Diabetes Mellitus Therapeutics

Front 1

Diabetes Mellitus is the most common endocrine disorder in the US (8.3%)

What characterizes DM?

Back 1

1. Hyperglycemia

2. Deficiency in insulin production

3. No response to insulin

Front 2

Type I DM

Epidemiology, MOA

Back 2

1. 5% of total DM pts (Usually in younger pts)

2. Immune mediated destruction of beta cells

--> Absolute insulin deficiency

Front 3

What is the tx of choice in Type I DM?

Back 3

Insulin replacement therapy

Front 4

Is family hx a risk factor for Type 1 DM?

Back 4

Family hx is LESS of a risk factor than in type II DM

Front 5

DM2

Epidemiology, MOA

Back 5

1. 95% of total DM pts

2. Combination of insulin resistance and relative insulin deficiency

Front 6

DM2

Tx

Back 6

Life-style modifications, oral medications,

injectable medications (including insulin) or a

combo of these

Front 7

DM

Clinical S/S

Back 7

1. Hyperglycemia

2. Polyuria

3. Polyphagia

4. Polydipsia

5. Blurred vision

6. Fatigue

Front 8

Long-term complications of DM

Microvascular dz's

Back 8

1. Retinopathy (common)

2. Nephropathy (can --> ESRD)

3. Peripheral neuropathy ( --> foot infections/amputations)

4. Autonomic neuropathy (Erect. dysfxn, gastroparesis, UTIs)

Front 9

Long-term complication of DM

Macrovascular dz's

Back 9

1. Coronary artery disease (HTN, MI, HF)

2. Cerebrovascular disease (stroke, TIA)

3. Peripheral artery disease

Front 10

Diagnosis of DM

ADA 2015 Guidelines

Back 10

1. A1C ≥ 6.5% (OR)

2. FPG ≥ 126 mg/dL (OR)

3. 2-h plasma glucose ≥ 200 mg/dL (OR)

4. In a pt with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose of ≥ 200 mg/dL

(in the absence of unequivocal hyperglycemia, repeat testing)

Front 11

Who should you screen for DM?

Back 11

Adults (any age) who are overweigh or obese or have other risk factors.

Or Without risk factors start screening at age 45 and every 3 years subsequently

Front 12

Treatment goals

A1C

Back 12

< 7%

Front 13

Treatment goals

Preprandial BG (FBS)

Back 13

80-130 mg/dL

Front 14

Treatment goals

Postprandial BG

Back 14

<180 mg/dL

Front 15

Treatment goals

BP

Back 15

≤ 140/90

Front 16

Treatment goals

LDL

Back 16

As low as possible based on CVD risks

Front 17

Treatment goals

Triglycerides

Back 17

< 150 mg/dL

Front 18

Treatment goals

HDL

Back 18

> 40 mg/dL (men)

> 50 mg/dL (women)

Front 19

Treatment goals

Newly diagnosed DM2 - low risk of hypoglycemic events

A1C goal?

Back 19

More stringent goal. Pt must be compliant.

A1C < 6.5%

Front 20

Treatment goals

Less compliant pt, higher risk of hypoglycemia, higher CVD risks, shorter life expectancy

Back 20

Less stringent goal.

A1C < 8%

Front 21

DM Lifestyle Modifications

Back 21

1. Weight loss

2. Physical activity (30 min 5 day/week)

3. Diet (low carb, low fat, mediterranean)

4. Smoking cessation

Front 22

Medication Induced DM

Atypical Antipsychotics

Back 22

Olanzapine

Monitor risk factors before initiation

Monitor BG and hyperglycemic symptoms

during tx

Front 23

Medication Induced DM

Glucocorticoids

Back 23

Prednisone

Dose dependent

Hyperglycemia within hours

Monitor pts with higher risk factors

Steroid induced DM, reported but not common

Front 24

Glucocorticoid induced hyperglycemia

MOA

Back 24

1. Increased gluconeogenesis

2. Decrease cellular glucose uptake

3. Decrease cellular response to insulin

4. Increased glycogenolysis

Front 25

Special Screening tests for DM pts

Back 25

1. Nephropathy screening

(albuminuria, micro and macro, check annually)

2. Retinopathy

(comprehensive dilated eye exam, check annually)

Front 26

How does diabetes affect the kidneys?

Back 26

The integrity of the renal vascular system is

diminished --> loss of proteins in the urine.

