Pitavastatin may increase new-onset diabetes risk

In a comparative analysis presented at WONCA 2024, individuals who are being treated with pitavastatin appear to be at greater risk of developing new-onset diabetes as opposed to those receiving rosuvastatin.

“Statins stand as the cornerstone therapy for managing atherosclerotic cardiovascular disease. Despite their efficacy, the administration of statins has been linked to a heightened susceptibility to developing new-onset diabetes,” said the researchers.

“However, comprehensive analyses drawing from real-world data and directly contrasting the new-onset diabetes risk profiles across various individual statins are scarce,” they noted.

Using data from the TriNetX researcher network, the researchers retrospectively evaluated 30,378 adults (mean age 63 years, 50 percent male) who were prescribed either pitavastatin or rosuvastatin (n=15,189 in each group) between January 1, 2015 and December 31, 2022.

After propensity-score matching, the most common comorbidity identified was hypertension, occurring at similar rates between the pitavastatin and rosuvastatin groups (45.6 percent vs 46.4 percent), followed by hyperlipidaemia (28.3 percent vs 29.1 percent) and atherosclerotic heart disease of the native coronary artery (22.8 percent vs 22.7 percent).

Approximately 9 percent of participants had chronic kidney disease, while about 3 percent had overweight and obesity.

Within the 7-year follow-up period, the incidence of new-onset diabetes was more than twofold higher in the pitavastatin than the rosuvastatin group (n=2,467 vs 1,093). The heightened risk of new-onset diabetes with pitavastatin corresponded to a hazard ratio [HR] of 1.58 (95 percent confidence interval [CI], 1.47–1.70; p<0.0001). [WONCA 2024, abstract 509]

This increased risk of new-onset diabetes was consistent even when stratified by sex (HR, 1.26, 95 percent CI, 1.18–1.34 [male] and HR, 1.14, 95 percent CI, 1.07–1.21 [female]) and age (HR, 1.20, 95 percent CI, 1.11–1.30 [40–64 years] and HR, 1.20, 95 percent CI, 1.14–1.30 [≥65 years]; p<0.0001 for all).

There was also a trend favouring pitavastatin over rosuvastatin in the subgroup of participants aged 18–39 years (HR, 1.18, 95 percent CI, 0.72–1.94), although this trend was not statistically significant.

“Overall, in this retrospective analysis, the utilization of pitavastatin was linked to a heightened likelihood of developing new-onset diabetes in contrast to rosuvastatin,” noted the researchers.

The findings correlate with those reported in a retrospective analysis suggesting an increased diabetes risk with pitavastatin vs with other statins. [Metabolism 2015;64:482-488]

This may be attributed to a class effect, as suggested by other trials demonstrating an increased risk of new-onset diabetes with statin use. [Lancet 2010;375:735-742; JAMA 2011;305:2556-2564; Diabetes Care 2009;32:1924-1929; N Engl J Med 2008;359:2195-2207] However, this effect does not appear to be sustained across all statins. [Atheroscler Suppl 2014;15:1-15; BMJ 2013;346:f2610; J Clin Endocrinol Metab 2018;103:4176-4186]

Inconsistent reports

In fact, there is evidence showing a reduced risk of new-onset diabetes with pitavastatin compared with rosuvastatin or atorvastatin in patients newly treated with statins. [Cardiovasc Diabetol 2022;21:82]

In another report, however, pitavastatin had no adverse impact on glucose metabolism compared with placebo or another statin. [Atherosclerosis 2015;241:409-418]

These contrasting results highlight the importance of a risk-benefit profile evaluation. A CDC report noted that despite the blood sugar level elevations tied to statin use, their benefits may outweigh the risks. [https://www.cdc.gov/diabetes/diabetes-complications/statins-and-diabetes.html, accessed September 24, 2024]

As with any prescription drug, weighing the potential risks against a drug’s benefit is imperative to guide clinicians in making informed decisions when prescribing a medication. [https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.112.122135]