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Attempted suicide with liraglutide overdose did not induce hypoglycemia
diabetes research and clinical practice 99 (2013) e3–e4
Contents available at Sciverse ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief report
Attempted suicide with liraglutide overdose did not induce hypoglycemia R. Nakanishi a, T. Hirose a,f,*, Y. Tamura a, Y. Fujitani a, H. Watada a,b,c,d,e a
Department of Metabolism and Endocrinology, Tokyo, Japan Center for Beta-Cell Biology and Regeneration, Tokyo, Japan c Center for Therapeutic Innovations in Diabetes, Tokyo, Japan d Center for Molecular Diabetology, Tokyo, Japan e Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan f Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan b
article info
abstract
Article history:
We document the first reported case of attempted suicide with the GLP-1 receptor agonist,
Received 29 June 2012
liraglutide. A 33-year-old Japanese woman with type 2 diabetes reported subcutaneously
Received in revised form
injected 72 mg of liraglutide. She experienced gastrointestinal symptoms but no hypogly-
10 October 2012
cemia.
Accepted 22 October 2012
# 2012 Elsevier Ireland Ltd. All rights reserved.
Published on line 11 November 2012 Keywords: Hypoglycemia GLP-1 receptor ageonist Type 2 diabetes Overdose
A 33-year-old Japanese female with type 2 diabetes reported injecting 72 mg of liraglutide (day 1; 4:00 a.m.) subcutaneously. Liraglutide 0.9 mg daily had been started as add-on therapy to 1 mg of glimepiride 7 months previously. Glycated hemoglobin was 7.7% and fasting blood glucose was 6.8 mmol/l on her last previous visit, 8 days before the suicide attempt. The patient stated that she did not take glimepiride on the day of attempting suicide. She reported self-injection of four pens of liraglutide (each pen containing 18 mg of liraglutide) and neither food nor sweet drink intake due to severe nausea with repeated vomiting after the injection, but no hypoglycemic symptoms. She monitored her blood glucose levels regularly with capillary fingertip blood sample after the liraglutide overdose and the
results ranged between 5.6 and 8.0 mmol/l. She presented to our hospital 37 hours after the liraglutide injection. On arrival she was able to walk unaided and there was no alteration in consciousness. Blood pressure was 110/80 mmHg and pulse rate was 78/min. The blood glucose concentration on arrival (37 hours after the injection: day 2, 7:00 p.m.) was 4.9 mmol/l after more than 24 hours of fasting due to nausea. After admission, blood glucose levels remained between 4.9 and 6.3 mmol/l with saline infusion only until the next morning (day 3). The gastrointestinal symptoms resolved after admission. Plasma liraglutide concentrations at 37 hours (day 2), 51 hours (day 3) and 75 hours (day 4) after the liraglutide injection were 299, 158 and 51.4 nmol/l, respectively (courtesy Dr. L. Andersen of Novo Nordisk,
* Corresponding author at: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo Japan. Tel.: +81 3 3762 4151; fax: +81 3 3765 6488. E-mail address: [email protected] (T. Hirose). 0168-8227/$ – see front matter # 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2012.10.017
e4
diabetes research and clinical practice 99 (2013) e3–e4
Denmark). From registration studies, the reported Cmax of plasma liraglutide after injection for 11 days with regular therapeutic dosage (10 mg/kg/day) is 11 2 nmol/l [5] indicating that the concentration of liraglutide in our patient was more than 25 times higher than the Cmax after regular dosing, even 37 hours after injection. Even though the concentration of plasma liraglutide was extraordinarily high, immunoreactive insulin and blood glucose levels measured at the same time were 9.5, 9.1, and 23.0 mU/ml, and 4.9, 8.9, and 10.9 mmol/l, respectively. She was discharged without complications on day 4.
1.
