2026 AAHA 猫糖尿病管理指南

This release covers the abstract, abbreviations, introduction and Sections 1–10; Tables 6.1 and 7.1; a bilingual node-and-link transcription of Figure 6.1; and the credentialed technician consultation box accompanying Section 10. Sections 11–15 and later figures are outside this release. Cross-references to later sections and figures are retained.

The official corrigendum is applied to glargine U-100 in Table 7.1: nadir 5–6 hr; duration 11–12 hr.

Table 6.1 notes a.1 and c retain the source notation <1.0–2.4 mmol/L. The relationship between the comparison sign and the range is ambiguous and has not been silently corrected.

Figure 6.1 retains >3.7 and <3.7 mmol/L, whereas the Section 6 package-insert discussion uses >3.6 mmol/L. Equality, unchanged ketones and all Boolean relationships are not fully specified by the source figure. The transcription is not an automated decision rule.

Read product-label instructions separately from the task force’s off-label anecdotal exceptions, including patient stability and monitoring requirements. The insulin concentrations, per-dose units and dosing intervals are distinct.

Source: the published JAAHA article, DOI 10.5326/JAAHA-MS-7572, with the official AAHA corrigendum. This is a partial Chinese reading release covering Sections 1–10, not a complete translation of the article.

The nutrient percentages in Section 8 are percentages of metabolizable energy (ME), not food weight. The source expressions >40–45% ME for protein and <12–15% ME for carbohydrate are retained alongside g/100 kcal. The task force’s approximately 12% ME carbohydrate recommendation remains a separate statement.

Remission is not cure. When withholding an SGLT2 inhibitor to assess remission, retain the source conditions: at least 90 days of prior treatment; close BG monitoring by CGM or 1–2 glucometer checks daily for at least a week; and BG >250 mg/dL with concurrent ongoing clinical signs indicating a need for continued treatment. This passage should not be extracted as advice for clients to stop medication on their own.

The Section 10 diarrhea passage describes reducing the dose by 25–50% for 3–5 days, not reducing it to 25–50% of the original dose. Withholding for 2–3 days and restarting at half the dose is a separate described option. Neither passage is converted into an automatic dose adjustment rule.

In the technician box, shaking versus rolling is a question about the client’s technique, not an instruction to shake every insulin product. Follow the specific product instructions. The source suggestion to consider replacing a vial used for more than 4 months is not a universal in-use expiration period for every insulin.

摘要 / Abstract A substantial number of cats develop diabetes mellitus (DM), a serious endocrine disorder that can lead to other physiologic complications. While DM management can be complex, successful control that alleviates the patient's clinical signs and avoids hypoglycemia is achievable in most cats. Diabetic remission is also possible. The 2026 AAHA Diabetes Management Guidelines for Cats retain clinically relevant information from the 2018 AAHA Diabetes Management Guidelines and present new findings and expert opinions. Subjects such as pathophysiology, diagnosis, how to treat and monitor cats receiving SGLT2 inhibitors, various insulin options for cats, how to monitor cats receiving insulin, diet and physical activity recommendations, advantages and disadvantages of at-home glucose monitoring devices, diagnosing and treating diabetic ketoacidosis, and client education are all discussed. The guidelines also cover how to identify patients who are at risk of developing DM and how to differentiate DM from transient or mild hyperglycemia.

引言 / Introduction Diabetes mellitus (DM) can be successfully managed in cats but requires an up-to-date understanding of feline diabetes pathophysiology and a thorough grasp of how to incorporate new treatments into therapeutic approaches. Staying informed about emerging treatment options is crucial. Diabetic feline patients need diligent clinical, observational, and diagnostic assessments and individualized treatment and monitoring plans. Rewarding diabetes management is intertwined with committed client education and communication.

These guidelines retain clinically relevant information from the 2018 AAHA Diabetes Management Guidelines [1] and present new findings and expert opinion on diagnosing, treating, and monitoring diabetes mellitus in cats, recognizing at-risk patients, and identifying patients with hyperglycemia who do not require diabetic treatment. The refreshed reorganization of these guidelines separates the feline and canine content into two distinct publications to provide veterinarians with an easier reference to managing the disease in each species.

These guidelines cover SGLT2 (sodium-glucose cotransporter 2) inhibitor drugs, a newly approved drug class for use with newly diagnosed diabetic cats, as well as traditional and new insulin formulations for cats and when and how to use each. Easy-to-use at-home monitoring tools such as continuous glucose monitors (CGMs) and glucometers and methods to help detect abnormalities in urine are highlighted. The guidelines also feature new or updated algorithms, tables, and boxes for quick reference on a variety of topics including managing hypoglycemia, addressing diabetic ketoacidosis, and troubleshooting suboptimal responses to therapy. Dietary management is also discussed, and key points in client education on treatment and monitoring, including the financial and time commitments and lifestyle changes, are emphasized.

三个核心要点 / Top 3 Takeaways 1. Insulin resistance (IR) and glucose toxicity play key roles in feline DM pathogenesis. 2. Effective management involves lowering blood glucose (BG) concentrations and mitigating factors contributing to IR. 3. Select insulins and SGLT2 inhibitors are licensed for the management of feline DM.

Feline DM pathogenesis is multifactorial, with numerous processes affecting pancreatic beta cell function and viability. However, most feline diabetes develops when insulin resistance places prolonged stress on pancreatic beta cells that may already be genetically vulnerable (see Box: Causes of Insulin Resistance) [2]. Diet formulation and exocrine pancreatic disease may also contribute to the development of DM [2]. Because, in part, of the impact of IR, feline DM shares strong similarities with human type 2 DM, although not all cats fit this pattern and many require exogenous insulin.

The initial consequence of IR is increased insulin secretion. At first this maintains euglycemia but simultaneously drives the accumulation of poorly soluble amylin within pancreatic islets. Progressive amyloidosis impairs beta cell function, which compromises insulin secretion and increases BG. Many diabetic cats appear to spend months in a subclinical/preclinical period, in which BG is significantly elevated but remains below the threshold for glucosuria (~250–300 mg/dL) [3].

Although the systemic effects of moderate hyperglycemia in cats have not been established, glucose toxicity—a complex process that causes widespread compromise to cellular function—occurs in people with BG >200 mg/dL [4]. Feline beta cells appear to be particularly vulnerable to glucose toxicity and either decrease insulin production or undergo apoptosis [5,6]. When insulin secretion is no longer sufficient to keep BG below the renal threshold, clinical signs of DM (polyuria [PU], polydipsia [PD], polyphagia [PP], and weight loss) become apparent. The other classic manifestation of glucose toxicity in cats is peripheral neuropathy [7]. This primarily impacts the rear limbs and causes a plantigrade stance that limits cats' ability to run and jump.

Treating feline DM relies on controlling hyperglycemia by giving insulin or an SGLT2 inhibitor, and by mitigating factors causing IR. In some cats, beta cell function may recover, and medical therapy can be withdrawn; this process is referred to as diabetic remission [2].

