Lecture 21: Management of Type 2 Diabetes Mellitus Flashcards
what investigations and support should a type 2 diabetic patient expect from their care?
list
- blood glucose level monitoring
- blood pressure monitoring
- blood lipids monitoring
- eyes screened
- feet checked
- kidney function checks
- weight
- smoking cessation support
- individual care plan
- education course
- emotional and psychological support
which drugs are offered to increase insulin release in type 2 diabetes?
list
- sulphonylureas
- metiglinides
- incretin mimetics
- DPPIV inhibitors
which group of drugs are used to increase excretion of glucose?
SGLT2 inhibitors
which treatments are used to improve insulin action in type 2 diabetics?
list
- biguanides
- thiazolidiones
- weight reduction
- physical activity
5 step framework for choosing a glucose lowering drug
- Set a target HbA1c
- ‘Take 5’ are there other risk factors that should also be treated?
- Are the current treatments optimised? Max dose? Tolerated? Taken?
- What are the glucose lowering options? > remove any that are contraindicated, of the remaining what are the pros and cons, select the preffered choice?
- Agree a review date and the target HbA1c with the patient.
why is metformin normally the first choice of medication used to treat type 2 diabetes?
- improves outcomes
- well-tolerated
- cheap
what class of drug is metformin?
biguanide
how does metformin work?
Improves insulin sensitivity:
- affects glucose production, decreased fatty acid synthesis
- improves insulin receptor function
- inhibits gluconeogenic pathways
what is the half-life of metformin?
6 hours
list the advantages of metformin
- improves CV outcomes and mortality in obese T2 DM patients.
- efficaceous: used alone can decrease fasting blood blucose by 22-26%.
- normally well tolerated
- not associated with weight gain
- HbA1c by 12-17% reduction
- also used in pregnancy
- cheap
disadvantages/side-effects of metformin
- GI side effects 20-30%
- risk of lactic acidosis by inhibiting lactic acid uptake by liver: hypoxia, renal failure, hepatic failure, alcohol abuse
- risk vitamin B12 malabsorption
give examples of sulphonylureas
The ‘Gli….ides’:
- Glimerpiride
- Gliclazide
- Glipizide
when are sulphonylureas indicated?
- if osmotic symptoms or HbA1c increasing rapidly titration based on home blood glucose monitoring.
target tissue of metformin
liver
target tissue of sulphonylureas
pancreas
mechanism of action of sulphonylureas
Increases insulin release:
- binds to sulfonylurea receptors (SUR-1) on functioning pancreatic beta-cells.
- binding closes the ATP sensitive K+ channels.
- decreased potassium influx depolarisation of the beta-cell membrane.
- voltage-dependent calcium channels open and result in an influx of calcium.
- causes translocation and exocytosis of secretory granyles of insulin to the cell surface.
advantages of sulphonylureas
- rapid improvement in blood glucose control
- rapid improvement if symptomatic
- rapid titration
- cheap
- generally well-tolerated
disadvantages of sulphonylureas
- risk of hypoglycaemia
- weight gain
- caution in renal and hepatic disease
- CI in pregnancy and breastfeeding
- Side effects: hypersensitivity and photosensitivity reactions, blood disorders.
target tissues of thiazolidinediones (‘…glitazones’)
adipose tissue
liver
muscle
mechanism of Pioglitazone
a thiazolidinedione
Improves insulin action:
- reduces insulin sensitivity in the liver and peripheral tissues
- increases the expense of insulin-dependent glucose
- decreases withdrawal of glucose from the liver
- reduces quantity of glucose, insulin and glycated haemoglobin in the bloodstream.
pioglitazone advantages
- good for people if insulin resistance significant
- HbA1c reduced by 0.6-1.3%
- cheap
- cardiovascular safety established
pioglitazone disadvantages
- increased risk of bladder cancer
- fluid retention - CCF
- weight gain
- small increased risk of fractures in females
supplementary insulin therapy drug names
Isophane insulin:
- Humulin I
- H insulatard
once daily injection, usually at bedtimes
list examples of SGLT2 inhibitors
’..gliflozins’:
- canagliflozin
- dapagliflozin
- empagliflozin
how do SGLT2 inhibitors work?
