Diabetes

Question 1

What are the side effects of insulin?

Answer 1

• Hypoglycaemia
• lipohypertrophy
• lipoatrophy
• renal impairment leading to hypoglycaemia risk

Question 2

What are the contraindications of insulin?

Answer 2

• increased dose with steroids

- caution when using other hypoglycaemic agents

Question 3

Metformin

Answer 3

• is a biguanide
• reduces hepatic glucose output (gluconeogenesis, glycogenolysis)
• increases glucose utilization in skeletal muscle (reduces plasma glucose)
• suppresses appetite to limit weight gain
• usually first line
• side effects: GI upset, nausea, vomiting, diarrhoea, lactic acidosis, stop of eGFR <30
• consider: ACEi, diuretics, NSAIDS, any drugs that can impair renal function (i.e. diuretics)

Question 4

Gliclazide

Answer 4

• sulfonylureas (SU)
• increases insulin secretion by blocking ATP-dependant K+ channels, causing more calcium to come in which allows release of insulin
• need residual pancreatic function
• weight gain through anabolic effects of insulin
• typically used in combination with other agents
• used alone if metformin is contraindicated
• side effects: mild GI upset, nausea, vomiting, diarrhoea, hypoglycaemia, some rare hypersensitivity reactions
• considerations: other hypoglycaemic agents, hepatic impairment, renal impairment, thiazide like diuretics (will increase glucose)

Question 5

Pioglitazone

Answer 5

• thiazolidinediones (glitazones)
• increases sensitivity of insulin in muscle and adipose
• decreases hepatic glucose output
• activates PPAR-y for gene transcription in adipose cell
• half-life is about 6-8 weeks
• weight gain due to fat cell differentiation
• used much less frequently than other agents
• side effects: GI upset, fluid retention, fracture risk, CVD concerns, bladder cancer
• consider: other hypoglycaemic agents
• increases risk of heart failure but produces more HDLs and less LDLs compared to rosuglitazone

Question 6

Rosiglitazone

Answer 6

• thiazolidinediones (glitazones)
• same as pioglitazone
• side effects: GI upset, fluid retention, fracture risk, CVD concerns, bladder cancer
• consider: other hypoglycaemic agents
• increases MI risk but produces more LDLs and less HDLs compared to pioglitazone

Question 7

Dapagliflozin

Answer 7

• sodium-glucose co-transporter (SGLT-2) inhibitor (gliflozins)
• decreases glucose absorption from tubular filtrate
• increases urinary glucose excretion
• competitive reversible inhibitor
• modest weight loss, hypoglycaemic risk is low
• used in type 1 (risk of DKA) and type 2 as add on therapy
• side effects: UTI and genital infection, thirst, polyuria
• consider: antihypertensive and other hypoglycaemic agents, do not give to people with bladder cancer

Question 8

Canagliflozin

Answer 8

• SGLT-2 inhibitor
• same as dapagliflozin
• side effects: UTI and genital infection, thirst, polyuria
• consider: antihypertensive and other hypoglycaemic agents
• decreases weight and BP which slightly increasing LDL

Question 9

Sitagliptin

Answer 9

• dipeptidyl peptidase-4 (DPP-4) inhibitor (gliptins)
• prevents incretin (GLP-1) degradation, allowing for increase of plasma incretin levels
• useful when glucose levels rise
• has low hypoglycaemic risk
• suppresses appetite, neutral weight
• used in combo with other agents
• or first line if metformin is contraindicated
• side effects: GI upset, small pancreatitis risk, avoid in pregnancy
• consider: other hypoglycaemic agents, drugs which increase glucose (ex: thiazide like, loop diuretics)
• short half-life

Question 10

Saxagliptin

Answer 10

• DPP-4 inhibitor
• same as sitagliptin
• side effects: GI upset, small pancreatitis risk, avoid in pregnancy
• consider: other hypoglycaemic agents, drugs, diuretics
• long half-life

Question 11

Exenatide

Answer 11

• Glucagon-like peptide-1 (GLP-1) receptor agonists (incretin mimetics which act like incretin hormones)
• increases glucose dependant synthesis of insulin secretion from B-cells
• activates GLP-1 receptors (not degraded by Dpp-4)
• subcutaneous injection
• promotes satiety, possible weight loss
• NICE suggest add-on if triple therapy is ineffective
• side effect: GI upset, GORD, stop if eGFR <30ml/min
• consider: other hypoglycaemic agents
• short half-life
• disease interactions: renal impairment, pancreatitis, thyroid carcinoma, renal dysfunction

Question 12

Liraglutide

Answer 12

• GLP-1 receptor agonist
• like exenatide
• used for type 2 diabetes but can also be used for weight loss, obesity, CVS risk reduction
• longer half life compared to exenatide
• disease interactions: pancreatitis, thyroid carcinoma, depression, renal dysfunction, CVS disease