Report from 2010 EASD Conference: No Significant Benefit of Intensive Therapy in Diabetes -- Type 2, NOT Type 1

Type 2
1

The European Association for the Study of Diabetes (EASD) just wrapped up their annual conference on Sept. 24th. Among the research presented in Stockholm was the following:

Conference report: Early intensive therapy of no benefit in diabetes?

Source: MedPage Today

Date published: 27/09/2010 16:08

Summary
by: Nicola Pocock

According to study findings reported at the European Association for the Study of Diabetes meeting, early intensive treatment of patients with screen-detected type 2 diabetes in primary care is feasible, but may not reduce cardiovascular complications compared to standard care.

The ADDITION included 3,057 patients aged 40-69 years who were tested positive for diabetes in primary care in Britain, the Netherlands, and Denmark. They were randomised to treatment with routine care (According to national guidelines) or intensive treatment according to the following protocol:

• Antihypertensive treatment with an ACE inhibitor was started at a blood pressure of ≥120/80mmHg, with directions to intensify treatment for blood pressures of ≥135/85mmHg or greater.

• Lipid-lowering medication was initiated if lipids were ≥3.5 mmol/l (135 mg/dL) with intensification if levels were ≥4.5 mmol/l (174 mg/dL).

• The treatment target for blood glucose was a haemoglobin A1c (HbA1c) of ≤6.5%.

The risk of composite cardiovascular events after five years was 7.2% with intensive management and 8.5% for routine care (hazard ratio 0.83; P=0.12). There was no statistically significant difference in any of the individual components of this endpoint, including cardiovascular death (0.88; 95% CI 0.51 to 1.51), myocardial infarction (0.70; 95% CI 0.41 to 1.21), stroke (0.98; 95% CI 0.57 to 1.71), and revascularisation (0.79; 95% CI 0.53 to 1.18). All-cause mortality also favoured intensive management but again without a statistically significant impact (HR 0.91, 95% CI 0.69 to 1.21).

Much like the ACCORD study, this research did not find any benefit for type 2s keeping their A1cs at or under 6.5%, their lipids under 135 mg/dL, or their blood pressure under 120/80mmHg. Yet, given the limited information published here, I have to wonder about other factors that could have had an impact on the outcome. For instance, this study appears to focus solely on medications, making the main question "will medicating individuals with diabetes to lower their blood glucose, lipids, and blood pressure improve mortality rates?" There doesn't appear to be any discussion of the impact of lifestyle modification in addition to the medication as another factor in reducing the mortality rate. Perhaps there might be a difference between the two groups if, in addition to intensive medication, there were also an intensive lifestyle modification treatment, too.

However, I did find the following that sheds a little light on how the researchers interpreted their study:

But some diabetes specialists weren't ready to write off the strategy.

The "fairer conclusion" is that intensive therapy is effective, just not more so than routine care, when compared with no screening and no diabetes treatment, said study discussant William Herman, MD, MPH, of the University of Michigan in Ann Arbor, at the session.

He showed a risk prediction model projection that if the patients in the trial had gone untreated over the same period, the primary composite endpoint rate would have been twice that of either type of care.

The intensive goals are fine and it's not too hard to achieve them, concluded Peter Gottlieb, MD, of the University of Colorado Denver, who was not involved in the trial.

If anything, "their control group was too good," he commented in an interview. "If you had the original control group that they expected, their results would have been totally statistically significant."

Not surprisingly, the biggest differences were between baseline and follow-up for treatment and risk factor profiles, rather than between the intensive intervention and routine control groups, Herman noted.

The majority of patients in both groups achieved the intensive group treatment targets with differences of only 2.86 mm Hg for systolic blood pressure, 0.27 mmol/l for total cholesterol, and 0.08% for hemoglobin A1c between groups -- though all favored intensive management -- at the average 5.3 years of follow-up.

So, what's your take-away?

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Thanks for reporting on this, this is Interesting. So let me see if I get this straight from the quoted comments. They did an experiement where they compared aggressive cholesterol lowering and blood pressure lowering, but apparently not blood sugar lowering (HbA1c dropped 0.08%, gimme a break). Then they concluded that for diabetics, intensive therapy did not impact mortality. We already know that the most effective treatment for early T2s is diet and exercise, I bet they did not even control for that. This study reeks of st*pid. I can smell the stink already. I’m going to have to explain to my doctors why this study does not say raise your blood sugar. Perhaps what I should really claim is that this study shows that lowering cholesterol and blood pressure is useless.

3

Not quite, BSC. That 0.08% HbA1c figure is not how much the A1c was lowered, but the difference between the people in the intensive management group and those in the standard group. IOW, both groups achieved comparable A1cs. They do not report how much each group lowered their A1cs, or what the final, average A1c (and standard deviation) of each group was. What is known is that the groups were comparable at the start, and they were comparable at the end.

You’re right in that the study does NOT give doctors permission to allow their type 2 patients to have higher bgs. What it does say is that it IS possible for people with newly-diagnosed type 2 diabetes to “tightly” (in comparison to ADA-sanctioned targets) manage their blood sugars, their cholesterol levels, and their blood pressure and it will not kill them. In that respect, it is a different message from ACCORD, but the way it’s been presented, it certainly sounds as if tight management of bgs will not help people with type 2 diabetes – the same message as in ACCORD.

