How to Use ADA’s Type 2 Diabetes Treatment … to Use ADA’s Type 2 Diabetes Treatment Algorithm...

How to Use ADA’s Type 2 Diabetes

Treatment AlgorithmCarlos Mendez, MD, FACP

Presenter Disclosure Information

In compliance with the accrediting board policies, the

American Diabetes Association requires the following

disclosure to the participants:

Carlos Mendez, MD, FACP

Disclosed no conflict of interest

Management of Hyperglycemia in T2DM

1. Patient-centered care

2. Anti-hyperglycemic therapy

3. Implementation strategies

4. Other considerations

American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: Standards of

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85

Learning Objectives

• Recognize drug-specific and patient factors of

antihyperglycemic agents to support patient-

provider shared decision making

• Demonstrate when and how to intensify therapy

• Identify opportunities to refer patients to

Diabetes Self-Management Education

Impact of Intensive Therapy for Diabetes:

Summary of Major Clinical Trials

Study Microvasc CVD Mortality

UKPDS

DCCT / EDIC*

ACCORD

ADVANCE

VADT

Long Term Follow-up

Initial Trial * in T1DMKendall DM, Bergenstal RM. © International Diabetes Center 2009

UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854.

Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977.

Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545.

Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum:

Moritz T. N Engl J Med 2009;361:1024) . Writing Group for the DCCT/EDIC Research Group. JAMA. 2015;313(1):45-53.

Multiple, Complex Pathophysiological Abnormalities in T2DM

Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

SGLT-2 inhibitors

Multiple, Complex Pathophysiological Abnormalities in T2DM

Diabetes Care 2012;35:1364–1379; Diabetologia 2012;55:1577.–1596

Patient-Centered Approach

• Gauge patient’s preferred level of involvement

• Explore therapeutic choices

• Consider using decision aids

• “Shared decision making”

• Lifestyle choices ultimately lie with the patient

“...providing care that is respectful of and responsive to individual patient preferences, needs, and values -ensuring that patient values guide all clinical decisions.”

Glycemic Recommendations: Individualized Treatment

* More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on duration of diabetes,

age/life expectancy, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and individual

patient considerations.

† Postprandial glucose measurements should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes

• <7.0%*

A1C

• 80–130 mg/dL*

(4.4–7.2 mmol/L)

Preprandial capillary plasma glucose

• <180 mg/dL*

(<10.0 mmol/L)

Peak postprandial capillary plasma glucose†



Approach to the Management of Hyperglycemia



Drug Adverse Effects



Disease Duration



Life Expectancy



Relevant Comorbidities



Established Vascular Complications



Patient Attitude and Expected Treatment Efforts



Resources and Support System



Lifestyle Management

• Diabetes self-management education (DSME)

• Diabetes self-management support (DSMS)

• Nutrition therapy

• Physical activity

• Smoking cessation counseling

• Psychosocial care

Lifestyle management is a fundamental aspect of diabetes care and includes

American Diabetes Association Standards of Medical Care in Diabetes.

4. Lifestyle Management. Diabetes Care 2018;41(Suppl. 1): S38-S50

Anti-Hyperglycemic Therapy in T2DM

Therapeutic options:

Oral Agents & Non-Insulin Injectables

Most Popular in U.S. and Europe Less Commonly Used

Metformin

SGLT-2 Inhibitors

GLP-1 Receptor Agonists

DPP-4 Inhibitors

Thiazolidinediones

Sulfonylureas

Meglitinides

A-Glucosidase Inhibitors

Colesevelam

Dopamine-2 Agonists

Amylin Mimetics



Metformin

Efficacy High

Hypoglycemia No

Weight ChangeNeutral (Potential for Modest Loss)

Cost Low

Oral/SQ Oral



Metformin

CV Effects ASCVD Potential Benefit

CHF Neutral

Renal Effects

Progression of DKD

Neutral

Dosing/Use Considerations

Contraindicated with eGRF <30

Additional Considerations

• Gastrointestinal side effects common • (diarrhea, nausea)

• Potential for B12 deficiency



SGLT-2 Inhibitors

Efficacy Intermediate

Hypoglycemia No

Weight Change Loss

Cost High

Oral/SQ Oral

Compounds: Canagliflozin; Dapagliflozin; Empagliflozin



SGLT-2 Inhibitors

CV Effects ASCVD Benefit: canagliflozin, empagliflozin

CHF Benefit: canagliflozin, empagliflozin

Renal Effects

Progression of DKD Benefit: canagliflozin, empagliflozin


Canagliflozin: Not recommended with eGRF <45Dapagliflozin: Not recommended with eGRF <60; contraindicated with eGRF <30Empagliflozin: contraindicated with eGRF <30



