Type 2 DiabetesThe Sweetness of Pharmacotherapy

WebinarJuly 15, 2020

LA2968 0720

Learning Objectives

• Given a patient, develop regimen for diabetes based on age, comorbid conditions, and current treatment guidelines

• Design evidence-based monitoring and treatment plans based on patient’s comorbid conditions, and concurrent medications

• Counsel a patient on appropriate use, drug interactions and expectations of anti-hyperglycemic agents

• Identify medication-related and patient factors of antidiabetic agents to support patient-pharmacist shared decision making

• Optimize drug regimen with respect to other comorbid conditions, potentially leveraging pharmacy management services (e.g., medication therapy management, medication reconciliation post-discharge, ambulatory care pharmacy)

Road Map

• Diabetes Pathophysiology

• Clinical Pearls• Pharmacological Agents

• Cardiovascular Risk Reduction

• L.A. Care Health Plan Services

• Questions

Background

• Type 1: Caused by autoimmune beta cell destruction, leading to absolute autoimmune deficiency

• Type 2: Progressive insulin secretory defect on background of insulin resistance

• Body overcompensates and starts to secrete more insulin and eventually pancreas dies out

Pathophysiology

Neurotransmitter

dysfunction

Increased lipolysis and

reduced glucose

uptake

Increased

glucose

reabsorption

Decreased glucose uptake

Decreased

incretin effect

Increased hepatic

glucose production

Increased glucagon

secretion

Impaired insulin

secretion

Diabetes Care 2013 Aug; 36(Supp 2): S127-S138.

Meds and Pathophysiology

Neurotransmitter dysfunction

• GLP-1 receptor

agonists

• Amylin

• Bromocriptine Increased lipolysis and

reduced glucose

uptake

• Thiazolidinediones

(TZDs)

Increased

glucose

reabsorption

• SGLT-2

inhibitors

Decreased glucose

uptake

• Metformin

• Insulin

• TZDs

Decreased

incretin effect

• Metformin

• α-

glucosidase

inhibitors

• Colesevelam

Increased hepatic

glucose production

• Metformin

• Insulin

• TZDs

Increased glucagon

secretion

• GLP-1 receptor

agonists

• DPP-4 inhibitors

• Amylin

Impaired insulin

secretion

• Sulfonylurea

• Meglitinide

• GLP-1 receptor

agonists

• DPP-4 inhibitors

Meds and Pathophysiology

Diabetes Care 2013 Aug; 36(Supp 2): S127-S138.

Progression of Type 2 Diabetes

Adapted from: International Diabetes Center (Minneapolis, Minn.)

Insulin

Resistance

Uncontrolled Hyperglycemia

Relative

Function

(%)

Glucose

(mg/dL)

350

300

250

200

150

100

50

250

200

150

100

50

0

Years of Diabetes

-10 -5 0 5 10 15 20 25 30

-10 -5 0 5 10 15 20 25 30

Fasting

Glucose

Insulin

Level

IGT Diabetes

-Cell

Failure

Complications of Diabetes

Diabetes Complications. Jan 2019. The Diabetes Centre.

Glycemic Recommendations for Adults with Diabetes

A1c

Clinical Pearls

Diabetes Medications

Efficacy Hypoglycemia

Diabetes Medications

Clinical Pearls

• DPP-IV inhibitors

• Thiazolidinediones

• Sulfonylureas

• Insulin

• Others

• Biguanides

• SGLT-2 inhibitors

• GLP-1 agonist

Clinical Pearls

• DPP-IV inhibitors

• Thiazolidinediones

• Sulfonylureas

• Insulin

• Others

• Biguanides

• SGLT-2 inhibitors

• GLP-1 agonist

alogliptin, Januvia, Onglyza, Tradjenta

Efficacy Intermediate

Hypoglycemia No

Weight change Neutral

Cost High

Dosage Form Oral

Cardiovascular(CV) Effects

Atherosclerotic cardiovascular disease: (ASCVD): NeutralHeart Failure (HF): Potential risk in saxagliptin

