General practitioners often face the common endocrinopathy diabetes mellitus (DM), which can be an ongoing headache for clinicians. This is because they must juggle patient needs and client expectations while overcoming the complications that arise along the way. So, it’s good news that new advice is making the rounds!
London Vet Show (LVS) hosted Dr David Church and Dr Stijn Niessen for their lecture “Brave new world: what’s new for managing diabetes in 2024?” This talk proved to be packed full of helpful tips for managing diabetic patients in first-line practice. It also considered a few of the concerns clinicians have around newer medications such as velagliflozin.
What’s new?
In a nutshell, veterinary surgeons managing the diabetic patient need to consider the following factors:
- Correct the underlying causes and factors that interfere with the action of insulin
- Adjust management to the needs of owner and patient but also be guided by the clinical signs
- Reduce hyperglycaemia to under 15mmol/l and minimise clinical hypoglycaemia
- Reduce the hyperglycaemic impact of meals using the most palatable food that has the lowest glycaemic index
So, how do we do this? Alongside the twice-daily injectable insulin and diet options we are familiar with, there are a few new treatments available.
Velagliflozin for feline diabetes
What do I need to know about velagliflozin?
Velagliflozin (Senvelgo) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor that promotes the excretion of glucose in the kidneys.
This once-daily oral treatment for cats has been available for a while, and when taken, euglycaemia is usually achieved in the “happy” cat within one to two weeks.
What defines a “happy” feline diabetic?
- Eating and drinking well
- Interactive/not lethargic
- No acute vomiting or diarrhoea
- No cachexia
- No dehydration
An “unhappy” cat is one that does not meet these criteria.
Once administered, there is a rapid return to euglycaemia, and this treatment also reduces the load on the beta cells and the clinical symptoms seen in patients. However, velagliflozin’s mechanism of action leads to an increase in urination (osmotic diuresis). Some clinicians are concerned about this exacerbation of polyuria by SGLT2-based drugs, but David and Stijn challenged this. “If the patient is euglycaemic and the owner can cope with this ‘side effect’, is there a true cause for concern?”, they argued.
Are there side effects, risks or complications with velagliflozin?
The most common self-limiting side effect of velagliflozin is diarrhoea, which affects around half of the cats who start this treatment. Most cases resolve within seven days but some patients can have persistent diarrhoea while on this medication.
When faced with the option of either trialling oral insulin medication or not pursuing treatment (ie euthanasia), some owners will opt to trial oral insulin with informed consent
An “unhappy” cat is more at risk of developing complications such as ketosis if started on oral insulin therapy. This is a known concern of veterinarians when considering whether to start their patient on oral insulin therapy and is listed as a complication on Senvelgo’s datasheet. However, Stijn noted that when faced with the option of either trialling oral insulin medication or not pursuing treatment (ie euthanasia), some owners will opt to trial oral insulin with informed consent. This, he suggests, may be contributing to the complication rate seen, as not every patient who starts velagliflozin would be considered an ideal patient.
When considering the risks of diabetic ketoacidosis (DKA) in patients taking velagliflozin, Stijn was keen to stress that ketosis is not equivalent to DKA. Ketosis is linked to the metabolism of fat instead of glucose for energy, which is a normal metabolic process. Therefore, a patient can be in a ketotic state without having ketoacidosis.
Clinicians should use the ALIVE project’s criteria for diagnosing true DKA:
- The presence of ketonaemia (increased beta-hydroxybutyrate concentration) and/or ketonuria/ketonaemia, using nitroprusside test strips to detect ketones in the blood or urine
- Demonstration of metabolic acidosis, which is defined as a venous/arterial blood pH under 7.35 and decreased bicarbonate
No blood gas machine? No problem! If the patient is clinically unwell and meets the other criteria, it can be assumed they are suffering from DKA.
After using the ALIVE-approved criteria, you should either discontinue oral insulin and commence treatment for DKA or continue oral treatment if the patient is clinically well and not acidotic, with a good response to oral insulin.
If your patient is stable and the owner is happy using injectable insulin, it is better to stick with what is currently working
Please note that David and Stijn remarked that patients that had started injectable insulin but switched to oral insulin had an increased risk of developing DKA. So, if your patient is stable and the owner is happy using injectable insulin, it is better to stick with what is currently working.
Toujeo for canine diabetes
What do I need to know about Toujeo?
Toujeo, a concentrated (300IU/ml) glargine insulin given once daily for the treatment of DM in dogs, has a good ability to control glucose levels over a 24-hour period.
Clinically, there is reduced day-to-day and inter-day variation of glucose levels when using this treatment, which means veterinarians can be bolder with their targets and aim to get glucose at the lower end of the acceptable range. By aiming for better glycaemic control, veterinarians can reduce the incidence of secondary complications, such as diabetic cataracts.
