An in-depth look at treating diabetes mellitus in cats

Diabetes mellitus (DM) is a condition characterized by inadequate insulin secretion by the beta cells of the pancreatic islets. Cats with DM present some unique challenges, and management strategies for feline diabetics are considerably different from those recommended for their canine counterparts. Practitioners need to understand the processes that drive this disease in cats, and strive to create plans tailored to the specific needs of both the patient and the owner. Recommendations regarding best practices have changed substantially over the last 20 years, and have impacted how diabetic cats are fed, treated, and monitored.1,2 In addition, novel therapeutic options are on the horizon and can be expected to dramatically impact how we care for these cats in the coming years. Etiology of feline diabetes mellitus The majority of diabetic cats fit a pattern consistent with human Type 2 diabetes, in which insulin resistance and associated pancreatic amyloidosis results in compromised beta cell function.1 Other processes likely play a role in some individuals, and may explain why some cats maintain euglycemia despite substantial insulin resistance. For example, there are strong genetic predispositions for DM in some breeds, in particular the European and Australian Burmese.3 In addition, chronic pancreatitis is a well-recognized cause of beta cell loss, and some cats become diabetic due to underlying acromegaly, i.e., excessive growth hormone secretion by a pituitary tumor.4 Insulin responsiveness (sensitivity) is defined as the effect of insulin on glucose uptake. In animals with insulin resistance, it takes more insulin to get the work done. In dogs, sustained insulin resistance does not cause problems because of species-related differences in physiology. In cats and people, increased insulin production is associated with the accumulation of amylin within pancreatic tissues. Amylin – also referred to as islet amyloid polypeptide – is 37-amino-acid peptide that is co-secreted with insulin by pancreatic β/beta cells.5 Its full functions are still poorly understood, but amylin is thought to slow gastric emptying and promote feelings of satiety. Amylin deposition within the pancreas results in progressive loss of β/beta cell viability, and eventually compromise the ability of the pancreas to release enough insulin to maintain euglycemia. Many diabetic cats probably spend some time in a “preclinical diabetic” state prior to diagnosis. These cats appear to be well, with a stable body weight, and unremarkable appetite and thirst. However, blood glucose (BG) levels are persistently higher than normal, despite robust insulin secretion.1 However, ongoing amylin deposition will result in progressive compromise to pancreatic function. As a consequence, BG slowly rises until overt DM is evident; this occurs when the renal threshold for glucose reabsorption by the proximal convoluted tubules is exceeded; this occurs when BG is between 250 and 300 mg/dl in cats. At this point in time, the cat will display the clinical signs associated with DM, namely polyuria, polydipsia, polyphagia, and weight loss. Causes of insulin resistance Numerous processes will hinder responsiveness to insulin. Some of these are metabolic (e.g., obesity, concurrent endocrinopathy) or related to inflammatory diseases (e.g., dental, pancreatic, intestinal). Various medications, particularly glucocorticoids, also impact insulin sensitivity.3,6 Obesity is an important cause of insulin resistance.7 Adipose tissue was traditionally thought to be metabolically inert and was regarded as simply a “warehouse” for fat. However, over the last half century, over 100 chemicals produced by adipocytes have been identified. Many of these “adipokines” are known to have profound metabolic effects on satiety and energy homeostasis. In addition, some adipokines are inflammatory and can antagonize the effects of insulin. Any obese animal should be regarded as being both insulin resistant and in a chronic inflammatory state. Every non-diabetic patient with a robust body condition score must produce more insulin than a slim animal in order to maintain euglycemia. Unfortunately, the effects of obesity are often compounded by lack of exercise and a sub-optimal muscle condition score. Muscle activity increases insulin responsiveness; even modest amounts of exercise can improve insulin