T2DM Drugs Flashcards
Examples of SGLT2 inhibitors
“flozins”
- Dapagliflozin
- Canagliflozin
- Empagliflozin
Examples of DPP-2 inhibitors
“gliptins”
- Alogliptin
- Linagliptin
- Saxagliptin
- Sitagliptin
- Vildagliptin
Examples of GLP-1
- Dulaglutide
- Exenatide
- Liraglutide
- Lixisenatide
- Semaglutide
Examples of Sulfonylurea’s
- Gliclazide
- Glimepiride
- Glipzide
- Tolbutamide
Contraindications of DPP-4 inhibitors “gliptins”
Ketoacidosis
Contraindications of GLP-1
- Ketoacidosis
- Severe GI disease (not for liraglutide or semaglutide)
- Liraglutide: diabetic gastroparesis, IBD
- Use with caution in patients with a history if acute pancreatitis and diabetic retinopathy
Contraindications of Pioglitazone
- History of HF
- Bladder cancer (previous or current)
- Uninvestigated macroscopic haematuria
use with caution in:
- elderly
- patients at risk of bone fractures
Contraindications of SGLT2 inhibitors “flozins”
Ketoacidosis
Contraindications of Sulfonylurea
- Pregnancy
- Ketoacidosis
- Acute porphyrias
- Caution in the elderly and those with G6PD deficiency
- When used as a monotherapy (which is not recommended due to adverse effects), gliclazide increases the risk of cardiovascular disease and myocardial infarction.
DPP-4 inhibitors (“Gliptins”) effect on weight
None
GLP-1 effect on weight
Loss
Insulin effect on weight
Gain
Pioglitazone effect on weight
Gain
SGLT-2 inhibitor effect on weight
Loss
Sulfonyylurea effect on weight
Gain
DPP-4 inhibitors (“Gliptins”) risk of Hypoglycaemia
Low
GLP-1 risk of Hypoglycaemia
Low
Insulin risk of Hypoglycaemia
High
Pioglitazone risk of Hypoglycaemia
Low
SGLT2 inhibitors (“flozins”) risk of Hypoglycaemia
Low
Sulfonylurea risk of Hypoglycaemia
Moderate, High in older people
Renal impairment with DPP-4 inhibitors (“Gliptins”)
Dose reduction or caution (not for linagliptin)
Renal impairment with GLP-1
Dose reduction or caution or avoid (depends on eGFR thresholds)
Renal impairment with Insulin
Dose reduction
Renal impairment with Pioglitazone
No warnings
Renal impairment with SGLT2 inhibitors (“flozins”)
Dose reduction or caution or avoid (check eGFR thresholds)
Renal impairment with Sulfonylurea
Dose reduction or caution or avoid (check eGFR thresholds)
Hepatic impairment with DPP-4 inhibitor (“Gliptins”)
Caution or avoid (not for linagliptin and sitagliptin)
Hepatic impairment with GLP-1
Caution or avoid (not for Dulaglutide, exenatide and lixisenatide)
Hepatic impairment with Insulin
Dose reduction
Hepatic impairment with SGLT2 inhibitors (flozins”)
Caution or avoid
Hepatic impairment with Pioglitazone
Avoid
Hepatic impairment with Sulfonylurea
Caution or avoid
Contraindications of Metformin
Acute metabolic acidosis (including lactic acidosis and diabetic ketoacidosis).
Use with caution in patients at risk of lactic acidosis (e.g., chronic heart failure, chronic alcohol abuse) and in patients with an eGFR less than 30.