框文：猫胰岛素抵抗的原因 / Causes of Insulin Resistance in Cats Causes of Insulin Resistance in Cats (a,b) - Obesity - Sarcopenia (suspected) - Sedentary lifestyle - Inflammatory/infectious conditions - Stomatitis/gingivitis - Degenerative joint disease - Chronic enteropathy - Chronic pancreatitis - Urinary tract infection - Medications - Glucocorticoids - Progestogens - Endocrinopathy - Hyperthyroidism - Hypothyroidism (infrequent in cats) - Hypersomatotropism (acromegaly) - Hypercortisolism a. Gostelow R, Hazuchova K. Pathophysiology of prediabetes, diabetes, and diabetic remission in cats. Vet Clin North Am Small Anim Pract 2023;53(3):511–29. b. Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J Vet Intern Med 2012;26(1):3–17.

三个核心要点 / Top 3 Takeaways 1. Obtain a complete history that includes diet and concurrent medication information and perform a thorough physical examination to detect risk factors for, and clinical signs of, DM. 2. Assess and monitor body and muscle condition scores in all patients. 3. Evaluate results of CBC, blood chemistry, urinalysis, total thyroxine (TT4), and blood pressure measurements in cats with clinical signs that suggest DM.

While diabetes can occur in cats of any age, most present at age 4 or older. One study showed that 82% of diabetic cats were >7 yr old and 50% of diabetic cats were between 10 and 15 yr of age [8]. Male cats constitute a greater proportion of the diabetic population than female cats, and it is unclear if neutering plays a role in diabetes development [9]. Most affected cats are mixed breed (i.e., domestic shorthair or domestic longhair); however, Burmese cats have been shown to have an increased risk of diabetes [9,10].

危险因素 Feline diabetes risk factors include [9,11]: - Obesity (factors that contribute to obesity include neutering, high-carbohydrate diets, and lack of environmental enrichment) - Sedentary lifestyle - Middle age and older life stages - Male

Diabetic cats are often obese, and clients may report that their cats exhibit signs of PU, PD, PP, weight loss, and lethargy. Hindlimb weakness (plantigrade stance) and an unkempt hair coat may be noted on physical examination [9]. However, the physical examination can be relatively normal, and gradual progression of PU, PD, or weight loss may be initially subtle and go unnoticed by the pet caregiver during early stages of disease onset. To catch these early signs, it is important to assess cats' body condition and muscle condition scores at every visit and ensure that team members consistently use the same condition scales (i.e., 5-point versus 9-point scales). See the AAHA Nutrition and Weight Management Guidelines at aaha.org for detailed information on body and muscle condition scoring systems. The presence of diabetic ketoacidosis (DKA) along with concurrent disease processes can also affect the examination findings (see Section 12, Diabetic Ketoacidosis) [9].

In cats with clinical signs of DM, BG exceeds the renal reabsorption threshold for glucose (~250–300 mg/dL) and cats will be hyperglycemic and glucosuric. However, these findings are not specific for DM. Evaluate the results of a CBC, blood chemistry, urinalysis, TT4, and blood pressure measurements in cats with clinical signs that suggest DM. Elevated BG in the absence of clinical signs may reflect transient hyperglycemia due to stress [12]. If stress hyperglycemia can be ruled out in an asymptomatic hyperglycemic cat, consider monitoring the patient as one at risk for developing DM (Section 5, Recognizing and Managing Cats at Risk of DM). Mild to moderate persistent hyperglycemia (BG <300 mg/dL) without glucosuria suggests subclinical diabetes [13,26], so it would be prudent to identify and address possible causes of IR (see Box, Section 1, Causes of Insulin Resistance in Cats). Definitively diagnosing feline DM requires evidence of sustained hyperglycemia (see Section 3, Diagnosing DM in Cats).

框文：Project ALIVE The task force referenced Project ALIVE for standardized DM terminology and to define criteria used for DM diagnosis. For more information on Project ALIVE, see https://www.esve.org/alive/search.aspx.

三个核心要点 / Top 3 Takeaways 1. A feline DM diagnosis requires evidence of sustained hyperglycemia, which includes one or more of the following: increased fructosamine or hemoglobin A1C concentration, or hyperglycemia or glucosuria documented on more than one occasion while in a nonstressed or home environment. 2. Fructosamine concentrations may be lower in cats with hyperthyroidism, protein-losing enteropathy, or nephropathy, independent of BG. 3. Continuous glucose monitors (CGMs) and glucosuria detection products help assess cats' BG status at home.

框文：对有糖尿病临床症状的猫推荐进行的实验室检查 Recommended Laboratory Tests for Cats with Clinical DM Signs: - Complete blood count (CBC) - Chemistry panel with cholesterol, triglycerides, and electrolytes - Urinalysis with sediment examination - Serum total thyroxine (TT4) concentration

Confirming a diagnosis of DM in cats exhibiting clinical signs requires proof of sustained hyperglycemia using one or more of the following methods:

糖化蛋白与果糖胺 Evidence of increased glycated protein concentrations, such as increased fructosamine [14]. Protein glycation is the nonenzymatic, insulin-independent, irreversible binding of glucose to the parent molecule, and glycation rates are therefore influenced by BG concentrations. Fructosamines are a group of glycated plasma proteins, including albumin, with a relatively short half-life. Fructosamine measurement therefore reflects average BG over the previous 7–10 days [15]. This value tends to be higher in male cats than females [16] and may be lowered by conditions that shorten the half-life of albumin, such as hyperthyroidism and protein-losing diseases [17,18].

糖化血红蛋白 Glycated hemoglobin (HbA1C; expressed as a percent) is widely used for diabetes diagnosis and monitoring in people, and it reliably reflects average BG in cats over the previous 2–3 mo [19]. Although a commercial test is available to veterinarians, the task force is not aware of any feline HBA1C assays that have been validated in diabetic cats [20]. More studies are needed to assess their clinical use in cats.

居家血糖与尿糖监测 Alternatively, a CGM placed on the patient, a portable blood glucose monitor (PBGM), or glucosuria detection products can assess whether persistent hyperglycemia or glucosuria occurs when cats are at home. CGMs record the interstitial glucose concentration continuously over multiple days. See Section 13, Glucose Monitoring, for more information.

并发酮症 Concurrent ketosis—diagnosed by a finding of ketonuria or blood beta-hydroxybutyrate (BHB) concentration >1.0 mmol/L (see Box) in a patient meeting DM diagnostic criteria—suggests a more complicated or advanced stage of disease (see Section 12, Diabetic Ketoacidosis).

检测条件受限时的诊断路径 If clients are unable to pursue fructosamine testing and/or use a CGM or PBGM, they can try to collect urine samples at home to check for glucosuria. It is ideal for clients to wait at least 2-3 days after an in-hospital examination or stressful event to begin collecting urine and aim to obtain at least 2 urine samples voided on different days to document persistence [14]. If that is not possible, clinicians can consider instituting therapy if clinical suspicion for DM is high, or recheck the cat's weight and laboratory evaluation within 1-2 weeks.

框文：血 β-羟丁酸 / Blood Beta-Hydroxybutyrate BHB is the earliest and most predominant ketone body produced during diabetic ketoacidosis in cats. Point-of-care whole blood ketone analyzers (ketone meters) are available to measure BHB, and a commercial model has been validated in cats (a). a. Weingart C, Lotz F, Kohn B. Validation of a portable hand-held whole-blood ketone meter for use in cats. Vet Clin Pathol 2012;41(1):114–8.

