Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.
OBJECTIVE
Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed.


METHODS
In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time.


RESULTS
Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides.


CONCLUSIONS
The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.
Chapman
I
I
Department of Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia.
Parker
B
B
Doran
S
S
Feinle-Bisset
C
C
Wishart
J
J
Strobel
S
S
Wang
Y
Y
Burns
C
C
Lush
C
C
Weyer
C
C
Horowitz
M
M
D000328:Adult; D000682:Amyloid / Q000627:therapeutic use*; D015992:Body Mass Index; D048909:Diabetes Complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D006815:Hunger; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010919:Placebos; D012527:Satiation
D000682:Amyloid; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D010919:Placebos; C105254:pramlintide