Sky Journal of Medicine and Medical Sciences Vol. 4(6), pp. 046 - 048, July, 2016 Available online http://www.skyjournals.org/SJMMS ISSN 2315-8808 ©2016 Sky Journals Case Report Dulaglutide replaces multiple daily insulin injections from dialysis patients with type 2 diabetes Satoshi Furukawa The Department of Legal Medicine, Shiga University of Medical Science. Setatsukinowa Otsu Shiga Japan. E-mail: [email protected]. Accepted 27 June, 2016 Glucagon-like peptide-1 (GLP-1) based therapy improves glycemic control through multiple mechanisms with a low risk of hypoglycemia. Dulaglutide is administered once weekly via subcutaneous injection. Two dialysis patients has used super-rapid insulin (3 shots/day) and one patient has done insulin aspart/aspart protamine 30/70 (2 shots/day). We switched injection regimen from multiple daily insulin injections to dulaglutide, and had glycemic control improved without hypoglycemia. The choice of injection regimen should consider the preferences, and resources of the individual and the family for adapting treatment of the patient needs. Dulaglutide minimizes the risk of hypoglycemia and injection burden. Key words: GLP-1 receptor agonist, dulaglutide, dialysis patients. INTRODUCTION The American Diabetes Association (ADA) recommends On September 18, 2014, dulaglutide (Trulicity; Eli Lilly), metformin as the initial for type 2 diabetes; if another a once-weekly subcutaneous injection, was approved by treatment or a combination therapy is needed, available the US Food and Drug Administration (FDA) as an agents include sulfonylureas, thiazolidinediones, adjunct to diet and exercise to reduce fasting and dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like postprandial glucose after a single dose (Indianapolis, peptide (GLP)-1 receptor agonists, insulin, and other 2014). agents (Insucchi et al., 201). The development of the Liraglutide is an analog of human GLP-1 produced by GLP-1 receptor agonist and the DPP-4 inhibitor classes, recombinant DNA technology. It was approved for clinical both of which target the incretin system, represents an use in Europe in 2009 and in USA in 2010 and has been important advancement in the management of type 2 available in India since 2010. We used liraglutide for 3 diabetes (2). The long-acting GLP-1 receptor agonists dialysis patients with type 2 diabetes. improve glycemic control and help to promote weight loss. Furthermore, based on their glucose-dependent mechanism of action, the GLP-1 receptor agonists have Case reports low risk for hypoglycemia (Garber, 2011). The most common adverse effect was mild to moderate Super-rapid insulin has a short duration of action and nausea and vomiting which decreased with time reduces blood glucose in a highly targeted fashion. (Princeton and Bristol-Myers, 2014). The incidence of Premixed insulin regimens are designed to maximize hypoglycemia was low when not given alongside patient convenience and reduce the number of daily concomitant sulfonylurea or insulin therapy (Princeton injections required by providing both rapid-acting and and Bristol-Myers, 2014). GLP-1 based therapies have intermediate-acting components in one formulation. We become integral in many treatment guidelines, such as had three dialysis patients with type 2 diabetes. Two ADA/ European Society for Study of Diabetes, the patients had used super-rapid insulin and one patient did American Association of Clinical Endocrinologists, and insulin aspart/aspart protamine 30/70 (Table 1). We the International Diabetes Federation (ADA, 2014; switched injection regimen from multiple daily insulin Garber et al., 2014; IDF, 2012). injections to dulaglutide. Their injection regimen changed Furukawa 47 Table 1. Insulin injection regimen with three dialysis patients. Age Sex Insulin Before Breakfast Before Lunch Before Dinner Case 1 75 M Super-rapid 4 3 3 Case 2 46 M Super-rapid 6 6 6 Case 3 75 M Aspart 30/70 6 0 4 Table 2. Blood glucose levels before-after hemodialysis (HD) therapy with three cases. Case 1 Before HD Under HD After HD 25th in March 200 165 179 28th 137 123 30th 239 120 111 1st in April 208 Dulaglutide 4th 136 107 103 6th 115 102 93 8th 152 133 111 Dulaglutide 11th 114 13th 161 134 117 15th 159 142 133 Dulaglutide 18th 146 96 20th 230 154 122 (mg/dl) Case 2 Before HD Under HD After HD 25th in March 192 162 119 28th 207 134 2nd in April 236 115 146 Dulaglutide 5th 154 119 118 7th 177 161 187 9th 184 129 93 Dulaglutide 12th 143 139 14th 102 77 16th 151 122 90 Dulaglutide 18th 241 134 97 21th 167 135 132 (mg/dl) Case 3 Before HD Under HD After HD 15th in April 105 121 136 18th 128 103 107 20th 195 170 22th 183 148 117 Dulaglutide 25th 152 107 100 27th 135 122 106 29th 152 119 109 Dulaglutide 2nd in May 143 106 92 4th 205 