三个核心要点 / Top 3 Takeaways 1. If not yet completed as part of the patient’s initial evaluation, perform a comprehensive laboratory evaluation in all newly diagnosed diabetics, including complete blood count; chemistry panel with cholesterol, triglycerides, and electrolytes; urinalysis with sediment examination; TT4; blood BHB; and consider retroviral testing. 2. Identify concurrent problems associated with diabetes or conditions that may interfere with the patient’s response to treatment. If cats present in an emaciated state, rule out comorbidities. 3. Diabetic cats who exhibit substantial clinical compromise such as hyporexia, vomiting, and dehydration may have DKA.

The task force recommends a full laboratory evaluation for every diabetic cat before selecting treatment (see Section 3, Box, Recommended Laboratory Tests). This includes a CBC; a chemistry panel with cholesterol, triglycerides, and electrolytes; a urinalysis (UA) with sediment examination; and a total T4 measurement if not done prior to diagnosis. Blood BHB should be measured in all newly diagnosed diabetic cats, as the results may affect treatment choices. [21] While not specific to DM, retroviral testing may be considered part of the minimum database for any sick feline patient evaluation.

Identify whether diabetic cats have complications associated with the disease (e.g., peripheral neuropathy) or concurrent problems often associated with the disease (e.g., pancreatitis). If the cat has signs of cystitis (i.e., dysuria, pollakiuria) and an active urine sediment, perform a quantitative urine culture and sensitivity, and then use the results to guide therapy. [22]

Also identify conditions that may interfere with the patient’s response to treatment (insulin-resistance-causing diseases such as obesity, pancreatitis, hyperthyroidism, renal disease, hypercortisolism, hypersomatotropism, and other risk factors such as the use of diabetogenic medications) so these can be addressed appropriately. As insulin is needed for insulin-like growth factor-1 (IGF-1) production in the body, IGF-1 concentrations may be unremarkable at DM diagnosis. However, if after 4-6 weeks of insulin treatment there is concern for IR or signs of hypersomatotropism, evaluating IGF-1 would be appropriate. [23]

Most newly diagnosed diabetic cats present with weight loss, but the magnitude of condition loss can vary. When a newly diagnosed diabetic cat presents with substantial weight loss (>15%), emaciated, or with cachexia or sarcopenia, evaluate for comorbidities such as pancreatitis, neoplasia, exocrine pancreatic insufficiency, hyperthyroidism, or chronic enteropathy. Depending on the cat’s specific history and clinical signs, consider performing additional diagnostics such as measuring feline pancreas-specific lipase immunoreactivity, serum folate and cobalamin, and serum trypsin-like immunoreactivity, along with abdominal and thoracic imaging. Diagnose and treat concurrent illnesses accordingly. [9]

Diabetic cats who exhibit substantial clinical compromise such as hyporexia, vomiting, and dehydration may have DKA. Documenting a high anion gap metabolic acidosis (e.g., low bicarbonate, low pH, +/- normal to low chloride at presentation) along with ketonuria or blood BHB >2.4 mmol/L confirms DKA (see Section 12, Diabetic Ketoacidosis in Cats).

三个核心要点 / Top 3 Takeaways 1. Use dietary and lifestyle interventions to optimize weight in obese cats who have mild hyperglycemia and monitor their BG and urinalyses at intervals tailored for each patient. 2. Investigate whether concurrent medications or conditions may be contributing to insulin resistance and manage them accordingly. 3. There is currently no evidence to support the use of an SGLT2-inhibitor drug, insulin, or any anti-diabetic drug in at-risk or subclinical cats.

This section concerns management of cats that are found to have intermittent or sustained mild to moderate hyperglycemia unrelated to stress, and who do not display clinical signs of DM. These cats should be considered “at-risk” for developing clinical DM or to have subclinical diabetes. Although some portion of at-risk cats may eventually develop clinical DM, they do not require diabetic therapy until a clinical DM diagnosis is confirmed. Transient stress hyperglycemia is a well-recognized phenomenon that occurs in normal cats but is also observed in at-risk cats. Hyperglycemia due to stress can be severe but is generally <250 mg/dl and by definition is a transient elevation. Glucosuria may occur with severe stress hyperglycemia; ketonuria is not expected. Stress hyperglycemia is confirmed in patients by demonstrating resolution of hyperglycemia after the cat is removed from the stressful situation. The recommended follow-up for stress hyperglycemia is to reassess BG and check urine for glucosuria and ketonuria several days after the stressful event (ideally blood and urine samples are obtained at home). In select cases, it may be necessary to place a CGM or measure a serum fructosamine concentration.

Obtain a thorough history for at-risk patients and evaluate for concurrent diseases or medications that may result in insulin resistance. Take steps to prevent at-risk patients from becoming overtly diabetic. Avoid administering medications such as corticosteroids or progestins. [24] Treat any concurrent diseases (e.g., obesity, chronic inflammatory conditions). Lifestyle and dietary modifications are logical first steps, with the goals of optimizing body weight, minimizing postprandial hyperglycemia, and controlling calorie, protein, carbohydrate, and fat intake. Replace food treats with playtime to encourage movement and potentially contribute to weight loss. Environmental enrichment may facilitate weight loss and reduce obesity, [25] therefore reducing cats’ risk of developing diabetes. [26,27]

Monitor at-risk patients regularly. Pet caregivers should weigh at home monthly and be advised to note any changes in water consumption or urine output. Tailor BG and urinalysis monitoring frequency to individual patient indications. CGMs may be helpful to determine which cats need further diagnostic evaluation. In overweight patients, such monitoring reveals whether hyperglycemia corrects with weight reduction. Monitoring is also essential to identify patients whose hyperglycemia does not resolve with previously mentioned interventions, or who develop overt DM.

At present, it is difficult to accurately predict whether or not an at-risk patient will progress to develop overt DM. Progression may be more likely when the patient has a risk factor that cannot be addressed or reversed with treatment. There is currently no known strategy to prevent DM. At this time, there is no evidence to support the use of SGLT2 inhibitor drugs, insulin, or any other anti-diabetic medication for at-risk or subclinical patients.

三个核心要点 / Top 3 Takeaways 1. SGLT2 inhibitors are only approved for newly diagnosed diabetic cats. 2. Not all cats are suitable candidates for an SGLT2 inhibitor; thoroughly evaluate patients for comorbidities and start insulin in those with conditions that contraindicate SGLT2 inhibitor use. 3. Monitor cats on SGLT2 inhibitors carefully for ketosis. Monitoring blood BHB is essential.

In the United States, two SGLT2 inhibitors are now licensed for use in newly diagnosed, otherwise healthy feline diabetics not previously treated with insulin and are an appropriate treatment option for a substantial proportion of patients. [28,29,30] Bexagliflozin tablets and velagliflozin oral solution are administered once daily, either directly into the mouth or given with a small amount of food. Oral administration spares clients the challenges associated with injecting insulin and allows for more flexible care plans. Traditional oral hypoglycemic agents such as glipizide (a sulfonylurea) and metformin (a biguanide) are routinely prescribed for people with type 2 DM but are not consistently safe or effective in diabetic cats and therefore are not recommended. [31,32]

The SGLT2 inhibitors lower BG by blocking most reabsorption of glucose in the renal proximal convoluted tubules. [33] This mitigates the clinical signs of DM (i.e., PU, PD, PP) while reversing glucose toxicity and allowing for beta cell recovery. SGLT2 inhibitors act independently of insulin, and there is minimal risk of clinical hypoglycemia due to increased SGLT1-mediated glucose reabsorption. [28,29,30] However, as endogenous insulin is needed to prevent ketosis, these drugs are an unsuitable choice for some cats (see below). Unfortunately, beta cell function cannot be reliably assessed in cats. An assay for quantifying C-peptide concentrations in cats is not currently commercially available.

