First AD

Second AD

RM, a 78-year-old woman, presents to the clinic to establish care. Her past medical history is significant for type 2 diabetes (T2DM), hypertension, and atrial fibrillation. Current medications are:



         500 mg/bid                      

      10 mg/day
Pioglitazone         45 mg/day                      Atorvastatin      10 mg/day  


             10 mg/day                     

     20 mg/day   
Metoprolol          100 mg/day
 

She states that she is happy with her current medications as all are “affordable” given her limited income and that it took her a long time to get her diabetes under control. Laboratory values include: HbA1c, 6.6%; basic metabolic panel, WNL (SCr, 1.2; eGFR, 45 mL/min). Vitals signs are: weight, 70kg; blood pressure, 126/72 mm Hg; pulse, 64. RM lives alone and tries to exercise 3 times per week and watches her diet. She notes that at least twice a week she obtains fasting blood glucose (FBG) readings <70 mg/dL but denies feeling poorly.

A. Yes, discontinue pioglitazone due to high likelihood of hypoglycemia

B. No, her A1c is well controlled and she is not experiencing symptomatic hypoglycemia 

C. Yes, discontinue glyburide and switch to an alternative sulfonylurea

D. No, her A1c is well controlled and she is not on therapy likely to cause hypoglycemia

E. Yes, increase glyburide to 20 mg daily to obtain a target A1c of <6.5%

Recommended answer: C. Yes, discontinue glyburide and switch to an alternative sulfonylurea



Sulfonylureas, which lower blood glucose by stimulating insulin release from Î²-cells, are the oldest class of oral agents used to treat T2DM.

 These agents are still in common use because they are effective (lower A1c by 1% to 1.5%) and because they are generally inexpensive.

 Because of the mechanism of action however, hypoglycemia is a major side effect associated with sulfonylurea therapy.

Elderly patients can be especially vulnerable to hypoglycemia and serious complications such as falls are more likely in this population.

of potentially inappropriate medications and classes to avoid in older adults specifically lists the second-generation sulfonylurea glyburide and advises the use of alternative, shorter-acting secretagogues or other agents.

  While the mechanism for the increased risk of hypoglycemia with glyburide compared to other second-generation sulfonylureas is not fully understood, it is likely a result of differences in duration of action, potency, and accumulation of active metabolites.

 Glipizide is generally recommended as the preferred alternative in older adults and in several clinical studies has been noted to have a lower incidence of hypoglycemia, especially in the elderly population.



In this patient, a switch to an equivalent dose of glipizide with further titration based on her home readings may result allow her to retain A1c control with less hypoglycemia.

 While she would also be a candidate for other oral medications or insulin analogues, these medications can be expensive and she has noted cost to be a concern. A significant advantage of the sulfonylureas is their low cost in addition to their efficacy. Given RM’s financial concerns, newer oral medications such as DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors may not be optimal.



 Pioglitazone is associated with a very low incidence of hypoglycemia, although use of this agent with sulfonylureas can increase the risk of hypoglycemia.

 Although RM’s A1c is well controlled, her home blood glucose readings indicate hypoglycemia. While she says that she is not symptomatic despite these readings, this could be a result of beta-blocker therapy for her atrial fibrillation. Beta-blockers may mask most signs of hypoglycemia and can make it very difficult for patients to identify symptoms other than sweating.

  For elderly patients, undetected symptoms of hypoglycemia can lead to serious consequences.



 RM’s A1c is well controlled; however, glyburide is a sulfonylurea agent capable of causing hypoglycemia, especially in the elderly.



. It is likely that the patient’s current dose of glyburide is contributing to her hypoglycemic blood glucose readings at home and so increasing the dose could expose her to further harm. Additionally, current American Diabetes Association goals include an A1c goal for most patients of <7%; at her current reading of 6.6%, she is at goal.







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RM is an active 78-year-old woman with no complaints about her health or her medications. Then she tells you about her home blood glucose readings. 

An Older Woman at A1c Goal with Asymptomatic Hypoglycemia: What Next?