sensitivity. Appropriate, gradual weight loss is, therefore, indicated for every over-conditioned feline diabetic. A loss of approximately two percent per week is a safe target; body weight should be checked every three to four weeks so intake can be adjusted as appropriate.1 The calories need to support weight loss can be calculated on various websites, such as the Pet Nutrition Alliance.8 Several endocrine disorders, namely hypersomatotropism (also known as acromegaly), hyperadrenocorticism and hyperthyroidism, are well recognized causes of insulin resistance in cats, and both cushingoid and acromegalic cats are often diabetic. The prevalence of feline acromegaly in the US is unclear, but studies in Europe suggest it is a fairly common condition in cats with DM.9 This condition should be considered if the cat is of large stature, with big feet and a flattened face (Figure 1). Figure 1: Eight-year-old castrated male domestic short-haired cat with hypersomatotropism/acromegaly. Note the broad facial features and prominent bones of the jaw. Courtesy Dr. Brigitte McAtee. Patients can be screened for this by measurement of insulin-like growth factor-1 (IGF-1). As insulin is needed for expression of IGF-1, cats should receive exogenous insulin for six weeks prior to testing. Hyperadrenocorticism is much less common in cats than in dogs, and is often suggested by changes in haircoat, evidence of skin fragility, central adiposity, and muscle wasting (Figure 2). Spontaneous hypercortisolemia can be confirmed with a low dose dexamethasone suppression test; however, interpreting the results of this test in a patient with poorly controlled DM can be challenging. Practitioners must also bear in mind the “low dose” of dexamethasone for feline patients is 0.1 mg/kg IV.10 Figures 2A, top, and 2B: Middle-aged spayed female domestic long-haired cat before (A) and after (B) the development of pituitary dependent hyperadrenocorticism. Note the alopecia and small skin wound in Figure 2B. Courtesy Dr. Brigitte McAtee. Cellular responses to insulin are blunted by many of the inflammatory mediators. Dental disease is a classic cause of insulin resistance in cats and can markedly impact insulin sensitivity. Performing a thorough dental evaluation on all diabetics is essential, and significant pathology should be addressed promptly. It is not necessary (and may be impossible!) to achieve good diabetic control prior to performing a dental cleaning. Glucose toxicity This term is used to describe the effect of sustained hyperglycemia on various tissues. Diabetic neuropathy is a classic example of glucose toxicity; although the specific mechanism of this condition is still poorly understood, it is characterized by a symmetrical compromise to the innervation of the distal limbs.11 Ironically, another organ markedly impacted by sustained hyperglycemia is the pancreas. In experimental studies, just 10 days of hyperglycemia results in substantial β/beta cell loss in previously healthy cats. Affected cells undergo apoptosis, which is a non-inflammatory cellular “suicide.”12 In cats with spontaneous DM, the exact same process occurs. However, along with apoptosis, we also get islet cell shut down. Essentially, some β/beta cells simply “hibernate” and stop making insulin. If BG is brought below 225 mg/dL, these cells may return to function. However, persistent hyperglycemia (i.e., more than two to three months) will result in progressive apoptosis of the remaining cells and irreversible impairment of endocrine pancreatic function. The concept of glucose toxicity is key to attempts to induce diabetic remission in cats. If BG levels can be effectively controlled, allowing the remaining β/beta cells to regain function, the patient may be able maintain euglycemia without the need for exogenous insulin injections. The impact of diet In the last 15 years, there has been a truly revolutionary change in the approach to nutrition for feline diabetics. Although work in the 1990s indicated high-fiber diets may improve glycemic control in cats, there is now substantial evidence to support the use of high-protein diets, with ≤ 14 percent of metabolizable energy (ME) coming from non-fiber carbohydrates (the so-called “Catkins” diet).1,2,13 The impact of these dietary changes is profound; low carbohydrate (CHO) diets facilitate effective weight loss and are strongly associated with the induction of remission in feline