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YA - Interactive seminars/University lectures > ENDO - Diabetes management and therapeutics > Flashcards

ENDO - Diabetes management and therapeutics Flashcards

1
Q

describe currently available oral hypoglycaemic agents used in Type 2 Diabetes and the rationale for drug use

A
  • Metformin (First line. CI in renal impairment)
  • Sulphonylureas (Second line. used if HbA1c is above target on metformin. Risk of hypos - CI in some professionals)
  • α-Glucosidase inhibitors
  • Thiazolidinediones (E.g. Glitazone. Third line if SU CI. no hypos but weight gain)
  • DPP4 inhibitors (Third line if SU CI. induces weight loss)
  • GLP-1 analogues (Third line if SU CI.induces weight loss)
  • SGLT2 inhibitors (will be available in Australia late 2013)
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2
Q

explain the indications of specific oral hypoglycaemic agents

A

(Step down every time HbA1c is above target)
1. Starting with metformin at diagnosis as first line.

  1. SU
    - DPP4 inhibitor if SU CI
    - GLP1 analogue if SU CI & significantly overweight
  2. Triple therapy
    - metformin + SU + DPP4i
    - metformin + DPP4i + SU
    - metformin + GLP1 + SU
  3. Add daily insulin (basal or premix). DPP4i or GLP1 are usually ceased when insulin is added!
    - metformin + SU + insulin
  4. Multiple insulin doses (SA + LA)
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3
Q

describe the major insulins and insulin regimens used to treat both type 1 and type 2 diabetes.

A

Short acting: aspart, glulisine, lispro

  • Onset 10-20 minutes
  • Peak, 1-3 hrs
  • Duration 3.5-4.5 hrs

Long acting: detemir, glargine

  • Onset: 2-4 hrs
  • Peak: 8-10 hrs detemir, variable for glargine
  • Duration: 14-16 hrs detemir 16-24 hrs for glargine

T1D:
Use short acting insulin just before meals with carbs calculation & use long acting at night before bed for a basal line to mimic the physiological insulin levels.

T2D:

  • Glargine (LA) before bed at initiation
  • Mixtard 30/70 at dinner (once a day) or Mixtard 30/70 BD at breakfast & dinner
  • concurrent use of Metformin BD (breakfast & dinner) + Gliclazide MR at breakfast if daily insulin at dinner
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4
Q

What is the evidence base for diet and lifestyle modifications in the management of diabetes?

A
  • intensive glycaemic control reduces compilcations in type 1 diabetes
  • early glycaemic control reduces CVD many years later; “legacy effect
  • Aim for very good control early in the course of diabetes
  • An individual’s HbA1c target must be balanced against the risk of hypoglycaemia
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5
Q

What are the aims of blood glucose management in diabetes?

A
  • Relieve Symptoms
  • Prevent or delay long term complications
  • Avoid adverse effects of treatment (hypoglycaemia)
  • Assist psychological adjustment and improve QOL
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6
Q

What is the balance between strict glycaemic control and hypoglycaemia?

A
  • EARLY intensive glycaemic control reduces mortality and complications (C.f. Tight control LATE in type 2 diabetes offers little benefit for CV complications)
  • HbA1c
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7
Q

What level of HbA1C reduces microvascular Cx irrespective of duration of disease?

A

less than or equal to 7.0%

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8
Q

How can you prevent a hypo by a dietary factor or a pharmagolocial factor? (e.g. hypo pre-lunch)

A

Switching to lower GI foods (whole grain bread, low GI cereal, porridge, baked beans, etc) -> slower carbohydrate absorption and higher pre-lunch glucose.

A mid-morning snack may be helpful

Changing to more frequent insulin administration is the optimal solution.
E.g. Novorapid (insulin aspart): 6, 6, 8. Lantus (Glargine): 14 before bed.

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9
Q

What are the principals of insulin therapy in T1D?

A

•Rapid acting analogues generally favoured for most patients
•Long acting analogues are best for basal insulin
•“Basal bolus” regimen preferred:
- Rapid acting insulin analogue with meals (bolus).
- Long acting insulin once or twice a day to provide background (basal) insulin level (which T1D lacks).
•Some patients will be suitable for continuous insulin infusion via a portable pump.

Ideally, basal insulin and mealtime short-acting insulin should be used to mimic normal insulin production and control post-prandial hyperglycaemia

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10
Q

When would you typically inject short acting & long acting insulin?

A

Short acting insulin just before meals (do carb calculation)

Long acting at night after dinner, which lasts throughout the day

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11
Q

What is a major contributor to HbA1C especially at lower HbA1c levels?

A

Post prandial glucose

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12
Q

Describe rapid acting insulin.

