A BRC-supported study has found patients taking statins following a stroke or heart disease have a small increase in the risk of developing new-onset type 2 diabetes and gaining an excess of half a pound in weight.
Using information from genetic studies and clinical trials, this large-scale analysis was carried out by an international team led by researchers from UCL and the University of Glasgow.
Nearly 130,000 participants from clinical trials that previously tested the effect of statins on heart disease and stroke (major vascular events) – those assigned statins vs. placebo, or higher vs. lower doses of statins – were noted to have a small increase in the risk of developing type 2 diabetes of about 12% over a four-year period, and also to gain an excess of 240g (around half a pound) in weight.
Dr David Preiss, co-lead author from the University of Glasgow Institute of Cardiovascular and Medical Sciences said: “Weight gain is a risk factor for diabetes which might help explain the small increased risk of diabetes observed in people taking statins.”
Statins work by reducing the efficiency of a liver enzyme involved in cholesterol production, which causes liver cells to trap more low-density lipoprotein (LDL-) cholesterol from the bloodstream, reducing its circulating level. This mechanism is thought to underlie the efficacy of statins in lowering the risk of major vascular events.
On top of the analysis of 130,000 clinical trial participants, 220,000 individuals in separate genetic studies, where the same enzyme which controls cholesterol production in the liver is inhibited, were investigated and found to be also associated with a higher weight and slightly higher type 2 diabetes risk.
Co-lead author Dr Daniel Swerdlow of the UCL Institute of Cardiovascular Science said: “Commonly occurring variants in the gene encoding the same liver enzyme are associated with a lower LDL-cholesterol. Incorporating information from up to 220 000 individuals, we found that these genetic variants were also associated with a higher weight and marginally higher type 2 diabetes risk. The effects were very much smaller than from statin treatment, but the genetic findings indicate that the weight gain and diabetes risk observed in the analysis from trials are related to the known mechanism of action of statins rather than some other unintended effect.”
Despite the study results, published today in the Lancet, the researchers say there is no warning that an individual’s genetic make-up will significantly affect their clinical reaction to statins.
Co-senior author Professor Aroon Hingorani, Director of the UCL Institute of Cardiovascular Science, said: “The genetic findings of our study help to explain the mechanism by which statins increase weight and diabetes risk. However, the effects of the genetic variants are orders of magnitude lower than the effects of statins. There is also no indication from this study that an individual’s genetic make-up will meaningfully affect their clinical response to statin treatment. Statin drugs should continue to be prescribed without the need for any form of genetic testing.”
Taking the known risk of new-onset diabetes into account, current guidelines from the UK National Institute for Health and Care Excellence suggest that statin treatment should be offered to people with a 10% or higher risk of developing cardiovascular disease in the next 10 years. Statins are also recommended for people who have had a heart attack or stroke to reduce the risk of future incidents. Statins are effective in reducing cardiovascular events in people with established diabetes.
Professor Naveed Sattar from the University of Glasgow Institute of Cardiovascular and Medical Sciences said: “Previous analyses have indicated that the cardiovascular benefits of statin treatment greatly outweigh the risk of new-onset type 2 diabetes. Nevertheless, many patients eligible for statin treatment would also benefit from lifestyle changes including increased physical activity, eating more healthily and stopping smoking. The modest increases in weight and diabetes risk seen in this study could easily be mitigated by adopting healthier diets and lifestyles. Reinforcing the importance of lifestyle changes when discussing these issues with patients would further enhance the benefit of statin treatment in preventing heart attacks and strokes.”
The research received support from the BRC, Medical Research Council, British Heart Foundation and Rosetrees Trust.
To read HMG-coenzyme A reductase inhibition, type 2 diabetes and bodyweight: evidence from genetic analysis and randomised trials in full click here.
