l, p < 0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p < 0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo.

CONCLUSIONS

Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion.

Authors+Show Affiliations

Department of Clinical Sciences, Lund University, Lund, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24641271

Citation

Ahrén, B, et al. "Pronounced Reduction of Postprandial Glucagon By Lixisenatide: a Meta-analysis of Randomized Clinical Trials." Diabetes, Obesity & Metabolism, vol. 16, no. 9, 2014, pp. 861-8.
Ahrén B, Gautier JF, Berria R, et al. Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16(9):861-8.
Ahrén, B., Gautier, J. F., Berria, R., Stager, W., Aronson, R., & Bailey, C. J. (2014). Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials. Diabetes, Obesity & Metabolism, 16(9), 861-8. https://doi.org/10.1111/dom.12290
Ahrén B, et al. Pronounced Reduction of Postprandial Glucagon By Lixisenatide: a Meta-analysis of Randomized Clinical Trials. Diabetes Obes Metab. 2014;16(9):861-8. PubMed PMID: 24641271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials. AU - Ahrén,B, AU - Gautier,J-F, AU - Berria,R, AU - Stager,W, AU - Aronson,R, AU - Bailey,C J, Y1 - 2014/04/11/ PY - 2013/11/12/received PY - 2013/12/19/revised PY - 2014/03/11/accepted PY - 2014/3/20/entrez PY - 2014/3/20/pubmed PY - 2016/5/7/medline KW - GLP-1 KW - diabetes mellitus KW - insulin secretion SP - 861 EP - 8 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 16 IS - 9 N2 - AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. METHODS: Six randomized, placebo-controlled studies of lixisenatide 20 µg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. RESULTS: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9 mmol/l, p < 0.001) and glucose excursion (LS mean difference vs. placebo: -4.5 mmol/l, p < 0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0 ng/l, p < 0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p < 0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. CONCLUSIONS: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/24641271/Pronounced_reduction_of_postprandial_glucagon_by_lixisenatide:_a_meta_analysis_of_randomized_clinical_trials_ L2 - https://doi.org/10.1111/dom.12290 DB - PRIME DP - Unbound Medicine ER -