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Case Study Diabetes Sodium-glucose Co-transporter-2 Inhibitors in Type 1 Diabetes—a Dangerous Ally Gagan Priya, 1 Sanjay Kalra, 2 and Vishal Bhambri 1 1. Fortis Hospital, Mohali, India; 2. Bharti Hospital, Karnal, India T here is an unmet need for adjunctive non-insulin-based therapies in type 1 diabetes (T1D). Weight gain, recurrent hypoglycemia and suboptimal glycemic control remain significant challenges. Sodium-glucose co-transporter-2 (SGLT2) inhibitors and dual inhibitors of sodium-glucose co-transporter-1 (SGLT1) and SGLT2 may have a potential role as an add-on therapy to insulin. The benefits include improved glycemic control, weight reduction, and reduced insulin dose requirement. However, the risk of diabetic ketoacidosis with SGLT2 inhibitors is significant and the diagnosis may be delayed due to absence of significant hyperglycemia. At present, SGLT2 inhibitors are not approved for use in T1D, and the risks should be discussed at length with the patient. We propose strategies to minimize the risk of diabetic ketoacidosis associated with off-label use of SGLT2 inhibitors in T1D. Keywords Type 1 diabetes, diabetic ketoacidosis, euglycemic diabetic ketoacidosis, sodium-glucose co-transporter-2 (SGLT2) inhibitors Disclosure: Gagan Priya, Sanjay Kalra, and Vishal Bhambri have nothing to declare in relation to this article. No funding was received in the publication of this article. Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: September 4, 2017 Accepted: November 13, 2017 Citation: US Endocrinology, 2017;13(2):75–8 Corresponding Author: Gagan Priya, Fortis Hospital, Mohali, India. E: gpriya77@gmail.com There is a rising trend of overweight and obesity in individuals with type 1 diabetes (T1D). The prevalence of overweight and obesity among newly diagnosed T1D subjects was 21–22% in the 2–19 year age group in the Pediatric Diabetes Consortium and the SEARCH for Diabetes in Youth study. 1,2 This has been attributed to a general worldwide increase in prevalence of obesity and similar risk factors such as family history, ethnicity, and sedentary lifestyle may be contributory. But several other factors related to insulin treatment may further exacerbate weight gain. Hypoglycemia and defensive snacking result in a state of calorie excess. Over-insulinization to achieve glycemic targets compounds the problem. In the DCCT (NCT00360815) and EDIC (NCT00360893) trials, excessive weight gain was associated with an increase in central obesity, insulin resistance, dyslipidemia, hypertension, and atherosclerosis. 3 Approximately 50% patients with T1D have features of metabolic syndrome. 4 Is there a need for adjunctive therapy in type 1 diabetes? T1D is caused by autoimmune destruction of pancreatic β-cells and consequent absolute insulin deficiency. Insulin, therefore, remains the cornerstone of treatment. However, despite significant advances in the availability of more physiological insulin preparations, insulin delivery devices including continuous subcutaneous insulin infusion (CSII) pumps and continuous glucose monitoring (CGM) systems, most patients fail to achieve glycemic targets. 5 There are periods of hyperglycemia and hypoglycemia with marked daily fluctuations in blood glucose. Weight gain associated with insulin, severe hypoglycemia, recurrent hypoglycemia, hypoglycemia unawareness, and poor postprandial glycemic control remain significant challenges. Non-insulin anti-diabetic medications have often been considered as adjunctive to insulin therapy to improve metabolic control in T1D. 6 The aim of such adjunctive therapy would be: • • • • • to improve glycemic control; to minimize weight gain; to reduce insulin dose requirement; to improve postprandial glucose control; and to improve cardiovascular and renal risk. Drugs which have been explored for their role in T1D, with limited success, include pramlintide, metformin, pioglitazone, glucagon-like peptide 1 (GLP-1) receptor agonists, SGLT2 inhibitors and dual SGLT1 and SGLT2 inhibitors. 5,6 Pramlintide, an amylin analogue, is the only drug currently approved for use as adjunctive therapy in T1D. Trials of GLP1 receptor agonists have demonstrated small reductions in glycated haemoglobin (HbA1c) levels accompanied by weight loss and reduced insulin dose but a significantly increased risk of hypoglycemia. 6,7 In the recently published TOU CH MED ICA L MEDIA 75