Metformin effect on weight
None
Metformin hypoglycaemia risk
Low
Renal impairment with Metformin
Dose reduction or avoid (check eGFR thresholds)
Hepatic impairment with Metformin
Withdraw if tissue hypoxia likely
What T2DM drug has a proven cardiovascular benefit
SGLT2 inhibitors
(Sodium-glucose co-transporter 2 inhibitors)
What is the first line pharmacological treatment of T2DM
Metformin
Or metformin MR if GI disturbance
First line treatment for T2DM in patients with Chronic heart failure or established atherosclerotic CVD
Start Metformin alone to assess tolerability THEN add a SGLT2 inhibitor (“flozin”) as it has a proven cardiovascular benefit
Offer SGLT2 alone of Metformin contraindicated
First line treatment for T2DM in patients with High risk of CVD or
Start Metformin alone to assess tolerability THEN add a SGLT2 inhibitor (“flozin”) as it has a proven cardiovascular benefit QRISK of 10% or higher or elevated lifetime risk
Offer SGLT2 alone of Metformin contraindicated
What is the first-line pharmacological treatment of T2DM if there is no high CVD risk and Metformin in contraindicated
- DPP-4 inhibitor “Gliptin”
- Pioglitazone
- Sulfonylurea
- an SGLT2 inhibitor for some people
Only a monotherapy in those who have contraindications to Metformin and if only a DPP-4 would otherwise be prescribed and a Sulfonylurea or Pioglitazone is not appropriate
What is the “rescue” therapy in a patient with T2DM
For symptomatic hyperglycaemia, consider insulin or Sulfonylurea and review when blood glucose control has been achieved
Further treatment for T2DM at any point if HBA1c not controlled or below individually agreed threshold
Switch or add treatments:
Consider:
- DPP-4 inhibitor “Gliptin” or
- Pioglitazone or
- Sulfonylurea
SGLT2 inhibitors optional in dual or triple therapy
Further treatment for T2DM at any point if cardiovascular risk or status changes e.g. person has or develops chronic HF or established atherosclerotic CVD or if a person has or develops high risk if CVD (QRISK >10% or elevated lifetime risk)
Switch or add SGLT2 inhibitor
When to give GLP-1 mimetic treatments
If triple therapy with Metformin and 2 other oral drugs is not effective, not tolerated or contraindicated = consider triple therapy by switching one drug with GLP-1 mimetic for adults with type 2 DM who:
- BMI 35 or higher (adjust according to ethnicity)
- BMI<35 BUT insulin is not suitable or weight loss would benefit other significant obesity related comorbidities
Side effects of GLP-1 agonists
- Nausea and vomiting
- Acute pancreatitis (rare)
- Lipodystrophy at site of injections if injection sites aren’t rotated
Side effects of Sulfonylureas
Common side effects of sulfonylureas include:
- Hypoglycaemia
- Weight gain
Less common side effects include:
- Hyponatraemia secondary to syndrome of inappropriate ADH secretion (SIADH)
- Hepatotoxicity
- Peripheral neuropathy.
Side effects of SGLT2 inhibitors “flozin”
- Genital and urinary tract infections
- Hypoglycaemia
- (Rarely) euglycaemic diabetic ketoacidosis
It is therefore important to have a low index of suspicion of this in any unwell diabetic patient on a gliflozin, regardless of them having a normal blood glucose level. - They may also cause weight loss, which may be useful in patients with type 2 diabetes mellitus.
Example of a Thiazolindinedione
Pioglitazione
Side effects of Pioglitazone
- Weight gain
- Liver impairment (LFTs before treatment and therafter)
- Bone fracture
- Fluid retention (they are therefore contraindicated in heart failure)
- Increased risk of bladder cancer
They are less commonly used due to their adverse effect profile.
Side effects of Metformin
- GI upset (diarrhoea and abdominal pain). This is intolerable in 20% of patients and may be discontinued due to this. Modified-release metformin should be considered instead. In order to reduce the incidence of gastrointestinal side-effects, the dose of metformin should be titrated up slowly.
- Lactic acidosis. This is a rare side effect, and mainly in patients with severe liver disease and renal failure, or if taken during a period where there is tissue hypoxia. For example, sepsis, acute kidney injury (AKI), severe dehydration or recent myocardial infarction.
Notably, it does not typically cause hypoglycaemia or weight changes.
Monitoring requirements with Metformin
Renal function before starting treatment and at least annually thereafter
