Fixed versus flexible combination of GLP‐1 receptor agonists with basal insulin in type 2 diabetes: A retrospective multicentre comparative effectiveness study

Abstract

Background and Aims The combination of basal insulin (BI) and GLP‐1 receptor agonists (GLP‐1RAs) is a rational and effective therapy for patients with uncontrolled type 2 diabetes (T2D). We compared the effectiveness of fixed and flexible BI/GLP‐1RA combinations using routinely accumulated clinical data. Methods This was a retrospective, multicentre, real‐world study concerning T2D patients initiating a fixed or flexible BI/GLP‐1RA combination (NCT03959865). The primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight, fasting plasma glucose (FPG) and systolic blood pressure (SBP). Confounding was addressed by propensity score matching (PSM) or multivariable adjustment (MVA). Results A total of 609 patients were included in the study, 131 in the fixed group and 478 in the flexible group. The two groups differed in terms of diabetes duration, body weight and concomitant medications. After 5.7 months, observed HbA1c reductions were 0.6% and 0.8%, and body weight reductions were 2.8 kg and 1.2 kg in the flexible and fixed groups, respectively. Following PSM, HbA1c declined similarly in the two groups, whereas reduction in body weight was significantly in favour of the flexible combination. Findings were robust in sensitivity analyses, with the exception that, with MVA, a significantly higher reduction in HbA1c was detected in the fixed group. Final doses of BI were higher in the fixed group, whereas those of GLP‐1RA were higher in the flexible group. Conclusions In routine specialist care, initiation of the fixed or flexible BI/GLP‐1RA combination allowed similar improvement in glycaemic control, but greater weight loss was observed with the flexible combination. This difference reflected dosages of BI and GLP‐1RAs.

Enrolment criteria for diabetes cardiovascular outcome trials do not inform on generalizability to clinical practice: The case of glucagon‐like peptide‐1 receptor agonists

“…Observational studies, although unable to substitute for CVOTs, complement CVOT findings and can provide an estimate of true effectiveness in real‐world patients often not represented in CVOTs. Real‐world studies on the glycaemic and extra‐glycaemic effectiveness of GLP‐1RAs have confirmed findings from phase III RCTs, but there is still a paucity of cardiovascular real‐world studies . In a small study from the UK, the intensification of oral therapy by adding GLP‐1RAs was associated with a lower cardiovascular events rate than the intensification with insulin .…”

Real-World Evaluation of Glycemic Outcomes and Extra-Glycemic Parameters in Diabetic Patients Treated with the Combined Formulation Degludec–Liraglutide (Ideglira)

“…In this context, the present work, which is the second real-world study involving IDegLira, was carried out in an Italian context, with the aim to compare the effectiveness of fixed and flexible BI/GLP-1RA combinations using routinely accumulated clinical data. The results show that in specialist routine care, treatment with fixed or flexible BI/GLP-1RA combinations provide comparable improvement in glycemic control, with lower treatment costs with the fixed combination [ 19 ].…”

Comparative effectiveness of dapagliflozin vs DPP‐4 inhibitors on a composite endpoint of HbA1c, body weight and blood pressure reduction in the real world

“…Therefore, missing data were handled with multiple imputation (MI). MI was performed as previously described 25 . Briefly a fully conditional specification (FCS) algorithm 26 was used to obtain 10 imputed datasets and including only covariates with less than 50% of missing values.…”