Lecture 29: Treatment of Diabetes 3 Flashcards
what is the first line drug treatment of diabetes
metformin (biguanides)
where is SGLT1 found in the body and what is its role
- highly expressed in small intestine
- responsible for glucose and galactose absorption
where is SGLT2 found in the body and what is its role
- highly expressed in S1 segment of PCT
- glucose reabsorption
(>90% glucose reabsorption occurs here)
how does SGLT2 inhibition lower plasma glucose levels
- inhibits glucose reabsorption
- reduces renal threshold for glucose
- excess glucose excreted in urine
- plasma glucose levels lowered
what name ending do SGLT2 inhibitor drugs commonly have
-gliflozin
give some SGLT2 inhibitor drug examples
- dapagliflozin
- canagliflozin
- empagliflozin
when is use of SGLT2i contraindicated
- if eGFR <45mL/min
- urinary glucose excretion depends on kidney function
how can SGLT2i be prescribed
- as monotherapy
- as add on therapy to metformin or other gluc. lowering drugs incl. insulin
give some side effects of SGLT2i
- loss of calories –> weight loss and dec. of SBP
- polyuria and ^ UTI
- ^ risk of acute kidney injury
- ketoacidosis (even w/o ^ in blood glucose)
- ^ risk of osteoporosis
- risk of lower limb complications; ^ risk of amputation (mainly toe)
what are some drug interactions SGLT2i has
ACEi/ARBs and NSAIDs
how is insulin prescribed to T2D Px and why
- added to oral therapies
- particularly metformin
- Px started on single daily dose of intermediate (first line) acting ordinary insulin
- reduces weight gain and offers CV protection
when introducing insulin to T2D Px why would you consider stopping sulfonylureas
- reduce risk of hypoglycaemia
- insulin is a very potent hypoglycaemic agent
outline some indications for insulin therapy in T2D
- significant hyperglycaemia at presentation
- hyperglycaemia despite max. doses of oral agents
- decompensation:
- -> stress, infection, acute injury
- -> sever hypergly. w. ketoanaemia and/or ketonuria
- -> uncontrolled weight loss
- surgery
- pregnancy
- renal disease
- allergy or serious reaction to oral agents
when might you need to give long acting insulin therapy (second line) for T2D Px
- depending on their lifestyle
- compliance might make freq. injections inappropriate
- if unable to self inject NPH insulin
- if target HbA1c not reached
- higher risk of hypo with NPH insulin
what are thiazolidinediones
insulin resistance reducer drugs
how do thiazolidinediones work
- impact fatty acid metabolism
- bind to peroxisome proliferator activated receptors (complexed with retinoid X receptor - RXR)
- located in adipose tissue, skeletal muscle and large intestine
- TZD acts as agonist
- causes PPARy-RXR complex to bind to DNA
- promotes transcription of genes –> products involved in insulin signalling e.g. GLUT4
- ^ tissue sensitivity to glucose
- so reduce insulin resistance, ^ gluc. uptake, dec. FFA and blood glucose levels
when are TZDs effective
only in presence of insulin, either injected or endogenous
when are TZDs used
- T2D Px w/ inadequate control of hyperglycaemia esp. if sig. insulin resistance
- not used in T1D
what is a contraindication of TZD
- potential hepatotoxicity so LFTs required before starting therapy and every 2-6 months after
what are some side effects of TZD
- weight gain
- potential for heart failure esp if in combination w/ insulin
what is the only oral TZD agent now available
pioglitazone
what are other examples of a hypoglycaemic agent (not insulin, SGLT2i or TZD)
- meglitinides
- acarbose
what name ending is commonly seen in meglitinides and give some examples
-glinide
- repaglinide
- nateglinide
what are meglitinides
non-sulfonylurea oral hypoglycaemic agents
what is meglitinides MoA
- stimulates insulin secretion (insulinotropic agent)
- fast acting, short duration (can be administered between 30min or right before meals)
- causes closure of ATP dependent K+ channels
what is acarbose and how does it work
- intestinal disaccharidase inhibitor, a-glucosidase inhibitor
- taken preprandially
- delays or inhibits carb absorption
what are some side effects of acarbose
- GI –> flatulence, diarrhoea, nausea, vomiting
- elevated serum aminotransferase
- hyperbilirubinaemia rare
what vascular risk managements should be in place when treating T2D Px
- BP < 130/80 esp if microalbunuria (UACR) or early nephropathy/retinopathy
- preferential use of ACEi and ARBs if not contraindicated
- agressive lipid management e.g. atorvastatin, rosuvastatin
