Sulfonylurea Use and the Risk of Hospital Readmission in Patients With Type 2 Diabetes

Pamela C. Heaton; Vibha C. A. Desai; Christina M. L. Kelton; Swapnil N. Rajpathak


BMC Endocr Disord. 2016;16(4) 

In This Article



This study documented, using a nationally representative database from 1999 to 2010, 2.6 million patients with type 2 diabetes and with multiple hospitalizations. Patients treated with SU monotherapy compared to those treated with other-AHA monotherapy experienced a significantly higher rate of readmission (23.2 % versus 16.1 %; p = 0.003). This study is the first to produce nationally representative readmission estimates and the first to study the relationship between pharmacotherapy and multiple admissions directly.


Hospital readmissions are a major concern of healthcare providers and policymakers because they indicate deterioration, instead of improvement, of patients' health. Whereas some readmissions have been associated with patient frailty and inevitable disease progression, many have been found to occur due to substandard care during the initial hospitalization, including poor resolution of the main problem, unstable therapy at discharge, and inadequate post-discharge care.[21] A section of the Patient Protection and Affordable Care Act of 2010, which allowed the Centers for Medicare & Medicaid Services to implement the Hospital Readmissions Reduction Program, has placed a spotlight on the need to reduce readmissions as a way to improve the quality of care and reduce costs across disease conditions, including diabetes.[22] To the extent that more effective medication management can occur pre- and/or post-discharge following an initial hospitalization, it may be possible to reduce the readmission rate for diabetes sufferers.

The number of people with diabetes and comorbid conditions is expected to increase precipitously in the near future. In fact, the $245 billion cost burden of diabetes in 2012 represented a 41 % increase over the $174 billion burden in 2007, in large part driven by a 27 % growth in diabetes prevalence over that five-year period.[3] According to the Centers for Disease Control and Prevention, an estimated 86 million adults are currently considered to have prediabetes, meaning that their blood glucose levels are higher than normal but below the diabetes range.[23] Moreover, one study has projected the incidence of diabetes to be about 15 cases per 1,000 in 2050 compared to 8 cases per 1,000 in 2008 (essentially a doubling, in other words).[24] Hence, to the extent that hospitalizations can be prevented by more effective pharmacotherapy in the future, there will be substantial potential cost savings available.

Consistency With Prior Work

The conservative readmission rates (approximately 15 %–25 %) in our study, relative to those mentioned in the introduction, probably result from the omission of insulin users, who are likely to be patients with more comorbidities. Ng and colleagues found that, for a Canadian cohort of patients with type 2 diabetes, those taking insulin had a significantly higher likelihood of a hospitalization (OR = 1.7, 95 % CI: 1.4–2.0), controlling for numerous demographic, socioeconomic, and health-status characteristics.[25]

Our study's results are consistent with research that has compared the antidiabetic drugs with respect to outcomes that could lead to hospitalizations. Bodmer and colleagues found that use of SUs was associated with a 2.8 times higher risk of hypoglycemia than metformin.[26] Evans and colleagues found that patients treated with SUs only were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.[27] Eurich and colleagues found that, compared with SU monotherapy, metformin, alone or in combination, was associated with a statistically significant lower morbidity and mortality for patients suffering from both type 2 diabetes and heart failure.[28] Finally, Horsdal and colleagues found lower 30-day mortality rates among users of metformin (HR 0.32, 95 % CI: 0.15–0.68) as well as patients without pharmacotherapy (HR 0.58, 95 % CI: 0.36–0.93) compared with users of SUs.[29]

In this study, the patients in the SU cohort were on average 8 years older than those taking a non-SU AHA, a fact that helps to explain the difference in readmission cost between the two cohorts. Older patients were both more likely to have additional comorbidities, requiring attention during the hospitalization, as well as more advanced diabetes. Moreover, as seen in Table 2, the SU cohort, before propensity-score adjustment, had a significantly higher percentage of patients with fair or poor perceived health status than those in the other cohort of patients, potentially lengthening and/or complicating their hospital stays. This result is consistent with that of Raebel and colleagues who found that older patients as well as those with elevated serum creatinine were more likely to initiate SU therapy than younger, less severe patients.[30] This result, however, is not consistent with that of Desai and colleagues who found that older patients (70 years old and older) were significantly more likely to receive metformin (not an SU) as initial therapy than those younger than 70.[31]

Unmarried patients had a statistically significant higher risk of hospital readmission than patients who were married. This result is consistent with a number of studies showing that marriage has a protective effect on mortality and hospitalization.[32,33] The statistically significant effect of eye disease makes sense given that the strongest predictor for development and progression of retinopathy is duration of diabetes.[34] Patients suffering diabetes for longer are more likely to develop eye problems as well as other complications leading to hospitalizations.

