Durability of Effectiveness Between Users of Once-Weekly Semaglutide and Dipeptidyl Peptidase 4 Inhibitors (DPP–4i) in US Adults with Type 2 Diabetes.

Introduction: Long-term effectiveness and durability of glucose-lowering medications are important considerations in managing type 2 diabetes (T2D). This study aimed to compare durability of treatment efficacy of once-weekly (OW) semaglutide for T2D with that of the dipeptidyl peptidase 4 inhibitor (DPP–4i) class. Methods: This observational cohort study used 2017–2022 data from the Optum® Clinformatics® Data Mart to compare long-term clinical outcomes associated with semaglutide or DPP–4i in US adults with T2D. The primary outcomes were HbA1c at 2-year follow-up, change in HbA1c from baseline, and the odds of achieving HbA1c targets. BMI at 2-year follow-up, change in BMI from baseline, odds of reducing BMI category, and the need for treatment augmentation were exploratory outcomes. Bivariate and multivariate analyses were conducted using inverse probability of treatment weighting (IPTW) weighted descriptive statistics. Results: Weighted HbA1c and BMI cohorts included 865 and 642 semaglutide users and 779 and 537 DPP–4i users, respectively. In the weighted HbA1c cohort, semaglutide and DPP–4i users had an average age of 60 years and similar baseline characteristics including HbA1c level and comorbidity status. Two-year follow-up HbA1c with semaglutide was 0.56% lower than with DPP–4i; reduction in HbA1c from baseline was 0.61% greater. Odds of achieving HbA1c level < 7% were 2.16 times greater after covariate adjustment (all, p < 0.001). Semaglutide was associated with 1.03 kg/m2 greater reduction in BMI and 2.27 times greater odds of reducing BMI category vs DPP–4i (p < 0.001). Semaglutide users were less likely to add new glucose-lowering treatment (hazard ratio [HR] 0.57; p < 0.001) or initiate insulin (HR 0.49; p < 0.001) vs DPP–4i users. Conclusion: Compared with DPP–4i, semaglutide was associated with lower follow-up HbA1c and BMI, greater reduction in HbA1c and BMI from baseline, and reduced likelihood of requiring treatment augmentation or insulin initiation to manage T2D in US adults, suggesting better durability of semaglutide vs DPP–4i. Infographic: Plain language summary: Type 2 diabetes (T2D) is a progressive disease. Over time, many patients with T2D will need multiple drugs to manage their disease. Long-term efficacy is important for achieving treatment goals, such as blood sugar control and weight loss. The amount of time that different types of diabetes drugs remain effective varies. This study used real-world data to compare two distinct types of diabetes drugs, semaglutide and dipeptidyl peptidase 4 inhibitors (DPP–4is). We looked at how blood sugar control and body weight changed with each drug after 2 years of use. We also compared how many patients needed to start using new drugs to meet their treatment goals and the odds that a patient would need to start using new drugs. Semaglutide was better than DPP–4i in reducing both blood sugar levels and body weight. Patients had over two times the odds of meeting target blood sugar levels with semaglutide. Fewer patients needed to start using new drugs with semaglutide, and patients were 43% less likely to start using new drugs to lower blood sugar than patients taking DPP–4is. [ABSTRACT FROM AUTHOR]