Applying Evidence-Based Concepts to Management of Overweight and Obese Pets

The grading system (evidence grades I to IV) used to systematically evaluate evidence for use of interventions in obese cats and dogs has been described.^1,2 However, recommendation of any specific strategies should be assessed on the basis of evidence grade and also on the basis of the clinical expertise of the attending veterinarian, pet owner preferences, and availability of resources. In addition, the impact that providing unnecessary or unproven treatments could have on the relationship between the pet and owner should be considered. Treatments that the pet or owner find undesirable may impair the relationship between the pet and owner.

Therapeutic foods for weight management in cats—Various commercial therapeutic foods (including dry^a–h and moist^i–o forms) have been used for approximately the past 20 years for nutritional management of overweight and obese cats (Tables 1 and 2). Most of the available foods provide 40% to 50% of their calories as protein and 25% to 40% of their calories as fat. The largest variation in weight management foods formulated for cats is in soluble carbohydrate (range, 7% to 43% of calories) and crude fiber (range, 1.1% to 16.8% of dry matter) contents. Traditional methods of weight management have included the use of low-fat, highfiber foods to reduce caloric intake and body weight while maintaining satiety.^3,p Low-fat foods with added L-carnitine also help cats lose fat safely while maintaining lean body mass.^4,5 Increases in dietary protein appear to promote weight loss and reduce loss of lean body mass during weight loss in cats.^6,q Newer concepts of weight management in cats include altering an animal's metabolism by use of low-carbohydrate, high-protein foods. Obese cats consuming restricted amounts of a moist low-carbohydrate, high-protein food lost weight and had increases in serum β-hydroxybutyrate concentrations.⁵ The increase in serum β-hydroxybutyrate concentrations indicated that there are metabolic changes when this type of food is fed to obese cats. These metabolic changes may contribute to weight loss.

Clinical studies conducted with commercial foods for weight management have primarily been unmasked, time-series designs with each obese animal or group of animals serving as their own control animal or control group (grade III evidence). In such studies, weight loss, changes in body composition (body fat and lean body mass), and metabolic changes (blood lipid concentrations, liver enzyme activity, and glucose tolerance) have been evaluated by allowing freechoice access to food or by feeding restricted amounts. Studies^3–12,r,s in obese cats have been conducted with various commercial therapeutic foods, including lowfat, low-fiber dry food; low-fat, high-fiber moist and dry foods; high-fat, low-carbohydrate, moderate-fiber moist and dry foods; and high-protein, low-fat, moderate-fiber dry food (Tables 1 and 2). All published studies revealed a significant decrease in weight and body fat and nonsignificant loss in lean body mass when the commercial therapeutic foods were fed to obese cats during a 14- to 24-week period. Diet-induced weight loss also appears to improve glucose tolerance, minimize oxidative damage to tissues, and improve the inflammatory status in obese cats.^13,14,t

Rebound weight gain is also evident in previously obese animals, similar to the situation in humans. Similar to results in other species, weight rebound in cats is most extreme when weight is rapidly lost and is more prevalent in cats allowed access to energy-dense food after weight reduction. In 1 study,¹⁵ approximately half of the weight loss achieved in colony-housed obese cats during a 16-week period (mean loss was 19% of initial body weight) was rapidly regained during a subsequent 14-day period when cats were given free-choice access to a highly palatable, energy-dense food. This suggests that weight management strategies that involve the use of low-calorie foods in limited amounts are important in obese-prone cats, especially during the period immediately after weight loss.

In summary, clinical studies have indicated that at least 7 commercial therapeutic foods specifically designed for weight management are safe and effective in obese cats. Most of the studies have been unmasked, time-series designs with each obese animal or group of animals serving as their own control animal or control group (grade III evidence). Studies have been performed in cats in colony and home settings with successful outcomes (loss of weight and body fat, maintenance of lean body mass, and improvement in metabolism). Goodquality evidence exists for use of many, but not all, commercial therapeutic foods for management of obese cats.

