Modulation of the Urea Cycle through the Combined Use of SGLT2 Inhibitors and Metformin - Scorecard - MDSpire

Modulation of the Urea Cycle through the Combined Use of SGLT2 Inhibitors and Metformin

  • By

  • Makoto Harada

  • Jonathan Adam

  • Siyu Han

  • Mengya Shi

  • Jianhong Ge

  • Jutta Lintelmann

  • Alexander Cecil

  • Sven Zukunft

  • Cornelia Prehn

  • Michael Witting

  • Markus F. Scheerer

  • Susanne Neschen

  • Martin Irmler

  • Johannes Beckers

  • Jerzy Adamski

  • Daniel Teupser

  • Birgit Linkohr

  • Christian Gieger

  • Martin Hrabě de Angelis

  • Annette Peters

  • Rui Wang-Sattler

  • January 8, 2026

  • 0 min

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Clinical Scorecard: Modulation of the Urea Cycle through the Combined Use of SGLT2 Inhibitors and Metformin

At a Glance

CategoryDetail
Condition
Key MechanismsCombined use of SGLT2 inhibitors and metformin enhances metabolic effects, including improved glycemic control and reduced risk of adverse effects associated with monotherapy.
Target Population
Care Setting

Key Highlights

  • Metformin is the first-line therapy for T2D; SGLT2 inhibitors are recommended as add-on therapy.
  • COMBI therapy shows promise in reducing adverse effects like diabetic ketoacidosis and lactic acidosis, particularly in high-risk patients.
  • Targeted metabolomics provides insights into the metabolic effects of COMBI therapy across various tissues, highlighting specific metabolic pathways.

Guideline-Based Recommendations

Diagnosis

    Management

      Monitoring & Follow-up

      • Regular monitoring of glycemic control, including HbA1c levels, and assessment of potential side effects from therapies, such as renal function and signs of acidosis.

      Risks

        Patient & Prescribing Data

        Participants aged 53-74 years with Type 2 Diabetes from the KORA-Fit study, including those with cardiovascular and renal risk factors.

        Clinical Best Practices

        • Utilize targeted metabolomics for a detailed understanding of metabolic pathways affected by therapies.
        • Consider patient-specific factors such as age, comorbidities, and previous treatment responses when prescribing combination therapies.

        References

        Original Source(s)

        Modulation of the Urea Cycle through the Combined Use of SGLT2 Inhibitors and Metformin

        • by Makoto Harada, Jonathan Adam, Siyu Han, Mengya Shi, Jianhong Ge, Jutta Lintelmann, Alexander Cecil, Sven Zukunft, Cornelia Prehn, Michael Witting, Markus F. Scheerer, Susanne Neschen, Martin Irmler, Johannes Beckers, Jerzy Adamski, Daniel Teupser, Birgit Linkohr, Christian Gieger, Martin Hrabě de Angelis, Annette Peters, Rui Wang-Sattler

        • January 8, 2026

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