患猫选择 / Patient Selection Consider an SGLT2 inhibitor for any newly diagnosed diabetic cat that is eating and well hydrated. SGLT2 inhibitors are contraindicated for cats with signs of systemic compromise such as vomiting, hyporexia, cachexia, or lethargy. Perform a thorough physical examination and diagnostic evaluation (CBC, chemistry panel, and urinalysis) for signs of comorbid conditions such as hepatopathy, significant chronic kidney disease (i.e., IRIS Stage 3), or hypercalcemia. [21] Screen any cat older than 7 yr for hyperthyroidism (see the AAFP Guidelines for the Management of Feline Hyperthyroidism at catvets.com). As a general rule, insulin therapy is the appropriate treatment for diabetic patients who are not metabolically stable.

Screen for ketosis in every candidate for an SGLT2 inhibitor. BHB measurement is preferred over other methods for assessing ketosis. Inexpensive, handheld ketone meters provide quick and reliable quantification of blood BHB, and the task force considers BHB measurement an essential part of SGLT2 inhibitor drug monitoring. The only currently validated ketone meter for use in cats is the Precision Xtra (Abbott), although non-validated meters have been used anecdotally by some task force members. [34] Alternatively, the acetoacetate concentration may be semi quantitatively assessed in plasma or urine using a standard ketone dipstick. [35]

The package insert states that bexagliflozin should not be initiated if the cat’s blood BHB is >3.6 mmol/L, or if BHB is >2.4 mmol/L and the cat has a history of acidosis or renal compromise. [36] Also, the bexagliflozin and velagliflozin package inserts warn not to start these drugs if ketonuria is detected, and detecting ketonuria during treatment should prompt discontinuation of the drug and transition to insulin. [36,37]

Since the original therapeutic recommendations were first released by the manufacturers of bexagliflozin and velagliflozin, the task force members have gained significant experience with this drug class in a variety of clinical situations. Clinicians should be aware of the published BHB recommendations and use them as guidelines. Clients should also be informed of and consent to any deviations from the FDA-approved guidelines, and this should be documented in the medical record. Some cats will mildly increase (<20%) their BHB level from baseline during the first 1-3 days following treatment initiation, with appetite and attitude remaining normal. In these situations, close daily monitoring may allow for continued drug administration if the BHB starts to decline by days 4-7 following therapy initiation, suggesting endogenous insulin production is becoming more effective with the sustained resolution of hyperglycemia. Many cats with a BHB higher than the published guidelines (>3.6 mmol/L) are not clinically ill. In these cases, some task force members may still start an SGLT2 inhibitor with caution and closely monitor the cat. (Figure 6.1). Monitoring includes daily BHB measurement and clinical assessment of patient status. Veterinary Practice Guidelines

Diabetic cats with readily reversible causes of IR, such as recent depot steroid administration, are particularly suitable candidates for an SGLT2 inhibitor. [21] These patients are more likely to go into remission after the cause of IR is removed and are therefore particularly vulnerable to hypoglycemia if treated with insulin. [2] Cats with hypersomatotropism (acromegaly) may also be candidates for treatment with an SGLT2 inhibitor, but the ideal protocol is unknown. A recent study of eight cats with diabetes and concurrent hypersomatotropism reported that the addition of velagliflozin to insulin therapy improved clinical and glycemic control of diabetes in most cats. [38] Ideally, clinicians should consult with a specialist before initiating SGLT2 inhibitor therapy in acromegalic cats as the risk for hypoglycemia is extremely high when used concurrently with exogenous insulin. [38]

饮食考量 / Dietary Considerations Carbohydrate restriction is discouraged in people receiving an SGLT2 inhibitor, [39] but no data in cats address this issue. Although food composition was not standardized in previous studies evaluating bexagliflozin and velagliflozin, some enrolled cats were fed diabetic prescription diets. [28,29] The task force recommends continuing the cat’s usual diet for the first 2 wk of SGLT2 inhibitor treatment, and if the cat is doing well, then slowly introduce a low-carbohydrate diet.

监测 / Monitoring Treatment goals for cats receiving SGLT2 inhibitors mirror those for patients receiving insulin, and monitoring is similarly focused on assessing glycemic control, body weight, and overall well-being. Because clinical hypoglycemia is rare, glucose curves and/or continuous glucose monitoring is usually unnecessary. However, carefully monitor for ketosis in cats on an SGLT2 inhibitor, particularly during the first 2 wk of treatment (Table 6.1), as DKA is most common during this period. It is substantially more important during this period to monitor blood BHB than BG.

In general, the blood BHB concentration should decrease from pretreatment values in most cats after starting an SGLT2 inhibitor. The bexagliflozin label suggests insulin is indicated if BHB increases from pretreatment values without providing specific BHB cutoffs, although clinicians have anecdotally applied previously reported values exceeding 2.4 mmol/L as a cutoff for DKA diagnosis (see Table 6.1).

However, anecdotal experience with SGLT2 inhibitors suggests there may be off-label exceptions which allow for continued treatment in the face of a mild increase in BHB from baseline. Some task force members tolerate mild increases in BHB (<20% from baseline) during the first 3 days of therapy if the cat is clinically well, eating, and can be regularly monitored with a daily BHB assessment (see Table 6.1). Additionally, some task force members initiate SGLT2 inhibitor therapy in cats whose BHB is >3.6 mmol/L at diagnosis (see above, Patient Selection, and Figure 6.1) and therefore tolerate a recheck visit BHB above 2.4 mmol/L as long as levels are declining compared with the previous assessment. Continued use of an SGLT2 inhibitor in the presence of clinical signs of illness, persistently increasing BHB concentrations after the first 3 days of therapy, or a lack of appropriate BHB monitoring puts the patient at marked risk for DKA.

治疗反应 / Response to Therapy In most diabetic cats, BG improves within hours of administering an SGLT2 inhibitor, and serum fructosamine concentrations are routinely within the reference range after 8 wk. [28,29,30] Despite persistent glucosuria, PU/PD also improves in most cats. Peripheral neuropathy improved in >75% of affected cats treated with velagliflozin. [28] Current evidence suggests assessing overall clinical response after 1 mo, and if the cat is still hyperglycemic with clinical signs of DM, discontinue the drug and provide insulin therapy. The likelihood of diabetes remission in cats receiving an SGLT2 inhibitor is currently unknown, but remission is likely possible when mitigating factors are addressed and resolved (see Section 9, Diabetic Remission).

副作用与不良事件 / Side Effects and Adverse Events Approximately 38-50% of cats have changes in stool consistency within the first 2 wk of SGLT2 inhibitor administration. [28,29] This is likely due to mild cross-inhibition of sodium-glucose transporter 1 in the small intestine, which transports luminal glucose into enterocytes, with inhibition resulting in osmotic diarrhea. As such, antibiotic therapy is not indicated. In most cats, the effect is modest and selflimiting and may be mitigated by a 25% dose reduction for several days or by switching to a low-carbohydrate or high-fiber diet in the experience of task force members. Other symptomatic therapies, such as pectin or kaolin, may also be helpful. Persistent or treatmentresistant diarrhea may be an indication to stop therapy and transition to insulin. Vomiting is also commonly reported but tends to be sporadic. If the cat is eating well and stable, both bexagliflozin and velagliflozin can be safely redosed if the cat vomits within 30 min of dosing.