Discussion
Various drugs are used in the treatment of type 2 diabetes. Several reports of overdosing of these drugs have been published including sulfonylurea, metformin, nateglinide, and dipeptidyl-peptidase (DPP)-4 inhibitors [1–4]. We report here an attempted suicide using an overdose of the GLP-1 receptor agonist, liraglutide. To our knowledge, overdose of GLP-1 receptor agonists including liraglutide has not been reported previously. In the presence of hyperglycemia, regular therapeutic doses of DPP-4 inhibitors and GLP-1 receptor agonists stimulate secretion of insulin and inhibit glucagon secretion. In our patient, even with very high plasma concentrations of liraglutide, blood glucose level did not decrease below the normal range, consistent with the glucosedependent mechanism of action of liraglutide. In conclusion, overdose with subcutaneously injected liraglutide resulted in gastrointestinal symptoms but no hypoglycemia.
Conflict of interest The authors declare that they have no conflict of interest.
Acknowledgments Dr. Hirose is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. R.N. and Y.T. are the treating physicians of the patient described in this case report, performed the practical collection of the clinical data. T.H. wrote and edited the manuscript and contributed discussion, Y.F. and H.W. contributed discussion. The patient described in this casereport has given written informed consent to publish her case anonymously.
references
[1] Klonoff DC, Barrett BJ, Nolte MS, Cohen RM, Wyderski R. Hypoglycemia following inadvertent and factitious sulfonylurea overdosages. Diabetes Care 1995;18: 563–7. [2] Teale KFH, Devine A, Stewart H, Harper JH. The management of metformin overdose. Anaesthesia 1998;53:691–701. [3] Nakayama S, Hirose T, Watada H, Tanaka Y, Kawamori R. Hypoglycemia following a nateglinide overdose in a suicide attempt. Diabetes Care 2005;28:227–8. [4] Furukawa S, Kumagi T, Miyake T, Ueda T, Niiya T, Nishino K, et al. Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: a case report and a review of the literature. Endocr J 2012;59:13 [Published online January]. [5] Agersø H, Jensen LB, Elbrønd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 2002;45:195–202.
Contents available at Sciverse ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief report
Attempted suicide with liraglutide overdose did not induce hypoglycemia R. Nakanishi a, T. Hirose a,f,*, Y. Tamura a, Y. Fujitani a, H. Watada a,b,c,d,e a
Department of Metabolism and Endocrinology, Tokyo, Japan Center for Beta-Cell Biology and Regeneration, Tokyo, Japan c Center for Therapeutic Innovations in Diabetes, Tokyo, Japan d Center for Molecular Diabetology, Tokyo, Japan e Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan f Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan b
article info
abstract
Article history:
We document the first reported case of attempted suicide with the GLP-1 receptor agonist,
Received 29 June 2012
liraglutide. A 33-year-old Japanese woman with type 2 diabetes reported subcutaneously
Received in revised form
injected 72 mg of liraglutide. She experienced gastrointestinal symptoms but no hypogly-
10 October 2012
cemia.
