Chapter 24: Alternatives to Insulin Therapy for Diabetes Mellitus in Cats

Web Chapter 24

Alternatives to Insulin Therapy for Diabetes Mellitus in Cats

Diabetes mellitus (DM) is one of the most common endocrine diseases of cats. Islet amyloid polypeptide (IAPP) is involved in the pathogenesis of feline non–insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes). In fact, recent publications have determined that IAPP concentrations increase in obese cats in direct correlation with increased body condition score. Early diagnosis of type 2 DM is the key to successful therapy using noninsulin alternatives. Cats with early type 2 DM are most likely to respond to an oral hypoglycemic agent. Therefore emphasis should be placed on identifying cats early in the development of the disease.

Physiologic abnormalities associated with early type 2 DM dictate the approach to therapy; the primary abnormalities are increased hepatic glucose production, insulin receptor and postreceptor resistance or defects, and impaired insulin secretion. Treatment is aimed at attenuating the physiologic abnormalities by decreasing hepatic glucose output and glucose absorption from the intestine, increasing peripheral insulin sensitivity, and increasing insulin secretion from the pancreas. This discussion considers noninsulin therapy for DM in cats using a physiologic approach.

Therapeutic Goals of Noninsulin Therapies

Therapeutic goals in the treatment of cats with DM include amelioration of the metabolic abnormalities of DM and extension of life. However, early diagnosis does permit a greater choice of therapeutic options than insulin-dependent DM. Human patients with type 2 diabetes can be divided into three therapeutic categories according to pancreatic beta-cell function: (1) those with advanced disease who require exogenous insulin to control hyperglycemia, (2) those who require only dietary therapy because of sufficient islet reserve and insulin sensitivity to maintain relatively normal glucose levels, and (3) those with sufficient islet reserve and insulin sensitivity to respond to oral hypoglycemic agents or incretins. Human beings with type 2 DM often are classified according to their beta-cell function based on provocative testing. In cats, the differentiation of these categories is almost impossible before treatment; therefore the clinician must rely on response to therapy as a guide to whether the cat has sufficient beta-cell function to be managed without insulin. Dietary therapy is the key to success with noninsulin alternatives, and the diet should be restricted in carbohydrates (<10% on a dry matter basis) and high in protein (50% on a dry matter basis) to allow the drugs to improve insulin sensitivity and insulin secretory capacity.

Noninsulin Alternatives: Indications

Oral hypoglycemic agents include the sulfonylureas (glipizide, glyburide, glimepiride), biguanides (metformin), thiazolidinediones (e.g., rosiglitazone), alpha-glucosidase inhibitors (acarbose), transition metals (chromium, vanadium), and more recently the incretins (exenatide) (Web Table 24-1). Most of these agents work either by increasing insulin secretion or by decreasing insulin resistance, glucose absorption, or hepatic glucose production (Web Figure 24-1). Indications for noninsulin therapy in cats include normal or increased body weight, lack of ketosis, probable type 2 DM with no underlying disease (e.g., pancreatitis, pancreatic tumor), and in some cases, the owner’s willingness to administer oral medications.

Drugs That Enhance Insulin Secretion

The mechanism of action of the sulfonylureas is to increase insulin secretion and reduce insulin resistance; however, some of these agents, such as glipizide, also cause an increase in hepatic glucose output. This leads to delayed hyperinsulinemia, weight gain, and atherosclerosis in humans undergoing sulfonylurea therapy. By provoking insulin release, sulfonylureas may promote the progression of pancreatic amyloidosis and hence increase the risk of long-term complications of DM. However, this has not been proven to be the case in either humans or cats with naturally occurring DM.

In cats, glipizide has been used successfully to treat diabetic patients at a dosage of 2.5 to 5 mg q12h (see Current Veterinary Therapy XII, p 401, for a full discussion). An outline for monitoring and managing cats undergoing glipizide therapy is shown in Web Figure 24-2. The evaluation of effectiveness should not be made until a cat has been on the drug for 16 weeks, as long as the cat is doing well. Side effects of glipizide include severe hypoglycemia (rare in cats), cholestatic hepatitis, and vomiting. Gastrointestinal side effects, which occur in about 15% of cats treated with glipizide, often resolve when the drug is administered with food (Ford, 1995). The author has noted that use of a lower dosage (2.5 mg/cat) of glipizide is associated with fewer side effects. Furthermore, glipizide does not have a taste; the author has had success adding it as a top dressing to canned food. The next-generation sulfonylurea, glimepiride (Amaryl), has fewer side effects than glipizide and causes less fasting hyperinsulinemia.

The first long-term prospective study of glipizide in 50 cats studied for 50 weeks showed 35% to 40% initial response rate (after 22 weeks); at the end of the study, seven cats remained regulated on glipizide, six experienced hypoglycemia and were in remission so glipizide was discontinued, six showed initial response but no further improvement in glucose concentrations, and three cats had recurrence of clinical signs that did not respond to further glipizide therapy (Feldman, Nelson, and Feldman, 1997). In a more recent retrospective study of 50 cats on a low-carbohydrate (<10% on a dry matter basis) diet combined with either PZI insulin or glipizide, the response to glipizide was the same as with PZI insulin (about 70% response) (Moeller and Greco, 2005). The difference in response between the two studies may have been the diet the cats were receiving. In the study by Feldman, Nelson, and Feldman, cats were fed a dry or canned high-fiber, high-carbohydrate diet (15% to 40% on a dry matter basis), whereas the cats in the study by Moeller et al were consuming a very low-carbohydrate diet (<5% on a dry matter basis). As in humans, the use of an ultra-low-carbohydrate, high-protein canned diet is the key to success with oral hypoglycemic agents.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Chapter 24: Alternatives to Insulin Therapy for Diabetes Mellitus in Cats

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