Modest increases in serum total calcium have been reported in a small number of cats. [28] The task force recommends monitoring ionized calcium concentrations in cats with a history of hypercalcemia, as SGLT2 inhibitor–induced changes in renal sodium handling and acid-base status may impact calcium homeostasis. [40]

The most serious complication with any diabetic cat, whether on insulin or an SGLT2 inhibitor, is DKA. [28,29,30] While typical DKA can occur, SGLT2-inhibitor-treated cats more commonly develop DKA without hyperglycemia called euglycemic DKA (EDKA).

第6节续文：EDKA与DKA If EDKA or DKA occurs, it usually develops within the first 2 wk of therapy. EDKA is diagnosed by identifying abnormalities expected in DKA (fluid, electrolyte, and acid-base derangements) in cats who remain euglycemic (i.e., BG <250 mg/dL). Reported incidence of EDKA in cats who have been treated with an SGLT2 inhibitor is the same (5–7%) as the incidence of DKA in cats treated with insulin. [28,29,30] Cats previously treated with insulin appear to be predisposed. [28] Affected cats are often hyporexic and lethargic; dehydration is variable but may be severe. Blood BHB is typically >2.4 mmol/L and acetoacetate will be detectable in urine in many, but not all, cases. Failure to promptly recognize and address this condition, especially in cats with unknown medical or medication histories, will result in significant progressive morbidity (see Figure 12.1).

转用胰岛素 / Switching to Insulin In nonresponder cats (i.e., BG >250 mg/dL), the SGLT2 inhibitor can be discontinued and insulin started the following day. If the cat is not hyperglycemic, it may take several days for the physiological effects of the SGLT2 inhibitor to abate and for BG to rise; in nonketotic cats, withhold insulin until hyperglycemia is documented.

Possible Risk Factors for DKAᵃ Weight loss >5% from baseline to days 2–3 Unintentional weight loss after day 7 Progressive cholesterol or triglyceride elevation 10-fold increase in the triglyceride concentration a. Behrend EN, Ward CR, Chukwu V, Cook AK, Kroh C, Lathan P, May J, Schermerhorn T, Scott-Moncrieff JC, Voth R. Velagliflozin, a once-daily, liquid, oral SGLT2 inhibitor, is effective as a stand-alone therapy for feline diabetes mellitus: the SENSATION study. J Am Vet Med Assoc 2024;262(10):1343–53.

a.1. Blood BHB has increased but the cat is eating/drinking normally: Proceed with caution and recheck daily. Blood BHB is unchanged but <2.4 mmol/L (25 mg/dL): Recheck in 2 or 3 days, sooner if ill. Blood BHB has decreased, and values are <1.0–2.4 mmol/L (10.4–25 mg/dL): Proceed to next recheck, sooner if ill.

a.2. Some cats show a mild BHB increase at their 2- or 3-day recheck but remain clinically stable. Drug discontinuation is not uniformly warranted, but BHB should be monitored every 1–2 days to ensure BHB eventually declines over the subsequent 2–5 days.

a.3. If a cat's BHB was >2.4 mmol/L before starting an SGLT2 inhibitor, the BHB at day 2–3 may be improved yet remain above the 2.4 mmol/L cutoff. In this circumstance, SGLT2 inhibitor therapy can be continued so long as the cat remains clinically stable and daily BHB monitoring shows continued improvement.

a.4. Unintentional weight loss of >5% from baseline at this visit is associated with an increased risk of DKA by day 14.**

b. Mild weight loss (<5%) may occur during the first week of therapy. However, significant unintentional weight loss after the first week is often an early indicator of a developing problem, such as possible DKA.

c. Blood BHB has increased, is unchanged, or remains >2.4 mmol/L (25 mg/dL): Switch to insulin. Blood BHB is normal or has further decreased to values <1.0–2.4 mmol/L (10.4–25 mg/dL): Proceed to next recheck, sooner if ill.

BG, blood glucose; BHB, beta-hydroxybutyrate; DKA, diabetic ketoacidosis; DM, diabetes mellitus.

*Reprinted from Cook AK, Behrend E. SGLT2 inhibitor use in the management of feline diabetes mellitus. J Vet Pharmacol Ther 2025;48 Suppl 1(Suppl 1):19–30. Copyright info: © 2024 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License. **(See Behrend EN, Ward CR, Chukwu V, Cook AK, Kroh C, Lathan P, May J, Schermerhorn T, Scott-Moncrieff JC, Voth R. Velagliflozin, a once-daily, liquid, oral SGLT2 inhibitor, is effective as a stand-alone therapy for feline diabetes mellitus: the SENSATION study. J Am Vet Med Assoc 2024;262(10):1343–53.)

* Only in clinically well cats. See Patient Selection text for details.

** Ketone checks can include blood BHB (recommended) or urine.

*** Some cats will mildly increase (<20%) their BHB level from baseline in the first 1–3 days, with normal appetite and attitude. Close daily monitoring may allow for continued SGLT2i administration if BHB starts to decline by days 4–7. See Section 6 for details.

BG, blood glucose; BHB, beta-hydroxybutyrate; IR, insulin resistance; SGLT2i, sodium-glucose cotransporter 2 inhibitor.

猫的胰岛素治疗：三个核心要点 / Insulin Treatment in Cats: Top 3 Takeaways 1. Diabetic remission is a reasonable goal in feline patients. 2. Successful treatment reduces clinical signs without hypoglycemia. 3. The starting insulin dose is typically 1 unit per cat every 12 hr.

Exogenous insulin administration is the traditional approach to managing diabetic cats. The goals of insulin treatment are the same as with other treatment options: improved glycemic control, mitigation of clinical signs, and improved quality of life for the cat and the clients. Tight glycemic control is not as readily achievable in feline patients as it is in humans.

胰岛素选择 / Insulin Selection A number of insulins are available for treating DM, and some are more effective than others in feline patients (Table 7.1). The most common choices for cats remain glargine (U-100) (approved for use in people) and protamine zinc recombinant human insulin (PZI) (approved for use in cats and dogs). Both have an acceptable duration of action in cats, provide more consistent glycemic control, and have been commonly associated with inducing diabetic remission.

Lente insulin (porcine insulin zinc suspension) is approved for and often used in cats; however, it is not routinely recommended by task force members as a first-choice insulin due to having a shorter duration of action as compared to other starting insulin options. Neutral protamine Hagedorn (NPH) insulin is not considered an acceptable choice for cats owing to a very short (<8 hr) duration of effect.

The basal insulin glargine U-300 is not currently widely used as a standard first choice option although it has been proven effective at controlling hyperglycemia, reducing daily glycemic variability, and achieving diabetic remission in cats. [41] It is more concentrated but less potent than glargine U-100 and therefore should be considered as a separate insulin type and not simply the equivalent of 3 times that of glargine U-100. Because of slowed absorption resulting from the reduced surface area of the injected depot, glargine U-300 exerts a prolonged duration of action possibly allowing for q 24 hr administration in some cats. [42] Task force members with experience using “peakless” insulin formulations, such as glargine U-300 and basal insulin degludec, report that many treated cats demonstrate a flat time-action profile more like basal insulin secretion and have used these products for treatment of newly diagnosed diabetics or as an option for difficult-to-regulate cats (see Table 7.1).

