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. 2019 Jul 27;10:2042018819863022. doi: 10.1177/2042018819863022

Table 3.

Predictors of response to obesity pharmacotherapies.

Author Inclusion criteria n Study design Predictors of response
ORLISTAT
Chanoine and Richard71 Adolescents (12–16 years), BMI ⩾ 2 kg/m2 above the 95th percentile (excluded BMI ⩾ 44 kg/m2; weight > 130 kg of < 55 kg) Retrospective analysis of a multicenter 1-year RCT (orlistat 120 mg 3 times daily versus placebo); assessed if 3- month weight loss predicted 12-month weight loss Greater weight loss at 3 months correlated with greater weight loss at 1 year.
Elfhag and colleagues72 Adults, BMI ⩾30 kg/m2 148 Retrospective analysis of self-reported data Men experienced greater weight loss than women; ‘order’ and ‘deliberation’ facets of conscientiousness positively correlated with weight loss
Hollywood and Ogden73 Adults prescribed orlistat 566 Retrospective analysis of a 6-month open-label study of participants prescribed orlistat; only those completing baseline and 6-month surveys included in analysis A decrease in unhealthy eating, increase belief in treatment control, increased belief that the unpleasant side effects of orlistat are both due to eating behavior and just part of the drug, and baseline greater endorsement of medical solutions predicted those most likely to reduce BMI at 6 months
Rissanen and colleagues74 Adults, BMI 28–43 kg/m2 220 Retrospective analysis of pooled data from two 2-year multicenter RCTs (orlistat 120 mg 3 times daily versus placebo) comparing those who lost ⩾5% versus <5% weight at 3 months Weight loss ⩾5% at 3 months predicted sustained weight loss at 2 years
Toplak and colleagues75 Adults, BMI 30–43 kg/m2, body weight ⩾90 kg, WC ⩾88 cm (female) or ⩾102 cm (male) 430 1 year, open-label, randomized, parallel group trial with all participants receiving 120 mg orlistat three times daily; compared 500 kcal versus 1000 kcal energy deficit diet;
orlistat discontinued in participants who did not achieve ⩾5% weight loss at 3- and 6-month assessment
⩾5% weight loss at 3 months associated with long-term weight loss at 1 year in both diet groups
Ullrich and colleagues76 Adults, BMI 30–40 kg/m2 62 Retrospective analysis of open-label 72 week trial (orlistat 120 mg three times daily versus placebo) Low fat and carbohydrate intake predicted increased weight loss
Lorcaserin
Farr and colleagues90 Adults, BMI >30 kg/m2 or >27 kg/m2 with ⩾1 comorbidities 48 Prospective 1-month RCT comparing lorcaserin 10 mg twice daily with placebo; assessed neuronal activation with fMRI at baseline, 1 week, and 1 month Activations in amygdala, parietal, and visual cortices at baseline correlated with decreases in caloric intake, weight, and BMI at 1 month
Smith and colleagues92 Adults, BMI 30–45 kg/m2 or 27–29.9 kg/m2 with ⩾1 comorbidities 6897 Retrospective analysis of pooled data from three trials (BLOOM, BLOSSOM, and BLOOM-DM) comparing lorcaserin + LMT with placebo + LMT; assessed if weight loss response at 3 months predicted response at 1 year ⩾5% weight loss at 3 months predicted greater weight loss at 1 year
PHENTERMINE
Thomas and colleagues93 Adults, BMI 30–40 kg/m2 35 Prospective 8-week trial of participants receiving phentermine comparing those with ⩾5% versus <5% weight loss Participants with ⩾5% weight loss had higher pre-breakfast hunger, desire to eat, prospective food consumption and lower baseline cognitive restraint; higher home prospective food consumption and lower baseline cognitive restraint predicted increased weight loss
Topiramate
Ben-Menachem and colleagues86 Adults with epilepsy 49 Prospective open-label trial adding topiramate to existing anticonvulsant regimen, assessing change in weight from baseline to 3- and 12-months after topiramate initiated 3-month weight loss correlated with reduced caloric intake; 1-year weight loss correlated with higher baseline BMI despite caloric intake returning to baseline levels; participants with obesity lost more weight than participants without obesity
El Yaman and colleagues87 Children and adults with epilepsy 120 Prospective cohort study of participants started on topiramate Participants with higher baseline BMI and younger age lost more weight at year 2; higher average topiramate dose (>6 mg/kg/day) associated with larger decrease in BMI from baseline
Iwaki and colleagues88 Adults with epilepsy 78 Prospective, open-label study assessing weight loss
1, 6, 12, 18 months after starting topiramate; compared those with no versus mild intellectual disability (ID)
Participants with no/mild ID lost more weight compared with those with moderate/profound ID
Kazerooni and Lim94 Adults, BMI ⩾25 kg/m2 767 Retrospective cohort study examining weight loss outcomes 1 year after topiramate initiated (for any indication) Higher prevalence of females lost ⩾5% compared with males;
adherent participants more likely to lose ⩾5% BW compared with nonadherent participants
