MKSAP Quiz: Poorly controlled type 2 diabetes
This month's quiz asks readers to evaluate a 72-year-old man during an office visit for type 2 diabetes.
A 72-year-old man comes to the office for a follow-up evaluation. He has had type 2 diabetes mellitus for 13 years. Over the past 5 years, his hemoglobin A1c value has slowly risen to 9.8%, and his fasting blood glucose levels at home have frequently exceeded 180 mg/dL (10.0 mmol/L). He has been adherent to recommended lifestyle changes. The patient is currently on metformin, 1,000 mg twice daily, and extended-release glipizide, 20 mg/d. He has hypertension treated with candesartan and hydrochlorothiazide and hyperlipidemia treated with atorvastatin.
Results of physical examination are normal.
Which of the following is the best next step in therapy?
A. Add exenatide
B. Add insulin glargine
C. Add pioglitazone
D. Add sitagliptin
E. Double his dosage of glipizide
MKSAP Answer and Critique
The correct answer is B) Add insulin glargine. This item is available to MKSAP 15 subscribers as item 8 in the Endocrinology section. Part A of MKSAP 16 was released on July 31. Part B, including the Endocrinology section, will be released at the end of the year. More information is available online.
Insulin glargine should be added to this patient's regimen. Type 2 diabetes mellitus is associated with progressive beta cell dysfunction, resulting in deterioration of endogenous insulin secretory capacity over time. This leads to secondary failure rates of previously successful oral pharmacologic therapy and, ultimately, the need for insulin therapy in most patients with diabetes.
This patient has poor glycemic control, despite combination therapy with metformin and extended-release glipizide (a sulfonylurea), and thus requires insulin. The standard method of initiating insulin therapy is to begin with a single daily injection of a basal insulin, such as insulin glargine, insulin detemir, or neutral protamine Hagedorn (NPH) insulin; this approach minimizes the risk of hypoglycemia. Starting doses in the 0.2 to 0.3 U/kg range will be well tolerated in most patients, with future titration based on the results of home glucose monitoring. Dose changes are typically made in increments of 2 to 4 units every few days or weekly until the fasting glucose level is consistently in the range of 70 to 130 mg/dL (3.9 to 7.2 mmol/L). The addition of insulin glargine or insulin detemir to this patient's regimen should result in a substantial reduction in his hemoglobin A1c value. Randomized studies of stepped therapy in type 2 diabetes showed that most patients were able to achieve target hemoglobin A1c goals of 7% using a combination of oral antihyperglycemic agents and basal insulin therapy. If such a reduction is not achieved and postprandial hyperglycemia occurs, the addition of a mealtime rapid-acting insulin analogue or the substitution of a premixed insulin should be recommended.
Adding the injectable agent exenatide or another oral agent to this patient's medication regimen is unlikely to reduce his hemoglobin A1c value sufficiently. When added to a combination oral regimen, exenatide has been shown to reduce hemoglobin A1c values by only 1% and the oral agents pioglitazone and sitagliptin by 1% or less.
In most studies of patients with diabetes, increasing the sulfonylurea dosage beyond the half maximal dosage has resulted in little to no improvement in glycemic control. Therefore, doubling this patient's dosage of glipizide is unlikely to be effective.
Key Point
- In patients who have persistent fasting hyperglycemia despite combination oral agents, the addition of insulin, typically a basal formulation, will improve glycemic control.