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Improvement in SF-36-derived health utility score with liraglutide 3.0 mg versus placebo over 3 years in prediabetes

Authors:
Fernando Goñi - Goicoechea at Hospital de Basurto
Fernando Goñi - Goicoechea
F. Poyato
F. Poyato
F. Poyato
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Ronette L Kolotkin at Duke University Medical Center
Ronette L Kolotkin
G. Somolarz
G. Somolarz
G. Somolarz
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Abstract

Objetivos: Liraglutida 3,0 mg es un análogo del péptido-1 similar al glucagón (GLP-1) aprobado para el control del peso en individuos obesos, o con sobrepeso y una comorbilidad relacionada con el peso. El objetivo de este análisis fue investigar los efectos, junto con dieta hipocalórica y aumento de la actividad física, de liraglutida 3,0 mg (n=1.505) frente a placebo (n=749) sobre el índice de utilidad para la salud en individuos obesos o con sobrepeso y una comorbilidad durante 3 años. Métodos: Estudio aleatorizado, doble ciego, controlado con placebo, con grupos paralelos, multicéntrico y multinacional, de 3 años de duración (NCT01272219). Participaron sujetos ≥18 años con prediabetes (sin diabetes tipo 2) y obesidad (IMC ≥30 kg/m2), o sobrepeso (IMC ≥27 kg/m2) acompañado de hipertensión o dislipemia. Se evaluó la calidad de vida relacionada con la salud mediante el cuestionario abreviado de salud SF-36 (Short-Form 36 v2), en la visita basal y a los 3 años. La utilidad para la salud (Short-Form 6D; SF-6D) se puntuó directamente utilizando el cuestionario SF-36 con un algoritmo validado. Para el análisis de sensibilidad, las puntuaciones SF-36 se asignaron al índice EuroQoL-5D (EQ-5D), y se analizaron las puntuaciones física (PCS) y mental (MCS) del cuestionario SF-36. Resultados: En la semana 160, los sujetos tratados con liraglutida 3,0 mg obtuvieron una mayor pérdida de peso respecto al valor basal ( 7,1±8,4%) que los del grupo placebo (-2,7±7,2%); la diferencia estimada entre tratamientos (ETD) fue de -4,3% [IC95% -4,9; -3,7], p<0,0001. La puntuación SF-6D [media (DE)] fue de 0,76 (0,11) y 0,75 (0,11) en la visita basal; en la semana 160 el cambio respecto al valor basal fue de 0,02 (0,12) y 0,01 (0,12) para liraglutida 3,0 mg y placebo, respectivamente. En la semana 160 la ETD fue de 0,014 [IC 95% 0,002; 0,025], p=0,0182. La puntuación EQ-5D apoyó estos hallazgos, siendo mayor para liraglutida 3,0 mg que para placebo; ED 0,007 [IC 95% 0,002; 0,013], p=0,0116. La variación en la puntuación PCS del cuestionario SF-36 fue significativamente mejor en la semana 160 respecto a placebo: ETD 0,87 [IC 95% 0,17; 1,58], p=0,0156. Conclusión: Liraglutida 3,0 mg. se asocia a una mejora respecto a placebo en el índice de utilidad para la salud en el control del peso de individuos con prediabetes durante 3 años.
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Improvement in SF-36-derived health
utility score with liraglutide 3.0 mg versus
placebo over 3 years in prediabetes
Goñi F, Poyato F, Kolotkin RL, Smolarz BG, Meincke HH, Bjørner JB
•Obesity has a detrimental effect on HRQoL1,2
•Often summarised as a single value (health utility) between
0 (equivalent to death) and 1 (perfect health), HRQoL outcomes are becoming
an increasingly important consideration in the assessment of the clinical
benefits of new therapies
•Health utilities are also the basis for estimation of QALYs when combined with a
time horizon
•These are often used in determining the cost–benefit of a treatment
Introduction
1. Ul-Haq et al. Obesity (Silver Spring) 2013;21:E322–7; 2. Warkentin et al. Obes Rev 2014;15:169–82
HRQoL, health-related quality of life; QALYs, quality-adjusted life years
Objective
SF-36, Short Form-36v2
To evaluate whether treatment with
liraglutide 3.0 mg was associated with an improved
SF-36-derived health utility score when
compared with placebo, over 3 years, in individuals
with prediabetes and BMI ≥30 kg/m2
or ≥27 kg/m2 + comorbidities
Methods
With
prediabetes1
Inclusion criteria:
•≥18 years
•Stable BW
•BMI ≥30 kg/m2
or
≥27 kg/m2 +
comorbidities
Trial design: SCALE Obesity and Prediabetes
Liraglutide 3.0 mg in weight management (160 weeks)
Placebo (n=749)
Trial objective
•Efficacy of liraglutide 3.0 mg (after 160 weeks of
treatment) in delaying the onset of type 2 diabetes in
participants with obesity or overweight with comorbidities,
and diagnosed with prediabetes at screening
Liraglutide 3.0 mg (n=1505)