A potentially promising ultra-long-acting insulin preparation is currently being developed. [43] A weekly injection would tremendously relieve caregiver burden and stress and would be a welcome addition to current tools for managing feline DM. Additionally, studies are being done to evaluate the viability of incretin hormones such as glucagon-like peptide-1 (GLP-1) for use in cats to increase pancreatic insulin secretion. [44]

胰岛素给药 / Insulin Administration Insulin is administered with either specific insulin syringes or insulin pens. Insulin syringes must match the concentration of insulin to be given; that is, use U-100 syringes with U-100 insulin and use U-40 syringes with U-40 insulin. Insulin syringes with a total volume no larger than 0.3 mL make dose visualization easier. Avoid ultra-short needles (<8mm), as it may be difficult to ensure proper administration through thick fur.

Glargine U-300 requires administration using the manufacturerprovided prefilled insulin pen that dials in increments of 1 unit. An appropriate needle (ideal needle length 10-12 mm) must be used with insulin pens, and the needle must be primed before administering insulin to ensure proper dosing (see the manufacturer provided recommendations). Insulin pens also have a variety of dosing options that range from 1/2-unit increments to 2-unit increments, which may not be suitable for small dosing changes. Clinicians should review manufacturer instructions for the insulin pen being used to identify the recommended injection times (often around 10 seconds), which is the amount of time the needle should remain in the patient’s skin after deploying the injection to ensure the entire dose is delivered to the cat.

胰岛素剂量 / Insulin Dosing Dosing common insulins for cats is not based on units per kilogram, except for glargine U-300 (considered a basal insulin). In overweight or obese cats, all weight-based insulin dosing should be calculated using the cat’s estimated ideal body weight.

For glargine U-100 or PZI, start most cats on 1 unit/cat every 12 hr.

Basal insulin glargine U-300 is dosed at a starting dose of 0.5 units/kg every 12–24 hr. [41]

See also Section 8, Dietary Management, for information on meal timing related to insulin administration.

接受胰岛素治疗患猫的监测：三个核心要点 / Monitoring Cats Receiving Insulin: Top 3 Takeaways 1. Monitor the cat, not just the numbers. 2. In-clinic blood glucose curves are not recommended. 3. Most cats will be regulated on less than 4 units of insulin twice daily.

DM is a serious, chronic disease with considerable consequences if the patient is not monitored and managed appropriately. Monitoring is more frequent in the period between starting insulin and achieving glycemic control, but long-term monitoring is essential. In cats achieving remission, approximately 25% were reported to occur within the first 2-3 months following diagnosis, while over 50% occurred within 6 months. [53,55] Monitoring during the first 3-6 months is especially critical to ensure the safety and success of insulin treatment. [2]

Monitoring can be divided into initial and long-term categories. Treatment success is not measured solely by laboratory values but also by improvement and resolution of clinical signs. With good regulation, PU, PD, and PP will drastically improve, and initially, weight gain or cessation of unintentional weight loss are positive indicators.

初始监测：甘精胰岛素U-100或PZI / Initial Monitoring: Glargine U-100 or PZI Perform the first glycemic check at 5–7 days after initiating treatment with glargine U-100 or PZI. Note clients’ observations of clinical signs and weigh the cat at every visit. If clinical signs have not improved or the cat has not maintained or gained weight, an increased insulin dose is likely needed. Clients should closely monitor their cat for clinical signs of hypoglycemia after starting insulin and if observed, seek veterinary assistance urgently (see Section 15, Figure 15.1). If the patient is hyporexic, vomiting, or generally unwell, assess for ketosis with blood BHB or urine ketone measurement.

Ideally, place a CGM [45] at the first recheck at 5–7 days, especially if the insulin dose will be increased. The initial regulation period is a critical time for the cat to potentially experience remission or develop hypoglycemic episodes, which makes the CGM an important tool. Hypoglycemia reported by a human-calibrated CGM may not accurately reflect the cat’s true BG, therefore correlate any low BG readings on CGM with a veterinary-calibrated PBGM and clinical signs.

It is important to note that occasionally cats will achieve excellent clinical control but have reported BG readings on CGM that are consistently higher (250–350 mg/dL) than the typical targeted range (80–300 mg/dL), highlighting the importance of considering clinical response in therapeutic decision making and not just BG values.

Continue rechecks every 5–7 days. At each recheck, confirm presence or absence of clinical signs, monitor weight, and evaluate glycemic control. The insulin dose can be adjusted every 5–7 days if complete information is available to support safely increasing the dose. If the client is unable to provide accurate and thorough home observations, consider more conservative dose increases and extend rechecks to every 10-14 days. Clients may choose to use urine glucose monitoring for additional information. A negative urine glucose, however, may mean either perfect regulation or a period of hypoglycemia. Fructosamine measurement can be a helpful addition to clinical impression and blood glucose monitoring, but it has limitations (see Section 3, Diagnosing DM in Cats and Section 14, Other Methods for Monitoring Glycemic Data).

In-clinic blood glucose curves are no longer recommended for routine monitoring of diabetic cats. Furthermore, in-home blood glucose curves for cats may also be influenced by stress hyperglycemia, making interpretation challenging (see Section 13, Glucose Monitoring). The use of a CGM, although not specifically calibrated for cats, provides significantly more information than the traditional blood glucose curve. They are simple to place on cats, and even if they do not stay in place for the full 14 days, they provide more complete information than a traditional 8 hr in-hospital or 10–12 hr in-home blood glucose curve.

If a cat is not regulated with 4 units or less given twice daily, additional evaluation is recommended before further increasing the dose. Proper insulin handling and administration must be evaluated, as well as considering other disease processes causing IR (see Section 10, Troubleshooting in Diabetic Cats).

初始监测：甘精胰岛素U-300 / Initial Monitoring: Glargine U-300 Initial monitoring of glargine U-300 involves placement of a CGM at the time insulin is started because dosing decisions can be made more quickly than with nonbasal insulins. After starting, the dose can be increased every 1–3 days until an appropriate nadir (80-120 mg/dL) has been achieved. When initiated at once-daily administration, if an appropriate nadir is reached within 2-3 days but BG remains above 300 mg/dL for more than 12 hr per day, a transition to twice-daily administration using the same dose should be considered. [41]

长期监测 / Long-Term Monitoring Once the correct insulin dose is identified, long-term monitoring is relatively straightforward. Recheck at 4–6 wk after establishing the correct dose, and evaluate the client’s impressions, the cat’s overall clinical signs, and available data such as home blood and urine glucose checks and fructosamine level. If there is any question about the cat’s glycemic control status, including concerns about hypoglycemia, place a CGM. In cats with diabetic remission potential, brief check-ins every 3 months may assist with early detection of downward trends in the BG. Perform routine full rechecks every 6–12 months like those for any cat with a chronic disease, and include a full physical examination and history, CBC, chemistry profile, TT4, urinalysis, and fructosamine measurement.

In-clinic blood glucose curves are no longer recommended for routine diabetic monitoring in cats.

