<<forEachTiddler  where 'tiddler.tags.contains(context.inTiddler.title)'
sortBy 
        tiddler.title
    ascending 
write '"*[["+tiddler.title+"]]\n"'>>
<<tiddler AutoRefresh with: force>>

''Metformin''
1st line if overweight and lifestyle change ineffective
step up dose slowly to avoid GI Sx (500mg od 1/52 then bd 1/52 and review SE, may inc to 1g bd)
Mainly works to reduce hepatic glucose output (inhibit gluconeogenesis), also inc peripheral glc uptake - does not directly affect insulin secretion so Hypoglycaemic risk low.
SE - GI - anorexia (metallic taste), d&v/n, abdo pain (20% people stop cos of GI upset - try "extended absorption")
Lactic acidosis - esp if renal impairment - suspend if contrast in Xrays or GA given
BUT - no wt gain, less hypoglyc, dec macrovascular complications (MI)
CI - renal impairment (review if eGFR<45(Cr130) and stop if <30(Cr150)), ketoacidosis, recent MI, acute illness which may cause hypoxia or renal impairment 


''Sulphonylurea'' eg.''Gliclazide'' (Glimepiride)
stimulates insulin secretion via activation of a membrane-bound receptor on pancreatic beta cells (ATP dependant K channel). (irrespective of glucose concentration, so may result in  hypoglycaemia), needs functioning beta cells.
SE - GI (n/v%d/c) - mild and infrequent cf Metformin, //wt gain//, //hypoglycaemia// (esp if renal impairment (stop if eGFR,10), longer acting drugs, elderly - needs Rx in hospital as maybe prolonged), deranged LFTs (even to cholestatic jaundice and hepatitis, so severe hepatic impairment is CI as is acute porphyria, pregnancy/breast feeding and ketoacidosis)
NOTE - 10-15% don't respond to Sulphonylurea, 5-7% stop responding each year and by 10 years most will need another drug
Rare SE - SIADH, bone marrow suppress, cholestatic liver damage, photosensitivity, peripheral neuropathy


''DPP4 inhibitor'' eg. ''Sitagliptin''
dipeptidyl peptidase type 4  
DPP4 breaks down incretin hormone glucagon-like peptide 1 (GLP1). So inhibiting DPP4 prolongs effect GLP1, GLP1 stimulates insulin secretion and inhibits glucagon (amoung other things).
Note - glc dependent so if glc normal less insulin stimulation so risk hypo is low
CI - pregnancy/breast feeding, ketoacidosis, beware in hepatic(vita),renal, or heart failure (monitour LFT's) only continue if HbA1C dec by >0.5% over 6/12
SE - rarely hypoglyc, oedema, nasopharyngitis and URTI, tremor (vita), arthralgia, dizzy, headache, GI


''Exenatide'' - ''GLP-1 analogue'' (also ''Liraglutide'')
stimulates glucose-dependent insulin secretion (so risk of hypo is low), 
inhibits glucagon secretion, 
delays gastric emptying,  
suppresses appetite (centrally) 
is injectable


''Acarbose''
Inhibits enzyme alpha glucosidase in intestinal brush border leading to impaired digestion of short chain sugars so delay of glc absorption.
No direct effect on insulin secretion so no hypo.
SE - flatulence(30%) diarrhoea(16%) nausea, abdo pain, deranged LFTs
CI pregnancy/breast feeding, hernia, abdo surgery, renal/hepatic impairment, inflammatory bowel


''Biphasic insulin''
risk of hypoglycaemia esp pre-lunch and early morning (midnight to 3:00 am).


''Thiazolidinedione'' eg ''Pioglitazone''
lowers insulin resistance (by stimulating peroxidase proliferator activated receptor in adipose tissue) which improves sensitivity of peripheral tissues to endogenous insulin so reduces glucose and insulin levels (no risk of hypoglycaemia).
SE - fluid retention so inc heart failure esp if used with insulin, inc fracture risk, headache, GI, liver dysfunction, anaemia
CI - hepatic failure, heart failure, pregnancy/breast feeding