How to Use ADA’s Type 2 Diabetes

Treatment Algorithm
Carlos 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   
Kendall DM, Bergenstal RM. © International Diabetes Center 2009 * in T1DM Initial Trial
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. Long Term Follow-up
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

Multiple, Complex Pathophysiological Abnormalities in T2DM

SGLT-2
inhibitors

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

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

• Gauge patient’s preferred level of involvement

• Explore therapeutic choices
• Consider using decision aids
• “Shared decision making”
• Lifestyle choices ultimately lie with the patient

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

 Glycemic Recommendations: Individualized Treatment

A1C
• <7.0%*
Preprandial capillary plasma glucose
• 80–130 mg/dL*
(4.4–7.2 mmol/L)

Peak postprandial capillary plasma glucose†

• <180 mg/dL*
(<10.0 mmol/L)
* 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
American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: Standards of
Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85

Approach to the Management of Hyperglycemia

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

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

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

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

Disease Duration

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

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

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

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

Relevant Comorbidities

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

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

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

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

Patient Attitude and Expected Treatment Efforts

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

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

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

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

Lifestyle Management

Lifestyle • Diabetes self-management education (DSME)

management is • Diabetes self-management support (DSMS)
a fundamental • Nutrition therapy
aspect of • Physical activity
diabetes care • Smoking cessation counseling
and includes • Psychosocial care

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 Meglitinides
SGLT-2 Inhibitors A-Glucosidase Inhibitors
GLP-1 Receptor Agonists Colesevelam
DPP-4 Inhibitors Dopamine-2 Agonists
Thiazolidinediones Amylin Mimetics
Sulfonylureas

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

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

Metformin

Efficacy High

Hypoglycemia No
Neutral (Potential for
Weight Change
Modest Loss)
Cost Low

Oral/SQ Oral

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 Metformin
ASCVD Potential Benefit
CV Effects
CHF Neutral
Progression of
Neutral
DKD
Renal Effects
Dosing/Use Contraindicated with
Considerations eGRF <30
• Gastrointestinal side effects common
Additional
• (diarrhea, nausea)
Considerations
• Potential for B12 deficiency

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

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

SGLT-2 Inhibitors
Compounds: Canagliflozin; Dapagliflozin; Empagliflozin

Efficacy Intermediate

Hypoglycemia No

Weight Change Loss

Cost High

Oral/SQ Oral

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 SGLT-2 Inhibitors
ASCVD Benefit: canagliflozin, empagliflozin
CV Effects
CHF Benefit: canagliflozin, empagliflozin

Progression of DKD Benefit: canagliflozin, empagliflozin

Canagliflozin: Not recommended
with eGRF <45
Renal Effects Dapagliflozin: Not recommended
Dosing/Use Considerations with eGRF <60; contraindicated with
eGRF <30
Empagliflozin: contraindicated with
eGRF <30
American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: Standards of
Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85

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

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 GPL-1RAs
Compounds: Exenatide; Exenatide extended release

Efficacy High

Hypoglycemia No

Weight Change Loss

Cost High

Oral/SQ SQ

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

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

GPL-1RAs
ASCVD Neutral: lixsenatide, exenatide
extended release
CV Effects Benefit: liraglutide
CHF Neutral

Progression of DKD Benefit: liraglutide

Dosing/Use Exenatide: not indicated with
Renal Effects Considerations eGRF<30
Lixsenatide: caution with eGRF <30
Increased risk of side effects in
patients with renal impairment

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

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

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

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

DPP-4 Inhibitors
Compounds: Sitagliptin; Saxagliptin; Linagliptin; Alogliptin

Efficacy Intermediate

Hypoglycemia No

Weight Change Neutral

Cost High

Oral/SQ Oral

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 DPP-4 Inhibitors
ASCVD Neutral
CV Effects
CHF Potential Risk: saxagliptin, alogliptin

Progression of DKD Neutral

Renal Effects Dosing/Use Renal dose adjustment required;
Considerations can be used in renal impairment

Additional • Potential risk of acute pancreatitis

Considerations • Joint pain

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

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

Thiazolidinediones
Compounds: Pioglitazone; Rosiglitazone

Efficacy High

Hypoglycemia No

Weight Change Gain

Cost Low

Oral/SQ Oral

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

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

ASCVD Potential Benefit: pioglitazone

CV Effects
CHF Increased Risk

Progression of DKD Neutral

• No dose adjustment required
Renal Effects Dosing/Use • Generally not recommended in
Considerations renal impairment due to
potential fluid rentention

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

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

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)

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 Sulfonylureas (2nd Generation)
Compounds: Glyburide; Glipizide; Glimepiride

Efficacy High

Hypoglycemia Yes

Weight Change Gain

Cost Low

Oral/SQ Oral

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

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

Sulfonylureas (2nd Generation)

ASCVD Neutral
CV Effects
CHF Neutral

Progression of DKD Neutral

Renal Effects Dosing/Use • Glyburide: not recommended
• Glipizide & glimepiride: initiate
Considerations
conservatively to avoid hypoglycemia

Additional FDA Special Warning on increased risk of cardiovascular mortality

Considerations based on studies of an older sulfonylurea (tolbutamide)

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

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

Efficacy Highest

Hypoglycemia Yes

Weight Change Gain

Human Insulin: Low
Cost
Analogs: High
Oral/SQ SQ

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

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

Insulin
ASCVD Neutral
CV Effects
CHF Neutral

Progression of DKD Neutral

Renal Effects Dosing/Use Lower Insulin doses required with
a decrease in eGRF; titrate per
Considerations
clinical response
• Injection site reactions
Additional
• Higher risk of hypoglycemia with a human insulin (NPH
Considerations
or premixed formulations) vs. analogs

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

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

Weight

Sex / racial / ethnic / genetic differences

Comorbidities
• Coronary artery disease • Liver dysfunction
• Heart Failure • Hypoglycemia-prone
• Chronic kidney disease
Identifying and addressing barriers to medication adherence
• Cost
• Side effects

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 Antihyperglycemic Therapy in Adults with T2DM

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

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

Antihyperglycemic Therapy in Adults with T2DM

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 Antihyperglycemic Therapy in Adults with T2DM

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

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

Pharmacologic Therapy For T2DM: Recommendations

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
American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: Standards of
Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 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.

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

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

Combination Injectable Therapy in T2DM

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 Therapeutic Options: Insulins
Human Insulin Biosimilar
Insulins Neutral Basal
Analogues analogues Insulin Basaglar
protamine
(glargine, (a biosimilar
Hagedorn
detemir, version of
(NPH)
degludec) insulin
Regular Rapid glargine);
human insulin analogues long-acting
(lispro, aspart,
glulisine)

Pre-mixed Pre-mixed
formulations formulations

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/

Anti-Hyperglycemic Therapy: Insulins

Rapid (Lispro, Aspart, Glulisine)

Insulin level

Short (Regular)
Long (Detemir)
(Degludec)

Long (Glargine)

0 2 4 6 8 10 12 14 16 18 20 22 24
Hours After Injection
 Approach to Starting and Adjusting Insulin in T2DM

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

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

Approach to Starting and Adjusting Insulin in T2DM

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

Medical Care in Diabetes. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
 Approach to Starting and Adjusting Insulin in T2DM

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

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

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

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?

Key Points
Individualize glycemic targets & BG-lowering therapies
Lifestyle foundation of any T2DM therapy program
Unless contraindicated, metformin is optimal first-line drug
• 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)

Comprehensive CV risk reduction - a major focus of therapy

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.
Thank You!