diabetics. Current theories suggest the impact of diet is mediated by the incretins; these are a class of hormones secreted by specialized enterocytes in response to the arrival of nutrients in the small intestine. The presence of the incretins has been known for many decades, but the actual molecules were only recently identified. Several incretins with various physiological effects have now been described, and two members of this group are known to have specific impacts on energy homeostasis.14 These two are glucose-dependent insulinotrophic peptide (GIP) and glucagon-like peptide 1 (GLP-1). In essence, the cells that release GIP and GLP-1 taste the contents of the small intestine and provide advanced warning to the liver, pancreas, and brain that nutrients are arriving; this means processes such as insulin secretion and gluconeogenesis are appropriately adjusted prior to the absorption of ingested nutrients. GLP-1 is a particularly important hormone, as it inhibits hepatic gluconeogenesis and stimulates the release of insulin from the pancreas. In addition, it supports the growth of β/beta cells within pancreatic islets. In people and dogs, CHOs are the most potent trigger for incretin release, followed by fat and then protein. In cats, the pattern for incretin stimulation is different. Protein and fat have the most impact, whereas CHOs have much more modest effects on incretin production. In fact, GIP is not released at all following dextrose (a pure CHO) administration in cats.15 This is likely the reason why low CHO diets have such an impact on our feline patients. By simply switching a cat from a high- to a low-CHO diet, we can improve glucose homeostasis, insulin sensitivity, and β/beta cell function. Although opinions differ regarding dietary recommendations for cats with DM, many experts feel low CHO diets make sense, and routinely recommend a high protein (>45 percent) canned diet with ≤ 14 percent ME from CHO.1,2 Fiber (a non-digestible CHO that does not contribute to ME) may provide some additional benefits, by slowing the absorption of nutrients and creating a sense of satiety. Soluble fibers have been shown in human diabetics to improve insulin sensitivity. It can be difficult to determine the percentage ME from the three major food groups from the routinely available nutritional information, and simply looking at the standard “nutrient analysis” can be misleading. Online calculators, such as the one provided by BalanceIt, can be used to estimate the percentage ME from protein, fat and CHO, based on the guaranteed analysis.16 It is important to bear in mind, however, the guaranteed analysis often lists the minimum amount of crude protein and fat, rather than the actual content. It is also worth looking at the energy density of the diet, along with the fiber content (in gm/100 calories) as these can affect feelings of satiety. Dry diets in the “diabetic” family tend to have more CHO than the canned versions and are generally thought to be a less-appropriate option. However, cats (or their owners) have strong preferences for dry food and may be reluctant to make the switch to a canned product. Monitoring the diabetic cat Many experts feel in-clinic BG measurements are of limited use in feline patients, as stress can markedly increase BG values. The traditional “glucose curve” collected in the hospital environment is often, therefore, of limited value unless hypoglycemia is documented.1 Monitoring strategies in which BG values are determined in the home environment are generally thought to be more appropriate. Many owners are able to learn to collect capillary blood for at-home testing, using a lancet or needle on the ear tip or the side of a paw pad. Numerous online videos can be accessed to show clients just how simple this process is and how well it is tolerated by most cats. Reliable glucose readings are essential, and selecting an appropriate glucose monitor is important. Some monitors read whole blood concentration, rather than serum or plasma values. This causes an “under-reading” effect, in which a true serum concentration of 65 mg/dl will be read out as 50 mg/dl. In addition, the distribution of glucose between red cells and plasma is different for cats and humans, so human-calibrated plasma monitors may also be misleading. It is, therefore, really important to use a veterinary validated device such as the AlphaTRAK. In the last few years, many