Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies

Abstract

Aims/hypothesis: We carried out a systematic review of clinical studies investigating glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test.

Methods: Random effects models for the primary meta-analysis and random effects meta-regression, subgroup and regression analyses were applied.

Results: Random effects meta-analysis of GLP-1 responses in 22 trials during 29 different stimulation tests showed that patients with type 2 diabetes (n = 275) and controls without type 2 diabetes (n = 279) exhibited similar responses of total GLP-1 (p = NS) as evaluated from peak plasma concentrations (weighted mean difference [95% CI] 1.09 pmol/l [-2.50, 4.67]), total AUC (tAUC) (159 pmol/l × min [-270, 589]), time-corrected tAUC (tAUC min⁻¹) (0.99 pmol/l [-1.28, 3.27]), incremental AUC (iAUC) (-122 pmol/l × min [-410, 165]) and time-corrected iAUC (iAUC min⁻¹) (-0.49 pmol/l [-2.16, 1.17]). Fixed effects meta-analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes. Subgroup analysis showed increased responses after a liquid mixed meal test (peak, tAUC and tAUC min⁻¹) and after a 50 g OGTT (AUC and tAUC min⁻¹), and reduced responses after a solid mixed meal test (tAUC min⁻¹) among patients with type 2 diabetes. Meta-regression analyses showed that HbA1c and fasting plasma glucose predicted the outcomes iAUC and iAUC min⁻¹, respectively.

Conclusions/interpretation: The present analysis suggests that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test, and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion.

Fig. 1

Meta-analysis of plasma total GLP-1 responses during an OGTT or meal test evaluated from tAUC (pmol/l×min) using a random effects model. WMD, weighted mean difference. Capital letters indicate different GLP-1 secretory stimuli in the same study

Fig. 2

Meta-analysis of peak plasma total GLP-1 concentrations (pmol/l) during an OGTT or meal test using a fixed effects model. WMD, weighted mean difference. Capital letters indicate different GLP-1 secretory stimuli in the same study

Fig. 3

Subgroup analysis, according to mean HbA_1c levels, of plasma total GLP-1 responses during an OGTT or meal test evaluated from iAUC (pmol/l ×min) using a random effects model. Subgroup 1 is composed of trials with mean HbA_1c≤7.5% (≤58.5 mmol/mol) and subgroup 2 is composed by trials with mean HbA_1c> 7.5% (>58.5 mmol/mol). WMD, weighted mean difference. Capital letters indicate different GLP-1 secretory stimuli in the same study