Front 27

Foot Care in DM

Back 27

see slides 24-27

Front 28

Dietary & Nutrition considerations

Back 28

1. Mediterranean foods (monunsaturated FA's)

2. Sodium intake < 2300 mg/day

3. Moderation in alcohol

Front 29

Metformin

Use and MOA

Back 29

1st line tx in DM2 if A1C < 9% (MUST)

↓ hepatic glucose production

↓ intestinal glucose abs

↑ Insulin sensitivity

Front 30

Metformin

How do you know when to adjust medication?

Back 30

If non-insulin mono therapy at "max tolerated dose" does not achieve the A1C target within 3 months, add the second agent or basal insulin

Front 31

Metformin

What if DM2 initial A1C ≥ 9%?

Back 31

Start with dual therapy

Front 32

Metformin

ADRs

Back 32

GI (N/V, diarrhea)

Weight neutral/loss

Metabolic (lactic acidosis)

Make sure renal function is normal

Little or NO risk of hypoglycemia

Front 33

Metformin

Renal insufficiency

Back 33

Contraindicated if

Female S-Cr ≥ 1.4 mg/dL

Male S-Cr ≥ 1.5 mg/dL

or

Cl-Cr < 60 ml/min

Front 34

Sulfonylureas

Drug(s) & MOA

Back 34

Glipizide, Glimepiride, Glyburide

Stimulate insulin secretion from the pancreatic

β cells

Front 35

Sulfonylureas

ADRs

Back 35

Watch for sulfa allergy

Cause hypoglycemia

Weight gain

Glyburide avoid in pts with Cl-Cr < 50 ml/min

Front 36

Meglitinides

Drug(s) & MOA

Back 36

Repaglinide

Nateglinide

Stimulate insulin secretion from the pancreatic

β cells -- like? (Sulfonylureas)

Front 37

Meglitinides

ADRs and contraindications

Back 37

DO NOT use with sulfonylureas (same MOA)

Hypoglycemia

Reduce post-prandial BG

Weight Gain

Front 38

Thiazolidinediones (TZDs)

Drug(s) & MOA

Back 38

Pioglitazone

Roziglitazone

Increase peripheral insulin sensitivity

Front 39

Thiazolidinediones (TZDs)

ADRs & contraindications

Back 39

Cause edema

Weight Gain

Avoid in advanced heart failure (exacerbate)

Avoid in pts with active or hx of bladder cancer

Front 40

α-glucosidase inhibitors

Drug(s) & MOA

Back 40

Acarbose

Miglitol

Cause reversible inhibition of poly &

disaccharides intestinal conversion to monosaccharides --> delayed glucose abs & lower post-prandial BS

Front 41

α-glucosidase inhibitors

ADRs & contraindications

Back 41

GI side effects

Wt neutral

Do NOT cause hypoglycemia by themselves but if hypoglycemia happens, pt MUST have glucose tablets or gels

Front 42

Dipeptidyl peptidase-4 inhibitors (DPP-4 Is)

Drug(s) & MOA

Back 42

Sitagliptin

Saxagliptin

Increase insulin release from β cells

Decrease glucagon release from α cells

Reduce hepatic glucose production

Front 43

DPP-4 Inhibitors

ADRs & contraindications

Back 43

Can cause acute pancreatitis

Edema

Hypoglycemia

Wt neutral

Front 44

Glucagon-Like Peptide-1 (GLP-1) Agonists

Drug(s) & MOA

Back 44

Exenatide

Liraglutide

Increase insulin secretion

Decrease Glucagon secretion

Slow gastric empyting

Improve satiety

Front 45

GLP-1 Agonists

ADRs & contraindications

Back 45

Hypoglycemia

Wt loss

Extended release eventide associated with thyroid cancer in rats, contraindicated with hx of medullary TC

Front 46

Pramlintide

Drugs(s) and MOA

Back 46

Pramlintide

Synthetic analog of human amylin (β cells)

Slows gastric emptying, inhibits rise in serum glucagon, increases satiety

Front 47

Pramlintide

ADRs & contraindications

Back 47

Hypoglycemia

Nausea

Anorexia

Wt Loss

Front 48

Na/Glucose Cotransporter-2 (SGLT-2) inhibitors

Drug(s) & MOA

Back 48

Canagliflozin

Dapagliflozin

Empagliflozin

Inhibit the renal reabsorption of glucose,

increasing glucosuria

Front 49

SGLT-2 inhibitors

ADRs & Contraindications

Back 49

Wt Loss

BP reduction

Polyuria and UTIs (increase sugar in urine)

Renal dose adjustments needed

Front 50

Insulin

Indications

Back 50

ALL DM1 pts start tx with insulin

Many DM2 pts eventually have insulin in addition to other meds

DM2 pts with A1C ≥ 10% may be started on insulin (even at initial diagnosis)