Hospital Readmission Trends in the 2000s

There was a significant fall in the number of multiple hospitalizations for patients with diabetes over time. Readmissions were less likely to occur later in the study period than earlier. This result is consistent with what Cunningham and Carrier found in their study of the trend in medical-care costs for nonelderly adults with diabetes.[35]

Pharmacotherapy Trends in the 2000s

The treatment of diabetes changed substantially over the decade of the 2000s. Specifically, there was a de-emphasis on the use of the SU drug class. From the MEPS data (Table 2), the share of SU patients was higher in the earliest time period than the latest, while the share of noSU patients was higher in the latest period. Consistent with our results, Desai and colleagues found that the proportion of patients initially treated with an SU decreased from 2006 to 2008. Over the same period, there was a significant increase in the use of metformin and DPP-4 inhibitors and a significant decline in the use of TZDs.[31] A longer trend analysis was undertaken by Alexander and colleagues. In their study, SU utilization (monotherapy or combined) decreased from 67 % of treatment visits in 1994 to 34 % in 2007.[36] A new class of antidiabetic agents for the treatment of type 2 diabetes, the sodium-glucose co-transporter 2 (SGLT2) inhibitors, has become available since the end of our study period. Canagliflozin (Invocana®), dapagliflozin (Forxiga®), and empagliflozin (Jardiance®) were approved by the Food and Drug Administration in April 2013, January 2014, and August 2014, respectively.[37–39] Additional treatment options may encourage a decline in the use of older medications.

In the 2015 position statement (2015 diabetes guidelines) of the American Diabetes Association, the suggested approach to the management of hyperglycemia in most individuals with type 2 diabetes includes intervention at the time of diagnosis with metformin (the only marketed biguanide in the U.S.) in combination with lifestyle changes.[9] If noninsulin monotherapy at maximal tolerated dose is not effective within 3 to 6 months, a second oral agent or insulin should be added as a means of achieving and maintaining recommended levels of glycemic control.[9] For some older adults, however, metformin may be contraindicated because of renal insufficiency or heart failure. Moreover, again a concern primarily for older adults, TZDs may cause fluid retention, which may lead to heart failure.[9] For these patients, the use of alternative AHAs, including SUs, may be warranted. Because our study period ended in 2010, healthcare providers did not have access to the 2015 guidelines. Earlier position statements (see Nathan and colleagues[40,41]), however, provided pharmacotherapy guidance for physicians. They also suggested reduced reliance on the SUs.


The MEPS has been widely used in the study of diabetes and has served as the database of choice to examine many aspects of this chronic condition. However, the lack of clinical data on disease severity (there are no Hba1c values, for example) and progression limits our ability to estimate causal relationships between drug use and risk of hospital readmission. To the extent that unobserved variables were associated with the propensity to receive SU treatment, our results may be biased. Additionally, we cannot rule out the possibility that differences in readmission rates may be related to beneficial effects of other AHAs, especially those of metformin, rather than detrimental effects of SUs. Because of the limited longitudinal nature of the MEPS database (as opposed to claims databases), we were unable to identify (1) patients who were initiating antidiabetic pharmacotherapy; (2) patients' incident hospitalizations, implying that their first hospitalizations may themselves have been readmissions; or (3) patients' prior healthcare utilization, which could be predictive of future utilization, including hospitalizations. Furthermore, we defined multiple-hospitalization patients as those who had two or more hospital admissions during a year's time. Whereas previous literature has looked specifically at time between discharge and readmission,[5,6] the MEPS data were not complete enough in many cases to measure time between hospitalizations that precisely.