title: Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial.
abstract: Preclinical evidence suggests that pharmacotherapy for obesity using combinations of agents targeted at distinct regulatory pathways may produce robust additive or synergistic effects on weight loss. This randomized placebo-controlled trial examined the safety and efficacy of the amylin analogue pramlintide alone or in combination with either phentermine or sibutramine. All patients also received lifestyle intervention. Following a 1-week placebo lead-in, 244 obese or overweight, nondiabetic subjects (88% female; 41 +/- 11 years; BMI 37.7 +/- 5.4 kg/m(2); weight 103 +/- 19 kg; mean +/- s.d.) received placebo subcutaneously (sc) t.i.d., pramlintide sc (120 microg t.i.d.), pramlintide sc (120 microg t.i.d.) + oral sibutramine (10 mg q.a.m.), or pramlintide sc (120 microg t.i.d.) + oral phentermine (37.5 mg q.a.m.) for 24 weeks. Treatment was single-blind for subjects receiving subcutaneous medication only and open-label for subjects in the combination arms. Weight loss achieved at week 24 with either combination treatment was greater than with pramlintide alone or placebo (P < 0.001; 11.1 +/- 1.1% with pramlintide + sibutramine, 11.3 +/- 0.9% with pramlintide + phentermine, -3.7 +/- 0.7% with pramlintide; -2.2 +/- 0.7% with placebo; mean +/- s.e.). Elevations from baseline in heart rate and diastolic blood pressure were demonstrated with both pramlintide + sibutramine (3.1 +/- 1.2 beats/min, P < 0.05; 2.7 +/- 0.9 mm Hg, P < 0.01) and pramlintide + phentermine (4.5 +/- 1.3 beats/min, P < 0.01; 3.5 +/- 1.2 mm Hg, P < 0.001) using 24-h ambulatory monitoring. However, the majority of subjects receiving these treatments remained within normal blood pressure ranges. These results support the potential of pramlintide-containing combination treatments for obesity.
authors.affiliation: Weill Cornell Medical College, New York, New York, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Aronne
authors.forename: Amy E
authors.initials: AE
authors.lastname: Halseth
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Burns
authors.forename: Stephan
authors.initials: S
authors.lastname: Miller
authors.forename: Larry Z
authors.initials: LZ
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003503:Cyclobutanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010645:Phentermine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016037:Single-Blind Method; D015431:Weight Loss / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D010645:Phentermine; C105254:pramlintide; C058254:sibutramine