Episode 60: Type 2 Diabetes – how sweet it isn’t – Part VI

by TEC on July 22, 2009

In episode 60, the sixth podcast in our saga on type-2 diabetes, we talk about what to do when metformin is not enough and get to the evidence surrounding other blood glucose lowering treatments. We fumble around in a pretty much evidence-free zone. James develops a bad case of hypoglycemia during the podcast because he hasn’t eaten since the start of the diabetes section of these podcasts; Mike comes to his aid by prescribing a low dose of a chocolate bar and eats the rest of it himself.

Show Notes

1) UKPDS (recent results)

NEJM 2008;359:1577-89

Table of results

2) Fluoxetine, orlistat, sibutramine for weight loss in type-2 diabetics

Arch Intern Med 2004;164:1395–404

3) Acarbose for impaired glucose tolerance

JAMA 2003;290:486-94

4) Glitazones meta-analyses

JAMA 2007;298:1180-8

JAMA 2007;298:1189-95

Table of results

5) Risks of an elevated A1c

Link to table

6) Long acting insulin analogues – no advantage

CMAJ 2009;180:385-97

{ 11 comments… read them below or add one }

clarencest10 July 22, 2009 at 10:35 pm

We have some idea of risk associated with rising HbA1C, thanks to UKPDS chart you guys posted. But you both seemed to hedge the benefit from using insulin and sulphonylureas. I think you said not very much. Well how much is not very much. If my risk of CHD goes form 8 to 16 over ten years with HbA1C going from 8 to 10, what does the evidence show I can reduce it by by adding either. If it’s bugger all why bother!!

clarencest10 July 23, 2009 at 4:23 am

Holman, R.R., et al, N Engl J Med 359(15):1577, October 9, 2008
So there was benefit of tight control – photocoagulation – and nothing else at end of trial. Then ten years later when HBA1Cs of different groups was now the same there is a benefit from having had tight control years ago. Weird!! There’s something not right here. If it is then the answer is to have tight control for X years and then relax!!

james August 2, 2009 at 9:45 pm

Hi clarencest10. Thanks for your question. I don’t know if I have any brilliant, or even less than brilliant answers to your questions. The effect seen with sulfonylureas and insulin in the 10 year UKPDS followup is outlined here. As you can see, the benefit seen is roughly half what was seen in the metformin arm. I think getting “reasonable” control (whatever that means) with proper eating, regular activity and using tolerated doses of metformin and low doses of glyburide (as long as there are no side effects) is what I would do – kind of what we outlined in our podcast. Other than that, who knows. Thanks again for your question.

clarencest10 August 2, 2009 at 10:49 pm

Have I got it right – benefits with tight control photocoagulation – at end of UKPDS trial – excluding metformin. Then when no longer tight control for further ten years there are benefits as shown here http://therapeuticseducation.org/wp-content/uploads/2009/05/ukpds-10-yr-follow-up.jpg. Isn’t this a suspect finding? How can it be explained?

nevermind701 August 3, 2009 at 9:24 am

This one is very insightful and refreshing to me.

http://www.cfp.ca/cgi/content/full/55/6/581

plind August 4, 2009 at 9:49 pm

A frustrating day that I hope the TEC clan can shed some light on. Just had a post MI diabetic patient show up with discharge papers that gave me pause. He was d/c on a bunch of things that I expected (asa, plavix (due to stent), ramapril, bisoprolol, atorvastatin 80 mg(jury still out on this still?), warfarin ) but when it came to the diabetes management I was stumped — (ok I know there is problems in the above list as well but can’t tackle everything)

Pre-admission he was on gluconorm 2mg tid (metformin= lactic acidosis and glicazide had “stopped working” due to gallstones (pt reported)). Gluconorm was controlling sugars fine right up to the heart attack. Discharge orders were to keep gluconorm going, add Avandia 4 mg qd, NPH insulin at night and Humalog at mealtimes on a sliding scale. Whew that’s a lot for one guy to handle. This is from the Cardiac intensive Care unit so one would assume that they know what they are doing — however — after listening to the podcasts (and my own reading) I can’t find a good reason to put a post a MI patient on Avandia and see even less sense in having a pt on all 4 medications.

These are the times that I feel like I’m missing something — can you explain the rationale — or is there one?

Penny

PS Pt refused the insulin and is going to hold off on the Avandia until he can have a discussion with his regular physician

james August 5, 2009 at 9:35 am

Hi Nevermind – I agree; that article was written by one of our colleagues (Tom Perry) at the Therapeutics Initiative in Vancouver.

james August 5, 2009 at 9:45 am

Hi Penny – you aren’t “missing” anything – his treatment is all about target shooting (unless he was truly symptomatic from his elevated glucose) – given that Avandia hasn’t been shown to reduce cardiovascular events – and may increase them – I have no idea why they would add this on. You unfortunately are stuck in the middle – hopefully his regular physician has some common sense.

I recently gave a talk on the whole issue of guidelines/targets/shared-informed decision making and came up with the 7 reasons one should consider changing if you are a “card-carrying biochemical target-shooter”

1 It forces you to learn a lot more about the evidence
2) ANY side effects become UNACCEPTABLE
3) Patients really like it – not as scared – “sharing”
4) You use both sides of your brain
5) Guidelines are NOT considered standard of care
6) Don’t have to have, or use, guilt
7) IT’S A LOT MORE FUN

james August 5, 2009 at 9:49 am

Hi clarencest10 – you have it right – I don’t know how to explain it other than it may take many years to see the effect of a cardiovascular risk reduction therapy – I don’t know if it is suspect but rather it is just what they found. Unfortunately that is all we have to go on when it comes to those drugs.

nevermind701 August 6, 2009 at 10:18 am

Plind: Let us look at the bright side of your patient’s situation. Even though avandia increases the chance of MI and heart failure, it doesn’t cause 100%. According to the table TEC arranged, it can cause cardiovascular events by ARI=1.2 % (0.4% for MI and 0.8% for heart failure). So just hope that your patient is one of the 82 out of 83 patients (NNH=100/1.2) who don’t have CVE while on avandia, not that unlucky one out of 83 patients.

auspharmacist March 30, 2010 at 6:06 am

Haha I’m almost a year late in commenting on this…
Plind: Could your patient’s discharge on insulin be temporary? I refer to the DIGAMI study where agressive insulin infusion in the first 24 hours of MI followed by minimum 3 months of subcut insulin reduced mortality at 1 year by 11%. I agree that this seems a little over zealous – is this actually done in practice?

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