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The first diabetes medication to show evidence of cardiovascular benefit in type 2 diabetes was empagliflozin – a sodium–glucose cotransporter 2 (SGLT2) inhibitor – in the placebo-controlled EMPA-REG OUTCOME trial (published in 2015). The number needed to treat to prevent a death from any cause was an impressive 39 in the 3-year trial.

Since then there has been evidence of cardiovascular benefit with other SGLT2 inhibitors, as well as evidence of benefit of SGLT2 inhibitors in both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

Glucagon-like peptide-1 (GLP-1) receptor agonists have also shown evidence of reducing cardiovascular risk in type 2 diabetes, in trials such as LEADER (liraglutide) and SUSTAIN-6 (semaglutide).

So, is there a synergistic benefit with respect to major adverse cardiovascular events if a person with type 2 diabetes is taking both agents?

An interesting study by Simms-Williams et al (summarised on Primary Care Notebook) explored this and found that being on both agents compared with being on either alone was associated with such a benefit.

In this population cohort study, the addition of an SGLT2 inhibitor to a GLP-1 receptor agonist was associated with a reduction in cardiovascular risk of 30% compared with being on a GLP-1 receptor agonist alone. Similarly, adding a GLP-1 receptor agonist to an SGLT2 inhibitor was associated with a risk reduction of 29%.

This study provides evidence, then, that the use of these agents together is associated with a similar additive benefit in terms of reducing cardiovascular risk whichever agent is the medication being “added to”. That is to say, there is more cardiovascular benefit from using both than either individually and so there is indeed a synergistic effect in terms of reducing cardiovascular risk when using both a GLP-1 receptor agonist and an SGLT2 inhibitor.

The same study investigated the renal benefits if either an SGLT2 inhibitor was added to baseline GLP-1 receptor agonist therapy or vice versa. Adding an SGLT2 inhibitor to a GLP-1 receptor agonist was associated with a significant 57% lower risk of serious renal events. The addition of a GLP-1 receptor agonist to baseline SGLT2 inhibition was associated with a less pronounced and non-significant risk reduction.

For more information, see Primary Care Notebook.

Other highlights in this month’s email include the use of aspirin in breast cancer, the influence of exercise on the incidence and management of inflammatory bowel disease, and the use of oxygen in chronic respiratory failure due to chronic obstructive pulmonary disease.

• Finasteride – risk of psychiatric side effects and sexual side effects: Can the sexual dysfunction (including decreased libido and erectile dysfunction) associated with the use of finasteride persist after the medication is stopped? Is depression or psychosis associated with the use of finasteride?
• Postponement of menstruation: For norethisterone 5 mg three times a day to be effective for postponement of menstruation, how long before the predicted menses should this medication be commenced? Oral medroxyprogesterone is an alternative to norethisterone in the management of postponement of menses – can this drug affect fertility?
• Use of oxygen in chronic respiratory failure due to chronic obstructive pulmonary disease: This section has been updated.
• Exercise and inflammatory bowel disease (IBD): The relationship between exercise and IBD is summarised.
• Aspirin and breast cancer: Is aspirin an evidence-based adjunctive therapy in breast cancer?
• Use of combination of SGLT2 inhibitor plus GLP-1 receptor agonist and cardiorenal benefits: The benefits associated with the combination of these agents are summarised.