UPDATES IN TYPE 2 DIABETES

David Doriguzzi, PA-C

Learning Objectives

Upon completion of this educational activity, the participant should be able to:

• Overcome barriers and attitudes that limit Clinician/Patient ability to adopt

standards of care for individualized patient management of type II diabetes

• Overcome resistance to early initiation and intensification of insulin therapy

through better understanding of the benefits and risks of insulin management

of type II diabetes

• Individualize therapy and management of patients with type II diabetes using

insulin and standard, new, and emerging agents as part of combination therapy

• Ensure safe use of insulin therapy in hospitalized patients and better focus on

the prevention of hypoglycemia

Impact of Diabetes II

• Type 2 Diabetes Mellitus (T2DM) affects 29.1 Million Americans and 368 Million people worldwide1

• Incidence of T2DM is growing rapidly (30 Million worldwide cases of T2DM in 1985)2

• T2DM carries an annual cost of $245 Billion in the US alone1

1. ADA Statistics about Diabetes. http://www.diabetes.org/diabetes-basics/statistics/2. Global Burden of Diabetes Study 2013. Lancet. 286(9995): 743-800

Where should we be?

• Are we meeting treatment recommendation standards for our diabetic patients?

• The American Diabetes Association (ADA) and American Academy of Clinical Endocrinologists (AACE) both provide recommendations diabetes treatment goals

ADA Treatment Goals• A reasonable A1c goal for

most patients with T2DM is <7.0% 1

• A1c < 6.5% is a good goal for healthier patients who can achieve goals without risk of hypoglycemia

• A1c < 8.0% is appropriate for patients with severe hypoglycemia, advanced complications, or shorter life expectancy

1. Diabetes Care. Volume 39, Supplement 1, January 2016

ADA Treatment Guide

1. Diabetes Care. Volume 39, Supplement 1, January 2016

AACE Treatment Goals

• A1c < 6.5% in patients without concurrent serious illness and at low hypoglycemic risk

• A1c > 6.5% in patients with concurrent serious illness and at risk for hypoglycemia

1. Diabetes Care. Volume 39, Supplement 1, January 2016

AACE Treatment Guide

Clinical Inertia in Diabetes Care

• Patients are commonly allowed to remain in poor glycemic control for several years before therapy is intensified.

• Clinicians wait an average of 6 years before initiating insulin therapy in patients with A1c > 8.0%.

0

2

4

6

8

>7.0% >7.5% >8.0%

Years

to inte

nsific

ation o

f th

era

py

Additional OAD Insulin

1. Khunti, et al. Diabetes Care. 36:3411-3417, 2013

Why Do We Wait?Numerous barriers stand in the way of advancing therapy

• Patient resistance to therapy

• Clinician resistance

• Fear of hypoglycemia

• Low clinician comfort level with more intensive/newer treatments

• Lack of familiarity with newer treatment mechanisms of action

• Limited time and training resources

• Cost limitations

• Fear of injections

Overcoming the Barriers

Improve Patient Knowledge

• Educate patients on medication purpose and mechanism of action

• Meaningful conversation about treatment benefits vs risks

• Early discussion on the role of insulin therapy

• Equip patients with adequate training on the use of their medications

Overcoming the Barriers

Team Approach to Therapy

• Make sure patient goals and provider goals coincide

• Cooperative decision-making in therapy adjustments

• Consider costs to patient in decision making

• Follow up regularly to evaluate progress

Overcoming the BarriersImprove Provider Knowledge

• Have realistic and accurate perceptions of treatment modalities

• Be familiar with potential adverse effects (also helps to prepare and educate patients)

• Understand the pathogenesis of Diabetes 2

• Understand how each medication functions in addressing hyperglycemia

Pathogenesis of Diabetes 2“Ominous Octet”

Metformin

• Decreases hepatic glucose output

• Increases muscular glucose uptake

T2DM Treatment Functions

Sulfonylureas

• Increase insulin secretion

• Most common glipizide, glyburide, glimepiride

• Meglitinides (Prandin & Starlix also increase insulin secretion, but with a shorter duration of action)

T2DM Treatment Functions

TZDs

• Increase insulin sensitivity

• Pioglitazone (Actos) & Rosiglitazone (Avandia)

T2DM Treatment Functions

DPP-IV Inhibitors

• Reduce the breakdown of GLP-1 in order increase the incretin effect (using native GLP-1)

• Januvia, Onglyza, Tradjenta, Nesina

T2DM Treatment Functions

GLP-1 Receptor Agonists

• Directly activate GLP-1 receptors to increase the incretin effect

• (More effective incretin activation than DPP-IV inhibitors)

• Byetta, Bydureon, Victoza, Trulicity, Tanzeum, Lyxumia

T2DM Treatment Functions

SGLT-2 Inhibitors

• Decrease kidney reabsorption of glucose

• Invokana, Farxiga, Jardiance

T2DM Treatment Functions

Insulin

• Direct stimulation of insulin receptors in cell membranes to activate cellular uptake of glucose

T2DM Treatment Functions

• Most diabetics eventually require multiple medications to reach goal

• Combining therapies with different actions can allow specific targeting of ominous octet defects

Combining Therapies

• Initiation of insulin has historically been an intimidating undertaking

• Older insulins (porcine, bovine, regular, NPH) brought frequent hypoglycemia, weight gain, and necessitated multiple daily injections

• These factors have contributed to several negative conceptions of insulin therapy for both patients and providers

What about Insulin?