Renal Dosing Progression of Diabetic Kidney Disease (DKD): Neutral Dosing/Use Considerations except linagliptin

Comments Potential risk of acute pancreatitis Joint pain

DPP-IV Inhibitors

DPP-IV Inhibitors

pioglitazone; Avandia

Efficacy High

Hypoglycemia No

Weight change Gain

Cost Low

Dosage Form Oral

CV Effects ASCVD: Potential benefit in pioglitazoneHF: Increased Risk

Renal Dosing Progression of DKD: Neutral Dosing/Use Considerations: No adjustment required but not recommended in renal impairment due to fluid retention

Comments FDA Black Box Warning (BBW): Congestive Heart Failure Fluid retention, risk of bone fracture, bladder cancer (P),↑LDL (R)Benefit in NASH

Thiazolidinediones

Thiazolidinediones

glyburide, glipizide, glimepiride

Efficacy High

Hypoglycemia Yes

Weight change Gain

Cost Low

Dosage Form Oral

CV Effects ASCVD: NeutralHF: Neutral

Renal Dosing Progression of DKD: Neutral Dosing/Use Considerations: Glyburide not recommended

Comments FDA Special Warning on increased risk of cardiovascular mortality based on studies of an older sulfonylurea (tolbutamide)

Sulfonylureas

Sulfonylureas

Insulin

Efficacy Highest

Hypoglycemia Yes

Weight change Gain

Cost Human insulin (NPH, premixed formulations): Low; Analogs: High

Dosage Form Human insulin: Subcutaneous, inhaled; Analogs: Subcutaneous

CV Effects ASCVD: NeutralHF: Neutral

Renal Dosing Progression of DKD: Neutral Dosing/Use Considerations: Lower insulin doses required with decreased eGFR, titrate with clinical response

Comments Injection site reactions Hypoglycemia higher with human insulin

Insulin

Others

• Alpha glucosidase inhibitors (Acarbose, Miglitol)

• Meglitinides analogues (Nateglinide, Repaglinide)

• Amylin Mimetics (Pramlinitide)

• Bile Acid Sequestrants (Colsevelam)

• Dopamine Agonist (Bromocriptine)

Others

Clinical Pearls

• DPP-IV inhibitors

• Thiazolidinediones

• Sulfonylureas

• Insulin

• Others

• Biguanides

• SGLT-2 inhibitors

• GLP-1 agonist

Biguanides

metformin, metformin ER

Efficacy High

Hypoglycemia No

Weight change Neutral (potential for modest loss)

Cost Low

Dosage Form Oral

CV Effects ASCVD: Potential Benefit HF: Neutral

Renal Dosing Progression of DKD: Neutral Dosing/Use consideration: Contraindicated with eGFR

Biguanides

Steglatro, Invokana, Farxiga, Jardiance

Efficacy Intermediate

Hypoglycemia No

Weight change Loss

Cost High

Dosage Form Oral

CV Effects ASCVD: Benefit in canagliflozin (C), empagliflozin (E)HF: Benefit in canagliflozin, empagliflozin, dapagliflozin (D)

Renal Dosing Progression of DKD: Benefit in C,E,DDosing/Use consideration: Renally dose in all

Comments FDA BBW: Risk of amputation: CRisk of bone fractures: CDKA risk (C, E, D) Genitourinary infections, risk of volume depletion, hypotension, ↑LDL, risk of Fourier’s gangrene

SGLT-2 Inhibitors

SGLT-2 Inhibitors

Ozempic, Rybelsus, Trulicity, Victoza, Byetta, Bydureon, Adlyxin,

Efficacy High

Hypoglycemia No

Weight change Loss

Cost High

Dosage Form Subcutaneous, Oral (semaglutide)

CV Effects ASCVD: benefit in liraglutide>semaglutide>exenatide ER HF: Neutral

Renal Dosing Progression of DKD: Benefit: liraglutideDosing/Use Considerations: Renal adjustments in liraglutideand exenatide

Comments FDA BBW: Risk of thyroid C-cell carcinoma Gastrointestinal side effects (nausea, vomiting, diarrhea) Injection site reactions Acute pancreatitis risk

GLP-1 agonists

GLP-1 agonists

Glucose-lowering medication in type 2 diabetes: overall approach.

