Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults

Abstract

BACKGROUND: Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the longterm effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. OBJECTIVE: To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. RESEARCH DESIGN: This was a retrospective cohort study. PARTICIPANTS: Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. INTERVENTION: We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. MAIN MEASURES: Outcomes assessed included newonset diabetes, diabetic complications, and overweight/ obesity. KEY RESULTS: A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67-2.01), diabetes with complications (OR 2.50; 95 % CI 1.88-3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04-1.25). Secondary and sensitivity analyses demonstrated similar findings. CONCLUSIONS: Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

Statin use and risk of new-onset diabetes: a meta-analysis of observational studies

“…Compared with RCTs, observational studies include, in fact, many more subjects followed for a longer time which may result in an increased chance to detect adverse events, in particular those that may require several years to occur or be detected, such as diabetes [16]. Furthermore, the rigorous selection of subjects recruited for an RCT may lead to the exclusion of individuals at higher risk for adverse events [16], and this may result in an underestimation of adverse events, in particular if their incidence is low.…”

“…In addition, randomized clinical trials (RCTs) have several limitations that might reduce the actual relevance of such increased risk [16]. RCTs in fact, did not include diabetes risk as a primary outcome; as a consequence, they could not reach adequate statistical power and sample size to find an association between statin use and diabetes risk.…”

Statins and Diabetes: The Plot Thickens

“…The study by Mansi et al 8 calls for more consideration of the consequences of statin treatment, particularly in primary prevention for patients at risk of developing diabetes (overweight/obese older individuals), and potentially on the development of microangiopathic complications, although these risks are far from established on the basis of this study and should be the subject of more rigorous prospective trials. Physicians should not alter their current practices based on this study, as the benefit of statin treatment on cardiovascular events has been rigorously demonstrated in multiple prospective intervention studies in diabetic patients over the last 20 years.…”

“…7 A new dimension in this saga is suggested in this issue of JGIM by Mansi et al, who report that statin use may be associated with diabetic complications in a retrospective cohort study of adult patients enrolled in the US military's Tricare program in San Antonio, TX. 8 The authors selected patients without cardiovascular problems or significant comorbid conditions and, using propensity scores to match the two groups, selected 3351 statin users and 3351 non-users. After follow-up of 6.5 years, the authors observed that statin users had an odds ratio (OR) of 1.87 for diabetes (30.9 % versus 19.4 %), 2.5 for diabetic complications (5.0 % versus 2.1 %), and 1.14 for overweight/obesity (46.7 % versus 43.4 %) compared to non-users.…”

“…7 A new dimension in this saga is suggested in this issue of JGIM by Mansi et al, who report that statin use may be associated with diabetic complications in a retrospective cohort study of adult patients enrolled in the US military's Tricare program in San Antonio, TX. 8 The authors selected patients without cardiovascular problems or significant comorbid conditions and, using propensity scores to match the two groups, selectedstatin treatment in patients with type 2 diabetes was shown to lead to a modest increase of 0.12 % in HbA1c levels compared to controls over a 3.6-year follow-up period, 5 although details were missing on the statin drugs and dosages as well as on whether antidiabetic treatment was more aggressive in statin users, two parameters that may have contributed to underestimation of the increase in HbA1c. However, this small change is unlikely to have a significant effect on the incidence or severity of diabetic complications (particularly cardiovascular events) in newly diagnosed diabetic patients.…”