What GPs need to know about GLP-1 RAs

When it comes to the treatment of type 2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have often been considered well down the line of treatment options.
 
But updated Australian guidelines are now recommending that clinicians consider them earlier, after, or in combination with, metformin to help patients lower their blood glucose levels.
 
Dr Konrad Kangru, a GP with a special interest in diabetes management, says GLP-1 RAs are ‘one of the most significant’ new diabetes medications that have become available in the past 5–10 years.
 
‘Diet and lifestyle are always number one and metformin is well acknowledged as being our first line intervention for medication,’ he said.
 
‘But now … we don’t have to put everybody on sulphonylurea if we don’t feel that’s the most appropriate second line.
 
‘We can use a DPP4 [dipeptidyl peptidase-4] inhibitor, we can use a SGLT2i [sodium-glucose co-transporter-2 inhibitors], or now we can actually use one of these GLP-1 RAs as our second line.’
 
Administered via injection, GLP-1 RAs work by mimicking the effects of the hormone GLP-1 produced in the body when eating, stimulating the pancreas to secrete insulin and reduce blood glucose levels.
 
The GLP-1 RAs available on the Pharmaceutical Benefits Scheme (PBS) come in multiple forms, including semaglutide and dulaglutide, taken once weekly, and exenatide, which is taken twice daily.
 
All GLP-1RAs are TGA indicated for use with other diabetes medications, including SGLT2is, and are PBS reimbursed for use together with metformin, sulfonylureas and insulin.
 
Dr Roy Rasalam, Head of Clinical Studies (Medicine) at James Cook University, says GLP-1 RAs are often differentiated according to structure and duration of action.
 
Newer GLP-1 RAs, such as dulaglutide and semaglutide, are based on human GLP-1.
 
‘These differences can translate to differences in efficacy and tolerance or side effects,’ Dr Rasalam said.
 
‘Size of molecule and half-life are important factors that result in differences in efficacy and weight loss, as well as similarity to human GLP-1. Side effects are broadly similar across the class, however individual response to therapy cannot be predicted.
 
‘In the clinical registration trials for these medications there was a broad range of responses to therapy, with some patients having limited response and some having excellent response.
 
‘This is typical of most medications. One can hope for a good response based on the mean glycameic lowering and mean weight loss achieved in the clinical trials.’
 
In addition to their main effect of glycaemic lowering, Dr Rasalam says this class of medication has additional effects on weight and appetite suppression, and for some GLP-1RAs, reduction in cardiovascular (CV) events.
 
‘The most common side effects experienced by patients are gastrointestinal [GIT],’ he said.
 
Beyond a HbA1c reduction, Dr Kangru says GLP-1 RAs can have cardiovascular benefits.
 
‘The big benefit certainly is the cardiovascular safety with this group of medications,’ he said.
 
‘For patients who are in a higher BMI above 30, then generally the GLP-1 RAs would be a great choice there. But these medications are safe and effective regardless of initial BMI, so I’d be happy to consider these in any of my patients with type 2 diabetes requiring additional help.’
 
Comparing SGLT2s to GLP-1 RAs, Dr Rasalam says while SGLT2is can be useful in reducing hospitalisation for heart failure, with some demonstrated CV benefit, they are generally less effective in lowering HbA1c and body weight.
 
‘It is important to consider the potential adverse effects of this class prior to initiation [and] should be discussed with the patient, and advice provided for preventing their occurrence,’ he said.
 
Dr Rasalam says the overall potential benefits of GLP-1 RAs far outweigh many of the older second-line therapy options.
 
‘If chosen for the right patient, the potential side effects are mainly GIT related and are generally manageable and of limited duration after starting therapy,’ he said.
 
‘The convenience of a once weekly therapy may [also] appeal to many patients over the additional burden imposed by adding an extra tablet [as with other therapies].
 
‘It is important that prescribers are aware of this important option in treatment of type 2 diabetes and discuss it with patients when HbA1c levels are not at target or, [if] patients have established cardiovascular disease [CVD] or a high risk of CVD.’
 
This content has been commissioned by Novo Nordisk and written and reviewed by newsGP.
 
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cardiovascular disease diabetes management GLP-1 RAs type 2 diabetes