4

Yes you are right, I used the wrong wording. The groups started at the same level of blood sugar control and despite claimed treatment differences ended up at basically the same level of blood sugar control (within 0.08%). So it is a null result.

I do think there are some real european politics on the spin for this study. There is a real debate in the UK on whether lower blood sugar targets are warranted. The UK moved their HbA1c target “down” to 7% raising a cry form doctors that the lower goal was going to “kill” diabetics. As I understand it, the target has been moved back “up” to 7.5% in order not to kill more diabetics. This study may have been spun as part of that ongoing argument.

5

No, A1c goals have not increased in the UK. If you read the information about A1c goals on the BDA’s site, it reads:

For most people with diabetes, the HbA1c target is below 6.5 per cent, since evidence shows that this can reduce the risk of developing diabetic complications, such as nerve damage, eye disease, kidney disease and heart disease.

Individuals at risk of severe hypoglycaemia should aim for an HbA1c of less than 7.5 per cent. However, any reduction in HbA1c levels (and therefore, any improvement in control), is still considered to have beneficial effects on the onset and progression of complications.

IOW, the A1c goals in the UK are actually more stringent than the goals in the US, at least as defined by the ADA. The 7.5% A1c is for people who are at risk for severe hypoglycemia, which usually does not include individuals with newly-dx’ed type 2 diabetes who are not on insulin. Goals for children, T1s with hypoglycemic unawareness, the very old, and those with concurrent serious illnesses (e.g. cancer, AIDS, MS, etc) are often times set higher than for an otherwise healthy young-to-middle-age adult. Given what I read, I do not believe the researchers used members of those groups for whom the looser goals would have been applicable. Thus, all subjects in the study most likely would have been told to get their A1cs down to 6.5 or less (given that Denmark and Norway both have similar A1c goals).

Yes, it is a null result. You cannot reject the null hypothesis, but you also cannot accept it either. All you can do is say that there are no differences between the groups that were studied. All that can be said is that, in contrast to the ADA’s assertion, it is possible for newly-dx’ed type 2s to achieve very good bgs without substantial risk.

6

I am referring to the NHS which backtracked after one year in which doctors were given an incentive to treat their patients to the more “aggressive” goal of 7% (http://www.straightstatistics.org/article/how-overtreatment-diabeti…). There was a community that argued that based on a study, aggressive treatment caused excess deaths. That retrospective study looked at historical insulin use (primarily mixtard) on older poorly controlled diabetics (see Jenny Rulh on that study http://diabetesupdate.blogspot.com/2010/02/lancet-study-old-patient…).

I think we are in total agreement. For many newly diagnosed T2s, proper diet and lifestyle changes can bring about good results without the need for aggressive and potentially hazardous medications. But I am particularly sensitive that there is “abundant” evidence that blood sugar levels of 7% and above present real risk of complications over the long-term and these results have been used to argue that these higher targets are appropriate for new diagnosed.

7

I look at this from a different viewpoint than maybe some others. I am T1 since I was a kid, but I’m now middle aged. My hair’s slowly turning grey. And I have a deep family history of heart disease.

So when it comes to points other than just bg control, I happen to also personally have chosen to intensively work on issues like blood pressure, cholesterol, etc., using all the tools possible, meaning medication where it’ll help.

And my goals for blood pressure, cholesterol, etc., are not just to “make them be normal range” but to purposefully choose goals that are well below normal range. e.g. for the average population a blood pressure of 120/80 might be OK. But I know I face multiple risk factors from any even slightly elevated blood pressure (remember, it’s not just a cardio issue, retinopathy and other complications of diabetes are also VERY STRONGLY related to blood pressure if maybe not quite as strongly as bg control) so my personal goal is to be well below 120/80. Same for cholesterol. etc.

And I’ve chosen doctors that will work with me on this aggressive stance.

And all of this I do, not so much because a study said it would be good to do it, but because common sense says to do everything I can to lower my risk. I might be just 30-years post diagnosis and in my 40’s right now but I want to become a senior citizen and see my kids have kids and grandkids of their own!!! So it’s a purely selfish decision in fact.

And very few diabetes studies extend past a few years - the one you wrote about was a 4 or 5 year study. 5 years is a good start to me, but I’m looking to spend not 5 years with diabetes, but have already spent 30 and plan on spending another 50!!! I think the long-term DCCT studies, now with a baseline extending back to the mid-80’s when the DCCT was started (25 year baseline now), as well as the Joslin medalist studies (50 years+) are probably the best bet in terms of truly long-term view of complications and living with diabetes and all the risk factors.

The DCCT had some early discoveries that were very important (e.g. that intensive bg control in fact does lower the risk of complications in T1’s and the simply WONDERFUL graphs showing that increasing A1C clearly results in increasing risk of complications were huge advances over the ignorance that preceded them) but over time I think that the 20 and 30 year follow-ups will yield the best and most complete picture.

In case you can’t tell, I think the DCCT is wonderful. I’m a little biased because my docs in the 80’s expended some effort trying to get me to participate in the study itself (I ended up not participating mainly because there was a 50/50 chance that I would’ve been put in the non-intensive group!!!)

8

It talks about “composite cardiovascular events”, but what about neuropathy, retinopathy etc etc. If that is covered under “all caused mortality” then what if you don’t die from it but you just live with it. Seems like the study left out many of us.