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What to do when a patient refuses insulin injections
A 72-year-old man presented in follow-up for insulin-requiring new-onset diabetes after kidney transplant. The patient had a history of hepatitis C virus infection, which led to hepatorenal syndrome. Subsequent end-stage renal disease necessitated a kidney transplant 10 years ago.
The patient was diagnosed with diabetes after his transplant and was started on insulin therapy at that time. Multiple attempts to switch him to oral therapy (combinations of metformin, pioglitazone, sulfonylurea) were unsuccessful, and his regimen has been up to 40 units of Levemir (insulin detemir, Novo Nordisk) and 12 units of meal-time insulin per day. He has since been successfully treated for his HCV.
The patient has had a problem with lipoatrophy since his transplant and has increasingly expressed that he has run out of sites in which he could comfortably inject insulin, even with the thinnest and shortest needles available. This was confirmed in a visit with our certified diabetes educator. His BMI fluctuates between 17.5 kg/m2 and 19 kg/m2.
Ronald Tamler
At his last visit, the patient refused further treatment with insulin. At the current visit, 4 weeks later, he was much happier on a regimen of Januvia (sitagliptin, Merck) and repaglinide that his physician had warned him would probably not be successful. He reported fasting blood glucose levels in the mid- to high 100s, but postprandial levels that rise to the high 200s and 300s.
His blood glucose level in the office is 332 mg/dL.
He describes his current diet as “healthy,” in general, and he walks for exercise.
He does not smoke or drink alcohol and is married.
Pertinent medical history consists of osteoporosis, hypertension, peripheral vascular disease, ESRD requiring transplant, HCV, anemia, hyperlipidemia, gallstones, antiphospholipid antibody syndrome, monoclonal gammopathy of unknown significance and cataracts.
Medications at time of visit included the following: Cozaar (losartan, Merck) 25 mg by mouth once daily; Zocor (simvastatin, Merck) 10 mg by mouth at bedtime; Coreg CR (carvedilol, GlaxoSmithKline) 10-mg capsule by mouth once daily; prednisone 5 mg by mouth once daily; sitagliptin 100-mg tablet by mouth once daily; Prandin (repaglinide, Novo Nordisk) 2-mg tablet with lunch and dinner; Prograf (tacrolimus, Astellas Pharma) 1.5 mg by mouth every morning and 1 mg every night; Cellcept (mycophenolate mofetil, Genentech) 250 mg by mouth two times a day; Plavix (clopidogrel, Bristol-Myers Squibb) 75 mg by mouth daily; Prilosec (omeprazole, AstraZeneca) 20 mg by mouth two times a day; Pletal (cilostazol, Otsuka) 100 mg by mouth two times a day; and Citracal + D (calcium citrate-vitamin D3, Bayer).
Physical exam is remarkable for a lean male with some temporal wasting. Blood pressure is 132 mm Hg/82 mm Hg, pulse 96 bpm, height 5’7” and weight 55.792 kg (123 lb). BMI is 19.26 kg/m2. He has impaired sense of vibration in both feet, but normal response to monofilament testing bilaterally, with trace dorsalis pedis and posterior tibial pulses bilaterally, and warm feet.
HbA1c has risen to 8.8% on his oral regimen, from 7.2% just 1 month ago. Serum chemistry, including renal function, is normal (with exception of glucose). The patient adamantly refuses any kind of injection therapy, be it once-daily insulin or a glucagon-like peptide-1 agonist. He points with exasperation to his buttocks and exclaims: “Where shall I inject it?”
What is the best agent to add for this patient with insulin-requiring new-onset diabetes after transplant?
A. Tradjenta (linagliptin, Lilly) 5 mg daily
B. Basal insulin therapy with Lantus (insulin glargine, Sanofi Aventis) 50 units once a day
C. Byetta (exenatide, AstraZeneca) 10 mcg twice a day
D. Afrezza (inhaled insulin microspheres, Sanofi U.S.), initially 4 units with breakfast and 8 units with lunch and dinner, to be titrated
E. Metformin 500 mg twice a day
Case Discussion
Answer: D
This patient has posttransplant diabetes that is exacerbated by continued requirement of daily steroid. His HbA1c is underrepresenting his true hyperglycemia because blood was drawn only 1 month after stopping insulin and because of his anemia.
The main concern for this patient is postprandial hyperglycemia, which is worse in the afternoon and returns to his baseline by morning. Although glargine (B) may be a good component of a basal-bolus insulin regimen, there is a risk for fasting hypoglycemia while not capturing the patient’s afternoon hyperglycemia. Human neutral protamine Hagedorn (NPH) insulin may be the better option, but the patient refuses injection therapy.
When the patient asked to start on a DPP-IV inhibitor (he had tried triple-combination therapy with sulfonylurea in the past), sitagliptin was selected because that agent has the least interaction with the cytochrome P450 system, pertinent to the patient’s antirejection treatment. Linagliptin (A) comes from the same family of drugs but does interact with cytochrome P450 and would not be expected to improve the patient’s glycemia.
Exenatide (C) and other GLP-1 agonists were refused due to the patient’s frustrations with injections.
Metformin (E) had been tried in the past at the maximum dose in oral combination therapy without success.
The fact that a good dose of repaglinide does not affect blood glucose levels much, along with the patient’s prior history of failed sulfonylurea treatment, indicates the need for insulin therapy. Since injections are not an option, we opted to try Afrezza rapid-acting inhaled insulin. The patient will likely still require some basal insulin therapy, but the inhaled insulin should effectively manage his main issue, which is postprandial hyperglycemia.
A final option that is not mentioned in the choices above is a sodium-glucose cotransporter 2 inhibitor, tried alone or combined with other oral agents.
Ronald Tamler, MD, PhD, MBA, is clinical director of the Mount Sinai Diabetes Center in New York. He also is an Endocrine Today Editorial Board member. He reports no relevant financial disclosures.