Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0–112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8–14.0% compared with 3.0–3.9% for placebo ( P  = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.     

Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers

The effects of dirlotapide on body weight (BW) reduction were investigated in overweight Labradors in two parallel-design studies. Study A involved 42 dogs randomized to 0.0, 0.025, 0.05, 0.1, 0.2 or 0.4 mg dirlotapide/kg/day orally for 4 weeks. Study B involved 72 dogs randomized to nine treatments: placebo (24 weeks); dirlotapide (24 weeks) followed by placebo (28 weeks); or dirlotapide (52 weeks); on diets containing 5%, 10% or 15% fat. Dirlotapide dose (initially 0.1 mg/kg) was adjusted monthly during 24-week weight-loss and subsequent 28-week weight-stabilization phases. Food was offered above maintenance energy requirements (MER× 1.1–1.2) based on initial BW. Body composition (body fat, lean tissue and bone mineral content) was monitored using dual-energy X-ray absorptiometry. After treatment, dogs that had received dirlotapide for 52 weeks were fed 90% of quantity consumed at week 52. In study A, BW and food intake decreased asymptotically with dose: mean weekly weight loss exceeded 1% at 0.1–0.4 mg/kg. In study B, dirlotapide resulted in significant mean weekly weight loss (>0.8%) and decreased food intake over 24 weeks compared with placebo ( P  = 0.0001) for all diets. Food restriction minimized post-treatment weight rebound. Dirlotapide administered daily to dogs for up to 52 weeks was clinically safe and resulted in sustained weight reduction.     

An evaluation of dirlotapide to reduce body weight of client-owned dogs in two placebo-controlled clinical studies in Europe

The clinical efficacy for weight loss and safety of dirlotapide in dogs were evaluated in two multi-centre studies with parallel designs. Overweight, adult dogs ( n  = 245) of various breeds were randomized to treatment with dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg/day commencing on day 0 and doubled after 14 days. Every 28 days, dogs were examined, weighed, body condition scores (BCS) were recorded, and dose was adjusted to meet weight loss targets. Each study comprised three consecutive phases: weight-loss (up to day 196); weight-stabilization (84 days); and post-treatment (28 days). pre-treatment feeding and exercise regimens were continued during treatment. Dirlotapide-treated dogs showed mean weight loss of 15.9% (study A) and 14.0% (study B) by the end of weight loss phase (up to day 196). Percentage weekly weight losses for dirlotapide were significantly greater than for placebo ( P  ≤ 0.0002). Emesis and diarrhoea were experienced in both treatments but were more frequent with dirlotapide; resolution was spontaneous. BCS improved for 75.7–82.5% of dogs on dirlotapide treatment compared with 15.4–41.4% for placebo. Mean dirlotapide dosage at end of weight-loss phase was 0.38 (study A) and 0.29 (study B) mg/kg initial body weight/day. Dirlotapide was found to be clinically safe and effective in the reduction of body weight in overweight dogs.     

Biologic activity of dirlotapide, a novel microsomal triglyceride transfer protein inhibitor, for weight loss in obese dogs

Dirlotapide is a novel microsomal triglyceride transfer protein inhibitor intended for the treatment and management of obesity in dogs. The biologic effects of dirlotapide, weight loss, decreased food intake, increased fecal fat, decreased serum cholesterol, and body composition, were evaluated in a controlled, blinded study. Sixteen obese beagles were randomized to treatment with placebo ( n  = 4) or dirlotapide ( n  = 12) following a 2-week acclimation period in which baseline data were collected. The dirlotapide dose, adjusted to produce weight loss for 3 months and then stabilize body weight for 1 month (weight management), produced a significant difference (expressed as a percentage of baselines) in weekly weight loss, food intake, fecal fat, serum cholesterol concentration, and body composition (measured by dual energy X-ray absorptiometry) compared with placebo treatment ( P  < 0.05). The initial dirlotapide dosage of 0.5 mg/kg (10 times the initial label dose) resulted in a high rate of weight loss (3.3% weekly) and anorexia, emesis, and loose stools for some dogs. A 25% dose reduction (mean dosage: 0.36 mg/kg) followed by biweekly 25% dose adjustments based on individual weight loss, produced 1–2% weekly weight loss and total weight loss of 18.8% in 12 weeks at a final mean dosage of 0.41 mg/kg (range: 0.15–0.60); a dosage range of 0.10–0.34 mg/kg stabilized body weight. Body weight changes for placebo-treated dogs were −0.8% to +0.9% weekly; total weight gain during the weight loss phase was 10.6%. No apparent change in food intake, percentage of fecal fat, and serum cholesterol was observed in the placebo group. Food intake and body weight increased when dirlotapide was discontinued. Dirlotapide produced weight loss by both reducing appetite (about 90% of the weight loss activity) and by increasing fecal fat excretion (about 10% of the weight loss activity).     

The safety of dirlotapide in dogs

The safety of dirlotapide in dogs was evaluated in two studies with parallel designs. In an acute tolerance study, 24 beagles (six dogs per treatment) were treated orally once daily for 14 days with placebo or dirlotapide at 2.5, 5.0, or 10.0 mg/kg/day. In a margin-of-safety study, 38 overweight, neutered beagles were treated orally once daily for 3 months with dirlotapide at doses up to 0.5 mg/kg/day (six dogs), 1.5 mg/kg/day (12 dogs) and 2.5 mg/kg/day (six dogs). Control dogs received placebo at 0.3 mL/kg/day (10 dogs) and 0.5 mL/kg/day (four dogs). Results were similar for both studies, and no serious adverse events were observed. Dirlotapide was clinically well-tolerated in dogs at dosages up to 10 mg/kg/day for 14 days and 2.5 mg/kg/day for 3 months. Dirlotapide produced the expected decrease in food intake and body weight (up to 20–40%) without ill effects. Clinical, pathologic, and histopathologic findings were reversible and consistent with suppression of food intake and rapid weight loss produced by elevated dirlotapide dosages. In both studies, sporadic emesis and loose stools were observed in both placebo and dirlotapide-treated dogs. Incidence of emesis generally increased with dose and decreased with treatment time. Elevations in hepatic transaminase activity were seen in dogs treated with more than 1.5 mg/kg dirlotapide daily, but were not associated with clinical signs or microscopic evidence of hepatic degeneration or necrosis.     

