European Journal of Internal Medicine 25 (2014) e38–e39
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor Liraglutide therapy in obese people with type 2 diabetes — Experience of a weight management centre Keywords: Glucagon-like peptide-1 receptor agonists Obesity Weight loss
Whilst many antidiabetic therapies aggravate weight gain, glucagon-like peptide-1 receptor (GLP-1R) agonists have been shown to promote weight loss in addition to improving glycaemic control [1]. We assessed the clinical effectiveness of the GLP-1R agonist liraglutide in obese people with type 2 diabetes (T2D) [2], in the clinical practice setting of a National Health Service medical weight management centre in a university teaching hospital in North West England. We studied 79 obese patients with T2D aged 19–80 years, of whom 50 (63%) were women, treated with liraglutide. Baseline mean (standard deviation) body weight was 118.8 (24.5) kg, body mass index (BMI) 42.5 (8.9) kg/m 2 and HbA 1c 69.1 (21.8) mmol/mol. Patients were recommended a reduced calorie diet supported by specialist weight management dietetic review. We analysed the data by descriptive statistics, Student t-test, one way analysis of variance (ANOVA) and χ2 test using SPSS 20.0.0 (IBM SPSS Inc., Chicago, IL) and Prism 4.03 (GraphPad Software Inc., La Jolla, CA, USA). P b 0.05 was considered statistically significant and 95% confidence interval (CI) was reported as a measure of precision. Permission was obtained from the Clinical Audit department of our institution. The 79 patients had median (range) duration of T2D of 10.0 (1–33) years. Major co-morbidities included hypertension in 47 (60%), sleep apnoea in 18 (23%), heart failure in 3 (4%), depression in 22 (28%), chronic back-pain in 14 (18%) and chronic joint pains in 25 (32%) patients. The median dose of liraglutide was 1.2 mg daily; other anti-diabetic therapies included metformin in 66 (84%), sulphonylureas in 18 (23%), glitazones in 10 (13%) and insulin in 22 (28%) patients. There was a significant reduction in BMI with mean (95% CI) difference of 1.9 (1.0–2.7) kg/m2 (P b 0.001) at 12 months from baseline (Fig. 1a). Reduction in BMI ≥ 5.0% (Group 1) occurred in 38% of patients with a median (range) reduction of 8.0 (5.0–23.8)%. Reduction in BMI of 0.0–4.9% (Group 2) occurred in 43% of patients with a reduction of 2.2 (0.2–4.7)%. Sulphonylureas were in use in 7.7% of patients in Group 1 compared to 31.0% in Group 2 (P = 0.031). There was no reduction in BMI in 19% of patients with a weight gain of 1.0 (0.1–2.5)%. HbA 1c reduced from 69.1 to 60.0 mmol/mol (ANOVA, P = 0.046) at 12 months (Fig. 1b). There was a reduction in HbA1c in 65.9% of patients. Sulphonylureas were in use in 25.9% of patients who achieved reduction in HbA1c compared to 6.7% of patients who did not (non-significant). Reductions in systolic and diastolic blood pressures were non-significant (Fig. 1c). There was
no significant change in high density lipoprotein (HDL) cholesterol. However, there was a significant reduction in non-HDL cholesterol with resultant significant reduction in mean (95% CI) total cholesterol of 0.64 (0.18–1.09) mmol/L (P = 0.007) at 12 months (Fig. 1d). Randomised trials of liraglutide treatment have demonstrated its effectiveness in weight reduction in obese people with or without T2D [3–5]. Whilst some studies have reported weight loss outcomes of GLP-1R agonists in clinical settings [6–9], little is known of the influence of concomitant anti-diabetic therapies. In our experience liraglutide induced significant reduction in weight and HbA1c comparable to previous studies, as well as reduction in total and non-HDL cholesterol. Concomitant sulphonylurea therapy was associated with poorer weight loss outcome. Our study reflects the real life experience of managing people with T2D and obesity in a pragmatic, clinical practice setting. Although limited by small numbers in subgroup analyses, our study included patients with a wider age range, longer duration of diabetes and greater BMI and HbA1c. Various anti-diabetic therapies may enhance one or more of the effects of liraglutide [3,6,10]. Our study showed that patients on simultaneous sulphonylurea therapy achieved HbA1c reduction but poorer weight loss outcomes. Specialist review of patient's knowledge, belief, attitude and interest in weight management, and their current antidiabetic therapies would enable selection of suitable patients for treatment with GLP-1R agonists. We conclude that the use of GLP-1R agonists in rational combination with other anti-diabetic therapies may have specific advantages in weight management and glycaemic control. Conflict of interests We wish to confirm that there are no conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome. Acknowledgements We gratefully acknowledge the contributions of Fiona Chan R.D., Jenny Fry R.D., Chris Slater R.D. (specialist weight management dietitians) and Louise Wong R.G.N. (advanced practitioner in diabetes). References [1] Vilsboll 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] NICE. Technology appraisals TA203. Liraglutide for the treatment of type 2 diabetes mellitus. London: National Institute for Health and Care Excellence; 2010 [Available from www.nice.org.uk/guidance/TA203]. [3] McGill JB. Insights from the Liraglutide Clinical Development Program — the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med 2009;121:16–25. [4] Seino Y, Rasmussen MF, Zdravkovic M, Kaku K. Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: a double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 2008;81:161–8.