Therapeutic foods for weight management in dogs—Various commercial therapeutic foods (including dry^u–aa and moist^bb–gg forms) have been used for > 50 years for nutritional management of overweight and obese dogs (Tables 3 and 4). Most of the available foods provide 30% to 40% of their calories as protein and 17% to 25% of their calories as fat. The largest variation in weight management foods formulated for dogs is in soluble carbohydrate (range, 6% to 59% of calories) and crude fiber (range, 2.0% to 23.2% of dry matter) contents.

Traditional methods of weight management in dogs have included the use of low-fat, high-fiber foods to reduce caloric intake and body weight while maintaining satiety.¹⁶ Despite the widespread use of increased dietary fiber in weight management programs for humans and other animals, the influence of dietary fiber on energy regulation remains controversial. Consumption of higher-fiber diets by healthy adult humans typically causes an increase in satiety, reduction in hunger, reduction in energy intake, and loss of body weight. Moreover, effects of higher-fiber diets typically are more pronounced in obese and overweight humans, which suggests that the ability of dietary fiber to promote negative energy balance may be most pronounced in individuals who most need to lose weight.¹⁷ Fat and fiber content of foods during energy restriction also appears to be important in the management of obese and overweight dogs.^18,19 Significantly greater decreases in body fat were detected in obese neutered male dogs during restricted feeding of low-fat, high-fiber foods, compared with results for dogs fed high-fat, low-fiber foods.¹⁸

The influence of dietary fiber on satiety in dogs also remains controversial. Some studies^20–22 failed to detect a benefit of low to moderate amounts of dietary fiber on satiety in dogs fed restricted amounts of moist foods, whereas other studies^23–27 have detected a considerable benefit of moderate to high amounts of dietary fiber in dogs fed dry foods. Higher-fiber foods designed for weight management have also been criticized because of perceived increases in fecal volume and poor coat condition in dogs consuming these foods.²⁸ However, this perception may not be prevalent among pet owners. In a blinded study,²⁹ pet owners reported an improvement in coat condition during the period when their dogs were consuming a commercial low-fat, highfiber food, and fecal volume and quality were not significantly different for dogs consuming a low-fat, highfiber food, compared with results for those consuming a lower-fiber food. Increased amounts of dietary protein also appear to promote weight loss and reduce loss of lean body mass during weight loss in dogs.^{19,27,30,hh,ii}

Clinical studies conducted with commercial therapeutic foods have primarily been unblinded, time-series designs with each obese animal or group of animals serving as their own control animal or control group (grade III evidence). A prospective, randomized, blinded, multiple-center clinical study²⁹ was performed with weight management foods formulated for dogs, but to our knowledge, results of that study have not yet been published. In all of the aforementioned studies, weight loss, changes in body composition (body fat and lean body mass), and metabolic changes (blood lipid concentrations and glucose tolerance) were evaluated by allowing free-choice access to food or by feeding restricted amounts. Studies^{29,31–39,jj,kk} have involved the use of various commercial therapeutic foods in obese dogs, including low-fat, low-fiber dry food; low-fat, high-fiber moist and dry foods; and high-protein, highfat, low-fiber moist food (Tables 3 and 4). All studies revealed a significant decrease in weight and body fat and a nonsignificant loss in lean body mass when the commercial therapeutic foods were fed to obese dogs during an 11- to 24-week period. Some studies^35,jj have yielded improvements in clinical conditions in dogs that lost weight, such as improved mobility in dogs with osteoarthritis. Greater food restriction appears necessary to induce weight loss in female dogs, compared with the food restriction necessary to induce weight loss in male dogs.^30,ll Similar to the situation in cats, diet-induced weight loss also appears to improve glucose tolerance in obese dogs.^31,mm

Investigators have also evaluated the effectiveness of computer software programs used in conjunction with therapeutic weight management foods in obese pets.³⁶ One software program uses current body weight and a desired weekly rate of weight loss to calculate the suggested daily calorie intake for weight loss. All overweight or obese dogs in 2 clinical trials lost weight and reached an optimal or lower body condition score with the aid of a software program and consumption of a therapeutic food for weight management.³⁶