clinicians have experimented with the FreeStyle Libre continuous interstitial glucometer. This device is marketed for use in human diabetics, and is not veterinary approved. However, in many small animals, it provides meaningful data that can be used to appropriately monitor glycemic control and adjust insulin doses.17 The sensor is a small, flat device that adheres to the skin and measures glucose concentrations within the interstitial fluid. Figure 3: FreeStyle Libre sensor placed on the neck of a diabetic cat. Courtesy Dr. Heather Kvitko-White. These values are not identical to BG, but provide a fair approximation, unless BG is increasing or decreasing rapidly. The sensor does not need to be calibrated, is read by an app on most smartphones, and provides up to 14 days of data. When scanned, the sensor provides an instant reading, along with a graph of the previous eight hours. Information can be downloaded to a computer, or uploaded to the cloud and accessed remotely by the veterinarian. It is always prudent to initially compare a couple of AlphaTRAK measurements to the readings provided by Libre to be sure it seems to be reliable in this particular individual. In stable patients, defined by an appropriate body weight, no signs of hypoglycemia, and minimal clinical signs of DM, a serum fructosamine may be used to provide a more global assessment of glycemic control over the previous seven to 10 days. A fructosamine concentration below the reference range indicates significant insulin overdose and merits an immediate dose reduction. A value above the reference range simply means the patient is poorly regulated, but does not provide enough data to safely increase the insulin dose. It is important to bear in mind the fructosamine reflects the average BG; brief periods of hypoglycemia followed by sustained hyperglycemia will, therefore, result in increased fructosamine concentrations. Diabetic remission Most experienced practitioners have witnessed the phenomenon of feline diabetic remission, in which the patient is able to maintain euglycemia without exogenous insulin. This usually occurs within the first three months, but can occur after prolonged dependence on exogenous insulin. Now there is a greater understanding of the processes that drive a cat to become diabetic, and the influence of factors such as body weight and diet on insulin responsiveness, it is reasonable–in carefully selected cats–to regard diabetic remission as a treatment goal.18 Not all cats are realistic candidates for remission, but studies suggest a sizeable proportion of suitable patients will become insulin independent within four months with protocols designed with this goal in mind.19 However, there is still significant uncertainty about the factors that influence diabetic remission and the current literature on this subject makes it difficult to create solid recommendations.20 The ideal candidate for remission is an overweight and sedentary cat on a high CHO diet, recently given a long-acting steroid injection. There is an excellent chance this cat will undergo remission following effective control of BG with exogenous insulin, combined with a low CHO diet and appropriate weight loss. Interestingly, an episode of diabetic ketoacidosis does not preclude the possibility of remission. Identifying a cat with a strong likelihood of remission is generally based on the physical examination, patient history (e.g. episodes of prior illness, current medication use, body weight changes, etc.), and standard laboratory evaluation. A complete blood count, chemistry panel, urine analysis, thyroid evaluation, retroviral testing, and measurement of feline pancreatic lipase immunoreactivity should be performed on all newly diagnosed diabetic cats, so concurrent or underlying issues can be promptly identified and addressed. Transient or reversible causes of insulin resistance include obesity, exogenous steroids, and dental disease; all of these should be addressed. If a cat has chronic stomatitis, inflammatory bowel disease, asthma, heart disease etc., it is much less likely to achieve a sustained remission. Under these circumstances, it is generally unhelpful to propose this as a treatment goal. If the patient’s history suggests a sustained period of preclinical diabetes, in which BG was routinely above 200 mg/dl but below the renal threshold, remission is unlikely. A big clue pointing toward this circumstance