The use of liraglutide, a GLP-1 agonist, in obese people with type 1 diabetes
DOI:
https://doi.org/10.15277/bjdvd.2014.022Abstract
Aims: Optimisation of glycaemic control in type 1 diabetes often results in unwanted weight gain. glucagon-like peptide-1 (GLP-1) agonist use is associated with weight reduction in type 2 diabetes but its use in type 1 diabetes is little studied.Methods: We developed a protocol for GLP-1 use in people with type 1 diabetes and obesity in which liraglutide was initiated and up-titrated whilst insulin doses were simultaneously titrated according to glycaemic parameters.
Results: Of 15 patients offered treatment, 8 proceeded. Baseline parameters were (n=8, mean + SD): (age 50 ± 6 years, BMI 40.4 ± 5.5 kg/m2, weight 123.0 ± 23.9 kg, HbA1c 8.5 ± 1.7%, total daily insulin dose 131 ± 112 units/day. By intention to treat analysis (n=8, 12 months), at 3, 6 and 12 months compared to baseline, weight loss was 6.8 ± 4.1 kg, 10.0 ± 5.6 kg and 8.9 ± 8.4 kg (p=0.026). The reductions in insulin dosage were significant over 6 months (n=8, p=0.045) or when analysing only those who completed 12 months of liraglutide therapy (n=6, p=0.044).
Conclusions: GLP-1 agonist use in patients with type 1 diabetes may be advantageous where weight reduction becomes both a constraint and a therapeutic objective.
References
The DCCT Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86. http://dx.doi.org/10.1056/NEJM199309303291401
Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes--causes, effects and coping strategies. Diab Obes Metab 2007;9:799-812. http://dx.doi.org/10.1111/j.1463-1326.2006.00686.x
Purnell J, Zinman B, Brunzell J. The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus. Circulation 2013;127:157-9. http://dx.doi.org/10.1161/CIRCULATIONAHA.111.077487
Brinkworth GD, Wycherley TP, Noakes M, et al. Reductions in blood pressure following energy restriction for weight loss do not rebound after re-establishment of energy balance in overweight and obese subjects. Clin Exp Hypertens 2008;30:385-96. http://dx.doi.org/10.1080/10641960802275734
Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005;353:2111-20. http://dx.doi.org/10.1056/NEJMoa050156
Czupryniak L, Strzelczyk J, Cypryk K, et al. Gastric bypass surgery in severely obese type 1 diabetic patients. Diab Care 2004;27:2561-2. http://dx.doi.org/10.2337/diacare.27.10.2561
Näslund E, Kral JG. Impact of Gastric bypass surgery on gut hormones and glucose homeostasis in type 2 diabetes. Diab Care 2006;55:92-7. http://dx.doi.org/10.2337/db06-S012
Horton E, Silberman C, Davis K, et al. Weight loss, glycaemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diab Care 2010;33:1759-65. http://dx.doi.org/10.2337/dc09-2062
Lisa MN, Robert FK. Emerging role of GLP-1 receptor agonists in the treatment of obesity. Diab Met Synd Obes: Targets and Therapy 2010;3 263-73.
Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analogue, Liraglutide. Int J Obes 2012;36:843-54. http://dx.doi.org/10.1038/ijo.2011.158
Varanasi A, Bellini N, Rawal D, et al. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol 2011;165:77-84. http://dx.doi.org/10.1530/EJE-11-0330
Kielgast U, Krarup T, Holst JJ, et al. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diab Care 2011;34:1463-8. http://dx.doi.org/10.2337/dc11-0096
Kuhadiya N, Malik R, Bellini N, et al. Long-term follow-up of patients with type 1 diabetes on liraglutide and the effect of liraglutide as additional treatment in obese patients with type 1 diabetes. Endocr Review 2012;33; (03 meeting abstracts): OR 17-1, http://edrv.endojournals.org/cgi/content/meeting_abstract/33/03_MeetingAbstracts/OR17-1, Last accessed 28/4/13.
Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nature Rev: Endocrinol 2009;5:262-9. http://dx.doi.org/10.1038/nrendo.2009.48
Flint A, Raben A, Astrup A, et al. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998;101:515-20. http://dx.doi.org/10.1172/JCI990
Egan JM, Meneilly GS, Habener JF, et al. Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state. JCEM 87:3768-73.
Wettergen A, Scholdager B, Mortensen PE, et al. Truncated GLP-1 (proglucagon 87-107amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993;38:665-73. http://dx.doi.org/10.1007/BF01316798
Madsbad S. Liraglutide Effect and Action in Diabetes (LEADTM) trial. Expert Rev Endocrinol Metab 2009;4:119-29. http://dx.doi.org/10.1586/17446651.4.2.119
Nayak UA, Govindan J, Baskar V, et al. Exenatide therapy in insulin treated type 2 diabetes and obesity. QJM 2010;103:687-94. http://dx.doi.org/10.1093/qjmed/hcq112
Creutzfeldt WO, Kleine N, Willms B, et al. Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients. Diab Care 1996;19:580-6. http://dx.doi.org/10.2337/diacare.19.6.580
Gutniak M, Orskov C, Hoist JJ, et al. Antidiabetogenic effect of glucagon-like peptide-l (7-36)amide in normal subjects and patients with diabetes. N Engl J Med 1992;326:1316-22. http://dx.doi.org/10.1056/NEJM199205143262003
“Liraglutide as Additional Treatment in Patients With Type 1 Diabetes Mellitus”, Clinical Trials US National Institute of Health, http://clinicaltrials.gov/show/NCT01299012, Last accessed 08/05/13
“The efficacy and safety of liraglutide as adjunct therapy to insulin in the treatment of type 1 diabetes”, ClinicalTrials.gov registration: NCT01836523, http://www.novonordisk-trials.com/website/search/trial-registry-details.aspx?id=37790&p=1&search=t, Last accessed 08/05/13.
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