Delays in treatment intensification with oral antidiabetic drugs and risk of microvascular and macrovascular events in patients with poor glycaemic control: An individual patient simulation study

Abstract

Aims:To use the Archimedes model to estimate the consequences of delays in oral antidiabetic drug (OAD) treatment intensification on glycaemic control and long-term outcomes at 5 and 20 years. Materials and methods:Using real-world data, we modelled a cohort of hypothetical patients with glycated haemoglobin (HbA1c) ≥8%, on metformin, with no history of insulin use. The cohort included 3 strata based on the number of OADs taken at baseline. The first add-on in the intensification sequence was a sulphonylurea, next was a dipeptidyl peptidase-4 inhibitor, and last, a thiazolidinedione. The scenarios included either no delay or delay, based on observed and extrapolated times to intensification.Results: At 1 year, HbA1c was 6.8% for patients intensifying without delay, and 8.2% for those delaying intensification. For no delay vs delay, risks of major adverse cardiac events, myocardial infarction, heart failure and amputations were reduced by 18.0%, 25.0%, 13.7%, and 20.4%, respectively, at 5 years; severe hypoglycaemia risk, however, increased to 19% for the no delay scenario vs 12.5% for delay. At 20 years, the results showed similar trends to those at 5 years. Conclusions:Timing of intensification of OAD therapy according to guideline recommendations led to greater reductions in HbA1c and lower risks of complications, but higher risks of hypoglycaemia than delaying intensification. These results highlight the potential impact of timely treatment intensification on long-term outcomes. K E Y W O R D Santidiabetic drug, DPP-4 inhibitor, macrovascular disease, sulphonylureas, thiazolidinediones

Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes

“…those who consistently had HbA 1c $7% ($53 mmol/mol) was associated with a 62% increase in the risk of fatal and nonfatal cardiovascular events (myocardial infarction, stroke, heart failure) during the 5-year median follow-up period (6). In another study, Folse et al (28) used a patient simulation method (based on the Archimedes model) and found that patients without a delay in intensification had lower HbA 1c levels after 1 year than did patients with delayed intensification (6.8% vs. 8.2%) and had ;20% lower risk for major adverse cardiac events and amputations at 5 years. Additional research is warranted to understand whether such effects persist among patients with type 2 diabetes more broadly (i.e., independent of disease duration).…”

Clinical Inertia in Poorly Controlled Type 2 Diabetes Mellitus Patients with Obesity: An Observational Retrospective Study

“…These results suggest limited adherence to current recommendations to intensify treatment every 3-6 months when the patient achieves/does not achieve the objectives established [5]. Studies have found that a high glycaemic burden is associated with an increased risk of myocardial infarction, stroke and heart failure and, therefore, reducing the time during which the patient is not within target range is important [21,22].…”

“…However, injectable therapy with GLP-1 RA is not associated with an increased risk of hypoglycaemia and is associated with weight loss; consequently, it should be considered as the first injectable therapy, before insulin [5]. These data are relevant given that it is known that delays in intensification are related to macro-and microvascular complications that will jeopardise the probability of achieving glycaemic control objectives [21,22,24]. Therefore, strategies that help reduce the time to intensification are required.…”

Eficácia em longo prazo das gliflozinas versus gliptinas no tratamento do diabetes mellitus tipo 2 após falência da metformina como monoterapia: revisão sistemática e metanálise em rede

“…A inércia clínica, que leva a um retardo na progressão do tratamento de pacientes com diabetes, pode levar a um aumento da prevalência de doenças macrovasculares em longo prazo (27,28).…”

“…We will follow a consistent process for screening full-text articles and abstracting data from included studies. We will abstract data on the following characteristics: studies (e.g., location of study conduct, study design), patients (e.g., mean age and standard deviation), and results (mean change from baseline HbA1c and weight and at least one episode of hypoglycemia analyzed on an odds ratio scale) 27 Risk of bias (quality) assessment…”