Pharmacy Management Services

Statin Therapy for Patients With Cardiovascular Disease (SPC)

• HEDIS* Accreditation Measure:

Medi-Cal and Medicare

• Description: The percentage of

males 21-75 years of age and

females 40-75 years of age who

were identified as having clinical

ASCVD and are taking a

moderate to high-intensity statin

medication. Two rates measured:

‒ Received statin therapy

‒ Remained on statin for at

least 80% of treatment

period

‒ Rationale: SPC measure is in

line with the 2019 American

College of Cardiology/American

Heart Association (ACC/AHA)

Guidelines, which recommends

statin use for nearly all patients

with clinical ASCVD*HEDIS: Healthcare Effectiveness Data and Information Set.

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;March 17

Statin Therapy for Patients With Diabetes (SPD)

• HEDIS Accreditation Measure: Medi-Cal and Medicare

• Description: The percentage of members 40-75 years of age with diabetes who do

not have clinical atherosclerotic cardiovascular disease (ASCVD) who are taking a

statin medication. Two rates measured:

‒ Received statin therapy

‒ Remained on statin for at least 80% of treatment period

• Rationale: Per 2019 ACC/AHA Guidelines and 2020 ADA Guidelines, a statin is

recommended for nearly all patients with diabetes

Standards of Medical Care in Diabetes—2020 Abridged for Primary Care Providers. American Diabetes Association. Clinical Diabetes 2019 Dec; cd20as01.

L.A. Care Pharmacy Dept. SPD and SPC Intervention

• To address statin non-adherence in Cal MediConnect (CMC) members with

diabetes and cardiovascular disease

• Intervention: High-touch telephonic member outreach to encourage

changes in behavior while addressing barriers that have previously

attributed to the members’ non-adherence (e.g., side effects, forgetfulness,

transportation issues)

• Tools and resources to promote medication adherence:

‒ 90-days supply of medication

‒ Health Education referrals

‒ Mail order pharmacy program

• PPG Performance: Diabetes, hypertension, and cholesterol medication

adherence reported in the quarterly CMC Provider Opportunity Report

(POR) – Gaps in Care

• Provider Performance: Diabetes, hypertension, and cholesterol

medication adherence and SPD/SPC performance reported in the quarterly

Prescriber Scorecard

Medication Therapy Management (MTM)

• Two types of clinical review provided free of cost:

1. Comprehensive Medication Review (CMR)

2. Targeted Medication Review (TMR)

• To qualify for L.A. Care’s MTM program, CMC members must meet ALL of the following criteria:

1. Have at least 3 of the following conditions or diseases:

2. Take at least 8 covered Part D medications

3. Likely to have medication costs exceeding $4,255 per year.

1. Comprehensive Medication Review (CMR) - An interactive, person-to-person, or telehealth medication review and consultation of the beneficiary’s medications (including prescriptions, over-the counter (OTC) medications, herbal therapies, and dietary supplements) performed in real time by a pharmacist or other qualified provider with a summary of the results of the review provided to the targeted individual in CMS’ standardized format.2. Targeted Medication Review (TMR) - TMR is distinct from a CMR because it is focused on specific actual or potential medication-related problems.