Rebound weight gain is also evident in previously obese dogs, similar to the situation in humans and cats. Similar to results in other species, weight rebound in dogs is most extreme when weight loss is rapid and is more prevalent in dogs allowed access to energy-dense food after weight reduction.³² In 1 study,⁴⁰ all dogs regained weight rapidly when food was provided ad libitum during the period after weight loss. Weight rebound was minimized by controlling food intake and adjusting the number of calories fed to meet the needs for weight maintenance in each dog. Similar to the situation in cats, this suggests that weight management strategies that involve the use of restricted amounts of low-calorie foods are important in obese-prone dogs, especially during the period immediately after weight loss.

In summary, clinical studies have revealed that at least 7 commercial therapeutic foods specifically designed for weight management are safe and effective in obese dogs. Most of the studies have been unblinded, time-series designs with each obese animal or group of animals serving as their own control animal or control group (grade III evidence). One prospective, randomized, blinded, multiple-center clinical study (grade I evidence) has also been performed, but to our knowledge, data from that study have not yet been published. Studies have been performed in dogs in research colony and home settings with successful outcomes (loss of weight and body fat, maintenance of lean body mass, improvements in metabolism, and improvements in clinical condition). Good-quality evidence exists for use of many, but not all, commercial therapeutic foods for management of obese dogs. Results of studies also suggest that computerized software programs used in conjunction with feeding therapeutic foods for weight management may be useful in determining daily calorie intake to induce weight loss.

Owner education programs—The human-animal relationship of owners of normal-weight and overweight cats and dogs has been evaluated.^41,nn Owners of overweight cats indicate that they have a closer relationship with their cats than do owners of normalweight cats, and the role of their cats as a substitute for human companionship is more important for owners of overweight cats.ⁿⁿ Owners of overweight cats indicate that feeding their cats is an important positive factor in their relationship with their pets. Unfortunately, most owners of overweight cats do not perceive their cats as overweight. Owners of obese dogs also believe their dogs are a substitute for human companionship and spend more time with their dogs during meals.⁴¹ They also perceive exercise, work, or protection provided by their dogs as less important. It is no surprise that the number of meals and snacks was greater for obese dogs in this study than for the normal-weight dogs.

Differences in motivational factors among pet owners and differences in human-animal relationships suggest that owner education programs and guidance by veterinary health team members are important factors to consider when planning and implementing weightmanagement programs. Primary reasons for owners to enroll their dogs in weight-loss programs include recommendations by a veterinarian or veterinary staff member, supervision of the program by members of the veterinary health-care team, and the perception that weight loss will improve the health of their dogs.^oo These same reasons, plus requirements to maintain a daily food diary and make biweekly visits to their veterinary hospital, were primary reasons for continuing a weightloss program. However, in 1 study,⁴² extended owner education (monthly classes that addressed nutrition-related topics) failed to improve mean weight loss or body condition score, compared with results for pets whose owners received no additional owner education. An obesity treatment program that included dietary changes and monthly evaluations of body weight during the weight loss and weight maintenance periods was sufficient to achieve good results. Major problems with continuing weight-loss programs in overweight dogs include difficulty keeping dogs from the food of other pets and limits on feeding snacks.^oo This suggests that plans for limiting access to other food sources, including food of other pets, human food, and snacks, should always be discussed with owners of obese or overweight pets.

In summary, obesity treatment programs that include dietary changes and monthly evaluations of body weight by veterinary health-care team members during the weight-loss and weight-maintenance periods appear to be successful. Analysis of the limited data does not support the need for extended owner education programs on the topics of nutrition or obesity. However, additional studies are needed to determine whether other support programs could benefit owners of overweight pets and enhance overall success of weightmanagement programs for dogs and cats.