It is recommended to use continuous glucose monitoring (CGM) when starting and titrating [toujeo]
The dose rate for Toujeo is wide, with variation in response between patients, so dosing depends on the individual response to the treatment. However, the concern for hypoglycaemic events is low due to the lack of variation in day-to-day glucose levels. It is recommended to use continuous glucose monitoring (CGM) when starting and titrating this medication.
For the small number of patients not able to be reliably controlled on once-daily Toujeo, it is possible to use concurrent insulin injections such as Caninsulin around one hour before a meal to help achieve good levels of stabilisation.
Novel developments: what’s new in treating canine and feline diabetes?
David and Stijn discussed cases of canine DM that were managed with a combination of SGLT2 oral medication and top-up insulin injections as needed. While it is not currently recommended to trial oral insulin in canine patients outside of a research setting, it is encouraging to think of the possibility of veterinarians using oral insulin as a treatment option for canine patients in the near future.
During the session, there was a discussion surrounding the use of longer-acting insulin, such as a weekly “shot” of insulin given at the veterinary clinic. This ultra-long-acting insulin evades clearance mechanisms by the body and persists to promote euglycaemia in patients. This could be a breakthrough treatment when considering the broader goals of reducing the complications of DM due to uncontrolled hyperglycaemia, diabetic neuropathy, diabetic cataracts, etc.
How can we improve glycaemic control in veterinary patients?
When it comes to the treatment of DM, rapid weight loss is still considered one of the best things we can advise for our patients, especially cats. An overweight patient is more likely to be insulin resistant and have a larger accumulation of fat in the pancreas. This accumulation decreases the availability of beta cells for producing the insulin needed to control glucose levels. Weight loss reduces both insulin resistance and the fat concentrations in the pancreas, and research has shown that overweight cats that lose weight in the first month of treatment are 15 times more likely to enter remission.
Weight loss reduces both insulin resistance and the fat concentrations in the pancreas, and research has shown that overweight cats that lose weight in the first month of treatment are 15 times more likely to enter remission
But improving glycaemic control is not limited to changing a patient’s diet to a low carbohydrate one to minimise the post-prandial spike in glucose. In addition, David and Stijn recommended changing the timing of insulin administration; advising owners to feed their pet first and then administer insulin between one hour and one and a half hours post-feeding can help improve glycaemic control. This will be an uncomfortable change for many of us, who have been primed over a lifetime to give insulin at the time of feeding; however, this small shift can help improve glycaemic control significantly, as it reduces post-prandial spikes in glucose. Still not sure? Try combining this shift in dosing with the use of CGM for your peace of mind.
Continuous glucose monitoring systems
One thing remained clear after David and Stijn’s session at LVS: our approach to glucose curves must change.
The goal of insulin treatment is to keep glucose between 4mmol/l and 15mmol/l, although the numbers do need to be considered in tandem with the patient and its clinical response to the medication. Using continuous glucose monitoring systems (CGMS), such as the Freestyle Libre, provides much more reliable and in-depth information than the traditional in-house glucose curve we have relied on for years.
The crucial benefit of [continuous glucose monitoring] is that it does not interfere with the regular pattern of insulin, exercise and food, leading to more reliable results
CGM is considered to be the new standard of care when looking at trends and making insulin dose changes. While the volume of information obtained from CGM devices can feel intimidating, the process of analysis remains the same and can lead to much quicker regulation of glucose levels. The crucial benefit of CGM, argue David and Stijn, is that it does not interfere with the regular pattern of insulin, exercise and food, leading to more reliable results.
It is important to appreciate that CGMS monitor interstitial glucose, so if you were to take a blood glucose sample, the readings may differ. This does not mean your CGMS is ineffective – it is reflective of the lag time between the diffusion of glucose from the bloodstream into the interstitial space. The measurement of interstitial glucose is a safe and effective way to monitor the diabetic response to insulin therapy.
With the commonplace use of CGMS in human diabetes management, many clients are now accepting the use of this technology and actively enjoy participating in collecting data. This subcutaneous device is easy to apply and can be replaced as often as required to help tailor individual treatment plans.
Summary
Complications can have significant welfare impacts on animals and should not be overlooked when considering quality-of-life discussions
There are lots of new advances in the treatment of diabetes mellitus, and it is encouraging to learn there is ongoing research and clinical trials in this space. The management of diabetes in practice can be tricky, and the complication rate is high. Complications can have significant welfare impacts on animals and should not be overlooked when considering quality-of-life discussions.
It is still true that there is no perfect fix for all diabetics – each case is individual – and in that sense, there is always a need for continual contact between the clinician, pet and owner to maximise treatment success.
