The comparative safety of frequently used second-line agents to treat type 2 diabetes (T2D) with respect to the risk of venous thromboembolism (VTE) in routine care is unknown. It has been hypothesized that the diuretic effect of SGLT2 inhibitors (SGLT2i) may have an unintended impact on VTE risk by increasing blood viscosity. Using Optum Clinformatics, a large U.S. commercial health insurance claims database, we assessed the risk of an incident hospitalization for VTE within two pair-wise 1:1 propensity score (PS)-matched cohorts of patients with T2D who initiated a SGLT2i or a comparator, i.e., a GLP-1 receptor agonist [GLP-1 RA (n=59,712 pairs)], or a DPP-4 inhibitor [DPP-4i (n=50,178 pairs)] between April 2013-March 2019. We estimated hazard ratios (HR) and 95% CI controlling for over 100 baseline characteristics including common risk factors for VTE, baseline comorbidites, medication use and healthcare utilization. SGLT2i had a similar risk of VTE compared to GLP-1 RA [HR (95% CI) = 0.99 (0.68, 1.44)] and DPP-4i [HR (95% CI) = 1.01 (0.66, 1.52)] (Table 1), with incidence rates ranging between 1.1 and 1.3 events per 1,000 person-years. Results were consistent within subgroups of age, frailty and cardiovascular disease. In a large population-based study of adult patients with T2D, SGLT2i had similar risk of VTE compared to GLP-1 RA and DPP-4i, with reassuringly low absolute rates overall.


C. Gopalakrishnan: None. R.J. Desai: Research Support; Self; Bayer AG, Novartis AG. S.C. Kim: Research Support; Self; AbbVie Inc., Bristol-Myers Squibb. E. Patorno: Other Relationship; Self; Boehringer Ingelheim International GmbH.


National Institute on Aging (K08AG055670)

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