Exercise and environmental enrichment programs—Excess body weight is generally the result of an imbalance between energy intake and energy expenditure. Physical activity is the most variable component of energy expenditure and therefore has been the target of behavioral intervention to modify body weight in humans and pet animals.^43–45 Inclusion of moderate, regular physical activity in weight-management programs may affect body weight in several ways, including increasing energy expenditure and thus contributing to an energy deficit necessary for loss of body fat and weight, aiding in regulation of food intake, and improving body composition (lean body mass) during both the weight-loss and weight-maintenance phases.^43,45–48 Increased amounts of physical activity also appear to result in improvements of metabolic abnormalities associated with obesity and excess body weight, even without significant changes in body weight or percentage of body fat. Increased amounts of physical activity can improve insulin sensitivity, partially reverse leptin resistance, and suppress the enhanced proinflammatory burden induced by obesity.^49–53 In obese humans, physical activity appears to have an effect on health-related outcomes that is separate from the effect attributable to body weight.⁴⁴ It is currently unknown whether exercise results in beneficial health effects in obese or overweight pet animals that are separate from those attributable to weight loss.

Physical inertia is considered to play an essential role in the development of obesity. However, the extent to which energy intake is regulated through physical activity remains unclear. A model of the relationship between food intake, body mass, and physical activity has been developed from data of rodent and human subjects.⁵⁴ For that model, a decrease in the amount of physical activity and an increase in sedentary lifestyle does not induce a compensatory reduction in food intake and leads to an increase in body mass, introduction of acute physical activity (≤ 1 h/d) on a short-term basis suppresses food intake (as a result of mobilization of stored fuels) and leads to a decrease in body mass, moderate to intense physical activity performed at regularly scheduled intervals by lean subjects increases food intake accordingly and maintains body mass, and obese subjects (because of their excess energy storage) do not have significant changes in food intake during regularly scheduled moderate to intense physical activity.⁵⁴

In humans, physical activity may or may not contribute to substantial weight loss but appears to be critical for prevention of substantial weight gain and maintenance of optimum body condition once there has been weight loss.^44,55,56 The risk of obesity in dogs appears to decrease for each hour of exercise per week,⁵⁷ whereas owners of overweight cats play with their cats less than do owners of normal-weight cats.ⁿⁿ There also appear to be gender differences, with concomitant changes in diet and exercise being more important in women than in men.⁵⁸ Greater food restriction is necessary to induce weight loss in female dogs, compared with the food restriction necessary to induce weight loss in male dogs.^30,ll There may also be differences between female and male dogs with respect to the importance or benefit of concomitant exercise, but additional studies are needed. Caloric restriction and weight loss appear to change the behavior and activity patterns of pen-housed obese dogs (mean of 20% above target body weight); whether there are similar changes in activity in obese dogs losing weight in a home environment is unknown.^59,60

Moderate, regular exercise is advocated in virtually all veterinary weight-management programs.^{15,45–48,61–64} Despite these recommendations, the optimal amount of physical activity to prevent or manage obesity in dogs and cats has not been determined. In 1 study,^oo neither prior regularly scheduled exercise nor increases in exercise during weight loss enhanced the rate of weight loss in dogs, although the amount and intensity of exercise was not reported. Adding to the dilemma is the fact that most dog owners already consider their dogs to be moderately to extremely active.⁶⁵ More than half of pet owners in 1 survey⁶⁶ indicated that they ensured their pet's quality of life by providing regular exercise, and 80% of owners in that survey indicated that they provided daily exercise for their pets. The gap between the reported and actual behavior of pet owners regarding physical activity for their pets may be quite large and likely contributes to the difficulty in prescribing appropriate exercise for obese and overweight animals.

