Randomized comparison of pramlintide or mealtime insulin added to basal insulin treatment for patients with type 2 diabetes.
OBJECTIVE
To compare the efficacy and safety of adding mealtime pramlintide or rapid-acting insulin analogs (RAIAs) to basal insulin for patients with inadequately controlled type 2 diabetes.


METHODS
In a 24-week open-label, multicenter study, 113 patients were randomly assigned 1:1 to addition of mealtime pramlintide (120 microg) or a titrated RAIA to basal insulin and prior oral antihyperglycemic drugs (OADs). At screening, patients were insulin naive or had been receiving <50 units/day basal insulin for <6 months. The basal insulin dosage was titrated from day 1, seeking fasting plasma glucose (FPG) > or =70-<100 mg/dl. Pramlintide and an RAIA were initiated on day 1 and week 4, respectively. The proportion of patients achieving A1C < or =7.0% without weight gain or severe hypoglycemia at week 24 was the primary end point.


RESULTS
More pramlintide- than RAIA-treated patients achieved the primary end point (30 vs. 11%, P = 0.018) with a similar dose of basal insulin. Pramlintide and an RAIA yielded similar mean +/- SEM values for FPG and A1C at 24 weeks (122 +/- 7 vs. 123 +/- 5 mg/dl and 7.2 +/- 0.2 vs. 7.0 +/- 0.1%, respectively) and similar least squares mean reductions from baseline to end point (-31 +/- 6 vs. -34 +/- 6 mg/dl and -1.1 +/- 0.2 vs. -1.3 +/- 0.2%, respectively). RAIAs but not pramlintide caused weight gain (+4.7 +/- 0.7 vs. +0.0 +/- 0.7 kg, P < 0.0001). Fewer patients reported mild to moderate hypoglycemia with pramlintide than with the RAIA (55 vs. 82%), but more patients reported nausea (21 vs. 0%). No severe hypoglycemia occurred in either group.


CONCLUSIONS
In patients taking basal insulin and OADs, premeal fixed-dose pramlintide improved glycemic control as effectively as titrated RAIAs. The pramlintide regimen sometimes caused nausea but no weight gain and less hypoglycemia.
Riddle
Matthew
M
Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Pencek
Richard
R
Charenkavanich
Supoat
S
Lutz
Karen
K
Wilhelm
Ken
K
Porter
Lisa
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000682:Amyloid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D016896:Treatment Outcome; D055815:Young Adult
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; C105254:pramlintide