Evaluation of lorcaserin on progression of prediabetes to type 2 diabetes and reversion to euglycemia.
OBJECTIVE
Lorcaserin is a selective 5-HT2C (5-hydroxytryptamine 2C) receptor agonist indicated for weight management. Here, we assess the impact of lorcaserin on progression from prediabetes to type 2 diabetes (T2D) and on reversion from prediabetes to euglycemia.


METHODS
This is a post hoc analysis of pooled data from two Phase 3 studies, BLOOM and BLOSSOM (N = 6136), evaluating the impact of lorcaserin on weight and glycemic parameters over 52 weeks in the subpopulation of obese/overweight subjects with prediabetes, alternately defined by fasting plasma glucose (FPG) 100-125 mg/dl or glycated hemoglobin (HbA1c) 5.7-6.4% at baseline.


RESULTS
At Week 52, in the subpopulation with prediabetes, nearly twice as many lorcaserin-treated subjects achieved ≥5% weight loss versus placebo (HbA1c: 55.6% vs. 27.5%, p < 0.001; FPG: 52.8% vs. 28.8%, p < 0.001), and a significantly lower percentage of lorcaserin-treated subjects progressed to T2D versus placebo based on HbA1c (lorcaserin 3.2%, placebo 5.0%, p = 0.032) but not FPG (lorcaserin 1.6%, placebo 2.6%, p = 0.227). A significantly greater proportion of lorcaserin-treated subjects versus placebo also reverted to euglycemia based on both HbA1c (lorcaserin 40%, placebo 29.5%, p < 0.001) and FPG (lorcaserin 52.4%, placebo 46.5%, p = 0.047).


CONCLUSIONS
In subjects with prediabetes, lorcaserin may contribute to weight loss and improve glycemic parameters, and thus may help with preventing progression to T2D and promoting reversion to euglycemia.


BACKGROUND
www.clinicaltrials.gov identifiers are NCT00395135 (BLOOM) and NCT00603902 (BLOSSOM).
a Department of Cardiovascular Medicine , Lahey Hospital & Medical Center , Burlington , MA , USA.
Richard
R
Nesto
b Medical & Scientific Affairs , Eisai Inc ., Woodcliff Lake , NJ , USA.
Randi
R
Fain
c Formerly of Eisai Inc ., Woodcliff Lake , NJ , USA.
Yuhan
Y
Li
d Preclinical and Clinical Drug Development, Arena Pharmaceuticals, Inc ., San Diego , CA , USA.
William
W
Shanahan
D000328:Adult; D001552:Benzazepines / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D058826:Serotonin 5-HT2 Receptor Agonists / Q000627:therapeutic use*
D001552:Benzazepines; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D058826:Serotonin 5-HT2 Receptor Agonists; C517652:hemoglobin A1c protein, human; C506658:lorcaserin
Obesity; anti-obesity agents; anti-obesity drugs; diabetes mellitus, type 2; prediabetic state