Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE).

BACKGROUND: The efficacy of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been established in several trials in people with type 2 diabetes mellitus (T2DM); however, real-world evidence on their effectiveness is limited. This study evaluated the effectiveness of OW GLP-1RA regarding glycemic and weight outcomes, and relative to DPP-4i in a comparator analysis. METHODS: This observational cohort study evaluated glycated hemoglobin (HbA1c) and weight outcomes in people with T2DM with two or more prescription claims for the same OW GLP-1RA using a pre-post study design (including for a semaglutide OW T2DM subgroup, hereafter referred to as semaglutide). Comparator analysis for the same outcome was performed for OW GLP-1RAs versus DPP-4i and semaglutide subgroup versus DPP-4i. A linked patient population from the IQVIA PharMetrics® Plus database and the Ambulatory Electronic Medical Records (AEMR) database was analyzed using data from January 2017 to April 2022. HbA1c and weight were assessed at baseline and at the end of the 12-month post-index period. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline patient characteristics in the comparator analysis. RESULTS: In the pre-post analysis, a greater numerical reduction in HbA1c and weight was observed for the semaglutide subgroup (N = 354) relative to the OW GLP-1RA cohort (N = 921). In the semaglutide subgroup, 52.5% and 34.2% of patients achieved HbA1c of < 7.0% and ≥ 5% weight loss, respectively. For the comparator analysis, the OW GLP-1RAs (N = 651) were significantly more effective (p < 0.001) in reducing HbA1c (- 1.5% vs. -  1.0%) and weight (- 3.2 kg vs. -  1.0 kg) than the DPP-4is (N = 431). Similarly, the semaglutide cohort (N = 251) also displayed more effectiveness (p < 0.001) in reducing HbA1c (- 1.7% vs. -  0.9%) and weight (- 4.1 kg vs. -  1.3 kg) than the respective DPP-4i cohort (N = 417). Patients initiating OW GLP-1RAs, including the semaglutide cohort, were at least twice as likely to achieve HbA1c and weight outcomes as well as composite outcomes compared with those initiating DPP-4is. CONCLUSION: The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world setting. These findings align with the recommendation in the current guidelines for utilizing glucose-lowering treatment regimens that support weight-management goals in people with T2DM.

In type 2 diabetes mellitus (T2DM), glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for managing blood sugar levels and major adverse cardiovascular event risk reduction. In clinical trials, once-weekly (OW) GLP-1RAs showed better control of blood sugar levels and body weight than those administered daily, as well as another class of daily T2DM medications called dipeptidyl peptidase-4 inhibitors (DPP-4is). However, there is limited evidence of OW GLP-1RAs-based routine care to confirm these findings. This study gathered prescription and outcomes data for people with T2DM (January 2017­April 2022) from two linked US databases. Body weight measurements and glycated hemoglobin (HbA_1c) test results (measuring average blood sugar levels) were used to evaluate the effectiveness of OW GLP-1RAs (exenatide, dulaglutide, and semaglutide) via a pre-post analysis, and compare OW GLP-1RAs with DPP-4is. We found that treatment with semaglutide lowered body weight and blood sugar levels to a greater extent than OW GLP-1RAs in the pre-post analysis. In the comparator analysis, people receiving OW GLP-1RAs, including semaglutide, were at least twice as likely to achieve reduced HbA_1c levels and body weight compared with those receiving DPP-4is. People receiving OW GLP-1RAs were three times more likely than those on DPP-4is to achieve the recommended target of HbA_1c < 7.0% and weight loss ≥ 5%, while treatment with semaglutide increased this likelihood by > 4.6 times. This study shows clear benefits of OW GLP-1RAs, building on current evidence for integration of this treatment into overall management of T2DM.

Contemporary use of cardiovascular risk reduction strategies in type 2 diabetes. Insights from the diabetes collaborative registry.

BACKGROUND: Cardiovascular disease remains the primary source of morbidity and mortality in type 2 diabetes (T2D). We characterized the change over time in the use of evidence-based therapies to reduce cardiovascular risk in US patients with T2D. METHODS: Data from a longitudinal outpatient diabetes registry were used to calculate the prescription of SGLT2i or GLP-1RA over time and among those with high-risk comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], chronic kidney disease [CKD]) and a diabetes cardiovascular composite score (DCCS; calculated as: #eligible medications prescribed/#eligible medications x 100 for SGLT2i, GLP-1RA, statin, antiplatelet/anticoagulant therapy, ACEi/ARB/ARNI). Scores ranged from 0% to 100% (higher=more optimal care). RESULTS: Among 1,001,542 outpatients from 391 US sites, 51.7% patients had ASVCD, 17.7% HF, and 23.0% CKD. The percentage of patients prescribed an SGLT2i or GLP-1RA increased over time (7.3% in 2013 to 28.8% in 2019), and 18.3% of patients with ASCVD, HF, or CKD were on at least one of these medications at last follow-up vs 25.5% of patients without any of these comorbidities. Mean DCCS was 54±36%; 54±25% in patients with ASCVD, HF, or CKD vs 52±50% in patients without any of these comorbidities (P<0.001 for both). In a hierarchical linear model, male sex, and a diagnosis of CKD were independently associated with higher DCCS whereas a diagnosis of HF or ASCVD was associated with a lower DCCS. CONCLUSIONS: In a large, contemporary cohort of patients with T2D, we found improvement in the use of SGLT2i and GLP-1RA but unexpectedly lower use in patients with ASCVD, heart failure, and CKD, highlighting a treatment-risk paradox. Further education is needed to shift the understanding of these medications as tools for glucose-lowering to cardiovascular risk reduction and to improve their implementation in clinical practice.

Injectable Antihyperglycemics: A Systematic Review and Critical Analysis of the Literature on Adherence, Persistence, and Health Outcomes.

INTRODUCTION: Improving real-world medication adherence to injectable antihyperglycemics in type 2 diabetes mellitus (T2DM) is a clinical challenge. Quantification of the level of adherence required to achieve a minimal clinically important difference (MCID) in glycemic control would assist in meeting this goal. The study objective was to review the literature regarding the relationships of medication adherence and persistence with health outcomes in adult T2DM patients using injectable antihyperglycemics. METHODS: Systematic searches were conducted using electronic databases to identify publications over the last decade. Publications were screened against established eligibility criteria. Study data were extracted, evaluated, and used to identify strengths, limitations, and gaps in current evidence. RESULTS: Eligibility criteria were met by 38 studies, and this report analyzed 34 studies related to glycemic control (n = 25), healthcare resource use (n = 9), and healthcare costs (n = 14). Eight of these studies examined adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RA), including 1 study regarding adherence to GLP-1 RA or to insulin, and 1 study investigating a GLP-1 RA/insulin combination; the remaining studies involved insulin. Studies used a broad range of measures to classify adherence and persistence, and most measures were unable to reliably evaluate the complexities of patient behavior over time. Better adherence to injectable antihyperglycemic medications was generally found to be associated with improved glycemic control, although no studies attempted to identify a MCID. Although higher diabetes-related pharmacy and total healthcare costs were reported for adherent or persistent patients, these patients tended to have lower diabetes-related and all-cause medical costs. CONCLUSION: Results of this review confirmed the effectiveness of injectable antihyperglycemic medications for glycemic control, suggesting that there are clinical and financial consequences to nonadherence. Although attempts were made to quantify the effects of nonadherence, the interpretation of study results was limited by the lack of a MCID and inadequate study design. FUNDING: Novo Nordisk, Inc., Plainsboro Township, NJ, USA. Plain language summary available for this article.