Minimal reduction in insulin dosage with pramlintide therapy when pretreatment near-normal glycemia is established and square-wave meal bolus is used.
OBJECTIVE
To evaluate the effect of near-normal glucose control before initiation of pramlintide therapy and square-wave meal bolus on self-reported hypoglycemia and the percentage change in dosing parameters after attaining the maximum pramlintide dosage.


METHODS
In this prospective study, insulin pump-treated patients with type 1 diabetes had insulin dosages optimally titrated on the basis of daily continuous glucose monitoring (CGM). Pramlintide therapy was initiated, and the dosage was increased 15 mcg/meal per week. Insulin dosage was adjusted during 30-minute visits after review of self-monitored blood glucose records, adverse effects, and hypoglycemia diary. Within 2 weeks of achieving a pramlintide dosage of 60 mcg/meal, the second CGM-guided insulin dosage adjustment was done. The primary end point was the percentage change in total basal insulin dosage (TBD) from baseline. The secondary end points were the percentage change in the insulin to carbohydrate ratio (ICR) and the assessment of symptoms of nausea and hypoglycemia during the pramlintide dosing escalation.


RESULTS
Nine patients were enrolled. The difference between before and during CGM-guided insulin dosing was a mean (+/- standard deviation) TBD change of -11.2 +/- 13.2% (P = 0.023) and mean ICR change of 7.8 +/- 13.4% (P = 0.053). Pramlintide was well tolerated and resulted in decrease in weight and hemoglobin A1c values. Hypoglycemia occurred in 6 patients during the study; the assistance of another person was not required in any of these cases. No hypoglycemia was reported in the first week of starting pramlintide. Mild to moderate nausea was reported in 6 patients during the titration phase.


CONCLUSIONS
Patients with near-normal glucose control who use a square-wave bolus may not need initial bolus dosage reduction. With weight loss, small adjustments in both TBD and ICR may be required. Greater incidence of hypoglycemia seen in previous studies may in part be due to mismatched insulin dosing.
The Diabetes Care Center, the University of California-San Francisco, Salinas, California, San Francisco, California 93901, USA. aking@diabetescarecenter.com
Allen B
AB
King
D000328:Adult; D000682:Amyloid / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism*; D015190:Blood Glucose Self-Monitoring; D002138:Calibration; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D004435:Eating / Q000502:physiology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007332:Insulin Infusion Systems; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000682:Amyloid; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; C105254:pramlintide