Type 1 Diabetes Treatment Options

Stanley Schwartz Mark Stolar Emeritus, Univ of Pa

Part 5

Potential Adjunctive Treatments for Type 1 Diabetes

IncretinsSGLT-2 InhibitorsInsulin Sensitizers

Potential for Incretin Rx in T1DM

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Drug Discovery Today Volume 17, Numbers 1/2 January 2012

Incretin Therapy in Type 1 DiabetesImproved glycemic variability

Liraglutide Vildigliptin

Data Suggests: less dawn effect, less variability, decrease insulin doses, less hypoglycemia

Potential Adjunctive Treatments for Type 1 Diabetes

IncretinsSGLT-2 InhibitorsInsulin Sensitizers

Mechanism of Action of SGLT-2 Inhibition

SGLT-2 Inhibition

SGLT-2 Inhibition in T1DMIn 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

IncretinsSGLT-2 InhibitorsInsulin Sensitizers

Multiple Causes IR-Type 1 Patients can have Insulin Resistance

- Identify by Insulin need > ~50u/day

PeripheralIR

PeripheralIR

Central IR/Appetite

Central IR/Appetite

Inflam-mation

IR

Inflam-mation

IR

BiomeIR

BiomeIR

TZD (Pio-)

Metformin

Bromocriptine-QR

Anti-Inflam.

Pro-Biotics,Pre-Biotics,Antibiotics

Weight ReductionAgents

MetforminMultiple studies show benefits, albeit to different degrees in different patients1.Decreased HgA1c2.Decreased Weight3.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 Practice1-16,2014,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

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 DiabetesNon-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

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