Factors associated with successful weight loss after liraglutide treatment for obesity

Abstract

Aim To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once‐daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity. Methods One hundred and thirty‐six obese adults (87% female) were randomized in a placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET1/2); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model. Results Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide‐ and 16% of placebo‐treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4‐kg weight loss were GET1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57‐3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602‐0.864) per 100 kcal. Among only the 60 liraglutide‐treated subjects, kcal intake at 16 weeks was associated with 4‐kg weight loss (AUROC = 0.757). Conclusions Slower GET1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide‐treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.

Potential contributors to variation in weight‐loss response to liraglutide

“…These findings are supported by a more recent randomized, placebo‐controlled trial in people with obesity ( n = 136) examining features associated with weight loss 65 . In this trial, >4‐kg weight loss was associated with ad libitum meal intake at baseline (OR = 0.71 [0.56–0.89]; P = 0.003) and 16 weeks (OR = 0.68 [0.53–0.87]; P = 0.0019; AUROC = 0.76) in the liraglutide‐treated group 65 .…”

“…In this trial, >4‐kg weight loss was associated with ad libitum meal intake at baseline (OR = 0.71 [0.56–0.89]; P = 0.003) and 16 weeks (OR = 0.68 [0.53–0.87]; P = 0.0019; AUROC = 0.76) in the liraglutide‐treated group 65 . The baseline findings may serve some predictive value, but those at 16 weeks could be an artifact of liraglutide's central satiating effects and have less practical use in predicting weight‐loss outcomes 65 …”

“…The authors speculated that GE delay accounts for approximately 20% of variance in the weight‐loss response on liraglutide based on their correlation coefficients 70 . However, post hoc analysis of this trial found baseline and week 16 GE measurements did not predict 16‐week weight loss of >4 kg for liraglutide‐treated patients 65 . Still, GE after 5 weeks on liraglutide may be a meaningful potential biomarker of drug sensitivity worth further inquiry.…”

“…Although researchers considered sociodemographic/metabolic factors, food consumption, smoking, and physical activity and their correlations with liraglutide efficacy, weight loss at 1 month was the lone variable predictive of positive response to liraglutide 64 . Similarly, a randomized, placebo‐controlled trial in people with obesity looking at predictors of weight loss success with liraglutide determined that >1‐kg weight loss in the initial 5 weeks (AUROC = 0.96) is likely predictive of >4‐kg weight loss at 16 weeks 65 …”

“…Ad libitum intake at baseline associated with >4-kg weight loss Pharmacogenomic RCT 65 Nausea Nausea/vomiting episodes à greater average 1-year weight loss Double-blind RCT with 84-week extension 48 Predictor of drug exposure Exposure-response analyses of SCALE trials 58 Gastric emptying of solids Greater absolute and change in degree of delayed gastric emptying at 5 and 16 weeks à greater weight loss Pilot RCT 69 Pharmacogenomic RCT 70 Delayed gastric emptying at 4-5 weeks à greater weight loss Pilot pharmacogenetics study 71 Genotype TCF7L2 CC variant à greater weight loss Pharmacogenomic RCT 70 Diabetes status Type 2 diabetes à less weight loss than normoglycemia or prediabetes 58,66 Exposure-response analyses of SCALE trials 58 Phase II, dose-finding trial 59 Abbreviations: BMI, body mass index; RCT, randomized controlled trial; SCALE, Satiety and Clinical Adiposity-Liraglutide Evidence; TCF7L2, transcription factor 7 like 2 gene.…”