Diabetes Mellitus in Cats: Treatment Options Outside of Insulin

Author: Dr. Kristin Heft, DVM, DACVIM (Internal Medicine)

Diabetes mellitus (DM) in cats is a common endocrine disorder characterized by chronic hyperglycemia resulting from either insufficient insulin production or insulin resistance. While insulin therapy remains the cornerstone treatment for cats, recent advancements have explored alternative therapies, including sodium-glucose cotransporter 2 (SGLT2) inhibitors for insulin resistant cats who may maintain some endogenous insulin production.
 

Mechanism of Action:

SGLT2 inhibitors exert their therapeutic effect by selectively inhibiting the renal SGLT2 transporter in the proximal renal tubules. This inhibition reduces glucose reabsorption, promoting glucosuria, and thereby lowering blood glucose levels independently of insulin. In diabetic patients, where the renal threshold for glucose reabsorption is exceeded, SGLT2 inhibitors enhance glucose excretion, effectively lowering blood glucose levels. Subsequently, when blood glucose levels are lowered, the effects of glucose toxicity on the insulin-producing pancreatic beta cells are diminished, promoting improved function of beta cells.

Efficacy and Safety Studies:

Studies evaluating SGLT2 inhibitors in cats with diabetes mellitus have shown promising results. Clinical trials have demonstrated significant reductions in blood glucose levels and improvements in glycemic control following treatment with SGLT2 inhibitors. These agents have primarily been tested and shown to be effective in newly diagnosed diabetic cats.

Studies also indicate minimal adverse effects when used at therapeutic doses with a favorable safety profile. The most common side effects reported are gastrointestinal upset and mild polyuria and polydipsia due to the osmotic diuretic effect of increased glucosuria. However, these treatments are generally well-tolerated and adverse effects do not typically necessitate discontinuation of treatment.

Clinical Applications:

SGLT2 inhibitors offer several clinical advantages in the management of feline diabetes mellitus:

• Efficacy: They provide effective glycemic control, potentially reducing reliance on exogenous insulin administration.

• Administration: Once daily oral administration (liquid or tablet) improves owner compliance and provides an alternative to injectable therapy

• Weight Management: SGLT2 inhibitors may promote weight loss by calorie loss through glucosuria, which can be beneficial in overweight or obese diabetic cats.

• Renoprotective Effects: By reducing glucose reabsorption in the kidneys, SGLT2 inhibitors may exert renoprotective effects, potentially beneficial in diabetic nephropathy.

• Cardioprotective Effects: Emerging evidence suggests potential cardiovascular benefits, although further research is needed to elucidate these effects in cats.

Challenges and Considerations:

Despite their promising benefits, several challenges and considerations exist regarding the use of SGLT2 inhibitors in cats:

• Monitoring: Regular monitoring of blood beta-hydroxybutyrate (ketone) levels via ketometer is essential to identify patients that require exogenous insulin administration (ketone levels may increase even if blood glucose levels improve or normalize).

• Cost: Affordability and availability may limit widespread adoption of SGLT2 inhibitors in veterinary practice.

• Patient Selection: Optimal patient selection criteria, including concurrent medical conditions, require further clarification. Currently, administration is not advised in patients with a history of previous insulin administration, history of DKA, IRIS stage III or higher CKD, or pancreatitis.

Future Directions:

The future of SGLT2 inhibitors in feline diabetes management holds promise for advancements:

• Clinical Trials: Continued research is needed to establish long-term safety and efficacy profiles in diverse feline populations.

• Combination Therapies: Exploration of SGLT2 inhibitors in combination with insulin or other treatment modalities to optimize therapeutic outcomes.

SGLT2 inhibitors represent a promising therapy for the management of diabetes mellitus in cats. Their unique mechanism of action, efficacy in glycemic control, favorable safety profile, and potential ancillary benefits make them a valuable addition to the veterinary armamentarium against feline diabetes. While further research and clinical experience are needed to fully establish their role, SGLT2 inhibitors offer a new avenue for optimizing diabetes management and improving the quality of life for diabetic cats and owners.