According to results of a quasi-experimental study, real-world (RW) effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP4) is significantly lower than clinical efficacy reported in randomized controlled trials (RCTs) assessing these medications.

Using retrospective claims, the study authors aimed to determine the extent as well as the cause of the gap seen between RW and clinical efficacy of both GLP-1RA and DPP4. The change in RW patient’s HbA1c 12 months after initiating a GLP-1RA or DPP4 were compared to results obtained from RCTs evaluating these medications.  The authors noted that RW patients were selected due to their similarity to patients included in the RCTs and that regression analysis was utilized to adjust for any differences in adherence between patients.

The study authors reported that smaller reductions in the HbA1c were seen in RW patients initiated on a GLP-1RA or DPP4 compared to reductions reported from RCTs. For RW patients initiated on a GLP-1RA (n=221), the HbA1c  was reduced by 0.52% (-6mmol/mol) compared to a –1.30% reduction (-14mmol/mol) reported from 7 GLP-1RA RCTs (n=2600).  Similarly, a 0.51% reduction (-6 mol/mol) in HbA1c was seen in RW patients initiated on a DPP4 (n=652) versus a 0.68% reduction (-8mmol/mol) reported from four DPP4 RCTs (n=1889). 

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The authors noted that, “baseline HbA1c, additional medications, and adherence were significant explanatory factors in the RW HbA1c change,” and that, “modeled estimates of RCT efficacy (−1.04% GLP-1RA [−12mmol/mol], −0.69% DPP4 [−8mmol/mol]) were within the RCTs’ reported range (GLP-1RA: −0.84% to −1.60% [−9 to −18mmol/mol]; DPP4: −0.47% to −0.90% [−5 to −10mmol/mol]).”

The analysis also found that about three-fourths of the gap between RW and expected RCT results was due to poor medication adherence among patients, with a reported gap of 0.51% (6mmol/mol) for GLP-1RA patients and 0.18% (3mmol/mol) for DPP4 patients.

In this quasi-experimental study, poor medication adherence was found to be the primary reason for the gap between RW effectiveness and reported RCT efficacy of GLP1-RA and DPP4 medications. Because of this, the study authors suggest that there is, “an urgent need to effectively address adherence among patients with type 2 diabetes.”

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