Is it okay to take a GLP-1 (Glucagon-like peptide-1) receptor agonist at the same time as an SGLT2 (Sodium-glucose linked transporter 2) inhibitor?

From the Guidelines

Yes, it is generally safe and often beneficial to take a GLP-1 receptor agonist at the same time as an SGLT2 inhibitor. These medications work through different mechanisms to help control blood glucose levels in people with type 2 diabetes. GLP-1 receptor agonists stimulate insulin release, slow gastric emptying, and reduce appetite, while SGLT2 inhibitors cause the kidneys to excrete excess glucose through urine. When used together, they can provide complementary effects for better glucose control, weight loss, and potential cardiovascular and kidney benefits, as suggested by the 2018 ACC expert consensus decision pathway 1.

Key Considerations

• The combination of GLP-1 receptor agonists and SGLT2 inhibitors may increase the risk of certain side effects, particularly dehydration and low blood pressure, as noted in various studies 1.
• It's essential to stay well-hydrated, monitor blood glucose levels regularly, and follow up with your healthcare provider to assess the effectiveness of the combination therapy.
• Dosing adjustments may be needed based on individual response, and the combination should always be prescribed and monitored by a healthcare provider familiar with your medical history.
• The most recent guidelines, such as the 2024 update on glycemic goals and hypoglycemia, suggest considering the addition of SGLT2 inhibitors or GLP-1 receptor agonists in individuals with established cardiovascular disease, chronic kidney disease, and heart failure, independent of baseline A1C or individualized A1C goal 1.

Mechanism and Benefits

• GLP-1 receptor agonists and SGLT2 inhibitors have different mechanisms of action that can provide additive benefits for glucose control and cardiovascular risk reduction.
• The use of these medications together can lead to improved weight loss, blood pressure control, and potential kidney benefits, as seen in studies like the DURATION-8 trial 1.

Clinical Decision Making

• The decision to use GLP-1 receptor agonists and SGLT2 inhibitors together should be based on individual patient needs, considering factors such as glycemic control, cardiovascular risk, kidney function, and potential side effects.
• Healthcare providers should carefully evaluate the benefits and risks of combination therapy and adjust treatment plans accordingly, taking into account the latest clinical guidelines and evidence, such as the 2022 KDIGO clinical practice guideline for diabetes management in chronic kidney disease 1 and the 2024 systematic review and network meta-analysis for the American College of Physicians 1.

From the Research

Combination Therapy of GLP-1 and SGLT2 Inhibitors

The use of GLP-1 receptor agonists and SGLT2 inhibitors in combination has been studied for its potential benefits in managing type 2 diabetes. Key points to consider include:

• The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action 2.
• Studies have shown that the combination of SGLT2 inhibitors and GLP-1 receptor agonists can have additive effects on lowering HbA1c levels, systolic blood pressure, and body weight 3, 4.
• This combination therapy may also have synergistic effects on reducing cardiovascular events and renal decompensation 3, 4.

Efficacy and Safety

Research has demonstrated the efficacy and safety of using GLP-1 receptor agonists and SGLT2 inhibitors together, including:

• Improved glycemic control and blood pressure management 5.
• Reduction in major cardiovascular events and renal decompensation 4, 6.
• Potential benefits in reducing hospitalization for heart failure, although SGLT2 inhibitors may have a greater benefit in this area 6.

Clinical Considerations

When considering the use of GLP-1 receptor agonists and SGLT2 inhibitors in combination, the following points should be taken into account:

• The combination of metformin with SGLT2 inhibitors, GLP-1 receptor agonists, and a potent statin may substantially reduce cardiovascular mortality and morbidity in high-risk patients with diabetes 3.
• Large prospective studies are needed to confirm the findings and establish the long-term benefits and risks of this combination therapy 3, 4.