is the presence of a peripheral neuropathy, as this finding strongly indicates chronic hyperglycemia. All nerves can be affected, but those supporting function in the rear limbs are predictably impacted. The cat may be noted to have an overtly plantigrade stance, or the owner may report difficulty getting up on to furniture. However, the signs of a peripheral neuropathy may be subtle and can be overlooked during a routine physical examination unless the cat is able to move freely and encouraged to jump. The other way to identify subtle changes in rear limb function is by scratching the base of the tail and seeing if the cat “tip toes” in response. Remission is also unlikely if the patient’s physical examination suggests hyperadrenocorticism; many cushingoid diabetic cats can be successfully managed, but diabetic remission is very uncommon.10 Definitive treatment of hypersomatotropism (acromegaly) with hypophysectomy often results in diabetic remission, but it is a costly option with limited availability in the U.S.21 The most effective way to support diabetic remission is to begin appropriate insulin therapy, with the intent to keep the BG below about 220 mg/dL. This is best achieved with long-acting insulins such as insulin glargine, insulin detemir, or protamine zinc insulin. Intermediate products such as pork lente or neutral protamine hagedorn insulin are widely regarded as less-suitable first choices for cats.1,2 Practitioners are encouraged to access current recommendations regarding appropriate starting doses or to consult with an internal medicine specialist for advice before using an unfamiliar insulin type. If the owner wishes to try for remission, BG must be carefully monitored so insulin doses can be adjusted as necessary. As a general rule, the dose should not be increased until a full 72 hours have elapsed on a new regimen, as it can take a few days to see the full effects. Owners need to be able to check BG at home so insulin therapy can be adjusted promptly. The goal is to keep blood glucose concentrations between 65 and 220 mg/dL. As insulin sensitivity improves and β/beta cell function is restored, the patient is likely to have BG values that stay consistently below 120 mg/dL. At this point, the insulin dose should be gradually decreased. It can be technically challenging to do this if the cat is only on one unit of insulin, as it can be difficult to reliably draw up smaller amounts. Remission can be transient, particularly if the cat regains weight. Careful long-term monitoring is essential, and triggers for DM such as glucocorticoids should be avoided. ‘Loose control’ approach This philosophy regarding the management of feline diabetics is in stark contrast to the idea of trying to induce diabetic remission. Instead, this strategy is designed to ease the psychological and financial burden on the owner by negating the need for close monitoring and frequent adjustments of the insulin dose. Essentially, the cat receives enough insulin to be a functional pet; this minimizes the risk of hypoglycemia, but does mean the cat is likely persistently polyuric and polydipsic. A recent report of 185 cats managed in a private practice setting with minimal monitoring suggests many cats may do well with this approach.22 These cats were primarily monitored on the basis of clinical status (weight, thirst, appetite) and pre-insulin BG levels, with the goal of keeping these over 300 mg/dL. All cats were on protamine zinc insulin, given every 12 hours, and most were fed a low CHO diet. Median survival time was over four years and both clinical hypoglycemia (<6% of cats) and diabetic ketoacidosis (less than four percent) were rare. This approach provides a useful option for owners with limited interest in more intensive monitoring, and emphasizes the importance of evaluating the patient’s clinical status when managing a feline diabetic. What lies ahead? Once weekly insulin. Preliminary data describing the effect of an insulin designed for once-weekly administration in cats was reported at the 2020 ECVIM Forum.23 This product combines a recombinant feline insulin molecule with the crystallizable fragment portion of immunoglobulin G via a linkage protein. After injection into the subcutaneous space, the insulin-crystallizable fragment unit is very slowly released due to its large size. When it does leave the subcutaneous space, the insulin-Fc unit is taken up by antigen