Shall We Be Afraid of Metformin in Chronic Kidney disease?
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Shall We Be Afraid of Metformin in Chronic Kidney disease?
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Hello Fellows: In the old times, Phenformin was a dangerous insulin sensitizer, and so, taken out of the market as an oral anti diabetic drug because it induced lactic acidosis. It was succeeded by M
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Forums » Open clinical » Diabetes » Shall We Be Afraid of Metformin in Chronic Kidney disease?
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Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 25/9/2012 12:23 AM BST
on bmj.com
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Posts: 624
First: 13/4/2011 Last: 15/5/2013 |
Hello Fellows: In the old times, Phenformin was a dangerous insulin sensitizer, and so, taken out of the market as an oral anti diabetic drug because it induced lactic acidosis. It was succeeded by Metformin but the fear remained about its use in Chronic Kidney Disease (CKD) with an estimated GFR (eGFR) below 60 ml/min. Now it shows-up a registry data driven study in BMJ Open involving a huge number of diabetic patients showing that Metformin is the most effective, and is indeed quite safe for most CKD patients until at least 30 ml/min of eGFR: "Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register" Conclusions: Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits ofmetformin use clearly outbalance the risk of severe side effects. Comments: This is a quite provocking and interesting study. |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 26/9/2012 5:34 PM BST
on bmj.com
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Posts: 453
First: 29/4/2011 Last: 14/5/2013 |
Anyone who understands the differences between the metabolism of phenformin and metformin knowns that lactic acidosis should not be an issue with metformin. The best study in man was done in 1995 http://www.nejm.org/doi/full/10.1056/NEJM199508313330903#t=articleDiscussion , but animal studies showed the same thing. Phemformin increased lactate levels; metformin does not. This is because while metformin reduces lactate incorporation into glucose by the liver, it also increases lactate turnover. Thanks for this post, Joey. |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 26/9/2012 5:59 PM BST
on bmj.com
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Posts: 92
First: 20/3/2012 Last: 25/10/2012 |
A good post Joey and it indicates an argument for the re-examination of the use in patients with CKD. After all, it was not long ago that Beta-Blockers were contraindicated in patients with COPD but some are now allowed. Thankyou for bringing this to our attention. |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 26/9/2012 6:28 PM BST
on bmj.com
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Posts: 1791
First: 7/3/2009 Last: 25/5/2013 |
As I said in previous posts regarding changing indications for medications, evidence is not just in a study, be it large as this one is, but in reproducing the results in other studies, biological plausibility, temporality, etc. Well known. As to metformin, I believe it is widely used all over the world and with good results. In CKD patients I would say one should be careful, I am not convinced about a threshold of 30 ml/min. If given, dosage should be adjusted. What do we know about hypoglycemic events in CKD patientsreceiving metformin vs those without CKD? |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 26/9/2012 7:46 PM BST
on bmj.com
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Posts: 3045
First: 27/3/2012 Last: 20/5/2013 |
There is no doubt that metformin has been well established as a safe hypoglycemic agent in CKD patients. Thanks for a good study which re-enforces the safety of metformin. The clinical evidence supports the safe use of appropriate doses of metformin in patients with chronic stable renal impairment, and highlights the important possible greater risks of the alternatives, most notably severe hypoglycaemia in patients taking sulphonylureas and/or insulin and fluid retention in patients taking a thiazolidinedione. |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 27/9/2012 8:36 AM BST
on bmj.com
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Posts: 92
First: 20/3/2012 Last: 25/10/2012 |
In Response to Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?: As I said in previous posts regarding changing indications for medications, evidence is not just in a study, be it large as this one is, but in reproducing the results in other studies, biological plausibility, temporality, etc. Well known. As to metformin, I believe it is widely used all over the world and with good results. In CKD patients I would say one should be careful, I am not convinced about a threshold of 30 ml/min. If given, dosage should be adjusted. What do we know about hypoglycemic events in CKD patientsreceiving metformin vs those without CKD? Posted by yoram chaiter You raise some valid points, specifically with reproducing the results in other trials. With regards to your concerns about a threshold of 30ml/min, it is a difficult one but, given that a lot of patients with CKD may not even have a GFR of 60, those patients would automatically be excluded. Personally, I just feel that 60 is too high in this context but whether 30 is too low or not, that is a difficult one and perhaps that also needs to be considered further
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 29/9/2012 2:12 PM BST
on bmj.com
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Posts: 624
First: 13/4/2011 Last: 15/5/2013 |
Thanks Dr. Diabetes for bringing this nice pathophysiological study in Humans with Metformin. The Article I presented here is not the first one to assess the safety and efficacy of Metformin, better, regarding Mortality, and safer, regarding Hypoglycaemia, than any other anti-diabetic agent in CKD untill an estimated GFR (eGFR) as low as 30 ml/min! Below 30 ml/min this drug should be stopped. Here it goes another previous article and the link to it. It comes from Diabetes Care - 2011. " Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency" It is also amazing how the clinical indications for the use of Metformin are increasing. One recent example is its safety and efficacy for the prevention and treatment of gestational diabetes in women with Ovary Polycystic Syndrome. Clearly, and fairly enough, more basic and clinical research with Metformin is needed. All the Best, Joey
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 30/9/2012 8:11 AM BST
on bmj.com
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Posts: 1791
First: 7/3/2009 Last: 25/5/2013 |
Recently it also became a habit of some to prescribe metformin to patients with impaired fasting glucose. Personally I think one should first try lifestyle modification before running to medications. Especially since all those medicatins are not safe proof from causing hypoglycaemia. |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 30/9/2012 2:19 PM BST
on bmj.com
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Posts: 624
First: 13/4/2011 Last: 15/5/2013 |
In Response to Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?: Recently it also became a habit of some to prescribe metformin to patients with impaired fasting glucose. Personally I think one should first try lifestyle modification before running to medications. Especially since all those medicatins are not safe proof from causing hypoglycaemia. Posted by yoram chaiter Hi Yoram: Many thanks for your excellent post. And I entirely agree with you. I do not stand with any drugs for diabetes prevention. Those who use Metformin for diabetes prevention look at a NEJM article about 10 years ago that has shown Metformin-induced moderate clinical benefits, with a very small weight loss. But, as I mentioned before, I think this use of Metformin is just overtreatment/overmedicalisation whatever name fits better. All Best to you, Joey |
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Re: Shall We Be Afraid of Metformin in Chronic Kidney disease?
posted at 30/9/2012 4:09 PM BST
on bmj.com
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Posts: 3045
First: 27/3/2012 Last: 20/5/2013 |
I also agree with respected Joey Rio & Yoram that metformin should not be used for prevention of pre-diabetes or reduced glucose tolerance, or impaired fasting glucose. |
Forums » Open clinical » Diabetes » Shall We Be Afraid of Metformin in Chronic Kidney disease?