SGLT-2 Inhibitors

Additional Considerations • FDA Black Box: risk of amputation (canagliflozin)

• Risk of bone fractures (canagliflozin)• DKA risk (all agents, rare in T2DM)• Genitourinary infections• Risk of volume depletion, hypotension• Increase LDL cholesterol



GPL-1RAs

Efficacy High

Hypoglycemia No

Weight Change Loss

Cost High

Oral/SQ SQ

Compounds: Exenatide; Exenatide extended release



GPL-1RAs

CV Effects

ASCVD Neutral: lixsenatide, exenatide extended releaseBenefit: liraglutide

CHF Neutral

Renal Effects

Progression of DKD Benefit: liraglutide


Exenatide: not indicated with eGRF<30Lixsenatide: caution with eGRF <30Increased risk of side effects in patients with renal impairment



GPL-1RAs

Additional Considerations • FDA Black Box: Risk of thyroid c-cell tumors (liraglutide, albiglutide, dulaglutide, exenatide extended release)

• Gastrointestinal side effects common (nausea, vomiting, diarrhea)

• Injection site reactions• Acute pancreatitis risk



DPP-4 Inhibitors

Efficacy Intermediate

Hypoglycemia No

Weight Change Neutral

Cost High

Oral/SQ Oral

Compounds: Sitagliptin; Saxagliptin; Linagliptin; Alogliptin



DPP-4 Inhibitors

CV Effects ASCVD Neutral

CHF Potential Risk: saxagliptin, alogliptin

Renal Effects

Progression of DKD Neutral


Renal dose adjustment required; can be used in renal impairment


• Potential risk of acute pancreatitis• Joint pain



Thiazolidinediones

Efficacy High

Hypoglycemia No

Weight Change Gain

Cost Low

Oral/SQ Oral

Compounds: Pioglitazone; Rosiglitazone



Thiazolidinediones

CV Effects ASCVD Potential Benefit: pioglitazone

CHF Increased Risk

Renal Effects



• No dose adjustment required• Generally not recommended in

renal impairment due to potential fluid rentention



Thiazolidinediones

Additional Considerations • FDA Black Box: Congestive Heart Failure (pioglitazone, rosiglitazone)

• Fluid retention (edema; heart failure)• Benefit in NASH• Risk of bone fractures• Bladder cancer (pioglitazone)• Increase LDL cholesterol (rosiglitazone)



Sulfonylureas (2nd Generation)

Efficacy High

Hypoglycemia Yes

Weight Change Gain

Cost Low

Oral/SQ Oral

Compounds: Glyburide; Glipizide; Glimepiride



Sulfonylureas (2nd Generation)


CHF Neutral

Renal Effects



• Glyburide: not recommended• Glipizide & glimepiride: initiate

conservatively to avoid hypoglycemia


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



Insulin

Efficacy Highest

Hypoglycemia Yes

Weight Change Gain

CostHuman Insulin: LowAnalogs: High

Oral/SQ SQ



Insulin


CHF Neutral

Renal Effects



Lower Insulin doses required with a decrease in eGRF; titrate per clinical response


• Injection site reactions• Higher risk of hypoglycemia with a human insulin (NPH

or premixed formulations) vs. analogs



Individualizing Treatment

American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes. Diabetes

Care 2018; 41 (Suppl. 1): S73-S85

Considerations in Designing an Optimal

Glucose Lowering Drug Regimen for PatientsAge

Weight

Sex / racial / ethnic / genetic differences

Comorbidities

Identifying and addressing barriers to medication adherence

• Liver dysfunction

• Hypoglycemia-prone

• Coronary artery disease

• Heart Failure

• Chronic kidney disease

• Cost

• Side effects



Antihyperglycemic Therapy in Adults with T2DM









In patients with T2DM and established ASCVD:

• antihyperglycemic therapy should begin with lifestyle management and metformin

– subsequently incorporate an agent proven to reduce major adverse CV events and CV mortality (currently empagliflozin and liraglutide), after considering drug-specific and patient factors (Table 8.1). A

– the antihyperglycemic agent canagliflozin may be considered to reduce major adverse CV events, based on drug-specific and patient factors (Table 8.1). C

Pharmacologic Therapy For T2DM: Recommendations



Insulin Therapy in T2DM

• The progressive nature of T2DM should be

regularly and objectively explained to T2DM

patients.

