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DIABETES MELLITUS TYPE 2 (Non-Insulin Dependent) 

S/O

Assessment

Plan

Problem: S/O evidence

Etiology

Evaluation for Need of Therapy

Recommended Therapy

Goals/Monitoring Parameters

Patient Education

 

 

Subjective:

-      Gradual and maybe w/o symptoms

-       Obesity

-       Weight changes

-       Fatigue due to dehydration

-       Pruritus

-       Polyphagia(hunger)

-       Polydipsia (thirst)

-       Polyuria

-       Suseptible to infections

 

 

 

 

Objective:

-    FFG ³ 126mg/dL

-   2hrPPG ³200mg/dL

-   HbA1c > 7%

-   BP³ 140/90 mmHg

 

 

 

Risk Factors:

-    Age > 40yrs

-    Family Hx of DM2

-    Smoking

-    Obesity

-    HTN

-    CAD

-    Alcoholic

 

 

-  Test Blood GlucoseG q3yrs after age of 45

 

-  Test BG in those who are high risk:

1) obese

2) BP ³ 140/90

3)TG ³ 250mg/dl

4) Ethnic (asian, blacks, Hispanic)

 

Non-Pharmacologic: (3 months)

-                Diet (low fat, carbohydrate, salt)

-                Exercise (3-5 times a week)

-                Goal: FPG < 126mg/dl; HbA1c <7%

 

*If gylcemic goal not achieved after 4-8wks (FPG . 140mg/dl; HbA1c >8) à Drug

 

Pharmacologic:

-   Monotherapy:

1st Line:

-    Sulfonylurea(lean and insulinopenic)

-    Metformin (overweight or dyslipidemic, insulin resistence):  500mg BID

2nd Line:

-    Thiazolidinediones (insulin resist. Or renal impaired)

-    Acarbose (PostPrand. Hyperglycemic): 25mg TID

-    Meglitinides (Erratic meals, renal impairment)

-    Insulin may be considered if very symptomatic.

 

    *If Glycemic goal not achieved after 4- 8wks:

 

-  Combination therapy:

Add 2nd Oral agent:

-    Sulfonylurea + metformin

-    Sulfonylurea + TZDs

Or

-    if Post Prandial hyperglycemia:  Sulfonylurea + acarbose

Or

-    Add insulin at QHS or BID

             Dose: 0.7-2.5 U/kg/day

 

    *If Glycemic goal not achieved:

 

-          Additional :

-          Add Insulin qhs

-          Add 3rd Oral agent

-          Switch to insulin monotherapy

-          Consider referral to specialist

 

 

 

Goals:

-   PPG: 90-130mg/dl

-   QHS PG:    110-150mg/dl

-   HbA1c: < 7%

-   FPG < 126mg/dl

 

 

Monitor:

-   Blood glucose

-  Adverse Effects

-   Weight

-   BP

-   HbA1c

-   Secondary diabetic conditions (retinopathy, neuropathy, etc.)

-    Foot care

-    Drug interactions

 

-   Daily Glucose monitoring

-   Stop smoking

 

-  Stop Drinking   alcohol

 

-  Low fat diet

 

-   Low carbohydrate diet

 

-   Low salt diet

 

-  BP control

 

-   Daily Exercise

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hypoglycemic Agents

Class:

Agents/Dosage Forms/Dosing:

Indications/ MOA:

PK:

Adverse Effects

Drug Interactions/

Contraindications

Patient Education

Sulfonylurea

1st Gen: 

Chlorpropamide (Diabeinese 100mg, 25mg): 100-500mg QD  

Tolazamide (Tolinase 100,250,500mg):200-1000mg QD-BID 

Tolbutamide(Orinase 250,500):  500-3000mg BID-TID                      

 2nd Gen:

Glipizide (Glucotrol 5,10mg):  2.5-40mg QD-BID                            

Glipizide extended release (Glucotrol XL 5,10mg):  5-20mg QD                

Glyburide (Diabeta, Micronase 1.25,2.5, 5mg):  1.25-20mg QD        

Micronized Glyburide (Glynase, PresTab 1.5, 3, 6mg):  1-12mg QD     

3rd Gen: 

Glimepiride (Amaryl 1,2, 4mg):  1-8mg QD

 * For Type 2 DM             

*  New onset disease      (<5yrs)                           

*  Mild hyperglycemia            

*  Normal weight to mild obesity

 

MOA: Primary:  Stimulate release insulin release from Beta cells of pancreas                               Secondary:                               

- inhibit glucagon release          

- increase insulin Receptor binding affinity                          - Increase insulin’s effect by post receptor action                 

- decrease hepatic insulin extraction

 

 

Hypoglycemia                      Weight gain                        GI: Nausea, fullness, indigestion - take with food if happens (except for glipizide-empty stomach only)                 Hematologic: anemia, leukopenia                     Disulfiram-like Rxn:  Alcohol-related flush, HA, Lightheadedness, N/V - mainly with chlorproamide                Hyponatremia/Syndrome of Inappropriate Anti-diuretic Hormone:  incr H2O intake                    Dermatologic:  rash 