- they selectively inhibit SGLT2 in the renal proximal tubule, preventing the reabsorption of glucose into the bloodstream.
- increases urinary glucose excretion.
effects of SGLT2 inhibitors
positive and negative
- gets rid of glucose/more glycosuria > lowers HbA1c
- gets rid of water/osmotic diuresis > can cause (postural) hypotension and dehydration
- gets rid of calories/wastes glucose > lose weight with same intake
- gets rid of sodium/less reuptake > lowers systolic blood pressure
- greater risk of urogenital infection > cystitis and cadidiasis
what is the 1st line therapy for those with a high CV risk when metformin not tolerated?
SGLT2 inhibitors
what is the 2nd line therapy in those at high CV risk (started immediately after metformin tolerability established)?
SGLT2 inhibitors
advantages of SGLT2 inhibitors
- weight loss
- no risk of hypoglycaemia
- good effects on glycemic control
- beneficial effect on CV morbidity and mortality and renal outcomes
- 2nd or 3rd line agents
- can add to insulin regimens in T2DM
disadvantages of SGLT2 inhibitors
- expensive
- side effects: UTI, fungal infections, osmotic symptoms
- risk of digital amputation
- risk of diabetic ketoacidosis (DKA)
- contraindicated in pregnancy and breastfeeding
- cannot use in renal impairment
Give examples of DPPIV inhibitors
incretin mimetics
…Gliptins:
- saxagliptin
- sitagliptin
- vildagliptin
mechanism of action of gliptins (DPPIV inhibitors)
delay the breakdown of incretins such as GLP1 and GIP and thereby increase active incretin levels > stimulate pancreatic B cells > secretion of insulin
DPPIV inhibitors (gliptins) advantages
- usually well-tolerated
- can be used as 2nd or 3rd line agent
- can be used in renal impairment
- no risk of hypoglycaemia
- weight neutral
DPPIV inhibitors (gliptins) disadvantages
- trial data shows relatively small effects on glycemic control
- contraindicated in pregnancy and breastfeeding
- side effects: nausea
give examples of GLP-1 analogues
incretin mimetics
‘…tides’:
- exenatide
- liraglutide
- lixisenatide
mechanism of actions of GLP1 analogues
act as incretin mimetic > stimulates pancreatic B-cells to secrete insulin
- resistant to enzymatic degredation
- greatly prolonged biological half-life
GLP-1 analogues advantages
- weight loss
- no risk of hypoglycaemia
- 3rd line agent
- can be used with basal insulin
- some have benfit for CV disease
GLP-1 analogues disadvantages
- injection
- expensive
- contraindicated in pregnancy and breastfeeding
- side effetcs: nausea and vomiting
For adults whose type2 diabetes is managed either by lifestyle and diet, or lifestyle and diet combined with a single drug not associated with hypoglycaemia, support them to aim for an HbA1c level of…
48 mmol/mol
For adults on a drug associated with hypoglycaemia, support them to aim for an HbA1c level of
53mmol/mol
In adults with type2 diabetes, if HbA1c levels are not adequately controlled by a single drug and rise to 58mmol/mol (7.5%) or higher, what is the course of action?
- reinforce advice about diet, lifestyle and adherence to drug treatmentand
- support the person to aim for an HbA1c level of 53mmol/mol (7.0%)and
- intensify drug treatment.
Consider relaxing the target HbA1c level on a case-by-case basis and in discussion with adults with type2 diabetes, with particular consideration for people who are older or frailer, if:
- they are unlikely to achieve longer-term risk-reduction benefits, for example, people with a reduced life expectancy
- tight blood glucose control would put them at high risk if they developed hypoglycaemia, for example, if they are at risk of falling, they have impaired awareness of hypoglycaemia, or they drive or operate machinery as part of their job
- intensive management would not be appropriate, for example if they have significant comorbidities.[2015, amended 2022]
