MD Lingo

Medicine as you will know it


Diabetes Treatment Intensification: Insulin vs Sulfonylureas

By Ryan Matthews

A recent retrospective study (one that looks back at already recorded events/information) investigated the outcomes of veteran patients initially prescribed metformin, before subsequently receiving insulin or sulfonylurea. Ultimately, the study sought to investigate the association of the intensification of treatments (insulin vs sulfonylurea) with cardiovascular disease and/or death. In other words, is the addition of insulin or sulfonylurea to patients receiving metformin more appropriate for the intensification of the treatment of type 2 diabetes?

Most individuals are familiar with the importance of insulin in the treatment of diabetes, which is responsible for the lowering of blood sugar levels. However, many people are unfamiliar with the use and significance of sulfonylureas in treating diabetic patients. Sulfonylureas are drugs used in the management of diabetes mellitus type 2 that function by stimulating beta cells of the pancreas to increase insulin release. Furthermore, this class of drugs constitutes one of the most commonly prescribed medications in the treatment of type 2 diabetes2. According to WebMD, sulfonylurea medications are able to lower hemoglobin A1c by as much as 1-2%.

Those unfamiliar with the specifics of diabetes may be unaware of the significance of hemoglobin A1c (HbA1c) levels. A patient’s HbA1c indicates his/her average blood sugar over approximately the last 3 months. In other words, it provides physicians with insight into how well the patient has been controlling their diabetes over the past several weeks. Although the average non-diabetic individuals exhibit HbA1c levels between 4-5.6%, a patient with diabetes strives to maintain an HbA1c below 7%4.

The study consisted of 14,616 total patients after careful eligibility criteria were followed, 2,436 of which belonged to the metformin + insulin group and 12,180 patients in the metformin + sulfonylurea group.

All-cause deaths were 33.7 and 22.7 per 1000-person years for insulin vs sulfonylurea, respectively. Furthermore, primary outcomes (where primary outcome includes acute myocardial infarction (heart attack), stroke hospitalization or all-cause death) of insulin vs sulfonylurea patients was 42.7 vs 32.8 per 1000 person-years, respectively. However, cardiovascular disease events occurred in 10.2 per 1000 person-years among patients who added insulin compared to 11.9 per 1000 per-years among those who added sulfonylurea. A quick glance at the accompanying graph demonstrates these results in a visual format.

Unfortunately, limitations exist within the construct of the study. For example, 95% of the patients used for this study were men and 70% were white. There were also a variable number of comorbities in each of the study groups, as well as other potential areas of bias or study design concerns that can be reviewed in the original article.

Diabetic patients receiving metformin who were additionally prescribed insulin had increased risk of cardiovascular events and death in comparison to those who received sulfonylureas as supplementary treatment to metformin. This result is substantiated by available clinical data of previous studies, several of which are mentioned in the original article. Insulin is a reliable form of treatment for patients with whom sulfonylureas are inadequate, but this study shows that insulin should be delayed if possible due to some additional risk. Further research is needed in order to substantiate the risks of insulin use compared to sulfonylureas.


What does this mean for you?

Diabetes affects between 5.8 and 12.9 percent of the population in the United Statess and accounts for as much as 14 percent of total healthcare expenditures1. As stated in the study article, “There is consensus that metformin is first-line diabetes treatment; however, uncertainty remains regarding additional therapy after inadequate control with metformin.”3 By comparing the time until cardiovascular disease or death in patients receiving the different treatments, the most appropriate intensification treatment can be distinguished in order to more appropriately treat the rising number of diabetic patients.

Furthermore, many patients want to delay their treatment due to a variety of personal anxieties. On the other hand, many physicians attempt to control diabetes as quickly as possible with the use of insulin or sulfonylurea therapy. Studies such as this one allow the practice of evidence-based medicine in order to obtain the best possible outcomes for patients. If you have diabetes please speak to your doctor regarding the best therapy for you.



1McCulloch, MD, D. K., Nathan, MD, D. M., & Mulder, MD, J. E. (2014, May 19). Overview of medical care in adults with diabetes mellitus. . Retrieved July 25, 2014, from

2McCulloch, MD, D. K., Nathan, MD, D. M., & Mulder, MD, J. E. (2013, May 15). Sulfonylureas and meglitinides in the treatment of diabetes mellitus. . Retrieved July 25, 2014, from

3Roumie, MD, MPH, C. L. et al. Association Between Intensification of Metformin Treatment With Insulin vs Sulfonylureas and Cardiovascular Events and All-Cause Mortality Among Patients With Diabetes. JAMA, 311, 2288-2296. Retrieved July 20, 2014

4Sulfonylureas for Type 2 Diabetes. (2012, May 2). . Retrieved July 25, 2014, from