Effect of dipeptidyl peptidase-4 inhibitors on postprandial glucagon level in patients with type 2 diabetes mellitus: A systemic review and meta-analysis

Abstract

AimsHyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM.Materials and methodsRandomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUCglucagon) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies.ResultsA total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, P<0.001; I2 = 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all P for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, P<0.001; I2 = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues (P for subgroup difference =0.03).Systematic review registrationhttps://inplasy.com/, identifier INPLASY202280104.ConclusionsDPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.

Glucagon in type 2 diabetes: Friend or foe?

“…131 On the other hand, in agreement with the 'bi-hormonal theory' accounting for the dysregulation of glucagon secretion and function in T2D, GCGR antagonists (GRAs) have been proposed as glucoselowering agents. 2 Interestingly, short-term use of several efficacious anti-diabetic drugs, such as metformin, DPP-4 inhibitors and GLP-1 receptor agonists (GLP-1RAs), has been associated with reduced glucagon levels 132,133 without hindering the physiological response to hypoglycaemia. 1 In experimental models, the inhibition of GCGR has been associated with reduced plasma glucose and triglycerides and increased GLP-1 levels.…”

Soy Extract, Rich in Hydroxylated Isoflavones, Exhibits Antidiabetic Properties In Vitro and in Drosophila melanogaster In Vivo

“…The incretin system relates to the gut hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulin polypeptide (GIP), which increase postprandial insulin production by acting on pancreatic beta cells. Dipeptidyl peptidase-4 (DPP-4) degrades circulating GLP-1 and GIP and reduces the circulating postprandial glucagon level [ 4 ]; hence, DPP4 inhibitors are regarded as a novel means for extending the action of insulin and treating T2DM. In addition, intestinal glucose absorption is largely achieved by sodium/glucose symporter 1 (SGLT1) [ 5 ].…”

Tirzepatide: A Systematic Update

“…GLP1 is able to stimulate insulin secretion and inhibit glucagon release; it also slows gastric emptying and induces a sense of satiety [ 9 ]. Incretins are rapidly degraded by dipeptidyl-peptidase 4 (DPP4) [ 10 , 11 ]. Thus, DPP4 inhibitors and GLP1 receptor agonists have been used to date as drugs for the treatment of T2DM acting on the incretin system [ 12 , 13 , 14 ].…”