Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes.
OBJECTIVE
Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.


METHODS
This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N = 211) using insulin glargine (without mealtime insulin) +/- oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120 mug with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of > or = 70 to < 100 mg/dL.


METHODS
Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.


RESULTS
Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (-1.6 +/- 0.3 kg vs. +0.7 +/- 0.3 kg, p < 0.001; mean +/- SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (-0.8 +/- 0.2 mg/L vs. 0.1 +/- 0.2 mg/L, p < 0.01; mean +/- SE). Patients with baseline hsCRP > 3 mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p < 0.05). Patients with baseline triglycerides > or = 150 mg/dL or > or = 200 mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (-43 +/- 14 mg/dL or -59 +/- 19 mg/dL; p < 0.05; mean +/- SE) but not with placebo (1 +/- 29 mg/dL or -3 +/- 54 mg/dL; mean +/- SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.


CONCLUSIONS
Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.
Wysham
Carol
C
Rockwood Clinic, Spokane, WA, USA.
Lush
Cameron
C
Zhang
Bei
B
Maier
Holly
H
Wilhelm
Ken
K
D000368:Aged; D000682:Amyloid / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D000682:Amyloid; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D058228:Islet Amyloid Polypeptide; D010919:Placebos; D014280:Triglycerides; D000069036:Insulin Glargine; D002097:C-Reactive Protein; C105254:pramlintide