160 weeks
End of trial
Key endpoints
•Primary: time to onset of type 2 diabetes at 160 weeks
•Secondary: weight measures, glycaemic control variables,
cardiometabolic risk factors, HRQoL, safety and tolerability
12-week
off-drug FU
Van Gaal et al. Obes Facts 2016;9(Suppl 1):182
1. ADA. Diabetes Care 2010;33(Suppl. 1):S11–61.
BW, body weight; D&E, diet and exercise; EOT, end of treatment; FU, follow-up; HRQoL, health-related quality of life
Without
prediabetes
Liraglutide 3.0 mg
Placebo
Dose
escalation 0–4 weeks
Treatment duration
156 weeks
Lifestyle intervention: -500 kcal/day diet + 150 min/week physical activity
Trial information
•June 2011 to
March 2015
•Randomised
controlled
double-blind study
•191 sites in 27
countries
Randomisation (2:1)
•HRQoL was evaluated using SF-36, a validated generic health survey composed of 36
questions
•SF-36 scores were mapped, as shown below, to the SF-6D and EQ-5D health utility indexes
using validated methods1
HRQoL evaluation and mapping
1. Brazier et al. J Clin Epidemiol 1998;51:1115–28
EQ-5D, EuroQoL-5D; HRQoL, health-related quality of life; SF-36, Short Form-36; SF-6D, Short-Form-6D
SF-36
Physical functioning
Role participation
Social functioning
Bodily pain
Mental health
Vitality
Scoring algorithm
Utility score
•Utility scores were analysed using a linear model with treatment, gender,
country, prediabetes status at screening, BMI stratum and an interaction
between status at screening and BMI stratum as fixed factors, and the baseline
value as covariate
Statistical analysis
Results
Liraglutide 3.0 mg
(n=1505)
Placebo
(n=749)
Age (years) 47.9
Gender (% female) 77.6
Body weight (kg) 108.2
BMI (kg/m2) 39.1
Baseline characteristics
Data are arithmetic means or percentage. HRQoL, health-related quality of life; SD, standard deviation; SF-6D, Short Form-6D health utility
•A total of 1505 and 749 patients were treated with liraglutide 3.0 mg and
placebo
•The SF-6D analysis included 1104 patients in the liraglutide 3.0 mg treatment arm and
514 patients in the placebo arm
Mean weight loss from baseline
Week 160, all patients entering the 3-year trial
-6,2
-1,8
-7
-6
-5
-4
-3
-2
-1
0
Full analysis set, fasting visit data only. Bars represent estimated mean change from baseline to week 160 with last observation carried forward.
Statistical analysis is ANCOVA (ETD ±95% CI). ANCOVA, analysis of covariance; CI, confidence interval; ETD, estimated treatment difference
Liraglutide 3.0 mg
(n=1467)
Placebo
(n=734)
Weight loss (%)
ETD: ‒4.3%
[95% CI ‒4.9; ‒3.7],
p<0.0001
Estimated 3-year treatment difference in utility
scores
Week 160
Data analysed using a linear regression model. Missing values post-baseline were imputed using last observation carried forward
CI, confidence interval; ETD, estimated treatment difference; EQ-5D, European Quality of Life 5 Dimensions model 4; SF-6D, Short-Form-6D health utility
-0,01 0 0,01 0,02 0,03 0,04 0,05
Favours liraglutide 3.0 mg Favours placebo
SF-6D
EQ-5D 993
1104 514
469 0.007
0.014 0.002;
0.025
0.002;
0.013
<0.0182
<0.0116
Liraglutide
3.0 mg
(n)
Placebo
(n)
ETD 95% CI p-value
Mean utility scores for SF-6D and EQ-5D
Week 160
Missing values post-baseline were imputed using last observation carried forward
EQ-5D, European Quality of Life 5 Dimensions model 4; SD, standard deviation; SF-6D, Short-Form-6D health utility
Source data n Estimate (SD)
Mean SF-6D estimate at baseline
Liraglutide 3.0 mg
Placebo
1162
576
0.76 (0.11)
0.75 (0.11)
Mean SF-6D estimate at week 160
Liraglutide 3.0 mg
Placebo
1117
517
0.78 (0.13)
0.76 (0.13)
Mean EQ-5D estimate at baseline
Liraglutide 3.0 mg
Placebo
1173
579
0.93 (0.06)
0.92 (0.07)
Mean EQ-5D estimate at week 160
Liraglutide 3.0 mg
Placebo
995
470
0.94 (0.06)
0.93 (0.07)
Conclusions
•Over 3 years, in comparison to placebo, liraglutide 3.0 mg was associated with:
Conclusions
1. Bjørner et al. Diabetes 2015;64(Suppl. 1):A565
EQ-5D, European Quality of Life 5 Dimensions model 4; HRQoL, health-related quality of life; SF-6D, Short-Form-6D health utility
These results reinforce the findings initially reported after 1 year of treatment
and suggest meaningful long-term HRQoL benefit with liraglutide 3.0 mg1
Mean percentage
weight loss
Health utility
(SF-6D and EQ-5D)
score
Long-term effects of weight-reducing drugs in people with hypertension
Article
  • Jan 2021
Background: This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect. Objectives: Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction. Search methods: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work. Selection criteria: Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity. Main results: This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension. Authors' conclusions: In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.
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