Background: Three randomized trials published in 2008 failed to settle the question about the harms and benefits of tight glycemic control (Hb A1c <7%) versus usual glycemic control (HbA1c 7% to <8%) for patients with type 2 diabetes. Questions remain about the impact of glycemic control on long term outcomes such as macrovascular disease, including myocardial infarction, and microvascular disease, including retinopathy and nephropathy. Patients who are already being treated fairly intensely (e.g., with either 2 or more oral medications, or with basal insulin), are of particular interest as these medications are associated with harms such as weight gain and hypoglycemia. In addition, patients with type 2 diabetes typically have other risk factors for vascular disease including hypertension and hyperlipidemia. Thus, the impact of glycemic control, in consideration of concurrent control of hypertension and hyperlipidemia, in individuals with type 2 diabetes requires further investigation in a diverse population.
Objectives and Research Questions: Among the key clinical questions is whether initiation of additional anti-diabetic medications (intensification) in the face of usual control, using either a third or fourth oral agent, basal insulin and/or or bolus short-acting insulin is beneficial to patient outcomes. It is quite possible that answers may differ depending on patients’ age, gender, race, ethnicity, the duration of their diabetes or severity, and the extent to which blood pressure and LDL-cholesterol are controlled.
Study Design: This is a cohort analysis in persons whose control on two oral agents or basal insulin has deteriorated to levels > 7%, and examines the impact of treatment intensification to tighten control on several outcomes.
Methods: This study addresses these questions in a large cohort (N~30,000) of patients with type 2 diabetes drawn from 5 health systems between 2002 and 2009. Patients will include those taking two anti-diabetic medications who have Hb A1c that increases from <7% to > 7%. These patients will be followed to see whether treatment intensification occurs and whether treatment intensification (versus non-intensification) impacts outcomes, after adjustment for potential confounders. Outcomes to be measured include weight gain, hypoglycemic episodes, cardiovascular endpoints, onset of diabetic nephropathy or chronic kidney disease, falls and/or fractures. Evidence of interactions between intensification of anti-diabetic medications and stratifying variables will be tested to determine if there is heterogeneity in response to intensification of therapy for glycemic control. Inverse-probability-of-treatment-weighted estimation for marginal structural models will be utilized to derive valid effect estimates as the treatment and confounders will vary over time, and the treatments-particularly the management of hyperlipidemia and hypertension-will likely affect the confounders.
Expected Outputs: Four scientific reports.
Expected date of project completion: Summer 2011.