Consequences of delaying treatment intensification in type 2 diabetes explored
medwireNews: Results of a modeling study suggest that timely intensification of oral antidiabetic treatment is associated with a lower risk for complications but a higher risk for hypoglycemia compared with delayed treatment among patients with type 2 diabetes.
“These results highlight the potential impact of treatment inertia and the importance that timely treatment intensification may have on long-term outcomes,” say the study authors.
Henry Folse (Evidera, San Francisco, California, USA) and colleagues modeled a cohort of 600,000 hypothetical patients with type 2 diabetes based on real-world data from the Inertia study. The patients were receiving metformin treatment at baseline, followed by an intensification sequence comprising a sulfonylurea, a dipeptidyl peptidase-4 inhibitor, and a thiazolidinedione.
In the No Delay group, patients received treatment intensification at time intervals recommended by the American Diabetes Association, whereas pooled data from three simulations of treatment delays (time to intensification: 0–6 months, 6–12 months, and >12 months) were used for the Delay group.
The researchers found that mean glycated hemoglobin (HbA1c) at 1 year was 6.8% for patients undergoing treatment intensification with no delay, compared with 8.2% for those in the Delay group.
The risk for major adverse cardiac events (MACE) – myocardial infarction, stroke, and death from coronary heart disease – was lower among patients in the No Delay versus Delay group, with, for example, 5-year incidence estimates of 4.7% versus 5.7% and 20-year estimates of 23.5% versus 25.6% among patients receiving one oral antidiabetic treatment at baseline.
And MACE risk was “substantially higher” among patients delaying treatment intensification for more than 12 months versus those with shorter delays, reports the team in Diabetes, Obesity and Metabolism.
Patients in the No Delay group also had a lower 5-year incidence of other complications than those in the Delay group, with the greatest difference observed for myocardial infarction, followed by heart failure and stroke (2.9 vs 3.9%, 3.1 vs 3.5%, and 1.8 vs 1.9%, respectively). The team identified “similar trends” at 20 years.
In scenario analyses carried out to test the robustness of the researchers’ model, increasing the HbA1c target from 7% to 8% reduced the difference in the incidence of complications between the two groups, suggesting “less benefit when a less aggressive HbA1c goal was used.”
But alongside the reduction in risk for complications, the incidence of severe hypoglycemia was increased among patients receiving timely treatment intensification versus those in the Delay group, with rates of 19.0% versus 12.5% at 5 years, and 58.3% versus 49.4% at 20 years.
Folse and colleagues note that although their study demonstrated a higher risk for hypoglycemia with guideline-recommended treatment intensification, “drug adverse effects other than hypoglycemia are not included,” and “the effects on costs, quality of life, and cardiovascular risk are not accounted for.”
Nevertheless, they believe that the study “provides important insights into the long-term clinical consequences of delays in treatment intensification that could not be obtained using a clinical trial.”
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