The deadline for submissions for this RFI was on Friday, August 9, 2019. We are no longer accepting submissions. Thank you.

Following the release of findings from the EMPA-REG OUTCOME trial (empagliflozin; SGLT2 inhibitor) in late 2015 indicating that empagliflozin may have a cardiovascular protective effect in patients with type 2 diabetes mellitus (T2DM) at high-risk for cardiovascular events, PCORI began to explore the potential value of a head-to-head comparison of second-line treatments for T2DM.1 This study would assess the difference in cardiovascular outcomes in a patient population including those at low to moderate risk for cardiovascular events.

Subsequent findings from the LEADER (liraglutide; GLP-1 receptor agonist)2, SUSTAIN-6 (semaglutide; GLP-1 receptor agonist)3, CANVAS (canagliflozin; SGLT2 inhibitor)4, and DECLARE (dapagliflozin; SGLT2 inhibitor)5 trials, all of which found cardiovascular benefit associated with the addition of either an SGLT2 inhibitor or a GLP-1 receptor agonist for at least a subset of outcomes, have underscored the timeliness and potential value of such a study.

The higher costs of these newer agents and their potential impact on cardiovascular disease endpoints make a study comparing them with older, lower-cost treatments (sulfonylureas and DPP-4 inhibitors) of importance to patients and clinicians.

While a large-scale randomized controlled trial on this topic would be desirable, the resources required to conduct such a trial limit its feasibility. PCORI is exploring whether a methodologically robust observational study may be a possible alternative or precursor to a large-scale randomized trial. Accordingly, PCORI seeks information about the availability of existing data sources needed to conduct an observational comparative effectiveness study that emulates a clinical trial on this important question.

Request for Information (RFI): Availability of Observational Data for the Analysis of Second-Line Pharmacological Agents for Type 2 Diabetes Mellitus

White Paper: Antihyperglycemic Therapy and Cardiovascular Risk:Design and Emulation of a Target Trial Using Healthcare Databases

For questions and inquiries about this RFI, please email [email protected].

 Posted: May 24, 2019; Updated: August 28, 2019


1 Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015;373:2117-28.
2 Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016;375:311-22.
3 Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016;375:1834-44.
4 Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017;377:644-57.
5 Wiviott S, Raz I, Bonaca M, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019;280:347-357.

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