presenting cells. The insulin is then subsequently released very slowly back into the circulation. In this pilot study, five cats with DM were transitioned to this product and the dose was then titrated using continuous glucose monitoring systems. After seven weeks of once-weekly injections, there were no changes in clinical signs, body weight, or fructosamine concentrations compared to baseline values. Once-weekly therapy would bring enormous benefits to both owners and cats, so it is hoped this product continues to move forward. Incretin analogues. Synthetic GLP-1 analogues (a.k.a. incretin analogues) are now licensed for use in people with Type 2 DM. In addition to improving insulin sensitivity, these therapeutic agents actually promote the growth of new β/beta cells. These drugs also suppress food intake and support gradual weight loss; similar effects have been reported in nondiabetic cats, along with the potentiation of insulin secretion.24,25 There is limited information about the effect of these drugs on cats with DM, although one placebo-controlled study looking at exenatide-extended release in newly diagnosed diabetic cats. All cats received insulin glargine and low CHO diet for the 16 weeks of the study; the cats in the treatment group were also given exenatide-extended release by injection once weekly. The results suggested exenatide may improve glycemic control (89 percent vs. 58 percent) and increase rates of remission (40 percent vs. 20 percent). However, the number of cats in each arm of the study was small (n=15 for each group), and the findings did not achieve statistical significance.26 In addition, glycemic variability (defined by the dispersion of BG values around the mean) was lower in the treated cats at various time points. This finding is tied in with an increased likelihood of remission.27 In another small study, short-acting exenatide was combined with insulin glargine; the combination was associated with improved weight loss and decreased insulin requirements.28 Sodium-glucose cotransporter 2 (SGLT-2) inhibitors. More than 90 percent of the glucose reclaimed from the filtrate in the proximal convoluted tubules of the kidney is pulled back into the body by special proteins called SGLT-2s. Drugs that inhibit these specialized transporters are called SGLT-2 inhibitors or gliflozins, and several are now approved for the management of Type 2 DM in people. These drugs are given orally and lower BG by promoting glucose loss through the kidneys; they have also been shown to improve other parameters, such as body weight and blood pressure.29 Side effects include urinary tract infection and euglycemic ketoacidosis. One recent report described the effect of an SGLT-2 inhibitor–velagliflozin–in normal cats; as expected, the drug increased water intake and urinary glucose excretion. Cats receiving velagliflozin also showed a tendency toward improve insulin sensitivity.30 In addition, bexagliflozin has been used in combination with insulin in five client-owned cats with poorly regulated DM. All cats had a significant reduction in their insulin needs, and two cats went into remission. Adverse effects were mild and hypoglycemia was not reported.31 More studies are needed, but this drug class certainly shows significant promise in managing feline DM. Audrey Cook, BVM&S, MRCVS, MSc Vet Ed, Dip ACVIM (SAIM), Dip ECVIM (CA), Dip ABVP (feline practice) is professor of Small Animal Internal Medicine at Texas A&M University. She is chief of the Internal Medicine Section, and currently divides her time between the Internal Medicine Service and the Interventional Radiology and Endoscopy Service. Additional resources ISFM Consensus Guidelines on Feline Diabetes Mellitus https://journals.sagepub.com/doi/pdf/10.1177/1098612X15571880 AAHA Guidelines on Diabetes Mellitus in Dogs and Cats https://www.aaha.org/globalassets/02-guidelines/diabetes/diabetes-guidelines_final.pdf AAFP Diabetes Educational Toolkit for Feline Diabetes Mellitus https://catvets.com/diabetes-toolkit/ Pet Nutrition Alliance Food calculator https://petnutritionalliance.org/ BalanceIt Guaranteed Analysis Converter https://secure.balanceit.com/tools/_gaconverter/index.php? References Sparkes AH, Cannon M, Church D, et al. ISFM consensus guidelines on the practical management of diabetes mellitus in cats. J Fel Med Surg. 2015;17(3):235-250. Behrend E, Holford A, Lathan P, et al. 2018 AAHA diabetes management guidelines for dogs and cats. J Am Anim Hosp Assoc. 