Should a diabetic patient with kidney disease and a history of stroke be on Januvia (Sitagliptin) and Trulicity (Dulaglutide), and can one be discontinued?

Should Trulicity Be Continued in This High-Risk Patient?

Yes, Trulicity (dulaglutide) should absolutely be continued and is the most critical medication for this patient's cardiovascular and renal protection, while Januvia (sitagliptin) can be discontinued as it provides no additional cardiovascular or renal benefit and may pose harm in this specific population. 1

Rationale for Keeping Trulicity (Dulaglutide)

Cardiovascular Protection Post-Stroke

• Dulaglutide specifically reduces stroke recurrence risk by 24% (HR 0.76,95% CI 0.62-0.94), with particular benefit for ischemic stroke (HR 0.75,95% CI 0.59-0.94). 2 This is critically important given the patient's stroke history.
• The REWIND trial demonstrated that dulaglutide reduces major adverse cardiovascular events (MACE) by 12% (HR 0.88,95% CI 0.79-0.99) over 5.4 years of follow-up, with benefits seen in patients both with and without established cardiovascular disease. 1, 3
• Dulaglutide also reduced the composite of non-fatal stroke or all-cause death by 12% (HR 0.88,95% CI 0.79-0.98) and disabling stroke by 26% (HR 0.74,95% CI 0.56-0.99). 2

Renal Protection in CKD

• Dulaglutide reduces composite renal outcomes by 15% (HR 0.85,95% CI 0.77-0.93), with the strongest effect on preventing new macroalbuminuria (HR 0.77,95% CI 0.68-0.87). 4
• Current guidelines strongly recommend GLP-1 receptor agonists with proven cardiovascular benefit (including dulaglutide) in patients with type 2 diabetes and chronic kidney disease, particularly with eGFR <60 mL/min/1.73m² or albuminuria. 1
• Dulaglutide can be used safely across all stages of CKD, including severe renal impairment, with appropriate caution. 1, 3

Guideline-Concordant Therapy

• The 2019 ESC Guidelines and 2019 ADA/EASD Consensus explicitly recommend GLP-1 receptor agonists like dulaglutide in patients with type 2 diabetes and established cardiovascular disease (including stroke) to reduce cardiovascular events, independent of HbA1c levels. 1
• The 2018 ACC Expert Consensus specifically identifies GLP-1 receptor agonists as having demonstrated cardiovascular benefit in patients with atherosclerotic cardiovascular disease. 1

Rationale for Discontinuing Januvia (Sitagliptin)

Lack of Cardiovascular Benefit

• DPP-4 inhibitors like sitagliptin have demonstrated cardiovascular safety but NO cardiovascular benefit in outcome trials. 1 The TECOS trial showed sitagliptin was non-inferior but not superior for MACE outcomes (HR 0.98,95% CI 0.88-1.09). 1
• Guidelines explicitly state that DPP-4 inhibitors have a "neutral effect" on cardiovascular risk and may only be "considered" when other agents are not appropriate. 1

Potential Harm in This Specific Population

• In ischemic stroke patients with type 2 diabetes and CKD, sitagliptin showed NO reduction in cardiovascular events (HR 1.05,95% CI 0.75-1.45) and similar risks across all cardiovascular endpoints. 5
• More concerning, in diabetic patients with CKD after acute myocardial infarction, sitagliptin was associated with increased risks of recurrent MI (HR 1.73,95% CI 1.15-2.58) and need for coronary revascularization (HR 1.43,95% CI 1.04-1.95). 6
• While this patient had a stroke rather than MI, the pattern of potential harm in high-risk cardiovascular patients with CKD is concerning.

Redundancy with Trulicity

• Both medications lower glucose, but dulaglutide provides superior glycemic control, weight loss benefits, and proven cardiovascular/renal protection that sitagliptin cannot match. 3, 1
• There is no evidence that combining a DPP-4 inhibitor with a GLP-1 receptor agonist provides additive cardiovascular or renal benefits.

Clinical Implementation

Discontinuation Strategy

• Sitagliptin can be stopped abruptly without tapering, as it has a short half-life and no withdrawal syndrome. 1
• Monitor glucose levels for 1-2 weeks after discontinuation, though significant hyperglycemia is unlikely if dulaglutide is continued at therapeutic doses.

Monitoring on Dulaglutide Monotherapy

• Continue monitoring HbA1c every 3-6 months with target <7% for most patients (individualize based on comorbidities). 1
• Monitor renal function (eGFR and UACR) every 6-12 months to assess for progression of kidney disease. 4
• Assess for gastrointestinal side effects, which are the most common adverse effects of GLP-1 receptor agonists but typically diminish over time. 3

Important Caveats

• Ensure the patient does not have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2), which are contraindications to GLP-1 receptor agonists. 1
• If the patient has diabetic retinopathy, monitor closely as rapid glucose reduction with GLP-1 receptor agonists has been associated with retinopathy complications. 1
• Consider adding an SGLT2 inhibitor if the patient has heart failure with reduced ejection fraction or progressive CKD, as these agents provide complementary cardiovascular and renal benefits. 1