Comparison of GLP-1 Analogues versus Sitagliptin in the Management of Type 2 Diabetes: Systematic Review and Meta-Analysis of Head-to-Head Studies

Abstract

BackgroundIncretin–based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone. The purpose of this study is to perform a systematic review with meta-analysis of existing head to head studies to compare the efficacy and safety of GLP-1 analogues with DPP-4 inhibitors.MethodsWe performed a systematic review and meta-analysis of head-to-head studies to compare GLP-1 analogues with DPP-4 inhibitors in the management of type 2 diabetes. A random effects model was selected to perform the meta-analyses, results were expressed as weighted mean differences for continuous outcomes and relative risks for dichotomous outcomes, both with 95% confidence intervals, and with I2 values and P values as markers of heterogeneity.ResultsFour head-to-head randomized controlled studies with 1755 patients were included. Compared to sitagliptin, GLP-1 analogues are more effective in reducing HbA1C (weight mean difference −0.41%, 95% CI −0.51 to −0.31) and body weight (weight mean difference −1.55 kg, 95% CI −1.98 to −1.12). Conversely, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events compared to sitagliptin: nausea (relative risk 3.14, 95% CI 2.15 to 4.59), vomiting (relative risk 2.60, 95% CI 1.48 to 4.56), diarrhea (relative risk 1.82, 95% CI 1.24 to 2.69), and constipation (relative risk 2.50, 95% CI 1.33 to 4.70).ConclusionsThe result of this meta-analysis demonstrates that compared to sitagliptin, GLP-1 analogues are more effective for glycemic control and weight loss, but have similar efficacy in reducing blood pressure and lipid parameters, however, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events and a similar incidence of hypoglycemia compared to sitagliptin.

Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus

“…These symptoms were in agreement with previous reports that side effects of fatigue,9 cough,9 headache,25 hypoglycemia,26 loss of consciousness,26 constipation,27 nausea,27 vomiting,27 and diarrhea28 are associated with long-term sitagliptin therapy. COS reduces these side effects and is beneficial to medical therapy of T2DM.…”

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Mellitus Patients with Moderate to Severe Renal Impairment: A Systematic Review and Meta-Analysis

“…These results are consistent with those obtained in T2DM patients in similar studies [30]–[31]. It was reported previously that GLP-1 reduced HbA1c levels to a greater extent than did DPP-4 inhibitors [32]–[33], yet data in this article showed no difference between DPP-4 inhibitors and GLP-1 in severe renal dysfunction while a relatively poorer reducing effect of DPP-4 inhibitors was indeed observed in moderate renal dysfunction. The results might become more consistent with the previous reports if there was a larger sample size.…”

Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor

“…The number of cases was too small to draw any conclusions, but nausea is an expected result of GLP-1 elevation and has been reported with GLP-1 analogs. 40 Transient declines in GFR have been reported with SGLT2 inhibitors, likely due to osmotic diuresis. [23][24][25] The same is expected with sotagliflozin.…”