  • examples
  • onset
  • peak
  • duration
A

aspart, glulisine, lispro

  • Onset 10-20 minutes
  • Peak, 1-3 hrs
  • Duration 3.5-4.5 hrs
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13
Q

Describe long acting insulin.

  • examples
  • onset
  • peak
  • duration
A

Insulin detemir (Levemir)
•Onset of action: 2 hours
•Peak action: 8-10 hours
•Duration of action: 14-16 hours

Insulin glargine (LANTUS)
•Onset of action: 2-4 hours
•Peak action: variable 8-16 hours
•Duration of action: 21-24 hours

True “peakless” insulins are currently in development

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14
Q

What are the principals of T2D therapy?

A
  • Weight loss (80% + overweight)
  • Exercise

•Oral anti-diabetic agents:

  • Monotherapy
  • Dual oral therapy
  • Triple oral therapy (sometimes used)
  • Insulin

•Manage CV risk factors: lipids, hypertension, smoking, etc.

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15
Q

What are types of oral anti-diabetic agents commonly used in T2D?

A
  • Metformin (CI in renal impairment) - first line. Except in renal function. Reduce dose if eGFR less than 40, and cease if less than 30.
  • Sulphonylureas (risk of hypos. e.g. Gliclazide).
  • α-Glucosidase inhibitors
  • Thiazolidinediones (e.g. glitazone)
  • DPP4 inhibitors (induces weight loss)
  • GLP-1 analogues (induces weight loss)
  • SGLT2 inhibitors (will be available in Australia late 2013)
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16
Q

What are the principals of drug therapy in T2D?

A

Choice of drug depends on the individual
•Renal impairment: caution with metformin
•Hypoglycaemia a danger: avoid SU and insulin (if possible)
•Overweight: GLP1 and DPP4i an advantage, avoid glitazone
•Long duration of diabetes: β cell function likely to be reduced - insulin often required

17
Q

Describe metformin as a treatment for T2D

A
  • Metformin is first line in most patients
  • Inhibits hepatic glucose production

(+): No weight gain; no major hypoglycaemia!!

(-): GI intolerance is main SE (nausea, diarrhoea) – minimised by using slow release form (XR)

•C/I in renal failure: risk of lactic acidosis. Reduce dose if eGFR

18
Q

Describe sulphonylurea as a treatment for T2D

A

E.g. Gliclazide (c.f. Glitazone), glipizide, glibenclamide, glimepiride

  • Stimulate B cell insulin release
  • Usually 2nd line in type 2 diabetes

(-): weight gain, hypoglycaemia (gliclazide less than others) - C/I or use with caution in pilots, professional drivers, etc.

  • Rapidly effective – start with a low dose
  • Added if HbA1C is above target on maximal tolerated metformin (up to 2000mg)
  • Gliclazide is the SU of choice: backed by good trial evidence. Has same efficacy but less hypoglycaemia than comparable SU’s
19
Q

What should you use if HbA1C is above target on metformin and SU is contraindicated? Discuss +s and -s of DPP4 inhibitors, GLP-1 agonists, Glitazone (pioglitazone)

A

You could use DPP4-inhibitors, GLP1 agonists or glitazone.

  • DPP4 I – efficacy fair, no hypo’s, no weight gain
  • GLP-1 – efficacy good, no hypo’s, WEIGHT LOSS but requires injection
  • Glitazone (pioglitazone) – efficacy good, no hypo’s but WEIGHT GAIN, fluid retention, bone loss etc.
20
Q

Describe managements at initiation of insulin in T2D

A
  • Most patients are insulin resistant and large insulin doses may be required
  • Metformin is usually continued
  • Sulphonylureas (SU) are continued if once daily insulin is started.

Insulin:
•Once daily: Pre-mixed insulin pre-dinner or glargine at bed time and continue oral agents
•Twice daily: BD pre-mixed insulin and continue metformin

21
Q

Describe Alpha-Glucosidase inhibitors (Acarbose) as an oral-hypoglycaemic agent

  • mechanism
  • (+)
  • (-)
A

•Inhibits gut alpha glucosidase , the enzyme that breaks down starches and disaccarides

(+): No weight gain or hypoglycaemia

(-): flatulence (poor tolerance). Must be used with first mouthfuls of food to be effective

22
Q

Describe thiazolidinediones (oral-hypoglycaemic agent)

A

(glitazones) pioglitazone, rosiglitazone

  • Stimulate ppar gamma and REVERSE insulin resistance
  • Effects additive to metformin and S/U (and insulin)

(+): no hypoglycaemia

(-): weight gain, fluid retention and CCF, bone fractures, possible bladder cancer risk (Pio), increase CV events (Rosi – now rarely used)

23
Q

Describe GLP-1 analogues (oral-hypoglycaemic agent)

A

Exenatide, liraglutide

  • Improve pancreatic islet glucose SENSING and insulin release
  • Slow gastric emptying and improve satiety leading to weight loss in most patients
  • Used mainly in obese patients with diabetes

