GLP-1 Agonists Superior to DPP-4 Inhibitors for Reducing HbA1c, Weight in T2D

hemoglobin A1c HBa1C
hemoglobin A1c HBa1C
Investigators analyzed glycemic control, weight, and incidence of adverse events of GLP-1 agonists compared with DPP-4 inhibitors.

Treatment with glucagon-like peptide-1 (GLP-1) agonists is associated with greater reductions in glycated hemoglobin (HbA1c) and body weight than dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes, according to a meta-analysis published in Diabetes, Obesity and Metabolism.

Investigators systematically searched randomized controlled trials (RCTs) that compared GLP-1 agonists with DPP-4 inhibitors for efficacy and adverse effects in an adult population with type 2 diabetes. In addition, the investigators sought out trials which included participants who switched from a DPP-4 inhibitor to a GLP-1 agonist. A total of 18 studies were included in the final analysis, of which 13 were RCTs and 5 were interventional trials that assessed participants who switched therapy.

According to the pooled analysis of the RCTs (n=4330), treatment with GLP-1 agonists for ≥12 weeks resulted in greater HbA1c reductions (-0.41% [95% CI, -0.53 to -0.30]) and weight (-2.15 kg [-3.04 to -1.27]) than treatment with DPP-4 inhibitors. In the pooled analysis of the interventional studies (n=433), investigators also observed a substantial mean HbA1c reduction and weight loss among participants who switched to a GLP-1 agonist (-0.69% [95% CI, -1.03 to -0.35] and -2.25 kg [-3.12 to -1.38], respectively).

Despite the benefit of GLP-1 agonists for reducing HbA1c and body weight, participants taking these medications were more likely to withdraw from the study for any reason than those receiving DPP-4 inhibitors (pooled risk ratio [RR] 1.53; 95% CI, 1.01-2.14). In addition, a higher number of gastrointestinal side effects were reported in the GLP-1 agonist vs DPP-4 inhibitor arms, including diarrhea (n=2913; RR 2.05 [1.58-2.67]), nausea (n=3229; RR 3.04 [2.22-4.18]), and vomiting (n=2913; RR 4.09 [2.83-5.91]).

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There was considerable variation in treatment duration among trials, which represents a potential limitation of this meta-analysis. Additionally, the investigators observed a significant between-study heterogeneity in the analyses, which further limits the findings.

The findings from this analysis, while not unexpected, suggest that GLP-1 agonist may be a treatment strategy “to consider when glycaemic goals are not achieved with a treatment regimen that includes a DPP-4 inhibitor.”


Tran S, Retnakaran R, Zinman B, Kramer CK. Efficacy of glucagon-like peptide-1 receptor agonists compared to dipeptidyl peptidase-4 inhibitors for the management of type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2018;20 Suppl 1:68-76.