中效胰岛素 / Intermediate-Acting Insulin — Lente

长效胰岛素 / Long-Acting Insulin — Glargine U-100

长效胰岛素 / Long-Acting Insulin — PZI

基础胰岛素 / Basal Insulin — Degludec

基础胰岛素 / Basal Insulin — Glargine U-300

a. Martin GJ, Rand JS. Pharmacokinetic and pharmacodynamics study of caninsulin in cats with diabetes mellitus. Internal Study Report. 2000.

b. Caney SM. Management of cats on Lente insulin: tips and traps. Vet Clin North Am Small Anim Pract 2013;43(2):267–82.

c. Nelson RW, Henley K, Cole C, et al. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. J Vet Intern Med 2009;23(4):787–93.

d. Gilor C, Culp W, Ghandi S, et al. Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats. Domest Anim Endocrinol 2019;69:19–29.

e. Gilor C, Fleeman LM. One hundred years of insulin: Is it time for smart? J Small Anim Pract 2022;63(9):645–60.

f. Linari G, Fleeman L, Gilor C, et al. Insulin glargine 300 U/ml for the treatment of feline diabetes mellitus. J Feline Med Surg 2022;24(2):168–76.

BG, blood glucose; PZI, protamine zinc insulin; U, units.

Top 3 Takeaways 1. Cats may benefit from a low-carbohydrate, high-protein diet. 2. Meal feeding is not essential but preferred. 3. Overweight or obese cats benefit from healthy weight loss.

Dietary Therapy Goals and Management In cats diagnosed with DM, dietary therapy is typically considered a complement to insulin or SGLT2 inhibitor use. Occasionally cats will successfully go into remission with a diet change, but this is not to be expected. However, diet modification and achieving an ideal body weight may be helpful in reducing DM risk in non-diabetic obese cats or subclinical hyperglycemic cats. Consider a diabetic patient’s individual needs when making a nutritional recommendation.

Dietary therapy aims to optimize body weight with appropriate macronutrient levels and calorie and portion control. Treatment goals include weight loss in obese patients and stopping DM-associated weight loss. Dietary management of DM involves the following:

• Calculate daily caloric intake based on optimized body weight and an accurate diet history. • Monitor body weight (using the same scale for consistency) at least once or twice monthly as therapy is instituted; a healthy rate of loss for an obese cat is 0.5–2% of body weight per week (see the AAHA Nutrition and Weight Management Guidelines at aaha.org for additional resources). • Monitor body and muscle condition scores to help direct adjustments in dietary therapy. • Manage protein and carbohydrate intake to minimize postprandial hyperglycemia. Protein normalizes fat metabolism and provides a consistent energy source. Arginine stimulates insulin secretion. • Prioritize a patient’s reliable food intake from a complete and balanced diet over modifying specific nutrients. • Adjust dietary recommendations if cats have concurrent diseases (e.g., chronic kidney disease, pancreatitis, intestinal disease). In these situations, the task force generally recommends selecting a diet based on which comorbidity is most likely to impact the patient’s survival, e.g., selecting a renal diet rather than a diabetic diet in a cat with both DM and advanced stage proteinuric renal disease. Consultation with a veterinary nutritionist can be helpful in formulating nutritional plans that work for multiple comorbid conditions.

It is ideal to use meal feeding with intermediate-acting insulins that peak within a few hours of injection; however, this is not essential in cats and graze eating over the day is acceptable. With glargine U-300, strict meal feeding is not required because the frequency of injections may be decreased and risk of hypoglycemia associated with missed meals is low. [43] The timing of meals can also be adjusted if the pet is eating a low–glycemic index diet. [46]

• Feeding portioned meals has several advantages for the dietary management of diabetic cats: ○ It is easier to monitor intake and appetite. ○ Portion control is facilitated. • Free-choice feeding is acceptable if a cat’s eating habits cannot be changed. (The task force recommends the daily ration be divided into multiple meals. Timed feeders may help in this scenario.) [47] • Canned foods are preferred over dry foods. Canned foods provide: ○ Lower carbohydrate levels. ○ Ease of portion control. ○ Lower caloric density; cats can eat a higher volume of canned food and obtain the same caloric intake as smaller volumes of dry food. ○ Additional water intake.

Commercially available therapeutic diets designed for diabetic cats are often calorie dense. For obese cats (BCS >7/9), feeding a diet with moderate carbohydrate content (15-25% metabolizable energy [ME]) and lower calories, such as a therapeutic diet designed for weight loss, may be considered. [46]

The ideal diet for most diabetic cats includes: [9] • High protein content (>40–45% ME, >10 g/100 kcal) and reduced carbohydrate content (<12–15% ME, <3 g/100 kcal). [47] • Canned food or a mix of canned and dry. [9] • Carbohydrate intake should be limited because carbohydrates may contribute to hyperglycemia and glucose toxicity. The task force recommends a diet carbohydrate content of ~12% ME, recognizing that there are a variety of expert opinions on this topic. [47,48] • In diabetic cats, remission rates between 15 and 100% have been reported when cats were given a combination of a high-protein/lowcarbohydrate diet and insulin. [49,50] • High-fiber diets are not typically recommended for cats with DM.

Pet food labels do not consistently include carbohydrates in the guaranteed analysis, although The American Association of Feed Control Officials Pet Food Label Modernization regulations require carbohydrates (see www.aafco.org/pflm/). If not listed, the carbohydrate content of a diet can be calculated by subtracting the listed percentages of protein, fat, fiber, moisture, and ash from 100. If ash content is also not listed, use an estimate of 2-3% for canned diets and 5-8% for dry diets. Then, online tools can be used to convert nutrient information to ME. Balance.it has a free guaranteed analysis to ME content of nutrients converter (balance.it/convert), and Tufts University also has a nutrient converter (sites.tufts.edu/petfoodology/ 2017/08/07/nutrient_converter/).

Top 3 Takeaways 1. Diabetic remission is almost exclusively a feline phenomenon, thus supporting the insulin-resistant model for this species. 2. Remission requires restoration of beta-cell function and relies on reversal of IR and glucose toxicity. 3. Cats receiving exogenous insulin that undergo unrecognized remission are vulnerable to life-threatening insulin-induced hypoglycemia.

Diabetic remission (i.e, euglycemia maintained for >4 wk without exogenous insulin or oral hypoglycemic agents) routinely occurs in diabetic cats. This transition reflects recovery of beta-cell function and relies on the reversal of IR and glucose toxicity. [2] However, diabetic cats undergoing remission are not cured, because pancreatic insulin reserve is permanently limited and relapse is common. [51]

Approximately 25% of cats achieving remission did so in the 2-3 months following diagnosis, while a majority of cats achieved remission within 6 months. [53,55] Reported incidences vary and appear to be influenced by patient characteristics and management strategies; however, the task force supports using an average remission rate of approximately 30% in the United States. [2] Cats with reversible causes of IR, such as obesity or recent glucocorticoid administration, are more likely to undergo remission, assuming that adiposity is addressed or insulin-antagonizing medications are withdrawn or both. [55] Promptly address other causes of IR such as dental disease, rather than postponing treatment until BG is adequately regulated. Canned high protein diets may also support remission by mitigating sarcopenia and boosting secretion of GLP-1, an incretin with a trophic effect on beta cells. [52,53] Cats with a history of DKA [54] and/or peripheral neuropathy may undergo remission, with a 2024 study reporting similar rates of remission between cats with historic DKA (9.8%) and those with neuropathy (8.5%) at diagnosis. [55]

Cats with hypersomatotropism (acromegaly) are not expected to undergo remission without definitive treatment for the underlying condition. [56]

For cats receiving insulin, diabetic remission is supported by effective glycemic control and indicated by a progressive decrease in insulin requirements or evidence of hypoglycemia. [2] Although some studies suggest that insulin type plays a key role, carefully monitoring and adjusting the treatment protocol to achieve good glycemic control within 6 months of DM diagnosis is probably more impactful than the product administered.