(+): weight loss
(-): nausea, vomiting, pancreatitis? (no long-term data), Hypoglycaemia – rare if used alone

•Given as s/c injection before meal ( liraglutide daily; exenatide BD)

24
Q

Describe DPP-4 inhibitors (oral-hypoglycaemic agent)

A

Sitagliptin, vildagliptin, saxagliptin, linagliptin

•Prolong GLP-1 action, leading to improved ß-cell sensing: INCREASE INSULIN SECRETION, decrease glucagon secretion

  • Commonly used second line after metformin if sulphonylureas are C/I
  • Several are available in combination with metformin

(+): no hypos if used alone
(-): occ nausea, hypersensitvity (no long term data)

25
Q

Describe SGLT2 inhibitors (oral-hypoglycaemic agent)

A

Gliflozins, Dapagliflozin

• (make you pee sugar) Promote glycosuria, thus lowering blood glucose

(+): mild weight loss, no hypo if used alone

(-): Candida genital infections

•Long term effects unknown (new drug – no post marketing information)

26
Q

Describe regular insulin (not SA or LA).

  • examples
  • onset
  • peak
  • duration
A

Actrapid
Humulin R

  • Onset of action: 30 minutes
  • Peak action: 2-4 hours
  • Duration of action: 5-8 hours

Used for IV injections & infusions when SA analogues have no advantage in IV use + cost more

27
Q

Describe medium-acting insulin (not SA or LA).

  • examples
  • onset
  • peak
  • duration
A

NPH (neutral protamine Hagedoorn)

  • Onset of action: 2 hours
  • Peak action: 6-10 hours
  • Duration of action: 12-16 hours

This is a cloudy insulin
Used in “pre-mixes”

28
Q

Describe pre-mixed insulin

  • examples
  • onset
  • peak
  • duration
A

A mixture of regular (Mixtard) or short acting analogue (Novomix, Humalog mix) with NPH insulin (medium acting)

  • Onset of action: 10 minutes
  • Double peak action: 1-3 hours and 6-10 hours
  • Duration of action: 12-16 hours
  • Frequently used BD in type 2 diabetes
29
Q

explain the mechanisms of action of oral hypoglycaemic agents

  • Metformin
  • SU
  • Alpha-Glucosidase inhibitors (Acarbose)
  • Thiazolidinediones
  • GLP-1 analogues
  • DPP4 inhibitors
  • SGLT2 inhibitors
A
  • Metformin (biguanide class): Inhibits hepatic glucose production
  • SU: Stimulate B cell insulin release
  • Alpha-Glucosidase inhibitors (Acarbose): Inhibits gut alpha glucosidase (the enzyme that breaks down starches and disaccarides)
  • Thiazolidinediones: Stimulate ppar gamma and reverse insulin resistance. But weight gain
  • GLP-1 analogues: Improve pancreatic islet glucose sensing and insulin release. Slow gastric emptying and improve satiety leading to weight loss in most patients
  • DPP4 inhibitors: Prolong GLP-1 action, leading to improved ß-cell sensing: increase insulin secretion, decrease glucagon secretion
  • SGLT2 inhibitors: Promote glycosuria, thus lowering blood glucose
30
Q

What oral hypoglycaemic agents can cause hypoglycaemia? What else should you avoid in risk of hypoglycaemia?

A

Sulphonylureas (Gliclazide)

Insulin

31
Q

What does DCCT (diabetes controlled complications trial) show?

A

Intensive glycaemic control reduces complications in type 1 diabetes over 6.5 years; retinopathy > neuropathy > nephropathy

32
Q

What does DCCT/EDIC (diabetes study) show?

A

Early glycaemic control reduces CVD many years later in type 1 DM: “(metabolic) legacy effect”. 57% risk reduction in non fatal MI, stroke or CVD death.

But also legacy effect in T2D.

33
Q

Intensity of glycaemic control for most benefit

A

Strict control early on (HbA1C less than 7.0) -> relax later on (Late tight control does little benefit in T2D)

HbA1C target is different for different conditions & criteria.

34
Q

Which oral hypoglycaemics are still continued on insulin?

A

Metformin

Sulphonylurea is also continued only on daily insulin (long acting; not short acting)

35
Q

Difference between Novomix & Mixtard

A

They are both combination insulins with short acting & medium acting.

Novomix has novorapid as its short acting insulin, which has a faster onset of 10-20 minutes compared to Mixtard which has Actrapid as its short acting insulin, which has a slower onset of 20-30 minutes.

Hence Novomix is taken with the meal, Mixtard is taken before the meal.

Novomix is more commonly used now due to less complications of delayed meal & causing hypoglycaemia etc

YA - Interactive seminars/University lectures (87 decks)

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