0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.12.009
Letter to the Editor
e39
Fig. 1. Clinical outcomes over 12 months in obese people with type 2 diabetes treated with liraglutide: change in body mass index (a), HbA1c (b), systolic and diastolic blood pressures (c) and total and non-high density lipoprotein cholesterol (d). Data points (±error bars) represent means (±standard errors). BP, blood pressure; HDL, high density lipoprotein.
[5] Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebocontrolled study. Lancet 2009;374:1606–16. [6] Dhesi B, Chauhan H, Basu A. Audit of clinical practice in the use of incretin mimetic agents for the management of patients with type 2 diabetes. Pract Diabetes 2013;30:159–62. [7] Kaimal N, Schofield J, Zaki A, Patel R, Sharma M, McCourt E, et al. Effects of exenatide in poorly controlled type 2 diabetes. QJM 2012;105:321–6. [8] Wessels L, Keigan S, O'Brien SV, Hardy KJ. What proportion of patients fail NICE criteria for continuing GLP-1 treatment beyond six months, and why? Pract Diabetes 2013;30:196–8. [9] Ryder B, Thong K. Findings from the Association of British Clinical Diabetologists (ABCD) nationwide exenatide and liraglutide audits. In: Vora J, editor. Hot topics in diabetes. 5 ed. London: Synergy; 2012. p. 49–61 [Available from www. diabetologists-abcd.org.uk/GLP1_Audits/ABCD_Hot_Topics_2012.pdf]. [10] Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, openlabel trial. Lancet 2010;375:1447–56.
Hanaa Elkhenini⁎ John P. New Lucinda K.M. Summers Akheel A. Syed Obesity Medicine and Endocrinology, Salford Royal NHS Foundation Trust and University Teaching Hospital, Salford, UK Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK ⁎Corresponding author at: Obesity Medicine and Endocrinology, Salford Royal NHS Foundation Trust and University Teaching Hospital, Stott Lane, Salford M6 8HD, UK. E-mail address: [email protected] (H. Elkhenini). 17 December 2013
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor Liraglutide therapy in obese people with type 2 diabetes — Experience of a weight management centre Keywords: Glucagon-like peptide-1 receptor agonists Obesity Weight loss
Whilst many antidiabetic therapies aggravate weight gain, glucagon-like peptide-1 receptor (GLP-1R) agonists have been shown to promote weight loss in addition to improving glycaemic control [1]. We assessed the clinical effectiveness of the GLP-1R agonist liraglutide in obese people with type 2 diabetes (T2D) [2], in the clinical practice setting of a National Health Service medical weight management centre in a university teaching hospital in North West England. We studied 79 obese patients with T2D aged 19–80 years, of whom 50 (63%) were women, treated with liraglutide. Baseline mean (standard deviation) body weight was 118.8 (24.5) kg, body mass index (BMI) 42.5 (8.9) kg/m 2 and HbA 1c 69.1 (21.8) mmol/mol. Patients were recommended a reduced calorie diet supported by specialist weight management dietetic review. We analysed the data by descriptive statistics, Student t-test, one way analysis of variance (ANOVA) and χ2 test using SPSS 20.0.0 (IBM SPSS Inc., Chicago, IL) and Prism 4.03 (GraphPad Software Inc., La Jolla, CA, USA). P b 0.05 was considered statistically significant and 95% confidence interval (CI) was reported as a measure of precision. Permission was obtained from the Clinical Audit department of our institution. The 79 patients had median (range) duration of T2D of 10.0 (1–33) years. Major co-morbidities included hypertension in 47 (60%), sleep apnoea in 18 (23%), heart failure in 3 (4%), depression in 22 (28%), chronic back-pain in 14 (18%) and chronic joint pains in 25 (32%) patients. The median dose of liraglutide was 1.2 mg daily; other anti-diabetic therapies included metformin in 66 (84%), sulphonylureas in 18 (23%), glitazones in 10 (13%) and insulin in 22 (28%) patients. There was a significant reduction in BMI with mean (95% CI) difference of 1.9 (1.0–2.7) kg/m2 (P b 0.001) at 12 months from baseline (Fig. 1a). Reduction in BMI ≥ 5.0% (Group 1) occurred in 38% of patients with a median (range) reduction of 8.0 (5.0–23.8)%. Reduction in BMI of 0.0–4.9% (Group 2) occurred in 43% of patients with a reduction of 2.2 (0.2–4.7)%. Sulphonylureas were in use in 7.7% of patients in Group 1 compared to 31.0% in Group 2 (P = 0.031). There was no reduction in BMI in 19% of patients with a weight gain of 1.0 (0.1–2.5)%. HbA 1c reduced from 69.1 to 60.0 mmol/mol (ANOVA, P = 0.046) at 12 months (Fig. 1b). There was a reduction in HbA1c in 65.9% of patients. Sulphonylureas were in use in 25.9% of patients who achieved reduction in HbA1c compared to 6.7% of patients who did not (non-significant). Reductions in systolic and diastolic blood pressures were non-significant (Fig. 1c). There was
