호주 - 당뇨약/ 당뇨병 치료약 종류 , 기전, 부작용

Types of drugs

1) Metformin

o   MOA (mechanism of action) 

     - Decreases hepatic glucose production

     - Increases glucose uptake into muscles

o   1.5-2% HbA1c decrease

o   Large decrease in fasting glucose production

o   Minor decrease in post-prandial glucose production

o   Adverse drug effect (ADE) 부작용 

  GIT nausea and B12 malabsorption - rare

o   As monotherapy - no hypoglycaemia risk

o   FIRST LINE AGENT   

    -  For nearly all patients

 

 

2) Sulfonylureas - Gliclazide

o   MOA

   -  Binds to sulfonylurea receptor on pancreatic beta cells

          ·       Increases insulin secretion INDEPENDENT of BGL

          ·       Not suitable for use in complete beta-cell failure

o   0.8-2% HbA1c decrease

o   Large fasting BGL reduction and moderate post-prandial BGL reduction

o   ADE

   -  Weight gain

         ·       Not suitable for obese patients

   -  GIT upset

o   Hypoglycaemia is common

      -  May not be suitable in elderly patient with high risk of falls

 

 

3)  GLP-1 agonist - Exenatide

o   MOA

   - GLP-1 analogue that binds to receptor

      ·       Stimulates insulin secretion in a BGL dependent manner

      ·       Decrease glucagon secretion

      ·       Reduces hepatic glucose production

      ·       Slows gastric emptying and increases satiation

o   0.5-1% HbA1c decrease

o   Large decrease in both fasting and post-prandial glucose

o   ADE

   -  GIT symptoms

   -  Decreased appetite and weight loss

       ·       Useful in obese patients

   -  Pancreatitis

o   Hypoglycaemia is rare with monotherapy

 

 

4)  DPP-4 inhibitors - sitagliptin

o   MOA

  -  DPP-4 inhibits GLP-1

  -  DPP-4 inhibitors block the DPP4 binding site on GLP-1

     ·       Inhibit DPP4 from inactivating GLP-1

  -  Increases activity of GLP-1

     ·       Increases glucose-dependent insulin secretion

     ·       Decreases glucagon secretion

o   0.5-0.8% HbA1c reduction

o   Minimal fasting glucose reduction

  -  Large post-prandial glucose reduction

o   ADE

  -  Pancreatitis

o   No hypoglycaemia with monotherapy

 

 

5)   SGLT-2 inhibitors - empagliflozin

o   MOA

   -  Binds and inhibits the Na/glucose transporter in PCT of nephron

o   0.7-1% decrease in HbA1c

o   Moderate decrease in fasting and post-prandial glucose

o   ADE

  -  Candidiasis

  -  UTIs

  -  Euglycemic DKA

o   Low risk of hypoglycaemia

o   Has cardiovascular disease benefits

   -  Preferentially given if patient has a history of CVDs

o   Not useful in patients with renal failure as target is in the kidney

Type 1

·       Insulin replacement

·       Insulin regiments

   o   Basal-bolus

      *  Basal - approx 40% of daily dose

           ·       Background - typically given at night

           ·       Intermediate or long acting insulin

      *  Bolus - approx 60% of daily dose

            ·       Used to cover carbohydrate intake with meals

            ·       Use short of ultra-short acting insulin

       *

  

    o   Split-mixed

        -  Limited role in therapy of type 1

        -  Combines a short/ultra short acting with intermediate acting

        -  Generally used to decrease number of daily injections

            ·       Difficult to tailor dose to specific BGL/patient

        -  Higher risk of hypoglycaemia due to dose stacking

   o   Continuous SC infusion

      -  Small programmable pump device outside the body

              ·       Fine needle and cannula below the skin

      - Delivers continuous steady rate of short or ultra-short acting basal insulin + bolus between meals

      -  Indications

         ·       Failed other regiments

      -  Improved HbA1c and QOL

      -  Expensive

 

Type 2

·       Lifestyle

      o   Exercise

      o   Dietary changes

      o   Weight loss

·       Non-T2DM pharmacology

     o   Management of BP

        -  ACEI or ARB

     o   Management of dyslipidemia

         -  Statin therapy

·       T2DM pharmacology

   o   First line

       -  Metformin

o   Second line

     -  Metformin + Addition depends on patient

          ·       Heart failure or high CVD risk

                     ·       SGLT2 inhibitor - empagliflozin

          ·       Renal failure

                     ·       CANNOT use SGLT-2 inhibitor

                     ·       Use DPP4-inhibitor - sitagliptin

           ·       Very high post-prandial BGL

                      ·       Sulfonylurea - gliclazide

           ·       Overweight patient

                       ·       CANNOT use sulfonylureas

o   Third line

       -  Consider triple oral therapy of metformin + 2 others

       -  OR metformin + exenatide OR insulin

o   Insulin

  -  Insulin can be added anywhere in the treatment algorithm

 

·       Management of hyperglycaemia

      o   Many considerations to take with how stringent the management is

 

 

·       Patient education

          o   Discuss at diagnosis that it is likely that the patient will require insulin

                  -  Insulin doesn't indicate patient failure or therapeutic failure - indicates pancreatic failure

          o   Needle phobias

          o   Weight gains