Long-term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second-line Type 2 diabetes mellitus treatment in a US veteran population.

Abstract

AIM:

To examine the risks of all-cause mortality and cardiovascular events associated with adding vs switching to second-line therapies in a comparative safety study of people with Type 2 diabetes mellitus.

METHODS:

We conducted a retrospective cohort study using an as-treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose-lowering treatments between 1998 and 2012. This study included 145 250 people with long follow-up. Confounding was addressed through several strategies, involving weighted propensity score models with rich confounder adjustment and strict inclusion criteria, coupled with an incident-user design.

RESULTS:

Second-line use of sulfonylureas was related to higher mortality (hazard ratio 1.39, 95% CI 1.14, 1.70) and cardiovascular risks (hazard ratio 1.19, 95% CI 1.09, 1.30) compared with thiazolidinedione therapy. Differential hazards were associated with discontinuing or not discontinuing metformin; switching to sulfonylurea therapy was associated with a higher risk of all-cause mortality and cardiovascular events compared with all other therapies. Furthermore, add-on sulfonylurea therapy was associated with an elevated risk for both outcomes when compared with thiazolidinedione add-on therapy.

CONCLUSIONS:

The results of the present study may inform decisions on whether to augment or discontinue metformin; when considering the long-term risks, switching to a sulfonylurea appears unfavourable compared with other therapies. Instead, adding a thiazolidinedione to existing metformin therapy appears to be superior to adding or switching to a sulfonylurea.

• Authors: W R Powell, C L Christiansen, D R Miller
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 36 Issue 11 Pg. 1384-1390 (11 2019) ISSN: 1464-5491 [Electronic] England
• PMID: 30343492 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2018 Diabetes UK.

Chemical References

• Hypoglycemic Agents
• Sulfonylurea Compounds
• Thiazolidinediones
• Metformin
• 2,4-thiazolidinedione

Topics

• Aged
• Diabetes Mellitus, Type 2 (complications, drug therapy, mortality, physiopathology)
• Diabetic Angiopathies (drug therapy, mortality, physiopathology)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Observational Studies as Topic
• Propensity Score
• Proportional Hazards Models
• Retrospective Studies
• Sulfonylurea Compounds (adverse effects, therapeutic use)
• Thiazolidinediones (therapeutic use)
• Treatment Outcome
• Veterans