Does Repatha Raise Glucose Levels?
No, Repatha (evolocumab) does not raise glucose levels or worsen glycemic control in patients with or without diabetes.
Evidence from Cardiovascular Outcomes Trial
The FOURIER trial—the largest and most definitive study of evolocumab involving 27,564 patients followed for a median of 2.2 years—demonstrated that evolocumab did not adversely affect glucose metabolism 1:
- No increase in new-onset diabetes: Among 16,533 patients without diabetes at baseline, evolocumab did not increase the risk of developing diabetes (HR 1.05,95% CI 0.94–1.17) 1
- No worsening of glycemic control: HbA1c and fasting plasma glucose levels remained similar between evolocumab and placebo groups throughout the study period in patients with diabetes, prediabetes, or normoglycemia 1
- Consistent safety in prediabetes: Among 10,344 patients with prediabetes at baseline, evolocumab showed no increased diabetes risk (HR 1.00,95% CI 0.89–1.13) 1
FDA-Approved Safety Profile
The FDA drug label for Repatha confirms neutral glycemic effects 2:
- Among patients without diabetes at baseline in the cardiovascular outcomes trial, new-onset diabetes occurred in 8.1% of evolocumab-treated patients versus 7.7% of placebo-treated patients—a clinically insignificant difference 2
- The overall safety profile showed no signal for glucose elevation or diabetes risk 2
Additional Supporting Evidence
A 52-week placebo-controlled trial (DESCARTES) specifically examined glycemic effects across different metabolic subgroups 3:
- No changes in glucose parameters: Fasting plasma glucose, HbA1c, insulin, C-peptide, and HOMA indices showed no significant differences between evolocumab and placebo at 52 weeks in any subgroup (type 2 diabetes, impaired fasting glucose, metabolic syndrome, or none of these) 3
- Similar new-onset diabetes rates: Overall incidence was 5.6% with evolocumab versus 6.6% with placebo; among those with baseline normoglycemia, rates were 2.7% versus 1.9%, respectively 3
Real-World Data Caveat
One recent retrospective real-world study from Saudi Arabia reported potential worsening of glycemic control in some patients 4. However, this single-center observational study has significant limitations compared to the large randomized controlled trials and should not override the consistent findings from multiple high-quality prospective studies 1, 3.
Clinical Implications
Evolocumab can be safely prescribed to patients with diabetes, prediabetes, or impaired glucose tolerance without concern for raising glucose levels or worsening glycemic control 1, 3. The drug's cardiovascular benefits are consistent across all glycemic subgroups, with hazard ratios of 0.83 for the primary composite endpoint in patients with diabetes and 0.87 in those without diabetes 1.
Common Pitfall to Avoid
Do not withhold or discontinue evolocumab in patients with diabetes or prediabetes due to unfounded concerns about glucose elevation; the robust clinical trial evidence demonstrates glycemic neutrality while providing substantial cardiovascular risk reduction 1, 3.