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Item #7 

Pramlintide Injections Improve Glycemic Control

Patients with type 1 diabetes mellitus not only have an absence of insulin but also an absence of the hormone amylin.

According to the results of a new study, mealtime injections of pramlintide, an amylin analogue, reduce insulin requirements and fluctuations in glycemic control.

"Despite important advances in the delivery and pharmacology of insulin,...many patients with type 1 diabetes still fail to achieve glycemic targets," says Claresa Levetan, MD, from the Medstar Clinical Research Center in Washington, D.C.. "An important barrier to achieving tight glycemic control with insulin therapy alone is...excessive glucose fluctuations throughout the day, most notably in the postprandial period."

Of 18 patients with type 1 diabetes in this study, 16 could be evaluated. Mean age was 44 ± 11 years, and mean HbA(1c) was 8.2 ± 1.3%. Subjects received mealtime injections of 30 µg pramlintide three times daily for four weeks in addition to their preexisting continuous subcutaneous insulin infusion regimen, which included lispro in 16 subjects and regular insulin in two subjects. During the first three days, mealtime insulin boluses were reduced by a minimum of 10%, and they were subsequently readjusted based on clinical judgment.

At baseline, patients had excessive 24-hour glucose fluctuations. Only 28% of the continuous glucose monitoring system (CGMS) measurements were in the euglycemic range (80-140 mg/dL), 59% were greater than 140 mg/dL, and 13% were less than 80 mg/dL.

After four weeks of pramlintide treatment, 37% of CGMS measurements were within the euglycemic range, 48% were in the hyperglycemic range, and 15% were in the hypoglycemic range. Postprandial glucose, glucagon, and triglyceride excursions were reduced by approximately 86%, approximately 87%, and approximately 72%, respectively (P < .05 vs. baseline). Mealtime insulin dosages were reduced by 17%, and there were no severe hypoglycemic events. At week six, when treatment had been discontinued, the 24-hour glucose profile and postprandial glucose, glucagon, and triglyceride excursions returned toward pretreatment values.

The authors suggest that pramlintide reduces postprandial glucose excursions via its dual effect on postprandial glucagon secretion and gastric emptying.

"In this study, the addition of pramlintide to insulin therapy reduced excessive 24-hour glucose fluctuations as well as postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with insulin pumps," the authors write. "Given that many patients with diabetes experience postprandial hyper- and dyslipidemia, and that this abnormality has been implicated as a potential cardiovascular risk factor, additional studies are warranted to further examine the postprandial lipid-lowering effect of pramlintide."

Amylin Pharmaceuticals supported this study and has financial arrangements with some of its authors.  Diabetes Care. 2003;26:1-8