Accepted 22 October 2012
# 2012 Elsevier Ireland Ltd. All rights reserved.
Published on line 11 November 2012 Keywords: Hypoglycemia GLP-1 receptor ageonist Type 2 diabetes Overdose
A 33-year-old Japanese female with type 2 diabetes reported injecting 72 mg of liraglutide (day 1; 4:00 a.m.) subcutaneously. Liraglutide 0.9 mg daily had been started as add-on therapy to 1 mg of glimepiride 7 months previously. Glycated hemoglobin was 7.7% and fasting blood glucose was 6.8 mmol/l on her last previous visit, 8 days before the suicide attempt. The patient stated that she did not take glimepiride on the day of attempting suicide. She reported self-injection of four pens of liraglutide (each pen containing 18 mg of liraglutide) and neither food nor sweet drink intake due to severe nausea with repeated vomiting after the injection, but no hypoglycemic symptoms. She monitored her blood glucose levels regularly with capillary fingertip blood sample after the liraglutide overdose and the
results ranged between 5.6 and 8.0 mmol/l. She presented to our hospital 37 hours after the liraglutide injection. On arrival she was able to walk unaided and there was no alteration in consciousness. Blood pressure was 110/80 mmHg and pulse rate was 78/min. The blood glucose concentration on arrival (37 hours after the injection: day 2, 7:00 p.m.) was 4.9 mmol/l after more than 24 hours of fasting due to nausea. After admission, blood glucose levels remained between 4.9 and 6.3 mmol/l with saline infusion only until the next morning (day 3). The gastrointestinal symptoms resolved after admission. Plasma liraglutide concentrations at 37 hours (day 2), 51 hours (day 3) and 75 hours (day 4) after the liraglutide injection were 299, 158 and 51.4 nmol/l, respectively (courtesy Dr. L. Andersen of Novo Nordisk,
* Corresponding author at: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo Japan. Tel.: +81 3 3762 4151; fax: +81 3 3765 6488. E-mail address: [email protected] (T. Hirose). 0168-8227/$ – see front matter # 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2012.10.017
e4
diabetes research and clinical practice 99 (2013) e3–e4
Denmark). From registration studies, the reported Cmax of plasma liraglutide after injection for 11 days with regular therapeutic dosage (10 mg/kg/day) is 11 2 nmol/l [5] indicating that the concentration of liraglutide in our patient was more than 25 times higher than the Cmax after regular dosing, even 37 hours after injection. Even though the concentration of plasma liraglutide was extraordinarily high, immunoreactive insulin and blood glucose levels measured at the same time were 9.5, 9.1, and 23.0 mU/ml, and 4.9, 8.9, and 10.9 mmol/l, respectively. She was discharged without complications on day 4.
1.
Discussion
Various drugs are used in the treatment of type 2 diabetes. Several reports of overdosing of these drugs have been published including sulfonylurea, metformin, nateglinide, and dipeptidyl-peptidase (DPP)-4 inhibitors [1–4]. We report here an attempted suicide using an overdose of the GLP-1 receptor agonist, liraglutide. To our knowledge, overdose of GLP-1 receptor agonists including liraglutide has not been reported previously. In the presence of hyperglycemia, regular therapeutic doses of DPP-4 inhibitors and GLP-1 receptor agonists stimulate secretion of insulin and inhibit glucagon secretion. In our patient, even with very high plasma concentrations of liraglutide, blood glucose level did not decrease below the normal range, consistent with the glucosedependent mechanism of action of liraglutide. In conclusion, overdose with subcutaneously injected liraglutide resulted in gastrointestinal symptoms but no hypoglycemia.
Conflict of interest The authors declare that they have no conflict of interest.
Acknowledgments Dr. Hirose is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. R.N. and Y.T. are the treating physicians of the patient described in this case report, performed the practical collection of the clinical data. T.H. wrote and edited the manuscript and contributed discussion, Y.F. and H.W. contributed discussion. The patient described in this casereport has given written informed consent to publish her case anonymously.
references
[1] Klonoff DC, Barrett BJ, Nolte MS, Cohen RM, Wyderski R. Hypoglycemia following inadvertent and factitious sulfonylurea overdosages. Diabetes Care 1995;18: 563–7. [2] Teale KFH, Devine A, Stewart H, Harper JH. The management of metformin overdose. Anaesthesia 1998;53:691–701. [3] Nakayama S, Hirose T, Watada H, Tanaka Y, Kawamori R. Hypoglycemia following a nateglinide overdose in a suicide attempt. Diabetes Care 2005;28:227–8. [4] Furukawa S, Kumagi T, Miyake T, Ueda T, Niiya T, Nishino K, et al. Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: a case report and a review of the literature. Endocr J 2012;59:13 [Published online January]. [5] Agersø H, Jensen LB, Elbrønd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 2002;45:195–202.