The recommended intensity and duration of physical activity for prevention and management of obesity varies greatly.⁶⁷ In humans, 60 to 90 minutes of moderate-intensity physical activity are required daily to achieve significant weight loss.^44,56 In 1 study,⁶⁸ 17.6 km (11 miles) of walking/wk prevented significant accumulation of visceral fat in humans, whereas 32 km (20 miles) of jogging/wk was required to decrease visceral fat, without concomitant changes in caloric intake. Among those who reported use of exercise as a weight-loss strategy, only 57% met the minimum recommendation of > 150 minutes of exercise/wk and 19% met the highest recommendation of 420 minutes of exercise/wk.⁶⁹

It is generally agreed that recommendations for increases in physical activity should consider the previous amount of activity and physical impairments of each pet and time constraints of each owner. For dogs, suggestions typically include walking for 15 to 30 minutes or swimming for 5 to 15 minutes 5 to 7 times each week.^16,42,45,48 It has been estimated that the daily energy requirement increases 7% to 15% when dogs traverse at least 5 km/d (3.1 miles/d).⁴⁷ Additional studies are needed on the amount, type, and duration of physical activity for prevention and management of obesity in pet animals.

Benefits may also be apparent when people and pets exercise together or when owners provide environmental enrichment during weight loss. People exercising with their dogs reported a substantial improvement in quality of life for themselves, and a combined dog-owner weight-loss program was more effective at maintaining participation in the canine portion of the program.^70,pp With increased retention in weight-loss programs, dogs should benefit from increased veterinary supervision and owner involvement. Results of another study⁷¹ suggested that dog walking contributes to a physically active lifestyle for dog owners.

The effects of environmental enrichment on weight loss in cats have been evaluated.^qq Cat owners were provided with feeding guidelines to reduce an obese cat's body weight; cats were then assigned in a randomized manner to a control group or a treatment group with environmental enrichments. These enrichments included additional food dishes, water bowls, and litter boxes plus climbing towers, window perches, scratching posts, cat spas, grooming supplies, and toys. Cats were weighed weekly, and some were monitored for the amount of activity. Owners were also surveyed at the end of the study to gauge their satisfaction with treatments. Cats in the environmental enrichment group had increased amounts of activity and a slight increase in weight loss, compared with results for cats managed by use of the feeding guidelines alone. Owners of cats in the environmental enrichment group had a more positive image of their cat and believed that they were playing a more active role in their cat's health. Data from these 2 studies^70,qq suggest that increased physical activity and environmental enrichment can benefit overweight cats, overweight dogs, and their owners.

In summary, increased amounts of physical activity are generally accepted as an important component of weight-management programs, especially in dogs. However, recommendations for increases in physical activity are based primarily on studies in rodents and humans (grade IV evidence), and no well-controlled clinical studies exist in pets. The optimal amount of physical activity to prevent or manage obesity in dogs and cats has not been determined, and the effect of exercise should not be overestimated. There is a strong need for specific studies of physical activity requirements in weight management of cats and dogs. Until better evidence is available, recommendations for increases in physical activity should consider the previous amount of activity and physical impairments of each pet and time constraints of each owner. Pet owners should also be informed that there appear to be benefits of providing environmental enrichments and in having pets and owners exercise together.

Pharmacologic agents—Numerous pharmacologic agents have been developed for management of obesity in humans. These generally include satiety agents (sibutramine, phentermine, and dexfenfluramine), appetite suppressants (phenylpropanolamine and nicotine), metabolic stimulants (caffeine, ephedrine [ma huang], sibutramine, and β₃-adrenergic receptor agonists), and inhibitors of dietary fat absorption (orlistat).⁷²

Sibutramine, a serotonin and norepinephrine reuptake inhibitor, promotes weight loss by inducing satiety after the onset of eating and by stimulating thermogenesis. A clinical trial⁷³ in obese humans revealed that those who received a combination of sibutramine in conjunction with lifestyle modification had greater weight loss than those who received medication or lifestyle modification alone. Safety studies⁷⁴ of sibutramine have been completed in dogs, but clinical data are not available regarding its effectiveness for managing obese pet animals. Dexfenfluramine was withdrawn from the human market because of problems with primary pulmonary hypertension; chronic intake of dexfenfluramine in dogs is also associated with a moderate increase in pulmonary vascular resistance,⁷⁵ which makes it inappropriate for obesity management in dogs. Herbal products containing guarana and ma huang have been associated with caffeine and ephedrine toxicosis in dogs⁷⁶ and are not recommended for weight management in pets.