• Fear of pain related to injections

• Fear of weight gain

• Fear of hypoglycemia

• Belief that insulin is “bad for you” and leads to complications

• Belief that initiation of insulin therapy implies failure as a diabetic

Patient Concerns

• Fear of hypoglycemia

• Lack of time

• Concerns about patient compliance or competence

• Lack of comfort in dose titration

Provider Concerns

• Insulin can be used as early as second-line therapy in most Type 2 patients

• AACE recommends immediate

initiation of insulin in symptomatic patients with A1c > 9%

• No medication is more effective in improving severe hyperglycemia than insulin1

Insulin’s Place in Treatment

1. Irl B. Hirsch, et al. A Real-World Approach to Insulin Therapy in Primary Care Practice. Clinical Diabetes April 2005 vol. 23 no. 2 78-86

ADA Treatment Guide

1. Diabetes Care. Volume 39, Supplement 1, January 2016

AACE Treatment Guide

Timely intensification of therapy has been shown to be associated with

• Better A1c control

• Delayed progression of diabetes disease process

• Reduced diabetes complications

• Reduced cardiovascular events

• Reduced microvascular complications

Importance of Early Insulin Initiation

1. Holman et al. 10-year follow-up of intensive glucose control in Type 2 Diabetes. N Engl J Med 2008;359:1577-15892. Stratton et al. Association of glycaemia with macrovascular and microvascular complications of Type 2 Diabetes. BMJ 2000;321:405-412

Newer developments in basal insulin have simplified insulin therapy for the patient and the primary care provider

• Significantly less hypoglycemia

• Significantly fewer injections

• Significantly less weight gain

• Significantly less injection pain

• Dose titration can be simple and managed by most patients

It’s Easier Than You Think

Basal insulin recently got even easier with concentrated formulations

• Higher concentration allows for higher doses with lesser injection volume

• Less patient discomfort and insulin pens last longer

• Concentrated insulins tend to have longer duration of action and flatter basal profile

Toujeo - 300 u/mL (glargine)

Tresiba - 200 u/mL and 100 u/mL

Recent Developments

Most patients can manage self-titration of insulin to help them reach goal

• Patients monitor fasting blood glucose (FBG) at home and adjust gradually until FBG goals are achieved

• Start at a low dose and make adjustments every few days, based on FBG readings

Dialing in the Dose

Titration algorithm example

Start at 10 units daily of basal insulin.

1 or 2 times per week, adjust insulin dose based on lowest FBG level

Lowest FBG Adjustment

> 140 + 4 units

100 - 140 + 2 units

75 - 99 No change

<75 - 2 units

Dialing in the Dose

• Generally, continuation of oral anti-diabetic drugs is not advised in the hospital.

• Insulin is the treatment of choice

• NPH and long-acting basal insulins have similar efficacy in management of hyperglycemia, but NPH carries a greater risk of hypoglycemia. 1

In the Hospital…

1. Umpierrez G, et al. J Clin Endocrinol Metab. 2009; 94(2):564-569.

• Glucose does not need to be as low in the hospital as in regular outpatient management

• No extra benefit to having BG < 120 mg/dL during the hospitalization

• Hypoglycemia during hospitalization is associated with increased risk of complications.

• Basal-Bolus therapy is more effective than Insulin Sliding Scales in maintaining glycemic goals 1

Glycemic Goals During Hospitalization

1. Umpierrez G, et al. Diabetes Care. 2007; 30(9):2181-2186

• Most patients' BG should be maintained between 140 and 180 mg/dL

• Adjust the target depending on the patient's clinical status

• 180-200 for patients with terminal illness

• Reassess therapy it blood glucose drops below 100 mg/dL

Glycemic Goals During Hospitalization

Determining Initial TherapyNew Admission to Hospital

No previous

insulin

No previous

insulin

Insulin experienced

Insulin experienced

Starting Total Daily Dose of 0.3 u/kg to 0.5

u/kg

Starting Total Daily Dose of 0.3 u/kg to 0.5

u/kg

Reduce outpatient dose

by 20-25%

Reduce outpatient dose

by 20-25%

(Lower in elderly and renal insufficiency)

Determining Initial TherapyBasal Only vs Basal-Bolus?

New Patient

NPO or Uncertain PO

Intake

NPO or Uncertain PO

Intake

Adequate PO Intake

Adequate PO Intake

BASAL ONLY

0.2 -0.25 units/kg/dayCorrection doses if needed

Adjust basal as needed

BASAL ONLY

0.2 -0.25 units/kg/dayCorrection doses if needed

Adjust basal as needed

BASAL/BOLUS

0.4 -0.5 units/kg/day1/2 Basal, 1/2 Bolus (div)Adjust doses as needed

BASAL/BOLUS

0.4 -0.5 units/kg/day1/2 Basal, 1/2 Bolus (div)Adjust doses as needed

Discharge Plan

> 10%> 10%

< 7%< 7%

> 8%> 8%

> 9%> 9%

Admission A1c

Adjust therapy. Add OAD or Basal Insulin

Add Basal Insulin

Add Basal or replace with Basal/Bolus

Resume Original Therapy

Conclusion

• Clinical inertia and resistance to treatment intensification is a major factor limiting potential improvement in patient outcomes.

• More tools are currently available than ever before to help patients reach T2DM goals

• A strong understanding of the benefits and risks of available treatments will help both the patient and the provider make better decisions pertaining to therapy.

• Insulin is the most therapy for managing severe hyperglycemia and it's easier to use than ever.