I would be guided by the NICE guidelines and usually go for a sulphonylurea. CG66 covers basic prescribing with detailed justification. The second URL is for the recent update covering 'newer agents.

http://guidance.nice.org.uk/CG66

http://www.nice.org.uk/nicemedia/live/12165/44318/44318.pdf

I should add of course that a HbA1c of 58mmol/mol may be acceptable in some patients with T2DM. I note that individualisation is assumed for the purposes of this discussion!

Hello Richard, So Which research guides the above answer, which may be correct but glucotoxicity still remains to cause metabolic mayham.

The research is all documented very clearly in the guidelines. Review of the ADA position statements and recent EASD guidelines is interesting also. Of course glycaemic control matters. Focusing on T2DM, UKPDS made this point very clearly. However, balance is everything. For a while, the drive was for ever tighter control. We then woke up and review of the more recent guidelines, in the context of those of the early 2000s, is fascinating as there has been a progressive backing off from this 'physiological' very tight control as the downsides have been recognised. Now of course being philosophical for a moment, this is only because our medications are imperfect and yes, if it could be achieved safely, perfect control would be best. But it can't. The ACCORD, ADVANCE and VADT studies have addressed this, overall the conclusion being that very tight control is associated with excess morbidity and mortality. Still the control achieved in these studies was better than the HbA1c of 58mmol/mol your quote. But we need to remember the aims here. In T2DM, and with a HbA1c of 58 mmol/mol, it is as much prevention of macro vascular disease as microvascular disease that is of interest. Proof of protection from macrovascular disease by tight glycaemic control is lacking. And tight control in someone with cardiovascular disease in particular, may be dangerous. So metabolic mayhem? I agree that there are multiple metabolic abnormalities inherent in the pathophysiology of T2DM, but we must remember that many of these are genetic including at least some of the beta cell dysfunction, and taking the glucose homeostasis abnormalities out of context can lead to us causing harm. Having said that, at 55 there is of course much that still must be done. As above, I just urge joined up thinking. Regarding this as mayhem may drive an overzealous focus on lowering blood glucose, causing harm. Energies directed at optimising cardiovascular risk profile would probably be of more, or at least equal, benefit. And the psychological damage done by sending out the message that the patient is failing if they cannot get their HbA1c lower is important also. Jane Speight (you can find her on RG) has written eloquently about this recently (attached below). So first do no harm! Many of the problems associated with T2DM cannot be corrected and it is essential that we do not do more harm in a vain attempt to restore normal physiology. In addition to the guidelines referenced in my first post I would recommend the ADA position statements and recent EASD guidelines. Reading of the position statements sequentially from 2004 through to the most current tells this story very clearly.

I look forward to https://grade.bsc.gwu.edu/web/grade/home?p_p_id=58&p_p_lifecycle=0&_58_redirect=%2F (GRADE) study results for definitive stratification for 2nd line add on therapy. Otherwise seek out appropriate cost effective individualised patent centred care.