The distinct patterns of benefits and risks associated between the sex and BMI of different patient subgroups and sulfonylurea and thiazolidinedione therapies allow for a framework to evaluate stratification for both research and treatment in type 2 diabetes, according to a study published in Diabetes Care.

Most clinical choices for post-metformin treatment of type 2 diabetes are guided by the side effects and glycemic responses observed in large-scale cohort studies. Investigators of the present study recognized that a stratified approach that identified subgroups of patients with markedly differing responses to sulfonylurea and thiazolidinedione therapies would allow for more targeted treatments and improved patient outcomes. Data for analysis were taken from the CPRD (U.K Clinical Practice Research Datalink), ADOPT (A Diabetes Outcome Progression Trial), RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes), and GoDARTs (Genetics of Diabetes Audit and Research in Tayside Scotland) trials.

Analysis found that in the CPRD (22,379 eligible patients: 10,960 thiazolidinedione therapy and 11,419 sulfonylurea therapy) trial, lower BMI and male sex were associated with a lesser glycemic response with thiazolidinediones and a greater response with sulfonylureas (P <.001 for both groups). In RECORD (n=2222) and ADOPT (n=2725), non-obese male patients experienced a greater HbA1c reduction on sulfonylureas compared with thiazolidinediones, and obese female patients experienced greater reduction of HbA1c with thiazolidinediones than sulfonylureas (P <.001 for both trials). 

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Risk for edema and weight gain were greatest for obese females with thiazolidinediones, and risk of hypoglycemia was similar in all subgroups with sulfonylureas.  Fractures were more common in females taking thiazolidinediones compared with sulfonylureas.

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Study investigators conclude that “simple patient characteristics alter the benefits and risks of type 2 diabetes therapy with sulfonylureas and thiazolidinediones. Our novel and practical framework for stratification research can be applied in type 2 diabetes and other chronic conditions and has great potential to improve output from future studies using shared trial data.”


Dennis JM, Henley WE, Weedon MN, et al. Sex and BMI alter the benefits and risks of sulfonylureas and thiazolidinediones in type 2 diabetes: a framework for evaluating stratification using routine clinical and individual trial data [published online August 2, 2018]. Diabetes Care. doi: 10.2337/dc18-0344