Front 51

Types of Insulin

Back 51

Based on the onset of action and duration

Rapid acting insulin

Short acting "

Basal "

Long acting "

Front 52

Rapid Acting Insulin

Drug(s), Instructions, Duration

Back 52

Aspart

Glulisine

Lispro

15 min b4 meal or injected immediately after

Duration: 3-5 hours

Front 53

Short Acting Insulin

Drug(s), Instructions, onset and duration

Back 53

Regular insulin

Injected 30 min b4 meal

Onset within 30-60 min

Duration: 6-10 hours

Front 54

Basal Insulin (NPH)

Instructions, onset, peak and duration

Back 54

To be used with rapid or short acting insulin

Onset: a few hours

Peak: 4-8 hours

(morning --> mid afternoon, evening --> early morning)

Duration: Up to 24 hours

Front 55

Which insulin is known as "cloudy"

Back 55

Basal Insulin (NPH)

All other insulins are clear

Front 56

Long Acting Insulins

Drug(s), onset, duration, peaks, indication?

Back 56

Detemir, Glargine

Onset: 1-2 hours

Duration: Lasts for 24 hours

Peak: NO peak

Very good basal insulin for many pts

Front 57

Insulin

Side effects & ADRs

Back 57

Hypoglycemia

Wt Gain

Local skin rxns

Front 58

Insulin

Dosing for DM1 pt

(total daily dose)

Back 58

Initiate insulin therapy for a pt with DM1

Starting dose: 0.6 units/kg/day

Individualize afterward

Front 59

Insulin

Dosing for DM2 pt

(total daily dose)

Back 59

Basal insulin therapy for DM2

Starting dose: 0.2 units/kg/day

May adjust the dose by 10-15% 1-2x weekly

Front 60

Know how to calculate insulin dosage for DM1 and DM2

Back 60

TDD --> 50% glargine 1x/day, 50% RAI divided at each meal

(if pt skips a meal, skip RAI dose)

Front 61

Insulin Dose Adjustment

A1C

Back 61

Every 2-3 months initially

2x/year when stable

Fasting BS, Pre-lunch BS, Pre-dinner BS

Front 62

Dose conversions

Back 62

All dose conversions are 1:1

Front 63

Hypoglycemia

What drugs cause it?

Back 63

Insulin (#1)

Also Sulfonylureas & Meglinitides

More...

Front 64

Hypolglycemia

Symptoms

What drug class blocks these? Except?

Back 64

Dizziness, HA, diaphoresis, excessive hunger, confusion, tremor palpitation, shakiness

B-blockers (except hunger and diaphoresis)

Front 65

Hypoglycemia

How to manage (conscious)

Back 65

If pt is conscious: 15 g glucose --> 15 min --> if still low --> 15 g glucose --> repeat as needed

15g = 1 glucose gel, 3-4 tabs, 4 oz juice, 1 tb sugar, 2 tb raisins

Front 66

Hypoglycemia

How to manage (unconscious)

Back 66

Dextrose 50% IV in both DM1/2 pts

Glucagon in DM1 (a must)

Front 67

Diabetic Keto-acidosis (DKA)

MOA

Back 67

When there is NOT enough insulin --> body starts burning fat for energy --> increase serum ketones

Front 68

Diabetic Keto-acidosis (DKA)

Symptoms

Back 68

Hyperglycemia, polyuria, polydipsia, blurred

vision, dehydration

Lab: BS >300 mg/dL, pH <7.2

Front 69

Diabetic Keto-acidosis (DKA)

Treatment

Back 69

IV fluids (normal or 1/2 saline)

Insulin Regular insulin IV infusion

Potassium must be corrected bc hypokalemia is an ADR of insulin --> arrhythmia

Front 70

"Re-feeding syndrome"

Back 70

Occurs if you feed a pt too quickly after prolonged hunger --> burst of insulin (hyperinsulinemia)

--> hypokalemia

Front 71

Statin tx in DM pts

Back 71

Statin therapy is recommended for ALL DM pts except for pts younger than 40 y/o and no CVD risk factor

(LDL ≥ 100 mg/dL, smoking, HTN, BMI ≥ 25)

Statins --> ↓ cholesterol, ↓ LDL, ↑ HDL

Front 72

Aspirin in DM pts

Back 72

Men > 50 y/o ; Women > 60 y/o

At least one CVD risk factor

(HTN, proteinuria, family hx, smoking, dyslipidemia)

Take 75-162 mg/day

In younger pts with multiple risk factors -->

clinical judgment

If ASA allergy --> use 75 mg clopidogrel