Study identification

PURI

https://redirect.ema.europa.eu/resource/27791

EU PAS number

EUPAS21368

Study ID

27791

Official title and acronym

Sodium-Glucose Cotransporter-2 Inhibitor (SGLT-2i) Use and Risk of Subsequent Amputation

DARWIN EU® study

No

Study countries

United States

Study description

Recent findings from the CANVAS clinical trials suggest a possible increase in the risk of amputation associated with use of canagliflozin, a SGLT-2i drug, versus placebo. To our knowledge, there has been no study of the association between SGLT-2i initiation and amputation risk performed using large healthcare databases, which may be more representative of real-world clinical practice in a broader target population of patients with Type II diabetes mellitus, and using an active comparator, new user study design.To address this gap in knowledge, we propose to evaluate and compare the association between SGLT-2i initiation, relative to initiation of other second-line glucose lowering drugs, on the incidence and risk of diabetes-related amputation, using observational data from the commercially-insured U.S. population (<65 years old patients) and Medicare (≥65 years old patients) from 2013-2015, and based on an active comparator, new user study design.New users of SGLT-2i drugs will be compared to new users of other second-line active comparators (DPP-4 inhibitors and sulfonylureas). Exposure will be defined by at least two same-drug class prescription dispensing claims of either a SGLT-2i or an active comparator drug. The primary outcome of interest is lower-extremity amputation, additional secondary outcomes will be considered. The primary analysis will be carried out in an "as-treated" fashion.We will use propensity scores to minimize imbalances in measured potential confounders between study cohorts. We will estimate and compare the cumulative incidence of both primary and secondary outcomes for each study cohort using weighted Kaplan-Meier methods. Crude and adjusted hazard ratios for both primary and secondary outcomes will be estimated using weighted Cox proportional hazards models, controlling for age, sex, as well as any potential confounders that remain unbalanced after propensity score implementation. A number of sensitivity analyses are planned

Study status

Ongoing
Research institution and networks

Institutions

Department of Epidemiology,Gillings School of Global Public Health

Contact details

Til Stürmer

Primary lead investigator
Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

Planned:
Actual:

Data analysis start date

Planned:
Actual:

Date of final study report

Planned:
Sources of funding
Other

More details on funding

Unfunded
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable