Understanding the Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use of GLP-1 RA and DPP-4 Therapies in Patients With Type 2 Diabetes

Authors: Carls GS, Tuttle E, Tan RD, Huynh J, Yee J, Edelman SV, Polonsky WH.

Abstract

Objective: The objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications.

Research design and methods: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA_1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide 1 receptor agonist (GLP-1 RA) or dipeptidyl peptidase 4 (DPP-4) inhibitor with published findings from randomized controlled trials (RCTs) evaluating these drugs. Selected RW patients were similar to RCT patients, and regression analysis was used in the RW data to adjust for differences between poorly adherent and adherent patients to explain why RCT and RW findings may differ.

Results: RW patients initiating a GLP-1 RA (n = 221) or a DPP-4 (n = 652) experienced smaller reductions in HbA_1c (GLP-1 RA: -0.52% [-6 mmol/mol], DPP-4: -0.51% [-6 mmol/mol])than reported in RCTs (-1.30% [-14 mmol/mol] from seven GLP-1 RA RCTs, n = 2,600; -0.68% [-8 mmol/mol] from four DPP-4 RCTs, n = 1,889). Baseline HbA_1c, additional medications, and adherence were significant explanatory factors in the RW HbA_1c change. Modeled estimates of RCT efficacy (-1.04% GLP-1 RA [-12 mmol/mol], -0.69% DPP-4 [-8 mmol/mol]) were within the RCTs’ reported range (GLP-1 RA: -0.84% to -1.60% [-9 to -18 mmol/mol], DPP-4: -0.47% to -0.90% [-5 to -10 mmol/mol]). Poor medication adherence accounted for approximately three-fourths of the gap between RW and expected RCT results (gap = 0.51% [6 mmol/mol] GLP-1 RA; 0.18% [3 mmol/mol] DPP-4).

Conclusions: Poor medication adherence is primarily why RW effectiveness is significantly less than RCT efficacy, suggesting an urgent need to effectively address adherence among patients with type 2 diabetes.

Source: https://pubmed.ncbi.nlm.nih.gov/28801475/

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BDI Monthly Events

June 5 - 8: It will be a busy time at the American Diabetes Association’s 85th Scientific Sessions (New Orleans, LA), with new projects to be developed, old friends to see, and much to learn. Dr. Polonsky, BDI President, will serve a co-author on four poster presentations

May 13: BDI hosts the San Diego-wide, monthly case consultation meeting (for mental health professionals working in the field of diabetes). Contact us at [email protected] if you are in the greater San Diego area and would like further information about this program.

August 14 - 16. Taking Control of Your Diabetes (TCOYD) will be hosting the in-person ONE event, an amazing weekend experience here in San Diego for more than 500 people with type 1 diabetes and their loved ones. Dr. Polonsky is honored to be one of the presenters, and we will hope to see many of you there. There are still a few spaces left, so if you’d like to know more, please visit

On October 24, BDI will host a live, one-day, CME workshop: Engaging the Disengaged: Innovative Strategies for Promoting Behavior Change in Diabetes. Run by Dr. Polonsky (BDI President) and Dr. Guzman (BDI Clinic Director), Participants will deepen their skills in recognizing and addressing common barriers to effective self-care and cardiometabolic medication initiation and maintenance, while fostering respectful, stigma-free clinical encounters.