How to manage type 2 diabetes mellitus (T2Dm) in a patient on metformin with a background of hypertension who cannot tolerate Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors?

From the Guidelines

For a patient with type 2 diabetes on metformin who has hypertension and cannot tolerate SGLT2 inhibitors, I strongly recommend adding a glucagon-like peptide-1 (GLP-1) receptor agonist. This recommendation is based on the most recent and highest quality evidence from the 2022 ADA/KDIGO consensus report 1, which suggests that a GLP-1 receptor agonist with proven cardiovascular benefit is recommended for patients with T2D and CKD who do not meet their individualized glycemic target with metformin and/or an SGLT2i or who are unable to use these drugs.

Key Considerations

• The patient's background of hypertension should be managed with ACE inhibitors or ARBs as first-line agents, as recommended by the 2022 ADA/KDIGO consensus report 1.
• GLP-1 agonists such as semaglutide (starting at 0.25mg weekly subcutaneously for 4 weeks, then increasing to 0.5mg weekly) or dulaglutide (starting at 0.75mg weekly subcutaneously) provide excellent glycemic control while offering cardiovascular benefits that are particularly valuable for patients with hypertension.
• If injectable therapy is not acceptable, consider a dipeptidyl peptidase-4 (DPP-4) inhibitor like sitagliptin (100mg daily) or a thiazolidinedione such as pioglitazone (15-30mg daily), as suggested by the 2021 KDIGO clinical practice guideline 1.
• Regular monitoring of HbA1c every 3-6 months is essential, with a target typically between 7-8% depending on the patient's age and comorbidities, as recommended by the 2016 American Diabetes Association standards of medical care in diabetes 1.

Benefits of GLP-1 Agonists

• Increase insulin secretion in a glucose-dependent manner
• Suppress glucagon
• Delay gastric emptying
• Reduce appetite, making them particularly effective for patients who also need weight management alongside diabetes control

By prioritizing the patient's morbidity, mortality, and quality of life, the addition of a GLP-1 receptor agonist to metformin is the most appropriate management strategy for a patient with type 2 diabetes and hypertension who cannot tolerate SGLT2 inhibitors, as supported by the highest quality evidence from the 2022 ADA/KDIGO consensus report 1.

From the Research

Management of Type 2 Diabetes Mellitus (T2Dm) without Tolerating SGLT2 Inhibitors

In patients with T2Dm who cannot tolerate Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, management of the condition requires careful consideration of alternative therapeutic options. Given the patient's background of hypertension and the fact that they are already on metformin, the following points are relevant:

• Alternative Therapies: For patients who cannot tolerate SGLT2 inhibitors, other classes of antidiabetic drugs can be considered as add-on therapy to metformin. This includes Dipeptidyl Peptidase-4 (DPP-4) inhibitors, which have been shown to be effective in reducing HbA1c levels when used in combination with other antidiabetic agents 2.
• Considerations for Hypertension: The management of T2Dm in patients with hypertension requires careful consideration of the effects of antidiabetic therapies on blood pressure. Some antidiabetic agents, such as SGLT2 inhibitors, have been shown to have beneficial effects on blood pressure 3, 4. However, in patients who cannot tolerate SGLT2 inhibitors, alternative therapies that have a neutral or beneficial effect on blood pressure should be considered.
• Combination Therapy: Combination therapy with metformin and another antidiabetic agent, such as a DPP-4 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist, can be an effective strategy for managing T2Dm in patients who cannot tolerate SGLT2 inhibitors 2, 5.
• Monitoring and Adjustment: Regular monitoring of blood glucose levels, blood pressure, and other relevant parameters is essential in patients with T2Dm, particularly in those who are on combination therapy. Adjustments to the treatment regimen may be necessary to achieve optimal glycemic control and to minimize the risk of adverse effects.

Key Points to Consider

• Metformin remains the first-line therapy for T2Dm, and alternative therapies should be considered as add-on therapy in patients who cannot achieve glycemic control with metformin alone.
• DPP-4 inhibitors and GLP-1 receptor agonists are potential alternative therapies for patients who cannot tolerate SGLT2 inhibitors.
• Combination therapy with metformin and another antidiabetic agent can be an effective strategy for managing T2Dm.
• Regular monitoring and adjustment of the treatment regimen are essential to achieve optimal glycemic control and to minimize the risk of adverse effects.