Remission onset is readily apparent if BG is routinely monitored, but remission may be overlooked in unmonitored cats until there are obvious signs of hypoglycemia. Urine glucose monitoring is less sensitive, but zero glucosuria for >48 hr suggests either excellent glycemic control or sustained hypoglycemia. Similarly, consider remission if serum fructosamine concentrations are within or below the reference range.

The incidence of remission for cats receiving an SGLT2 inhibitor has not been evaluated at this time. As these drugs cause persistent glucosuria irrespective of BG concentration and insulin secretion, the drug must be withheld to identify remission. If clients have cost concerns or want to assess if the SGLT2 drug is required long term, it is reasonable to check for remission after at least 90 days of therapy. Closely monitor BG with a CGM or 1–2 glucometer checks per day for at least a week; values >250 mg/dL with concurrent ongoing clinical signs indicate the need for continued treatment. [21] Alternatively, clients can monitor urine at home, bearing in mind that it may take several days for the glucosuric effects of the drug to wear off and even short periods of hyperglycemia impact beta cell viability and drive apoptosis. [5,6] Cats that undergo remission but subsequently relapse often lose enough beta cells to ultimately require exogenous insulin permanently. Achieving a second remission is less common, with reported rates ranging between 0-22%. [57,58]

Although further studies are needed to evaluate strategies for maintaining diabetic remission, diligent weight management and continued use of a canned low-carbohydrate diet are recommended for all cats. [53] Additionally, relapses in cats previously treated with insulin may possibly be prevented by long-term use of an SGLT2 inhibitor (an extra-label use), although more research is needed. Physical examination with continued monitoring of clinical signs, weight, and appropriate laboratory evaluation every 6 mo may allow early detection of possible diabetic relapse.

Top 3 Takeaways 1. Teach clients how to recognize potential complications. 2. Increasing insulin dose requirements may signal other underlying diseases. 3. Consult a specialist as needed.

Managing diabetic cats is not always straightforward. The approach to troubleshooting problems with diabetic management differs between patients who receive SGLT2 inhibitors and those treated with insulin.

When using a CGM to monitor either SGLT2 inhibitor or insulin use, if persistent moderate hyperglycemia is seen in a cat who is otherwise not showing clinical signs and maintaining or gaining weight, therapy adjustment may not be necessary. Task force members have frequently managed clinically well cats with glucose concentrations persistently >250 mg/dL as determined by CGM.

Troubleshooting SGLT2 Inhibitor Treatment Clinical hypoglycemia is not a concern with SGLT2 inhibitor treatment, and unresponsive hyperglycemia is uncommon. If hyperglycemia persists, ensure that the cat is receiving the prescribed dose. If clients are mixing the drug with food, they should avoid mixing the dose with a full meal as cats may be under-dosed if not all food is consumed. If hyperglycemia remains despite accurate dosing and administration, discontinue the SGLT2 inhibitor and transition to insulin. Persistent biochemical changes such as hypercalcemia or severe hyperlipidemia may also require discontinuing the SGLT2 inhibitor and transitioning to insulin. Although perineal mycotic infections are routinely reported in human patients treated with SGLT2 inhibitors, these infections have not been described in feline patients.

One of the most common complications with SGLT2 inhibitors is diarrhea. This can be managed with symptomatic care or a 3- to 5-day 25-50% reduction in dose, as it tends to be transient in most cases. In some instances, it may help to discontinue the SGLT2 inhibitor for 2–3 days and allow the diarrhea to improve, then restart treatment at half the dose and gradually increase it to the prescribed dose. Changing to another SGLT2 inhibitor may be helpful in some cats. For persistent diarrhea, antibiotics are not indicated, and the patient may require transition to insulin.

Troubleshooting Insulin Treatment (See Also Figure 15.2) Problematic patients who are receiving insulin usually fall into two categories: cats who become hypoglycemic and cats who exhibit persistent hyperglycemia.

Always confirm that insulin is being handled and administered correctly. Check the dose on the syringe and injection routine with the client and ensure that doses are not skipped or accidentally administered more than once. Credentialed technicians can perform initial consultations to gather this information and provide additional client education (see Box, Technician Initial Consultations).

Hypoglycemia may occur with excessive insulin administration, waxing and waning IR conditions, or with unrecognized diabetic remission, and can be life threatening (Figure 15.1, Managing Hypoglycemia). It is important for caregivers, including hospital staff, to know the clinical signs of and risks for hypoglycemia (see Section 11, Client Education). If a cat becomes hypoglycemic, investigate insulin administration, appetite or vomiting, and general health over the previous days to weeks. Diet changes, intestinal disease, and pancreatitis are just a few reasons a cat may eat less and become at risk for hypoglycemia if the same dose of insulin is administered.

Persistent hyperglycemia despite increasing doses of insulin may be due to IR, but proper insulin care and administration should always be confirmed first. Once confirmed, consider any concurrently administered medications. Discontinue insulin-resistancecausing medication(s) if possible, and if still uncontrolled 2 wk after discontinuation, increase insulin dose.

Multiple diseases and conditions can complicate diabetic regulation with insulin by inducing IR, including dental disease, bacterial infections, pancreatitis, inflammatory bowel disease, and hypersomatotropism (acromegaly). Second-level diagnostics, including gastrointestinal testing (fPLI, trypsin-like immunoreactivity, cobalamin, folate), abdominal ultrasound, and hormonal testing, may be appropriate. [59,60] Note that unregulated hyperthyroidism may cause a decrease in insulin-like growth factor (IGF-1), [61] and IGF-1 may be increased in obese cats. [62] IGF-1 testing should be done at least 4–6 wk after starting insulin in newly diabetic cats, as they have significantly lower IGF-1 levels before starting insulin administration. [63] Resolution of concurrent diseases may eliminate the need for an increased insulin dose and, in some cases, may reduce or eliminate the need for insulin administration altogether.

If no underlying disease is identified and the patient is not regulated, consider changing to another type of insulin. When changing insulins, it is safest to initiate the new type at a standard starting dose, such as 1 unit/cat twice daily for glargine U-100 or PZI. Consult with a specialist if the patient still cannot be regulated. Diabetic ketoacidosis is a serious and potentially fatal complication of diabetes, whether on insulin or SGLT2 inhibitors (see Section 12, Diabetic Ketoacidosis).

Ask about current food (type, amount, timing), any dietary changes, and any new medications, supplements, or clinical signs suggestive of insulin resistance.

Ask the client how they store and prepare the insulin (i.e., shaking versus rolling).

Ensure that the syringes match the insulin concentration (U-100 versus U-40).

If using an insulin pen, ask the client whether they prime needles before each use.

Assess how long the insulin vial has been in use since being opened or uncapped; consider replacement if in use more than 4 mo.

Using sterile saline, have the client demonstrate how they administer injections to their cat.

Have the client keep a log that family members initial when they administer the insulin to ensure doses are not skipped or doubled.