The β₃-adrenergic receptors are found in adipocytes of rodents, humans, and dogs, and they appear to play a major role in the adrenergic stimulation of lipolysis.⁷⁷ In dogs, treatment with a β₃-adrenergic receptor agonist stimulates expression of mitochondrial uncoupling proteins, which may lead to an increase in energy expenditure.⁷⁸ Administration of β₃-adrenergic receptor agonists may be helpful in the treatment of obese dogs and prevention of obesity, but clinical studies are needed to validate their usefulness. Inhibitors of pancreatic lipase, such as orlistat, affect gastric emptying and fat absorption in dogs.⁷⁹ However, adverse effects of these agents, which include diarrhea, steatorrhea, excessive flatus, and fecal incontinence, are similar to clinical signs in subjects with fat malabsorption. Currently, these agents are not recommended for routine management of obese pet animals.

Dirlotapide^rr is an inhibitor of microsomal triglyceride transfer protein developed specifically for weight reduction in dogs.⁸⁰ Microsomal triglyceride transfer protein has an important role in the transfer of triglyceride, cholesterol ester, and phosphatidylcholine between membranes as well as transfer of other fat-soluble compounds and vitamins. In addition to reducing intestinal fat absorption, dirlotapide also reduces food intake in a dose-dependent manner, probably via altered release of gastrointestinal tract hormones.⁸¹ A decrease in food intake appears responsible for most of the weight reduction.⁸¹ Multiple randomized, controlled clinical studies^81–84 have been conducted to evaluate the use of dirlotapide in obese dogs. These studies revealed that dirlotapide significantly reduced food intake and body weight when used in conjunction with foods with a fat content of 5% to 15%. Higher drug doses may be required with use of food with a lower fat content. It would be anticipated that dogs consuming foods with > 15% fat would respond well to dirlotapide administration, but such studies have not been completed.⁸² When administration of dirlotapide is discontinued, food energy intake must be controlled and amounts of food offered should be restricted appropriately. Dogs will regain weight in the posttreatment period when there is a lack of appropriate dietary and exercise management.

In summary, grade I evidence in the form of randomized, controlled clinical studies supports the use of dirlotapide to promote weight loss in obese dogs. However, dogs will regain weight in the posttreatment period when there is a lack of appropriate dietary and exercise management. Sibutramine and β₃-adrenergic receptor agonists appear to offer promise as pharmacologic agents for management of obese pets, and further investigation of these products is warranted.

Conclusions

The concepts of evidence-based medicine can be readily applied to management of overweight and obese pets. Quality-of-evidence guidelines published in the human and veterinary literature serve as an excellent example of a rigorous application of an evidence-based appraisal system. In this system, grade I, II, and III evidence is the most reliable predictor of likely results for weight management of pets in a clinical practice setting. Grade IV evidence provides substantially less robust support for recommendations. On the basis of this grading system, it is apparent that the best evidence exists for the use of many therapeutic foods designed for weight management and for the administration of dirlotapide (Table 5). Strength of evidence should be used primarily to prioritize recommendations for treatment. As a general rule, treatments that have the strongest evidence to support their effectiveness should be recommended first. Prioritization of treatment options is particularly relevant when resource issues or clientanimal preferences limit application of all appropriate management recommendations.

Increased amounts of physical activity are generally accepted as an important component of weightmanagement programs, especially in dogs. However, no well-controlled clinical studies exist for use of exercise and environmental enrichment programs in obese pets. Until better evidence is available, recommendations for increases in physical activity should consider the previous amount of activity and physical impairments of each pet and time constraints of each owner. Animal owners should also be informed that there appear to be benefits of having pets and owners exercise together.