Objective. While dulaglutide has been approved inpatients with type 2 diabetes (T2DM) in combination with insulin, it has not been studied in insulin-deficient patients, not whether they have type 1 diabetes (T1DM) or T2DM. The aim of this study is to assess the efficacy and safety of dulaglutide 0.75 mg/once weekly (QW) in patients with absolute insulin deficiency (n=10).
Subjects and Results. Significant reductions of HbA1c (9.30±1.03% to 8.61±1.21%; p<0.02) and body mass index (BMI; 23.61±3.95 to 23.41±4.24; p<0.02) levels were observed at 3 months with the addition of dulaglutide to the existing pharmacotherapy. However, in all the patients, post-meal C-peptide levels remained undetectable. One patient had gastrointestinal adverse events and discontinue dulaglutide within the first month. One patient was a non-responder, who had little if any changes in HbA1c levels at 3 months.
Conclusions. The results indicate that dulaglutide is effective in patients with T1DM or T2DM with absolute insulin deficiency, though gastrointestinal adverse events might be of concern. The improvements in glycemic control could not be due to enhanced insulin secretion, but may be as a result of a combination of the other effects of glucagon like peptide 1 (GLP-1), such as postprandial glucagon suppression, delayed gastric emptying, and weight loss.
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Caprio S Amiel S Tamborlane WV Gelfand RA Sherwin RS. Defective free-fatty acid and oxidative glucose metabolism in IDDM during hypoglycemia. Influence of glycemic control. Diabetes 39 134–141 1990.
Carlsson A Sundkvist G Groop L Tuomi T. Insulin and glucagon secretion in patients with slowly progressing autoimmune diabetes (LADA). J Clin Endocrinol Metab 85 76–80 2000.
Emami A Youssef JE Rabasa-Lhoret R Pineau J Castle JR Haidar A. Modeling glucagon action in patients with type 1 diabetes. IEEE J Biomed Health Inform 21 1163–1171 2017.
Gutniak M Grill V Wiechel KL Efendic S. Basal and meal-induced somatostatin-like immunoreactivity in healthy subjects and in IDDM and totally pancreatectomized patients. Effects of acute blood glucose normalization. Diabetes 36 802–807 1987.
Kielgast U Asmar M Madsbad S Holst JJ. Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients. J Clin Endocrinol Metab 95 2492–2496 2010.
Kielgast U Krarup T Holst JJ Madsbad S. 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. Diabetes Care 34 1463–1468 2011.
Kugler AJ Thiman ML. Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: a report on the emerging new data. Diabetes Metab Syndr Obes 11 187–197 2018.
Kutoh E Hori T. Effect of sitagliptin in type 1 or type 2 diabetic patients with absolute insulin deficiency: A 48 weeks observational study. BrJ Med Med Res 3 1910–1917 2013.
Sandoval DA D’Alessio DA. Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease. Physiol Rev 95 513–548 2015.
Sherr J Tsalikian E Fox L Buckingham B Weinzimer S Tamborlane WV White NH Arbelaez AM Kollman C Ruedy KJ Cheng P Beck RW; Diabetes Research in Children Network. Evolution of abnormal plasma glucagon responses to mixed-meal feedings in youth with type 1 diabetes during the first 2 years after diagnosis. Diabetes Care 37 1741–1744 2014.