Sex, BMI influence response to common second-line diabetes medications
medwireNews: Researchers have used data from clinical practice and randomized trials to identify simple predictors of patient response to sulfonylureas and thiazolidinediones.
“Our results provide the first example of stratification of therapy in type 2 diabetes based on simple patient characteristics,” write Andrew Hattersley (University of Exeter Medical School, UK) and colleagues from the MASTERMIND Consortium in Diabetes Care.
The team identified BMI and sex as important determinants of response using UK Clinical Practice Research Datalink data for 10,960 patients taking a thiazolidinedione and 11,419 taking a sulfonylurea.
Men who were not obese (BMI <30 kg/m2) had a significantly better 1-year response with sulfonylureas than with thiazolidinediones, with glycated hemoglobin falling by 13.2 mmol/mol (3.4%) on average, compared with 9.7 mmol/mol (3.0%). The reverse was true for obese women, at corresponding values of 9.4 and 13.8 mmol/mol (3.0 vs 3.4%). Obese men and nonobese women appeared to do equally well with either medication.
The same patterns were apparent when the team looked at these subgroups in the patient populations of the ADOPT and RECORD clinical trials, which directly compared sulfonylureas with thiazolidinediones in nearly 5000 people with type 2 diabetes.
The researchers stress that their findings “do not allow prediction at an individual level,” but do “better reflect the likely outcome for an individual patient within that subgroup than outcome estimates derived from whole trial populations.”
They add: “Whether this alters a decision on therapy will depend on the individual circumstances of the patient, because the trade-off between early response, long-term durability, and risk of side effects will be different.”
The team notes that both ADOPT and RECORD involved rosiglitazone, which has since been withdrawn because of cardiovascular concerns. “Routine clinical data support a thiazolidinedione class effect of differential response by sex and obesity, but trial data were not made available to repeat our analysis for pioglitazone,” they say.
Looking further at the clinical trial data, Hattersley and team found that, with the exception of nonobese men, all patient subgroups were more likely to experience treatment failure within 5 years with sulfonylureas than thiazolidinediones. Conversely, all subgroups gained more weight with thiazolidinediones than sulfonylureas, with obese women at the highest risk.
Women, but not men, had a higher risk for fracture if they were taking thiazolidinediones compared with sulfonylureas, which did not vary with obesity status. Sulfonylureas carried the highest risk for moderate/severe hypoglycemia for all patients.
“Our findings will allow for much more informed discussion of the benefits and risks of these therapies than the present ‘one size fits all’ approach,” say the researchers.
They add that the approach used in their study can in future be used to assess subgroup responses to other diabetes medications; they chose sulfonylureas and thiazolidinediones because of their low cost to clinical practice and the availability of head-to-head clinical trial data.
But they stress: “Given the greater expense of newer therapies, cost-effectiveness evaluation will be necessary in this work.”
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