A T2DM Patient Persistently Above Glycemic Control Goal - What would you suggest?


Weigh in on how you would manage this patient’s situation.

[[{"type":"media","view_mode":"media_crop","fid":"39475","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_1605166213247","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"3962","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 195px; height: 94px; float: right;","title":"© areeya.ann/Shutterstock.com","typeof":"foaf:Image"}}]]What would you advise for a type 2 diabetes (T2DM) patient who, despite his or her best efforts, remains persistently above goal for glycemic control? Increasing insulin dosages has led to larger volumes of injections and patient complaints of discomfort. The patient may very well be absorbing significantly less than the doses injected, but needing to inject more than 1 syringe of insulin each time could hamper adherence. This patient has marked insulin resistance – defined, though arbitrarily, as requiring >200 units of insulin/day.

How would you approach this situation?


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One treatment option is using U-500 insulin, which has been available since 1952 (the first formulation was derived from beef; a human-derived form was introduced in 1997).

1. As you know, the concentration of U-100 insulin is 100 units/mL. U-500 is a regular insulin that is 5 times more concentrated than U-100. U-500 acts more like NPH insulin, with a 45-minute time of onset, and a duration of action of 11.5 hours.

2. Using a different syringe to administer U-500 may help patients avoid dosing confusion. A tuberculin syringe has volume, instead of unit markings. A key point to remember is that, unlike the case for U-100 insulin, the dose of U-500 does not equal the units of insulin, as given via a usual insulin syringe.1

If a patient is prescribed an insulin dose of 200 units, you could write the Rx as: “Regular Insulin U-500, 200 units, inject 0.4 ml subcutaneously, QAC.”

3. For those requiring >200 units/day, a suggested regimen is to administer U-500 at least twice a day, for instance, before breakfast and before dinner.

• If the total daily dose of insulin is >300 units/day, the recommendation is to administer TID.

• For patients with total daily dose requirements of >750 units/day, consider QID, including a bedtime dose.

• Consider using an insulin pump if the daily total requirement exceeds 2000 units/day.

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Few reports on clinical experience have been published. Boldo and colleagues conducted a retrospective review of 53 patients, one of the largest such studies of patients on U-500.2 The mean HbA1C level decreased from a baseline of 10.1% to 9.1% after 6 months of using U-500, to 8.6% at the last follow-up visit (the mean follow-up was 36.6 ± 24 months). At the most recent follow-up, body weight increased by a mean of 6.8 kg and insulin dosage increased by a mean of 0.44 units/kg.

For the right patient, U-500 insulin may be worth considering. You should carefully assess whether the patient and caregiver could adapt to the difference in dosing, and be clear when writing orders for this agent, whether for an inpatient or an outpatient.




1. Cochran E, et al. The use of U-500 in patients with extreme insulin resistance. Diabetes Care. 2005;28(5):1240-1244.

2. Boldo A, Comi RJ. Clinical experience with U500 insulin: risks and benefits. Endo Practice. 2012;18(1):56-61.

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