Re: Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials
Thank you for your response.
Our meta-analysis provides evidence that the GLP-1 receptor agonists, when given to obese patients with or without diabetes for at least 20 weeks, results in clinically relevant reduction in body weight(1). In respect to the treatment of type 2 diabetes, any weight benefit obtained is likely to be of particular value considering 1) that obesity is a significant risk factor for increased morbidity and mortality in patients with type 2 diabetes and 2) that weight gain often worsens glycaemic control and increases the risk of type 2 diabetes progression(2). In contrast, weight loss or prevention of weight gain can have a favourable effect on glycaemic control and reduce morbidity and mortality associated with type 2 diabetes. Taken together, the clinical data obtained to date support the rationale for GLP-1 receptor agonist for the treatment of patients with type 2 diabetes, with beneficial effects on body weight and glycaemic control, with a low incidence of hypoglycaemia. We agree with Iverson that only limited long term data are available. Nevertheless, there are no data to suggest diminution of the weight reduction over time and recent 2-year data demonstrated that the GLP-1 receptor agonist, liraglutide, when given as add-on to life-style intervention (and compared to placebo), was well tolerated, sustained weight loss over 2 years and improved cardiovascular risk factors in obese non-diabetic participants(3). However, we agree that it is of crucial importance to confirm these results in larger phase III programs in obese adults, both in terms of efficacy and (particularly) safety and tolerability, before GLP-1 receptor agonists are introduced as a new treatment for obesity.
Finally, Iverson suggests that the effect on body weight is due to gastrointestinal side effects and not because of the effect of GLP-1 on insulin and glucagon. We would like to point out that the role of endogenous GLP-1 as an appetite hormone (besides the effects on the endocrine pancreas) is well established in preclinical and clinical models (4,5). Furthermore, side effects during treatment with GLP-1 receptor agonists are in general mild to moderate and much more transient in nature than the effects on weight loss. Last but not least, recent data that have demonstrated clinically significant reductions in body weight also in patients without the gastrointestinal side-effects.
1. Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.
2. Ross SA, Dzida G, Vora J, Khunti K, Kaiser M, Ligthelm RJ. Impact of weight gain on outcomes in type 2 diabetes. Curr Med Res Opin. 2011 Jul;27(7):1431–8.
3. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean MEJ, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. International Journal of Obesity 2011 Aug 1
4. Holst JJ. The physiology of glucagon-like peptide 1. Physiol. Rev. 2007 Oct;87(4):1409–39.
5. De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, et al. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab. 2011 Nov 2;14(5):700–6.
Competing interests:
No competing interests
21 February 2012
Tina Vilsbøll
Ass. Prof. MD DMSc
Mikkel Christensen, Anders Junker, Filip K. Knop, Lise Lotte Gluud
Gentofte Hospital, University of Copenhagen, Denmark
Rapid Response:
Re: Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials
Thank you for your response.
Our meta-analysis provides evidence that the GLP-1 receptor agonists, when given to obese patients with or without diabetes for at least 20 weeks, results in clinically relevant reduction in body weight(1). In respect to the treatment of type 2 diabetes, any weight benefit obtained is likely to be of particular value considering 1) that obesity is a significant risk factor for increased morbidity and mortality in patients with type 2 diabetes and 2) that weight gain often worsens glycaemic control and increases the risk of type 2 diabetes progression(2). In contrast, weight loss or prevention of weight gain can have a favourable effect on glycaemic control and reduce morbidity and mortality associated with type 2 diabetes. Taken together, the clinical data obtained to date support the rationale for GLP-1 receptor agonist for the treatment of patients with type 2 diabetes, with beneficial effects on body weight and glycaemic control, with a low incidence of hypoglycaemia. We agree with Iverson that only limited long term data are available. Nevertheless, there are no data to suggest diminution of the weight reduction over time and recent 2-year data demonstrated that the GLP-1 receptor agonist, liraglutide, when given as add-on to life-style intervention (and compared to placebo), was well tolerated, sustained weight loss over 2 years and improved cardiovascular risk factors in obese non-diabetic participants(3). However, we agree that it is of crucial importance to confirm these results in larger phase III programs in obese adults, both in terms of efficacy and (particularly) safety and tolerability, before GLP-1 receptor agonists are introduced as a new treatment for obesity.
Finally, Iverson suggests that the effect on body weight is due to gastrointestinal side effects and not because of the effect of GLP-1 on insulin and glucagon. We would like to point out that the role of endogenous GLP-1 as an appetite hormone (besides the effects on the endocrine pancreas) is well established in preclinical and clinical models (4,5). Furthermore, side effects during treatment with GLP-1 receptor agonists are in general mild to moderate and much more transient in nature than the effects on weight loss. Last but not least, recent data that have demonstrated clinically significant reductions in body weight also in patients without the gastrointestinal side-effects.
1. Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771.
2. Ross SA, Dzida G, Vora J, Khunti K, Kaiser M, Ligthelm RJ. Impact of weight gain on outcomes in type 2 diabetes. Curr Med Res Opin. 2011 Jul;27(7):1431–8.
3. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean MEJ, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. International Journal of Obesity 2011 Aug 1
4. Holst JJ. The physiology of glucagon-like peptide 1. Physiol. Rev. 2007 Oct;87(4):1409–39.
5. De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, et al. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab. 2011 Nov 2;14(5):700–6.
Competing interests: No competing interests