Publication/Presentation Date

7-25-2014

Abstract

Abstract:

Although sulfonylureas are useful in reducing blood glucose levels in the outpatient management of diabetes, continued use in the hospital is discouraged by professional organizations such as the American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), and Endocrine Society (Umpierrez, 2012) (Moghissi, 2009). This class of oral agents is well known to contribute to hypoglycemia, especially in patients with renal insufficiency and nutritional irregularities. The network’s DMQIT team would like to propose either the complete removal of sulfonylureas from inpatient formularies or consideration to limit the use for new starts as part of discharge planning.

Background:

One of the major concerns with sulfonylurea utilization in the hospital are their extremely long half-lives of 16-24 hours (dependent upon the sulfonylurea used), resulting in prolonged hypoglycemia (Barrueto, 2010). This is especially the case in patients with acute or chronic renal issues, and patients with altered nutritional intake (such as NPO and loss of appetite). Renal issues elongate the retention time the drug is in body, thereby extending the effect of the drug. Altered nutritional intake augments patient’s already low blood sugar with sulfonylureas (Vigersky, 2013) (Clement, 2013). One study spanning nearly 50 years reviewed 1418 cases of severe drug-induced hypoglycemia; recognizing that 63% of the cases were due to sulfonylureas (advanced age and fasting were others) (Seltzer, 1989). Duesenberry CM and colleagues completed a study observing adults who took a sulfonylurea during their hospitalization between November 1, 2008 and October 31, 2009. They found that 19% of patients ingesting a sulfonylurea also had one or more incidents of hypoglycemia during their stay (Duesenberry, 2012). Adrian Jennings did a similar study spanning six months in which 41 out of 203 hospital patients (20.3%) on a sulfonylurea experienced symptoms of hypoglycemia (Jennings, 1989). Significant data has been presented for the ADA to “suggest the discontinuation of oral hypoglycemic agents and initiation of insulin therapy for the majority of patients with type 2 diabetes at the time of hospital admission for acute illness” (Umpierrez, 2012, 5).

Through benchmarking it has been documented and confirmed that three other hospitals have officially removed sulfonylureas from their drug formularies to some degree. Memorial Sloan-Kettering Cancer Center, located in New York City with 469 inpatient beds, removed all sulfonylureas from their formularies more then 5 years ago. Spectrum Health System, located in Grand Rapids Michigan with 1048 inpatient beds, stopped all oral agents in May 2011. Additionally Redland Community Hospital, located in Redland California with 229 inpatient beds, has only one sulfonylurea still on formulary. Specifically all sulfonylureas are stopped upon entrance into the hospital, however upon discharge planning Glipizide (the only sulfonylureas still on formulary) may still be used. In addition, many other diabetes educators stated on the American Association of Diabetes Educators (AADE) website that their respective hospital was too in the process or planning on removing sulfonylurea from their drug formularies. The ADA has recognized this issue and stated “Noninsulin antihyperglycemic agents are not appropriate in most hospitalized patients who require therapy for hyperglycemia” (Moghissi, 2009,1127).

Methods:

The study was conducted in two major portions, literature reviews and data collection. The first step in the process was evaluating work that attempted to make the public mindful of the risks that are associated with sulfonylurea use in an hospital setting. Scholarly work on sulfonylurea-induced hypoglycemia was found by using ‘Google Scholar’, utilizing the search engine to find qualitative and quantitative research. Also, journals provided by the Inpatient Diabetes Team to the AADE, ADA, and Endocrine Society were an essential resource; providing assessments from professional organizations on sulfonylurea use in an inpatient setting. Subsequently, posts made by certified diabetes educators on the AADE website were examined, networking with those that encompassed the same concern. Personally reaching out and communicating with educators that have removed sulfonylureas from hospital formularies, or those in the process of doing so. Both the literature reviews and networking with diabetes educators created the foundation for the research. Providing a focus on the data and evidence that would be required in order to remove this drug off Lehigh Valley’s drug formularies.

To proceed with the data collection the number of patients (with diabetes) fromLVHN that ingested a sulfonylurea during their inpatient stay was gathered. In addition, through the Lehigh Valley database one was able to locate all patients with diabetes that had at least one hypoglycemic event during there hospitalization. The number of days and events each patient was hypoglycemic was also provided. By the use of excel one was able to match patient account numbers between the two listed provided; patients with at least one hypoglycemic event and patients ingesting a sulfonylurea. This produced data on patients that were prescribed a sulfonylurea and experienced at least one hypoglycemic event, each respective patients’ days and events hypoglycemic were also included.