Klein and colleagues89 Children (⩾12 years) and adults with epilepsy 22 Prospective study assessing 3 week, 3 month, 6 month, and long-term weight loss after starting topiramate Weight loss, reduction of appetite, and amount of intake at 3 months predicted BMI decrease at 6 months; high initial BMI and body fat predicted lower BMI reduction at 6 months
Li and colleagues91 Adults, BMI 30–50 kg/m2 or 27–50 kg/m2 with ⩾1 comorbidities 1004 Retrospective study of DNA samples from participants previously completing clinical trials, assessing efficacy of topiramate for obesity Carriers of haplotype T-C-A in INSR had greater weight loss than noncarriers; Rs55834942 SNP from HNF1A associated with increased weight loss response
Phentermine/topiramate
Acosta and colleagues95 Adults, BMI 30–40 kg/m2 24 2-week RCT assessing effects of phentermine/topiramate on weight and quantitative traits Higher intake at baseline buffet meal satiety test associated with greater weight loss at 2 weeks
Naltrexone/bupropion
Dalton and colleagues96 Adults, BMI 30–45 kg/m2 or 27–45 kg/m2 with ⩾1 comorbidities 2,046 Retrospective analysis of four 56-week RCTs (COR-I, COR-II, COR-BMOD, COR-DM) comparing NB32, NB16, and placebo Participants with the greatest improvement in craving control at 8 weeks had greater weight loss after 56 weeks
Fujioka and colleagues97 Adults, BMI 30–45 kg/m2 or 27–45 kg/m2 with ⩾1 comorbidities 3362 Retrospective analysis of four 56-week RCTs (COR-I, COR-II, COR-BMOD, COR-DM) comparing NB32, NB16, and placebo Participants with ⩾5% weight loss at 4 months more likely to maintain clinically significant weight loss at 1 year
Liraglutide
Ard and colleagues77 Adults, BMI ⩾30 kg/m2 or ⩾27 kg/m2 with ⩾1 comorbidities 5325 Retrospective analysis of data from five RCTs (liraglutide 3.0 mg versus placebo) comparing weight loss by race/ethnicity No significant weight loss response differences by race/ethnicity
Dahlqvist and colleagues78 Adults, BMI 27.5–45 kg/m2, HbA1c 7.5–11.5%, c-peptide ⩾10 nmol/l, treated with multiple daily injection insulin for ⩾6 months 124 Retrospective analysis of a 24-week RCT comparing liraglutide 1.8 mg with placebo as adjunct to multiple daily injection insulin regimen with or without metformin Lower HbA1c and mean glucose level predicted greater weight loss response to liraglutide
Fujioka and colleagues79 Adults, BMI ⩾30 kg/m2 without DM or BMI ⩾27 kg/m2 with ⩾1 comorbidities not including DM (SCALE Obesity and Prediabetes), or BMI ⩾27 kg/m2 with DM (SCALE Diabetes) 4577 Retrospective analysis of data from SCALE Obesity and Prediabetes and SCALE Diabetes trials Greater proportion of those with ⩾4% weight loss at 4 months achieved ⩾5, ⩾10%, and ⩾15% weight loss at 56 weeks compared with those with <4% weight loss at 4 months
Gomez-Peralta and colleagues80 Adults with T2DM on liraglutide 799 Retrospective chart review of electronic medical records Higher baseline weight and longer treatment duration predicted improved weight loss response
Halawi and colleagues81 Adults, BMI ⩾ 30 kg/m2 or ⩾27 kg/m2 with ⩾1 comorbidities 40 Prospective 4-month RCT assessing effect of liraglutide versus placebo on gastric motor function, satiety, and weight Delayed gastric emptying at 5 weeks correlated with increased weight loss with liraglutide at 4 months
Wilding and colleagues82 Adults, BMI ⩾30 kg/m2 without DM or BMI ⩾27 kg/m2 with ⩾1 comorbidities not including DM (SCALE Obesity and Prediabetes), or BMI ⩾ 27 kg/m2 with DM (SCALE Diabetes) 4372 Retrospective analysis of data from SCALE Obesity and Prediabetes and SCALE Diabetes trials Increased drug exposure correlated with increased weight loss
EXENATIDE
Anichini and colleagues83 Adults with T2DM and therapeutic failure on oral therapy (metformin or metformin + SU) 315 Retrospective analysis of participants prescribed exenatide 10 µg twice daily Longer DM duration in males, lower baseline A1c in females predicted those most likely to lose ⩾8.5% weight at 1 year
Gorgojo-Martínez and colleagues84 Adults, T2DM, BMI ⩾ 30 kg/m2 148 Retrospective analysis of participants prescribed exenatide 2 mg weekly Higher BMI, previous use of DPP4 inhibitors predicted weight loss ⩾3% after 6 months
Nathan and colleagues85 Children (12–19 years), BMI ⩾1.2 times 95th percentile or BMI ⩾35 kg/m2, without DM 32 Retrospective analysis of 2 RCTs comparing exenatide 10 µg twice daily versus placebo Higher baseline appetite, female sex predicted greater BMI loss at 3 months

BMI, body mass index; DM, diabetes mellitus; DPP4, dipeptidyl peptidase-4; fMRI, functional magnetic resonance imaging; HbA1c, hemoglobin A1c; HNF1A, hepatocyte nuclear factors 1-alpha; INSR, insulin receptor; LMT, lifestyle modification therapy; NB16, 16 mg naltrexone SR/360 mg bupropion SR; NB32, 32 mg naltrexone SR/360 mg bupropion SR; RCT, randomized controlled trial; SCALE, Satiety and Clinical Adiposity Liraglutide Evidence; SNP, single nucleotide polymorphism; SU, sulfonylureas; T2DM, type 2 diabetes mellitus; WC, waist circumference.