• Avoid using insulin as a threat, describing it as a

failure or punishment.

• Give patients a self-titration algorithm.



Combination Injectable Therapy in T2DM



Neutral protamineHagedorn(NPH)

Regular human insulin

Pre-mixed formulations

Human Insulins Basal

analogues (glargine, detemir, degludec)

Rapid analogues (lispro, aspart, glulisine)

Pre-mixed formulations

Insulin Analogues Basaglar

(a biosimilarversion of insulin glargine); long-acting

Biosimilar Insulin

Therapeutic Options: Insulins

Diabetes Care 2012;35:1364–1379; Diabetologia 2012;55:1577–1596

Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0

https://investor.lilly.com/releasedetail.cfm?ReleaseID=1004325

https://www.basaglar.com/en/

Long (Detemir)

Rapid (Lispro, Aspart, Glulisine)

Long (Glargine)

0 2 4 6 8 10 12 14 16 18 20 22 24

Short (Regular)

Hours After Injection

Ins

uli

n l

eve

l

(Degludec)

Anti-Hyperglycemic Therapy: Insulins

Approach to Starting and Adjusting Insulin in T2DM









Case Study: Introduction

• Mrs. G, a 58-year-old African American, has had

T2D for 8 years

• Currently being treated for hypertension (12 years)

and dyslipidemia (10 years)

• Concerned about uncontrolled blood glucose level, a

recent increase in weight (5 lbs)

• Non-smoker and only occasionally consumes alcohol

• Walks 15-20 minutes, three times a week

• Diet has improved over last 5 years after consult with

RD, but she admits to having a “sweet tooth” (Continued…)

Case Study (cont’d)• Physical exam:

– General examination normal, No pallor, cyanosis, clubbing or

lymphadenopathy

– Height, 5’2” (157 cm); weight, 152 lbs (69 kg)

– BMI, 27.8 kg/m²

– BP, 132/86 mmHg

– Pulse 80/min, regular, peripheral pulses well felt

– Systemic examination- normal

– Foot examination is normal

– Fundus examination :Grade I non proliferative diabetic retinopathy

• Medication history: Glimepiride 2 mg daily BID • Metformin sustained

release preparations 1000 mg daily • Telmisartan 40 mg daily •

Atorvastatin 10 mg at night • Aspirin 75 mg at night (Continued…)

Case Study (cont’d)

Lab results (recent):A1C 8%

FPG 130 mg/dL

2-hour postprandial (dinner) 252 mg/dL

Total cholesterol 197 mg/dL

HDL-C 35 mg/dL

LDL-C 101 mg/dL

TG 147 mg/dL

Blood Urea Nitrogen 19 mg/dL

Creatinine 1.3 mg/dL

Urine routine Sugar, ketones, negative

Case Study: Discussion Question

From the lab results, which plasma glucose patterns

of hyperglycemia are present?

A. Fasting

B. Preprandial

C. Postprandial

D. Nocturnal

E. B and C above

Case Study: Discussion Question

A drug from which of the following drug classes could

you suggest to intensify Mrs. G’s treatment to manage

her hyperglycemia?

A. GLP-1 receptor agonist

B. DPP-4 inhibitor

C. SGLT2 inhibitor

D. Basal insulin

E. A, B, C, or D above

Case Study: Think-Pair-Share

• What option you would have tried first?

• Would you discontinue the sulfonylurea or add the

GLP-1 receptor agonist to the

metformin/sulfonylurea?

Diabetes Care 2012;35:1364–1379; Diabetologia 2012;55:1577–1596

Diabetes Care 2015;38:140-149; American Diabetes Association Standards of Medical Care in Diabetes.

Diabetes Care 2018; 41 (Suppl. 1): S73-S85

Inzucchi SE et al. Diabetologia 2015;58(3):429–442.

Key PointsIndividualize glycemic targets & BG-lowering therapies

Lifestyle foundation of any T2DM therapy program

• In patients with ASCVD and T2D, subsequent treatment should incorporate agent proven to ↓ CV events and/or CV mortality

• Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain BG control

• Shared decision making (focus on his/her preferences, needs & values)

Unless contraindicated, metformin is optimal first-line drug

Comprehensive CV risk reduction - a major focus of therapy

Thank You!

How to Use ADA’s Type 2 Diabetes Treatment … to Use ADA’s Type 2 Diabetes Treatment Algorithm...

Documents

Transcript of How to Use ADA’s Type 2 Diabetes Treatment … to Use ADA’s Type 2 Diabetes Treatment Algorithm...