Results:

Since sulfonylureas lack flexibility when it comes to titrations, an essential asset to have in an acute care setting, then one would expect its use to increase inpatient hypoglycemia incidences (Clement, 2013). The data collected demonstrated this hypothesis.

The ADA defines hypoglycemia as a blood glucose level less than 70 mg/dL (Moghissi, 2009). Both LVHN campuses, Cedar Crest and Muhlenberg, had a significantly high percent of patients with sulfonylurea-induced hypoglycemia, 18.7 and 16.2 respectively. Producing data that corresponds with Seltzer, Deusenberry, and Jennings work indicates that sulfonylurea-induced hypoglycemia is prevalent at Lehigh Valley Health Network. Additionally, both campus hospitals had substantial ratios of total days and events blood glucose less than 70 mg/dL stimulated by a sulfonylurea. At Cedar Crest campus these were 1.73 and 2.8 respectively, and 1.53 and 2.5 at Muhlenberg campus.

Mechanism of Action

Pancreatic Mechanism

Sulfonylureas prevent the efflux of Potassium ions from Beta-cells of the pancreas. Resulting in the depolarization of the Beta-cells and consequently calcium channels (which are voltage-dependent), open and calcium ions flow into the cell. Proceeding in the exocytosis of insulin.

Extra-Pancreatic Mechanism

Decrease in glucagon levels. Exact mechanism is not known.

* Source (DeRUITER)

Sulfonylureas on Lehigh Valley Health Network Formulary

Drug

Contraindications

Precautions

Glimepiride (Amaryl)

-Acknowledged hypersensitivity to this drug or any of the components that comprise it

-Patients with history of allergic reaction to sulfonamide derivatives also have chance of reacting to Glimepiride

-Hypoglycemia

-Hypersensitivity reactions

-Increased risk of cardiovascular mortality

-Hemolytic Anemia

Glyburide (Micronase/Diabeta)

- Acknowledged hypersensitivity to this drug or components that comprises it

- Type one diabetes, diabetic ketoacidosis (situation recommended to be treated with insulin)

-Patients also treated with bosentan

-Hypoglycemia

-Hemolytic Anemia

Glyburide micronized (Glynase)

-Acknowledged hypersensitivity to this drug

- Type one diabetes, diabetic ketoacidosis (situation recommended to be treated with insulin)

- Treated also with bosentan

-Hypoglycemia

-Loss of control of BG

-Hemolytic Anemia (with patients that have G6PD deficiency)

Glipizide

- Acknowledged hypersensitivity to this drug

-Diabetic ketoacidosis (situation recommended to be treated with insulin)

-Renal and Hepatic Disease

-Hypoglycemia

-Loss of control of blood glucose

Glipizide XL

- Acknowledged hypersensitivity to this drug or components that comprises it

- Type one diabetes, diabetic ketoacidosis (situation recommended to be treated with insulin)

-Renal and Hepatic Disease

-GI disease

-Hypoglycemia

-Loss of control of BG

-Hemolytic Anemia

-Glipizide/Metformin

- Renal disease or renal dysfunction

-Acknowledged hypersensitivity to glipizide or metformin

- Acute or chronic acidosis (situation recommended to be treated with insulin)

-Hypoglycemia

-Renal and Hepatic Disease

-Hemolytic Anemia

-Use of concomitant medication that alters renal function or disposal of metformin

*Source: Daily Med Current Medication Information

Data:
*Data collected from LVHN inpatient admissions from July 2013-March 2014
**All patients were 18 years of age or older, non-pregnant, and had diabetes

Campus

Cedar Crest

Muhlenberg

Adult Diabetes Patients Experiencing BG/dL

1310

485

Adult Patients Prescribed Sulfonylureas During Stay

566

105

Adult Patients Taking Sulfonylurea that had BG/dL During Stay

106

17

Total Days Adults Taking Sulfonylureas Had BG/dL During Stay

183

26

Total Events Adults Taking sulfonylureas Had BG/dL

302

42

Campus

Cedar Crest

Muhlenberg

Percent Patients having Sulfonylureas Induced Hypoglycemia

18.7%

16.2%

Total Days BG/dL per Sulfonylurea Induced Hypoglycemia

1.73

1.53

Total Events BG < 70 mg/dL per Sulfonylurea Induced Hypoglycemia

2.85

2.5

Conclusion:

The importance of this proposal is to reduce hypoglycemic risk. Hypoglycemia can be fatal, cause brain death, lead to confusion, loss of consciousness, and result in seizures (Vigersky, 2013). By removing and/or reducing sulfonylurea use in the hospital setting one may minimize this risk.

