Statins do not worsen diabetes microvascular complications, may be protective

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Promising hints, but caution indicated

Pharmacoepidemiological studies need cautious interpretation and can be regarded only as hypothesis generating; Dr. Nielsen and Dr. Nordestgaard are appropriately circumspect.

The study has many strengths, such as its size, the quality and coverage of the national registry, and external validity – i.e., statin use was associated with an increased risk of diabetes, an effect size similar to that reported in randomized trials of statins. However, important weaknesses of the study include the absence of data on important predictors of microvascular disease – e.g., hemoglobin A1c, urine albumin, and blood pressure. For now, any benefit of statins on microvascular complications remains unproven.

Dr. David Preiss, of the University of Glasgow (Scotland), is cochair of the Scottish Lipid Forum, whose annual meeting is supported by grants from pharmaceutical companies including MSD, AstraZeneca, and Sanofi. The remarks are taken from his accompanying commentary (Lancet Diabetes Endocrinol. 2014 Sept. 10 [doi: 10.1016/S2213-8587(14)70173-1]).




Contrary to expectations, statin use before the development of type II diabetes did not worsen microvascular complications such as retinopathy, neuropathy, and gangrene of the foot.

In fact, despite concerns that statins have been seen to increase glucose levels and the risk of diabetes development, they may provide a protective effect from these conditions in newly developed diabetic patients, according to an analysis of data from more than 60,000 individuals in the Danish Patient Registry.

Copyright National Eye Institute

Statins may help, not hurt, in preventing microvascular complications, according to a new study.

"The cumulative incidences of diabetic retinopathy, diabetic neuropathy, and gangrene were reduced in statin users compared with non–statin users, but [the] risk of diabetic nephropathy was similar for all patients with diabetes," stated Dr. Sune F. Nielsen, Ph.D., and Dr. Børge G. Nordestgaard of the Herlev Hospital, Copenhagen University Hospital. However, they did find that statin use, as previously seen, did significantly increase the risk of developing diabetes in the first place. Their study was published online Sept. 10 in the Lancet Diabetes & Endocrinology (2014 Sept. 10 [doi: 10.1016/S2213-8587(14)70173-1]).

The researchers performed a nested matched study of all men and women living in Denmark who were diagnosed with incident diabetes during 1996-2009 at age 40 years or older, and assessed their outcomes through use of the Danish Civil Registration System, the Danish Patient Registry, and the Danish Registry of Medicinal Product Statistics. After exclusions, 62,716 patients with diabetes were randomly selected for the study: 15,679 statin users and 47,037 non–statin users. The primary outcome was the incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot. The design "captured 100% of individuals in Denmark who had ever used a statin within the time frame of the study."

Follow-up was censored at date of death for 9,560 individuals. During 215,725 person-years of follow-up, diabetic retinopathy was recorded in 2,866 patients, diabetic neuropathy in 1,406, diabetic nephropathy in 1,248, and gangrene of the foot in 2,392.

Over a median follow-up of 2.7 years, statin users were significantly less likely to be diagnosed with diabetic neuropathy (hazard ratio, 0.66; 95% confidence interval, 0.57-0.75: P less than .0001) and diabetic retinopathy (HR, 0.60; 95% CI 0.54-0.66: P less than .0001) than were those who had not received statins. However, no difference was noted in the incidence of diabetic nephropathy (HR, 0.97; 95% CI, 0.85-1.10; P = .62).

In contrast, the researchers found that statin use significantly increased the risk of developing diabetes in people who did not have the disease when the study began. When they compared a random selection of 272,994 non–statin users with 90,998 statin users, the multivariable adjusted hazard ratio for the risk of developing diabetes was 1.17 (95% CI, 1.14-1.21). These results are similar to those seen in previous randomized studies of statin use.

"In conclusion, we found no evidence that statin use is associated with an increased risk of microvascular disease; this result is important and clinically reassuring on its own. Whether or not statins are protective against some forms of microvascular disease, a possibility raised by these data, and by which mechanism, will need to be addressed in studies similar to ours, or in Mendelian randomization studies," said Dr. Nielsen and Dr. Nordestgaard. "Ideally, however, this question should be addressed in the setting of a randomized controlled trial," they added.

Dr. Nordestgaard has received consultancy fees or lecture honoraria from AstraZeneca, Pfizer, and Merck, and Dr. Nielsen declared no competing interests. The work was supported by Herlev Hospital, Copenhagen University Hospital.

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