‒ Bone Disease

(Arthritis/Osteoporosis)

‒ Chronic Heart Failure (CHF)

‒ Diabetes

‒ Dyslipidemia

‒ Hypertension

‒ Depression

‒ Asthma

‒ Chronic Obstructive Pulmonary

Disease (COPD)

‒ Hepatitis C

Medication Reconciliation Post-Discharge (MRP)

• PPG Performance: Reported in the quarterly CMC Provider

Opportunity Report (POR) – Gaps in Care

2020 2019 2018 2017 2016

18.00% 13.57% 8.47% 1.67% 0.43%

• HEDIS Accreditation Measure: Medicare

• Description: The percentage of inpatient discharges for members ≥

18 y.o. for whom medications were reconciled the date of discharge

through 30 days after discharge.

• HEDIS Rates:

MRP Benefits & Challenges

Benefits

• Medication reconciliation by L.A. Care Pharmacy Department

- Coordination of care, provide medication counseling, and prevent medication-

related problems

- Address gaps in information for PCPs

• Outpatient prescriptions picked up by members

• Knowledge of members admitted & discharged from hospital

• Collaboration between L.A. Care and PPGs to align resources and improve MRP

measure

• Timely transfer of key data across care settings

- L.A. Care Pharmacy team has been manually outreaching to request discharge

paperwork from hospitals by phone and sending medication reconciliation to

PCPs by fax

Challenges

MRP Action Items

• Establish a communication channel with PPGs

- PPGs to send discharge paperwork to L.A. Care Pharmacy Dept., if available

- L.A. Care Pharmacy Dept. to send medication reconciliation to PPGs, so PPGs

can share with their care transition team and member’s PCP

L.A. Care

• Provide health insurance

• Minimize system costs and maximize health care delivery

Medical Groups

• Provide health care services

• Deliver outcomes and maximize patient care

Ambulatory Care Pharmacy Program

L.A. CareClinical Pharmacist will be dispatched to medical group

partners and work at provider clinics to manage mutual

patients

Community Pharmacy Value-Based Program

• Provide Comprehensive Medication Management (CMM) services to L.A. Care

high-risk members by utilizing a network of community pharmacies

• Key players:

- California Rights Med Collaborative

- USC School of Pharmacy

- L.A. County Department of Health

- Inland Empire Health Plan

- L.A. Care Health Plan

Questions?

Appendix

Antidiabetic Combinations with metformin

Antidiabetic Combinations with metformin

Antidiabetic Combinations

Diabetic Supplies

Class Medication Reduced eGFR Recommendations

Biguanides Metformin 30-45 Do NOT INITIATE

References

American Diabetes Association. Standards of Medical Care in Diabetes-2020 Abridged for Primary Care Providers. Clin Diabetes. 2020;38(1):10‐38. doi:10.2337/cd20-as01

Type 2 DiabetesThe Sweetness of PharmacotherapyLearning ObjectivesRoad MapBackgroundPathophysiologyMeds and PathophysiologyProgression of Type 2 DiabetesComplications of DiabetesGlycemic TargetsGlycemic Recommendations for Adults with Diabetes

Clinical PearlsDiabetes MedicationsClinical PearlsDPP-IV Inhibitorsalogliptin,Januvia, Onglyza, Tradjenta

Thiazolidinedionespioglitazone; Avandia

Sulfonylureasglyburide, glipizide, glimepiride

InsulinInsulin

OthersBiguanidesmetformin, metforminER

SGLT-2 InhibitorsSteglatro, Invokana, Farxiga, Jardiance

GLP-1 agonistsOzempic, Rybelsus, Trulicity, Victoza, Byetta, Bydureon, Adlyxin,

Pharmacy Management ServicesStatin Therapy for Patients With Cardiovascular Disease (SPC)Statin Therapy for Patients With Diabetes (SPD)L.A. Care Pharmacy Dept. SPD and SPC InterventionMedication Therapy Management (MTM)Medication Reconciliation Post-Discharge (MRP)MRP Benefits & ChallengesBenefitsChallenges

MRP Action ItemsAmbulatory Care Pharmacy ProgramCommunity Pharmacy Value-Based Program

Questions?AppendixAntidiabetic Combinations with metforminAntidiabetic CombinationsDiabetic Supplies

References