no significant change in high density lipoprotein (HDL) cholesterol. However, there was a significant reduction in non-HDL cholesterol with resultant significant reduction in mean (95% CI) total cholesterol of 0.64 (0.18–1.09) mmol/L (P = 0.007) at 12 months (Fig. 1d). Randomised trials of liraglutide treatment have demonstrated its effectiveness in weight reduction in obese people with or without T2D [3–5]. Whilst some studies have reported weight loss outcomes of GLP-1R agonists in clinical settings [6–9], little is known of the influence of concomitant anti-diabetic therapies. In our experience liraglutide induced significant reduction in weight and HbA1c comparable to previous studies, as well as reduction in total and non-HDL cholesterol. Concomitant sulphonylurea therapy was associated with poorer weight loss outcome. Our study reflects the real life experience of managing people with T2D and obesity in a pragmatic, clinical practice setting. Although limited by small numbers in subgroup analyses, our study included patients with a wider age range, longer duration of diabetes and greater BMI and HbA1c. Various anti-diabetic therapies may enhance one or more of the effects of liraglutide [3,6,10]. Our study showed that patients on simultaneous sulphonylurea therapy achieved HbA1c reduction but poorer weight loss outcomes. Specialist review of patient's knowledge, belief, attitude and interest in weight management, and their current antidiabetic therapies would enable selection of suitable patients for treatment with GLP-1R agonists. We conclude that the use of GLP-1R agonists in rational combination with other anti-diabetic therapies may have specific advantages in weight management and glycaemic control. Conflict of interests We wish to confirm that there are no conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome. Acknowledgements We gratefully acknowledge the contributions of Fiona Chan R.D., Jenny Fry R.D., Chris Slater R.D. (specialist weight management dietitians) and Louise Wong R.G.N. (advanced practitioner in diabetes). References [1] Vilsboll 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] NICE. Technology appraisals TA203. Liraglutide for the treatment of type 2 diabetes mellitus. London: National Institute for Health and Care Excellence; 2010 [Available from www.nice.org.uk/guidance/TA203]. [3] McGill JB. Insights from the Liraglutide Clinical Development Program — the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med 2009;121:16–25. [4] Seino Y, Rasmussen MF, Zdravkovic M, Kaku K. Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: a double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 2008;81:161–8.
0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.12.009
Letter to the Editor
e39
Fig. 1. Clinical outcomes over 12 months in obese people with type 2 diabetes treated with liraglutide: change in body mass index (a), HbA1c (b), systolic and diastolic blood pressures (c) and total and non-high density lipoprotein cholesterol (d). Data points (±error bars) represent means (±standard errors). BP, blood pressure; HDL, high density lipoprotein.
[5] Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebocontrolled study. Lancet 2009;374:1606–16. [6] Dhesi B, Chauhan H, Basu A. Audit of clinical practice in the use of incretin mimetic agents for the management of patients with type 2 diabetes. Pract Diabetes 2013;30:159–62. [7] Kaimal N, Schofield J, Zaki A, Patel R, Sharma M, McCourt E, et al. Effects of exenatide in poorly controlled type 2 diabetes. QJM 2012;105:321–6. [8] Wessels L, Keigan S, O'Brien SV, Hardy KJ. What proportion of patients fail NICE criteria for continuing GLP-1 treatment beyond six months, and why? Pract Diabetes 2013;30:196–8. [9] Ryder B, Thong K. Findings from the Association of British Clinical Diabetologists (ABCD) nationwide exenatide and liraglutide audits. In: Vora J, editor. Hot topics in diabetes. 5 ed. London: Synergy; 2012. p. 49–61 [Available from www. diabetologists-abcd.org.uk/GLP1_Audits/ABCD_Hot_Topics_2012.pdf]. [10] Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, openlabel trial. Lancet 2010;375:1447–56.
Hanaa Elkhenini⁎ John P. New Lucinda K.M. Summers Akheel A. Syed Obesity Medicine and Endocrinology, Salford Royal NHS Foundation Trust and University Teaching Hospital, Salford, UK Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK ⁎Corresponding author at: Obesity Medicine and Endocrinology, Salford Royal NHS Foundation Trust and University Teaching Hospital, Stott Lane, Salford M6 8HD, UK. E-mail address: [email protected] (H. Elkhenini). 17 December 2013
