From the Guidelines
Taking DPP-4 inhibitors and GLP-1 receptor agonists concurrently is generally not recommended for most patients. These medication classes work through related mechanisms - DPP-4 inhibitors prevent the breakdown of naturally occurring GLP-1, while GLP-1 receptor agonists directly stimulate GLP-1 receptors at much higher levels. Using both simultaneously provides minimal additional benefit while potentially increasing costs and side effects.
Key Considerations
- Most clinical guidelines suggest choosing one class over the other rather than combining them, as seen in the 2024 clinical guideline from the American College of Physicians 1.
- If a patient is already on a DPP-4 inhibitor and needs additional glucose control, it's typically recommended to discontinue the DPP-4 inhibitor when starting a GLP-1 agonist.
- The 2022 KDIGO clinical practice guideline for diabetes management in chronic kidney disease also advises against using GLP-1 receptor agonists in combination with DPP-4 inhibitors 1.
- Additionally, the 2024 DCRM 2.0 multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases caution against combining incretin classes, including GLP-1 RA and DPP4i 1.
Clinical Decision Making
The decision to use these medications concurrently should always be made by a healthcare provider who can evaluate the individual's specific situation, diabetes control needs, and risk factors. However, in rare specific cases with complex diabetes management needs, some specialists might consider combination therapy under close monitoring.
Prioritizing Outcomes
When making decisions about diabetes management, it's essential to prioritize outcomes such as all-cause mortality, major adverse cardiovascular events, and progression of chronic kidney disease, as emphasized in the clinical guidelines 1.
From the Research
Safety of Concurrent Use of DPP4 and GLP1
- The safety of taking DPP4 and GLP1 concurrently is not explicitly stated in the provided studies, but some information can be inferred from the available data.
- A study from 2017 2 found that adding a DPP4 inhibitor to ongoing therapy with a GLP1 receptor agonist did not have significant effects on glycaemic control, but increased intact GLP1 and GIP concentrations.
- The same study suggests that GLP1 receptors may be maximally stimulated by GLP1 receptor agonists, which could imply that adding a DPP4 inhibitor may not provide additional benefits in terms of glycaemic control.
- Another study from 2018 3 compared the efficacy of GLP1 receptor agonists to DPP4 inhibitors and found that GLP1 agonists yielded greater reductions in HbA1c and weight, but were associated with a greater likelihood of gastrointestinal side effects.
- A study from 2020 4 mentions that DPP4 inhibitors are generally well tolerated, but some agents should be used with caution in people with risk factors for heart failure.
- It is also worth noting that a study from 2010 5 states that GLP1 receptor agonists and DPP4 inhibitors can be used in patients not adequately controlled by metformin monotherapy or as initial therapy in those for whom metformin is contraindicated.
Potential Interactions and Side Effects
- The concurrent use of DPP4 and GLP1 may increase the risk of gastrointestinal side effects, as both classes of medications can cause these types of adverse events 3.
- However, the risk of hypoglycaemia does not appear to be increased with the concurrent use of DPP4 and GLP1 2, 3.
- It is essential to carefully evaluate the potential benefits and risks of concurrent use of DPP4 and GLP1 in individual patients, taking into account their specific clinical characteristics and medical history.