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

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

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

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

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

Mechanism of Action of SGLT-2 Inhibition SGLT-2 Inhibition

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

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

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

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: / Pioglitazone Effect of Pioglitazone on the Course of New-Onset Type 1 Diabetes Mellitus J Clin Res Pediatr Endocrinol 2013;5(4): DOI: /Jcrpe.981

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