The effects of GLP-1 analogues in obese, insulin-using type 2 diabetes in relation to eating behaviour

Abstract

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RA) added to insulin in type 2 diabetes patients have shown to lower body weight, improve glycaemic control and reduce total daily insulin dose in short term studies, although the individual response greatly varies. Objective To evaluate GLP-1 RA treatment on body weight, glycaemic control and total daily insulin dose in obese, insulin-using type 2 diabetes patients after 2 years follow-up in a real life setting and to explore a possible relation with eating behaviour. Setting The Martini Hospital and the University Medical Center in Groningen in the Netherlands. Methods Eligible patients were at least 18 years of age, were on insulin therapy and obese (BMI > 30 kg/m2), started GLP-1 RA treatment. At baseline eating behaviour was classified according to the validated Dutch Eating Behaviour Questionnaire. A 2 years follow-up was performed. Main outcome measures Body weight, HbA1c and total daily insulin dose. Results 151 Patients started with exenatide or liraglutide. 120 patients completed the 2 years follow-up. From baseline to 2 years, body weight (mean ± SD) changed from 117.9 ± 22.1 to 107.9 ± 22.9 kg (P < 0.0001), HbA1c (median, IQR) changed from 7.9 (7.2–8.9) to 7.6 (6.9–8.3) % [63 (55–74) to 60 (52–67) mmol/mol] (P < 0.0001), total daily insulin dose changed from 90 (56–150) to 60 (0–100) Units/day (P < 0.0001). Weight change differed between eating behaviour groups (P < 0.001) in which external eating behaviour (n = 17) resulted in the smallest decline (−3.1 %) and restrained (n = 41) in the greatest (−10.3 %) in comparison with emotional (n = 37, −8.5 %) and indifferent (n = 25, −9.6 %) eating behaviours. Conclusion Two year of GLP-1 RA treatment resulted in a sustained reduction of weight, HbA1c and total daily insulin dose in obese, insulin-using type 2 diabetes patients in a real life setting. Largest weight loss was achieved in patients with a predominant restraint eating pattern while a predominant external eating pattern resulted in the smallest weight reduction.Electronic supplementary materialThe online version of this article (doi:10.1007/s11096-015-0219-8) contains supplementary material, which is available to authorized users.

Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

“…Using eye tracking can give an implicit measure of attentional bias to rewarding foodsNijs et al (2010) [6]Cue specific inhibitory control taskInhibitory controlFood-cue-specific inhibitory control taskHouben et al (2014) [59] Subjective measures :Satiety VASSatietyHunger, fullness, prospective consumption, desire to eat—100 ml VAS at hourly intervals to assess fluctuations in appetite throughout the dayHalford et al (2010) [43] SibutramineChange in expected SatietySatietyFood portions shown to patient who is asked to indicate how satiating they think it would beBrunstrom et al (2008) [60]Satiety quotientSatietyPre-meal hunger—post-meal hunger, divided by amount consumed. A measurement of satiating properties of a mealHalford et al (2010) [43] SibutramineControl of eating questionnaireReward/inhibitory controlCOEQ—1) general food craving, 2) craving for sweet, 3) craving for savoury, 4) control over appetiteGreenway et al (2010) [39] Bupropion/naltrexonePower of foodInhibitory controlA tool developed to assess effects of obesity treatments on feelings of being controlled by foodCapelleri et al (2009) [61]Dutch eating Behaviour questionnaire (DEBQ)Inhibitory controlExternal, emotional and restrained eating patternsDe Boer et al (2016) [62] LiraglutideThe mindful eating scaleInhibitory controlKey environment stimuli associated with reduced control of eatingFramson et al (2009) [63] Physiological and neurophysiological measures :fMRISatietyActivity in response to food cues in fed and fasted statesFarr et al (2016) [32] Liraglutide 1.8 mgfMRI—reward systemRewardActivity and functional connectivity of reward system during receipt of palatable tastes (e.g. chocolate milk)Van Bloemendall et al (2014) […”

Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity

“…По данным литературы, терапия аГПП-1 (эксенатид 20 мкг и лираглутид 1,8 мг в сутки) более успешна относительно снижения массы тела у пациентов с исходно более высоким ИМТ [17,18]. Также отмечено, что большая продолжительность СД является предиктором большей потери массы у больных, получающих эксенатид [18].…”

“…Данные голландских исследователей показывают, что пациенты с эмоциональным типом пищевого поведения менее чувствительны к центральным эффектам эксенатида [27]. В работе S.A. de Boer у 120 пациентов с СД2 и ИМТ >30 кг/м 2 , завершивших 2-летнюю терапию аГПП-1 (эксенатид 20 мкг или лираглутид 1,8 мг в сутки), изменение массы тела отличалось между группами пищевого поведения: экстернальное пищевое поведение привело к наименьшему снижению (-3,1%), а ограничительноек наибольшему (-10,3%) по сравнению с эмоциональным (-8,5%) и индифферентным (-9,6%) пищевым поведением (р<0,001) [28]. Согласно нашим результатам, пациенты с ограничительным типом пищевого поведения имели тенденцию к большему снижению массы тела по сравнению с больными с сочетанием двух или трех типов [29].…”

“…В нашем исследовании имелась лишь тенденция к наилучшему ответу у пациентов с ограничительным типом пищевого поведения. В то же время, по данным литературы, отмечался плохой ответ в отношении снижения веса у пациентов с экстернальным типом пищевого поведения [27,28], что перекликается и с нашими более ранними результатами [29]. Тот факт, что различия в нашем исследовании не достигли статистической значимости, может быть объяснен малым количеством пациентов с экстернальным типом пищевого поведения в обследованной группе.…”

Use of glucagon‐like peptide‐1 receptor agonists among individuals on basal insulin requiring treatment intensification

“…Postprandial glucagon release is reduced and postprandial insulin release is enhanced 30; however, these GLP‐1RAs are less available during fasting states and are therefore less effective for reducing fasting measures. In contrast, for the long‐acting GLP‐1RAs exenatide once weekly, liraglutide, albiglutide and dulaglutide, effects on gastric emptying are not as strong as their short‐acting counterparts 31 or decline over time 32, probably as a result of the continuous GLP‐1RA exposure causing tachyphylaxis 33, leading to less pronounced PPG reductions 34. Instead, these agents appear to reduce HbA 1c concentration through sustained increase in fasting insulin 34, suppression of fasting glucagon 31, and subsequently lower fasting glucose levels.…”