What is the best time to take DPP-4 (Dipeptidyl Peptidase-4) inhibitors and SGLT-2 (Sodium-Glucose Linked Transporter-2) inhibitors?

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Last updated: June 28, 2025View editorial policy

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From the Guidelines

DPP-4 inhibitors and SGLT-2 inhibitors should be taken in the morning, with or without food, to minimize disruptions to sleep and maintain steady blood levels, as recommended by recent guidelines 1. The timing of these medications is crucial to maximize their efficacy and minimize potential side effects.

  • DPP-4 inhibitors, such as sitagliptin, saxagliptin, and linagliptin, can be taken once daily with or without food, and consistency in timing is key to maintaining steady blood levels 1.
  • SGLT-2 inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are best taken in the morning to avoid increasing urination at night, which can disrupt sleep 1. Some important considerations when taking these medications include:
  • Monitoring for signs of volume depletion, such as orthostatic lightheadedness, especially in elderly patients or those on diuretic therapy 1.
  • Being aware of the potential risk of genital mycotic infections and taking steps to maintain good personal hygiene 1.
  • Regularly monitoring renal function, particularly in patients with impaired renal function at baseline, as SGLT-2 inhibitors may cause a modest decrease in eGFR 1. It is essential to consult with a healthcare provider to determine the optimal timing and dosage of DPP-4 and SGLT-2 inhibitors based on individual needs and health status, as dosing can vary by brand and individual requirements 1.

From the Research

DPP-4 Inhibitors and SGLT-2 Inhibitors Administration Timing

  • The optimal timing for taking DPP-4 inhibitors and SGLT-2 inhibitors is not explicitly stated in the provided studies 2, 3, 4, 5, 6.
  • However, it is mentioned that DPP-4 inhibitors can be administered as a once-daily oral dose 2, 3.
  • SGLT-2 inhibitors are also typically taken once daily, but the exact timing may depend on the specific medication and individual patient factors.
  • Combination therapy of SGLT-2 inhibitors and DPP-4 inhibitors has been approved as single-pill formulations, which can be taken once daily 4.
  • The choice between a DPP-4 inhibitor and a SGLT-2 inhibitor should be based on individual patient characteristics, such as the presence of coronary heart disease or risk of hypoglycemia 5.

Key Considerations

  • DPP-4 inhibitors and SGLT-2 inhibitors have complementary mechanisms of action, making them a suitable combination for managing type 2 diabetes mellitus 4.
  • The combination of DPP-4 inhibitors and SGLT-2 inhibitors has been shown to be safe and effective, with no increased risk of hypoglycemia, cardiovascular events, or weight gain 6.
  • Clinical trials have demonstrated the cardiovascular safety of DPP-4 inhibitors and a reduction in cardiovascular events with SGLT-2 inhibitors, such as empagliflozin and canagliflozin 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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