Lehigh Valley has no restrictions on sulfonylurea use in the hospital setting (see above chart for available sulfonylureas at LVHN), and after identifying a relationship with ingestion of sulfonylurea and hypoglycemia, this proposal was crafted. The metrics derived above, as well as the associated literature, indicate that we are not maximizing the quality of care provided by keeping these drugs on formulary. Moreover, increased costs begin to become a concern when one episode of hypoglycemia increases the length of stay by 2.8 days (Turchin 2009). Consequently, two of the three “Triple Aim” aspects are not met while this drug is available for use.

There are other medications that can reduce blood glucose levels more safely than sulfonylureas in the inpatient setting. For example, the ADA recommends “scheduled subcutaneous administration of insulin, with basal, nutritional, and correction components, is the preferred method for achieving and maintain glucose control” (Moghissi 2009). Indeed, the use of sulfonylureas in hospital setting has decreased as more physicians are educated about the matter discussed in this proposal. Nonetheless, LVHN is still generating significantly high figures, indicating that sulfonylurea-induced hypoglycemia is still prevalent. Furthermore, removing sulfonylureas from the hospital formularies will directly contribute to reducing hypoglycemic rates, one of the network’s diabetes management quality improvement goals.

Sources:

Barrueto, F. (2010, August 19). Sulfonylureas. . Retrieved July 9, 2014, from https://umem.org/educational_pearls/1171/

Clement, S., Braithwaite, S., Magee, M., Ahmann, A., Smith, E., Schafer, R., et al. (2013, April). Management of Diabetes and Hyperglycemia in Hospitals. American Diabetes Association, 2,7, 553-591.

Daily Med Current Medication Information. (n.d.). Food and Drug Administration . Retrieved July 14, 2014, from http://dailymed.nlm.nih.gov/dailymed/about.cfm

DeRUITER, J. (n.d.). OVERVIEW OF THE ANTIDIABETIC AGENTS. Retrieved July 8, 2014, from http://www.auburn.edu/~deruija/endo_diabetesoralagents.pdf

Deusenberry CM, Coley KC, Korytkowski MT, Donihi AC. (2012, May). Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy 2012, 32.

Jennings, A., Wilson, M., & Ward, J. Symptomatic Hypoglycemia in NIDDM Patients Treated With Oral Hypoglycemic Agents. 1989, March. American Diabetes Association, 12 (3), 203-208.

Moghissi, E., Korytkowski, M., DiNardo, M., Einhorn, D., Hellman, R., Hirsch, I., et al. (2009, June) American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control. American Diabetes Association , 32 (6), 1119-1131.

Seltzer, HS. Drug-induced hypoglycemia. A review of 1418 cases. (1989, March) Endocrinology and Metabolism Clinics of North America, 18 (1), 83-163. Retrieved July 7, 2014, from http://www.ncbi.nlm.nih.gov/pubmed/2645125

Turchin, A., Scanlon, J., Matheny, M., Shubina, M., Greenwood, B., & Pendergrass, M. (2009, July). Hypoglycemia and Clinical Outcomes in Patients with Diabetes Hospitalized in the General World. American Diabetes Association, 32(7), 1153-1157.

Umpierrez, G., Hellman, R., Korytkowski, M., Kosiborod, M., Maynard, G., Montori, V., et al. (2012, January). Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Setting: An Endocrine Society Clinical Practice Guideline. The Journal of clinical Endocrinology and Metabolism, 97(1), 16-38.

Vigersky, R., Seaquist, E., Anderson, J., Childs, B., Cryer, P., Dagogo-Jack, S., et al. (2013, May). Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care, 32(5), 1384-1395.

Comments

Mentor: Joyce Najarian

Department(s)

Research Scholars, Research Scholars - Posters

Document Type

Poster

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