 1st Gen:  are highly protei(albumin) bound, interxn with other highly protein bound drugs(ie. Warfarin, aspirin, sulfonamide, phenyl butazone, clofibrate,  chloramphenicol)

CI:

Type I DM                           

Pregnancy                           

Hypersenstivity Rxn                   

Severe Hepatic/Renal Dysfunc    

Severe illness,surgery, stress  

 

Common SE:  GI (constipation/diarrhea heartburn, lack appetite)                   May cause alcohol intolerance                May have skin rxn       Make sensitive to sun   If forget to take a dose, take as soon as remember;  Do not double up if too close to next dose

Meglitinides

 

Repaglinide (Prandin 0.5, 1, 2mg):  0.5-4mg before meals:  Max 16mg/day

 

Nateglidine (Starlix-Norvartis)

*FDA approved for monotherapeutic use and for use in combination with metformin                     Good for ESRD

MOA:  A benzoic acid derivative;      A nonsulfonylurea insulinotropic agent;  Like sulfonylurea, stimulates insulin release from B-cells     Is Glucose dependent and is reduced at low glucose conc

Excreted in bile/ No active metabolites

Hypoglycemia- less severe than sulfonylureas                  Weight gain                           Hematologic:  thrombocytopenia; leukopenia                   Hepatic: elevated LFTs

DI:

Is metabolized by CYP450 isozymes - affected by inducers and inhibitors

 CI:

Same as above            

 

 

Take before meals 15-30mins;   If skip a meal, skip a dose;  Add a meal, add a dose for that meal.

Alpha-glucosidase

Acarbose(Precose 25,50,100 mg): 25-300mg/d QD-TID

                      

Miglitol (Glyset 25,50,100mg):  25-100mg/d  QD-TID

* A monotherapy +MNT / exercise                      * Adjunct therapy with insulin/sulfonylureas in Type 2 DM(non-FDA)    * Adj with insulin with Type I DM to reduce insulin dosage(non-FDA)

MOA:  A complex oligosac that competively inhibits intestinal enz; of small intestine.  Delays intestinal conversion of SUCROSE to glucose/fructose;  Delays starch digestion;   NO effect on absorption of Glucose, Lactose, or Dextrose;  No effect on Weight gain/lipids

< 1% systemic absorption;  Fecal elimination, degraded by GI microorganism.

GI:  flatulence, ab distention, diarrhea           Hepatic: reversible incr in LFTs

DI:

Metformin:  decr absorption of Metformin;  Chlestyramine:  enhance effect by acarbose              Miglitol: decr levels of ranitidine/propanolol

 

CI:  Type I DM;  Pregnancy /lactating. GI disorders;  Pts with cirrhosis; Renal impairmt (SCr>2); Hypersensitivity rxn    

Severe illness, surgery or stress

GI side effects- take with meals;  Have metallic taste                    Combo therapy with insulin-hypoglycemia risk                     Cause weight lost                      Decrease Lipid levels

Biguanides

Metformin (Glucophage 500, 850, 1000mg):  500-2550 mg BID-TID

MOA:  Decrease hepatic glucose output;  Increase peripheral insulin sensivity in skeletal muscle.

 

T ½ = 3 hrs

Duration: 6-12hrs

Renal Elimination;

Dialyzable

GI: Nausea, bloating, cramping, diarrhea           CNS:  H/A, agitation, dizziness, tiredness        Lactic Acidosis:rare        Malabsorption: B12 and folic acid   

DI:  Cimetidine competes with Metformin at renal tubule inhibiting its clearance and increase availability

CI:  Renal impairmt: SCr>1.5mg/dl males;   SCr>1.4 mg/dl females   Hepatic dysfunc           Alcoholism ; Lactic acidosis              Acute conditions: MI,CHF, infections, trauma, surgery

GI side effects- take with meals;  Have metallic taste; Combo therapy with insulin-hypoglycemia risk;  Cause weight lost; Decrease Lipid levels

Thiazolidinedione

Rosiglitazone (Avandia 2,4,8mg): 4-8mg/d QD-BID                              

Pioglitazone (Actos 15,30,45mg): 15-45mg/d QD                                 Troglitazone (Rezulin)-(off the market)

MOA:  Decrease insulin resistance;  Increase insulin sensitivy in hepatic, muscle and adipose tissue;  Decrease Hepatic glucose output.

T ½ = 3-7hrs

Hepatically metabolized;  Eliminate in urine/feces.  Absorption peak at 2 hrs.

Hepatic: LFTs, reversible jaundice; idiosyncratic drug rxn                           Hypoglycemia: combo therapy 

CI:  Hypersenstivity or allergy                         Hepatic impairment

If dose missed at usual meal, take at next meal;   Combo therapy:  risk of hypoglycemia;                    Reduce effectiveness in Oral ontraceptives

 

*Use these information at your own discretion.  I compiled the information from various sources.  Please don't hold me to it if the information is wrong.  If there are some mistakes...please email me and tell me.  Thanks.