185 112 (mg/dl) from 2-3 shots daily to 1 shot weekly. We measured human GLP-1 (Rigato and Fadini, 2014). There is no blood glucose levels under hemodiafiltration therapy and structural modification to render it resistant to DPP-4, but showed their results (Table 2). the slow absorption from the site after subcutaneous administration can be attributed to self-association RESULTS leading to the formation of heptamers at the injection site (Rigato and Fadini, 2014). Once in plasma, 99% remains We had improved glycemic control without hypoglycemia bound to plasma albumin, with the bound molecule and enabled to reduce injection to be taken. Dulaglutide having a half-life of 13 h, thereby making it suitable for minimized the risk of hypoglycemia and injection burden. administration. Liraglutide should be initiated with the dose of 0.6 mg for a week (Rigato and Fadini, 2014; Bagsvaerd, 2013). Starting with such low dosage helps Discussion reduce gastrointestinal symptoms during initial stage but is not effective for glycemic control. After a week, the This engineered peptide shares 97% homology to native dose should be increased to 1.2 mg. If the 1.2 mg dose 48 Sky. J. Med. Med. Sci. does not result in an acceptable glycemic control, the 2014. Diabetes Care 2014; 37: 14-80. dose can be further increased to 1.8 mg. Liraglutide is Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA (2013). American Association of Clinical Endocrinologists’ available in disposable, prefilled, and multi-dose pens comprehensive diabetes management algorithm 2013 consensus (Bagsvaerd, 2013; Lund, 2014). Dulaglutide is statement. Endocrine Practical, 19: 536-557. administered once on a weekly basis at any time of the Brussels, Belgium: Internatinal Diabetes Federation (2012). day via subcutaneous injection into the abdomen, thigh, International Diabetes Federation. Clininal Guidelines Task Force. Global Guideline for Type 2 Diabetes. or upper arm (Indianapolis, 2014). Trulicity (dulaglutide) injection. Indianapolis, IN: Eli Lilly and Company; The initial dose of dulaglutide is 0.75 mg administered September 2014. subcutaneously once on a weekly basis. Dulaglutide can Rigato M, Fadini GP (2014). Comparative effectiveness of liraglutide in be administered with or without (Indianapolis, 2014). The the treatment of type 2 diabetes. Diabetes Metab. Syndr. Obes., 7: 107-120. rate of hypoglycemia was low, except when liraglutide Bagsvaerd, Denmark: Novo Nordisk 2013. US Prescribing Information. was used in combination with sulfonylureas when there Lund A, Knop FK, Vilsboll T (2014). Glucagon-like peptide-1 receptor was an increased risk of hypoglycemia. Anti-liragulutide agonists for the treatment of type 2 diabetes: Differences and antibodies were detected in 8.6% of liraglutide-treated similarities. Eur. J. Intern. Med., 25: 407-414. Loretta Fala. Trullicity (Dulaglutide) (2015). A new GLP-1 recepter patients, relatively lower than that seen with exenatide agonist once-weekly subcutaneous injection approved for the owing to high sequence identity with native GLP-1 treatment of patients with type 2 diabetes. Am Health Drug Benefits, (Bagsvaerd, 2013). In general, the presence of antibodies 8: 131-134. did not impact the clinical efficacy. In 6 clinical studies which included a total of 3342 patients with type 2 diabetes, treatment with dulaglutide resulted in greater reductions from baseline in HbA1c levels compared with placebo, with no overall differences in glycemic reductions across age, sex, race/ethnicity, or duration of disease (Loretta, 2015). With the recent FDA approval of dulaglutide, a new, once-weekly subcutaneous injection became available as an adjunct to diet and exercise for adult patients with type 2 diabetes. Dulaglutide, a GLP-1 receptor agonist, provides a once-weekly treatment option that can be used as monotherapy or as an add-on therapy to existing treatment regimens. The once-weekly therapy may provide another therapeutic alternative when oral antihyperglycemic medications are unable to provide adequate glycemic control. A once-weekly treatment may provide an attractive option for dialysis patients with type 2 diabetes. Conclusion The GLP-1 receptor agonist improves glycemic control through multiple mechanisms with a low risk of hypoglycemia. Dulaglutide is being recognized as an important therapy in management of dialysis patients with type 2 diabetes. REFERENCES Insucchi SE, Bergenstal RM, Buse JB (2012). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35: 1364-1379. Garber AJ (2011). Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care; 34: 279-284. Princeton NJ, Bristol-Myers Squibb Company (2014). US Prescribing Information. American Diabetes Association. Standards of medical care in diabetes .