2018;54(1):1-21. Rand JS. Pathogenesis of feline diabetes. Vet Clin NA: Small Anim Pract. 2013;43(2):221-231. Fleeman L, Gostelow R. Updates in feline diabetes mellitus and hypersomatotropism. Vet Clin NA: Small Anim Pract. 2020;50(5):1085-1105. Lutz TA. Creating the amylin story. 2022;172:105965 Gottlieb S, Rand J. Managing feline diabetes: current perspectives. Vet Med: Res Rep. 2018;9:33. Appleton DJ, Rand JS, Sunvold GD. Insulin sensitivity decreases with obesity, and lean cats with low insulin sensitivity are at greatest risk of glucose intolerance with weight gain. J Fel Med Surg. 2001;3(4):211-228. Pet Nutrition Alliance custom tools https://petnutritionalliance.org/ Accessed July 7, 2022 Niessen SJ, Petrie G, Gaudiano F, et al. Feline acromegaly: an underdiagnosed endocrinopathy?. J Vet Inter Med.2007;21(5):899-905. Cook AK, Evans JB. Feline comorbidities: recognition, diagnosis and management of the cushingoid diabetic. J Fel Med Surg. 2021 Jan;23(1):4-16. Feldman EL, Callaghan BC, Pop-Busui R. et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5: Zini E, Osto M, Franchini M, et al. Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia. 2009;52(2):336-346. Zoran DL, Rand JS. The role of diet in the prevention and management of feline diabetes. Vet Clin NA: Small Anim Pract. 2013;43(2):233-243. Boer GA, Holst JJ. Incretin hormones and type 2 diabetes—mechanistic insights and therapeutic approaches. Biology. 2020 Dec 16;9(12):473. Gilor C, Graves TK, Gilor S, et al. The incretin effect in cats: comparison between oral glucose, lipids, and amino acids. Dom An Endo. 2011;40(4):205-212. BalanceIt Guaranteed analysis converter https://secure.balanceit.com/tools/_gaconverter/index.php? Accessed July 7, 2022. Del Baldo F, Fracassi F, Pires J, et al. Accuracy of a flash glucose monitoring system in cats and determination of the time lag between blood glucose and interstitial glucose concentrations. J Vet Intern Med. 2021;35(3):1279-1287. Gostelow R, Niessen S. Feline diabetic remission: what is the recipe? Compan Animal. 2015;20(6):340-346. Roomp K, Rand J. Intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. J Fel Med Surg. 2009;11(8):668-682. Gostelow R, Forcada Y, Graves T, et al. Systematic review of feline diabetic remission: separating fact from opinion. Vet J. 2014;202(2):208-221. Fenn J, Kenny PJ, Scudder CJ, et al. Efficacy of hypophysectomy for the treatment of hypersomatotropism-induced diabetes mellitus in 68 cats. J Vet Intern Med. 2021;35(2):823-833. Restine LM, Norsworthy GD, Kass PH. Loose-control of diabetes mellitus with protamine zinc insulin in cats: 185 cases (2005–2015). Can Vet J. 2019;60(4):399. Gilor C, Huselboch S, Pires J, et al. A novel once-a-week feline recombinant insulin for the treatment ofdiabetes mellitus in cats (Abstract). J Vet Intern Med. 2020;34(6):3087. Rudinsky AJ, Adin CA, Borin-Crivellenti S, et al. Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats. Dom Anim Endo. 2015;51:78-85. Gilor C, Graves TK, Gilor S, et al. The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats. Dom Anim Endo. 2011;41(1):42-49. Riederer A, Zini E, Salesov E, et al. Effect of the glucagon-like peptide-1 analogue exenatide extended release in cats with newly diagnosed diabetes mellitus. J Vet Intern Med. 2016;30(1):92-100. Krämer AL, Riederer A, Fracassi F, et al. Glycemic variability in newly diagnosed diabetic cats treated with the glucagon-like peptide-1 analogue exenatide extended release. J Vet Intern Med. 2020;34(6):2287-2295. Scuderi MA, Petito MR, Unniappan S, et al. Safety and efficacy assessment of a GLP-1 mimetic: insulin glargine combination for treatment of feline diabetes mellitus. Dom Anim Endo. 2018 Oct 1;65:80-9. Verma S, McMurray JJ. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61(10):2108-2117. Hoenig M, Clark M, Schaeffer DJ, et al. Effects of the sodium-glucose cotransporter 2 (SGLT 2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats. J Vet Pharm Thera. 2018;41(2):266-273. Benedict SL, Mahony OM, McKee TS, et al. Evaluation of bexagliflozin in cats with poorly regulated diabetes mellitus. Can J Vet Res. 2022;86(1):52-58.

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An in-depth look at treating diabetes mellitus in cats

Many special factors exist for felines, from diagnosis to treatment

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