A Caucasian Man with Newly Diagnosed Type 2 Diabetes and Renal Insufficiency, PART 2

Which pharmacologic therapy options for type 2 diabetes would improve Mr. Walker's glycemic control without being contraindicated due to his renal insufficiency or cardiovascular disease?

1. Start metformin 500 mg twice daily
2. Start glipizide ER 5 mg daily
3. Start liraglutide Initiate at 0.6 mg per day
4. Start sitagliptin 50 mg daily
5. Either answer "2" or "4" is an appropriate option

Either glipizide ER 5 mg daily or sitagliptin 50 mg daily would improve Mr. Walker's glycemic control without being contraindicated by his renal insufficiency or cardiovascular disease.

Either glipizide ER 5 mg daily orsitagliptin 50 mg daily would improve Mr. Walker's glycemic control without being contraindicated by his renal insufficiency or cardiovascular disease.  

Either sitagliptin, a DPP-4 inhibitor, or glipizide ER, a sulfonylurea, could be considered as a treatment option for Mr. Walker to reduce his glycemic control closer to a goal. Mr. Walker and his physician can decide which treatment option is best after discussing the pros and cons of each medication regimen.

Sitagliptin -- DPP-4 inhibitors act to enhance endogenous glucagon-like peptide-1 (GLP-1), an incretin hormone, by decreasing its inactivation by the DPP-4 enzyme, thereby elevating active GLP-1 levels. Sitagliptin, the only medication in this class currently approved for use in the United States, has been shown to be weight neutral, with no effect on body weight. DPP-4 inhibitors also have a low incidence of hypoglycemia and other side effects, and are effective at improving both fasting and postprandial hyperglycemia. The dose would need to be reduced (from the usual dose of 100 mg daily to 50 mg daily) due to Mr. Walker's renal insufficiency. Benefits of taking a DPP-4 inhibitor include once-a-day dosing and a low incidence of hypoglycemia or other side effects, but sitagliptin is more expensive than some other medications available to treat type 2 diabetes. DPP-4 inhibitors are included as a part of the ACE/AACE Roadmap to maximize therapy for patients with an A1C between 6.5% and 8.5%. 

Glipizide ER -- This medication would be another therapeutic choice with the primary benefit that it is less expensive than a DPP-4 inhibitor. Sulfonylureas enhance insulin secretion by interacting with sulfonylurea receptors on pancreatic β-cells, which results in the closure of ATP-sensitive potassium channels. Treatment with glipizide ER would increase Mr. Walker's risk of hypoglycemia due to his chronic renal insufficiency and may lead to weight gain. Sulfonylureas, as a drug class, were once thought to increase cardiovascular mortality in patients with type 2 diabetes, but this was not substantiated by the UKPDS or ADVANCE studies. Sulfonylureas are also included as part of the ACE/AACE Roadmap to maximize therapy for patients with an A1C between 6.5% and 8.5%.

Either glipizide ER 5 mg daily orsitagliptin 50 mg daily would improve Mr. Walker's glycemic control without being contraindicated by his renal insufficiency or cardiovascular disease.

Rationale for other treatment options not recommended at this time 

Metformin -- This medication is not recommended in patients with renal insufficiency because it increases the risk of lactic acidosis, a rare but serious complication. Further, metformin is not recommended in men with a serum creatinine ≥1.5 mg/dL.

Pioglitazone -- Although pioglitazone is not contraindicated and requires no dosing adjustment in renal disease, it may increase the risk of fluid retention and congestive heart failure, which would not be desirable in a patient with renal insufficiency and peripheral edema.

Liraglutide -- A GLP-1 receptor agonist, this medication is effective at treating postprandial hyperglycemia, no dosing adjustments are needed for mild to moderate renal insufficiency, and weight loss is common, which would be desirable for Mr. Walker, but GI side effects are common as well and the medication is expensive. More important, however, it is not approved for use as monotherapy and thus is not the best therapeutic choice for Mr. Walker.

Insulin -- If Mr. Walker's A1C was >10%, insulin would be recommended as initial therapy by the ACE/AACE Roadmap. Although basal insulin is not contraindicated in renal disease, it is more likely to cause hypoglycemia and weight gain than other medication choices. Use of sitagliptin together with insulin would be considered off-label, as they have not yet been studied in combination.

The treatment options were discussed with Mr. Walker and his wife, and it was decided that he would start sitagliptin 50 mg daily. Mr. Walker stated he preferred to start treatment with a medication that was less likely to cause weight gain and had a low incidence of side effects.  

A prescription was also given for furosemide 40 mg daily to improve his hypertension and 1+ ankle edema. 

After a serious discussion with his physician, Mr. Walker stated that he now understood how important good glycemic control is to improving his type 2 diabetes, preventing further decline in his renal function, and decreasing his cardiovascular disease risk. He was told that lifestyle changes could be just as important as medication in improving his health, and he agreed to attend a series of diabetes self-management education (DSME) classes with his wife.

Three months after his initial visit, Mr. Walker and his wife returned for a follow-up visit. Mr. Walker reported he was tolerating the medication well and that he had learned a great deal from the DSME classes taught by a nurse and a dietitian, both of whom were diabetes educators. Although the class format and group support was nice, he found he still had some questions about how much protein and salt he should eat due to his kidney disease and hypertension.

He reported that even though he learned that sitagliptin is unlikely to cause hypoglycemia, he is now self-monitoring his blood sugars occasionally after meals, and this was helping him adjust his diet and portion sizes. However, he was still having difficulty finding time to exercise, but he was walking with his wife after dinner for 20-30 minutes several days a week.

His wife said she was much happier now that her husband was taking better care of himself and she reported that her A1C had also improved.