Feline diabetes management can be challenging for clinicians and pet owners, but research and advancements in less invasive treatment and monitoring options are available. Following are the most promising and accessible management tools, according to the authors.
Refresh yourself on key principles of diagnosis and management of diabetes in cats with this quiz.
1. Sodium-Glucose Cotransporter 2 Inhibitors
Bexagliflozin tablets and velagliflozin oral solution (sodium-glucose cotransporter 2 [SGLT2] inhibitors) have been FDA-approved for management of feline diabetes.1 The SGLT2 protein is expressed primarily in the early segment of the renal proximal convoluted tubule and is responsible for ≈90% of glucose reabsorption from urinary filtrate.2 Inhibition of SGLT2 thus results in increased urinary glucose wasting and subsequent reduction of blood glucose. SGLT2 inhibitors can be administered orally once daily, and risk for inducing hypoglycemia is low when these drugs are used as sole therapy due to modest glucose absorption by the uninhibited SGLT1 protein.2
Bexagliflozin and velagliflozin administered at labeled dosages have been shown to rapidly and sustainedly reduce blood glucose.3-5 Although these medications are relatively safe, appropriate case selection is critical when considering SGLT2 inhibitors because the mechanism of action does not stimulate cellular uptake of glucose. Patients should therefore have some endogenous insulin-producing ability, as use of these medications in cats with little to no endogenous insulin can result in euglycemic diabetic ketoacidosis.4 Cats given exogenous insulin concurrently with SGLT2 inhibitors have increased risk for hypoglycemia3; therefore, SGLT2 inhibitors should be used only in cats with newly diagnosed diabetes, that have not been treated previously with insulin, and are not known to have insulin-deficient diabetes mellitus.6,7
SGLT2 inhibitors should not be used in patients that are clinically unwell (eg, chronic vomiting, anorexia) or have significant comorbidities (particularly, significant renal or hepatic disease).6,7 The most observed adverse effects are GI related, including diarrhea and vomiting.4,5 Careful patient selection and comprehensive screening, including total thyroxine and ketone assessment (with beta-hydroxybutyrate being the earliest and most abundant ketone body produced8), are recommended before initiation of therapy to reduce the risk for euglycemic ketoacidosis. Blood ketone monitoring can be accomplished with a validated handheld ketone meter, which is more sensitive than traditional urine dipstick monitoring of acetoacetate for early detection of ketosis.8-10 A cutoff value of 3.7 mmol/L is used by the authors; patients with values above this level should be managed with insulin rather than an SGLT2 inhibitor.4 Additional monitoring recommendations are available in the literature.6,7
2. Ultra-Long-Acting Insulins
Use of basal (ie, ultra-long-acting) insulins has recently been considered in veterinary patients. These insulins typically have predictable and sometimes peakless (minimal within-day variability) pharmacodynamic profiles that more closely simulate basal insulin release than traditional insulin formulations. In contrast to dogs and humans, cats appear to experience sustained insulin secretion with a comparatively mild postprandial peak in health, suggesting basal insulin formulations may mimic normal physiology of cats more closely than traditional bolus insulins.11 The duration of action of basal insulins appears substantially shortened in cats compared with humans.12
Studies of insulin glargine U300 and insulin degludec use in cats are limited, and additional studies are needed to assess their clinical utility. Although these formulations appear to have a comparable onset and peak activity, insulin degludec has a substantially shorter duration of action (mean, 621 ± 183 minutes) relative to insulin glargine U300 (mean, 871 ± 138 minutes), suggesting insulin degludec is not suitable for once-daily administration in cats.12 Insulin glargine U300 has a prolonged metabolic effect but a duration of action of <24 hours and moderate interindividual variability.12,13
Insulin glargine U300 and insulin degludec may help manage feline diabetes but are unlikely to produce optimal glycemic control when administered once daily in most cats. Administration strategies are not yet well established for either insulin but have been described for insulin glargine U300.14 Concurrent use of a continuous glucose monitoring (CGM) system and/or consultation with a veterinary internist may therefore be helpful when initiating these therapies.
3. Continuous Glucose Monitoring
CGM is an increasingly popular alternative to glucometer-based glucose curves. CGM systems rely on an implantable, disposable sensor that measures the interstitial glucose concentration and can remain effective up to 14 days. Advantages include minimized need for repeated blood sampling, assessment of glycemic control in the home, and longer periods of glycemic data to evaluate. Application of commonly available sensors is relatively simple and can be performed in the clinic or in the home by pet owners.
Several monitoring systems are available, but a flash CGM system (Figure) has been well studied and is commonly used. The sensors are tolerated by most patients, provide a high level of owner satisfaction, and report glucose trends that correlate well with blood glucose levels15,16; however, keeping the sensors attached to patients during the curve period can be difficult, interstitial readings may reflect a lag (≤15 minutes) between blood glucose increases, and owners with access to real-time glycemic data may alter treatment without consulting the clinician.16 In the second generation of the flash system, readings correlate strongly with blood glucose levels in cats but may underestimate blood glucose, except in cases of severe hypoglycemia, in which overestimation may occur.17 The third generation has not been studied in cats but has a reduced sensor size compared with previous versions.
Sensors can be easily applied to cats and are ready for use following a brief warm-up period. Designated readers are available, although cell phone applications can also be used for convenience.
A long-term implantable glucose monitoring system was recently described in a small number of dogs but has not yet been described in cats.18 A more detailed overview of CGM is available in the literature.19
Conclusion
Awareness of what feline diabetic management tools are available and how they can improve glycemic control and patient quality of life is important.