1. Type 1 Diabetes Treatment Options Stanley Schwartz Mark Stolar Emeritus, Univ of Pa Part 5

2. Potential Adjunctive Treatments for Type 1 Diabetes Incretins SGLT-2 Inhibitors Insulin Sensitizers

3. Potential for Incretin Rx in T1DM 3 Drug Discovery Today Volume 17, Numbers 1/2 January 2012

4. Incretin Therapy in Type 1 Diabetes Improved glycemic variability Liraglutide Vildigliptin Data Suggests: less dawn effect, less variability, decrease insulin doses, less hypoglycemia

5. Potential Adjunctive Treatments for Type 1 Diabetes Incretins SGLT-2 Inhibitors Insulin Sensitizers

6. Mechanism of Action of SGLT-2 Inhibition SGLT-2 Inhibition

7. SGLT-2 Inhibition in T1DM In Clinical Practice SGLT-2 Inhibition has shown benefits: decreased variability, especially ppg; with appropriate reduction in insulin dosing-less hypoglycemia However, few studies done worry about potential for DKA with increased glucagon as response to glycosuria

8. Potential Adjunctive Treatments for Type 1 Diabetes Incretins SGLT-2 Inhibitors Insulin Sensitizers

9. Multiple Causes IR- Type 1 Patients can have Insulin Resistance - Identify by Insulin need > ~50u/day Peripheral IR Peripheral IR Central IR/ Appetite Central IR/ Appetite Inflam- mation IR Inflam- mation IR Biome IR Biome IR TZD (Pio-) Metformin Bromocriptine-QR Anti- Inflam. Pro- Biotics, Pre-Biotics, Antibiotics Weight Reduction Agents

10. Metformin Multiple studies show benefits, albeit to different degrees in different patients 1.Decreased HgA1c 2.Decreased Weight 3.Decreased Insulin requirements 4.Decreased FBS, PPG Alternative Agents in Type 1 Diabetes in Addition to Insulin Therapy: Metformin, Alpha-Glucosidase Inhibitors, Pioglitazone, GLP-1 Agonists, DPP-IV Inhibitors, and SGLT-2 Inhibitors,Michelle DeGeeter, PharmD, CDE1, and Bobbie Williamson, PharmD, BCACP, CDE1,Journal of Pharmacy Practice 1-16,2014,DOI: 10.1177/0897190014549837 Pioglitazone Effect of Pioglitazone on the Course of New-Onset Type 1 Diabetes Mellitus J Clin Res Pediatr Endocrinol 2013;5(4):236-239 DOI: 10.4274/Jcrpe.981

11. Summary DM control in T1DM decreases adverse outcomes Albeit at risk of variability, hypo, weight gain Standard basal-bolus care not ideal Data exists for those that address hyperglucagonemia – Pramlintide on label – Incretins based therapy not approved for type 1 Diabetes Non-insulin mediated mechanism of lowering postprandial glucose in Type 1 diabetes through renal or motility modifying agents has potential to improve glycemic variability and overall diabetic control 11