Influence of dirlotapide, a microsomal triglyceride transfer protein inhibitor, on the digestibility of a dry expanded diet in adult dogs

The objectives of this study were to evaluate the effects of dirlotapide, a microsomal triglyceride transfer protein inhibitor, on apparent nutrient digestibility of an expanded dry dog food, on defecation frequency and fecal consistency. Eighteen beagles were randomized to either placebo ( n  = 6) or dirlotapide ( n  = 12). Testing was divided into a 21-day adaptation phase (days −21 to −1) and a 35-day treatment (digestibility testing) phase (days 0–35). During the treatment phase, dogs were administered oral dirlotapide (0.3 mg/kg) or placebo (0.06 mL/kg) once daily. For digestibility testing, feces were collected over two periods for 7 days each starting on days −9 and 28. All dogs were fed a commercial adult dog food throughout the study. Food intake was adjusted to maintain body weight during adaptation, followed by pair-feeding placebo dogs the amount of food ingested by the dirlotapide dogs during the treatment period. Dogs in both groups had reduced food intake and lost similar amounts of body weight during treatment. Dogs receiving 0.3 mg dirlotapide/kg once daily had a small but significant ( P  = 0.018) decrease (6.16 ± 2.22%, mean ± SD) in crude fat digestibility compared with the placebo-treated food-restricted dogs, but no difference in crude protein, dry matter, or energy digestibility was observed. Fecal consistency and volume and defecation frequency were similar between groups. Dirlotapide effectively reduced appetite and energy intake without affecting nutrient digestibility, except for a minimal decrease in fat digestibility.     

Dirlotapide: a review of its properties and role in the management of obesity in dogs

Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor developed specifically for canine weight reduction. MTP catalyzes the assembly of triglyceride-rich apolipoprotein-B containing lipoproteins to form chylomicrons in the intestinal mucosa and very low-density lipoproteins in the liver. Following oral administration, dirlotapide has in vivo selectivity for intestinal MTP compared with hepatic MTP. In addition to reducing intestinal fat absorption, dirlotapide also reduces food intake in a dose-dependent manner, probably via increased release of peptide YY into the circulation. The decrease in food intake is responsible for the majority of the weight reduction effect. In clinical use, it is recommended to adjust the dose according to the observed weight loss of each individual. The initial dose of 0.05 mg/kg is doubled after 14 days and then adjusted monthly, the maximum permitted daily dose is 1.0 mg/kg, although doses as high as 10 mg/kg have been administered to dogs without severe adverse experience in safety studies. Dirlotapide can be used without necessitating changes to the current feeding or exercise regimens, but it is desirable to monitor the food intake during weight-stabilization to establish revised feeding and exercise routines that will minimize the risk of weight regain post-treatment. The drug offers a novel approach that is applicable in cases where dietary management alone has proved to be unsuccessful.     

Cohort Study of the Success of Controlled Weight Loss Programs for Obese Dogs

Background

Most weight loss studies in obese dogs assess rate and percentage of weight loss in the first 2–3 months, rather than the likelihood of successfully reaching target weight.

Objective

To determine outcome of controlled weight loss programs for obese dogs, and to determine the factors associated with successful completion.

Animals

143 obese dogs undergoing a controlled weight loss program.

Methods

This was a cohort study of obese dogs attending a referral weight management clinic. Dogs were studied during their period of weight loss, and cases classified according to outcome as “completed” (reached target weight), “euthanized” (was euthanized before reaching target weight), or “stopped prematurely” (program stopped early for other reasons). Factors associated with successful completion were assessed using simple and multiple logistic regression.

Results

87/143 dogs (61%) completed their weight loss program, 11 [8%] died or were euthanized, and the remaining 45 [32%] stopped prematurely. Reasons for dogs stopping prematurely included inability to contact owner, refusal to comply with weight management advice, or development of another illness. Successful weight loss was positively associated with a faster rate (P < .001), a longer duration (P < .001), and feeding a dried weight management diet (P = .010), but negatively associated with starting body fat (P < .001), and use of dirlotapide (P = .0046).

Conclusions and Clinical Relevance

Just over half of all obese dogs on a controlled weight loss program reach their target weight. Future studies should better clarify reasons for success in individual cases, and also the role of factors such as activity and behavioral modification.     

Long-term follow-up after weight management in obese dogs: the role of diet in preventing regain

Regain after weight loss is widely reported in humans, but there is little information on this phenomenon in dogs. The current study aim was to determine long-term success of a weight loss regime and those factors linked with regain. Thirty-three obese dogs, that had successfully lost weight, were included, all enrolled between December 2004 and May 2009. After weight loss, dogs were switched to a maintenance regime and follow-up weight checks were performed periodically. A review of cases that had completed their weight programme was held during the summer of 2010 and a follow-up check was subsequently conducted, where dogs were reweighed and information was collected on current feeding practices. Median duration of follow-up was 640 days (119-1828 days). Fourteen dogs (42%) maintained weight, 3 (9%) lost >5% additional weight, and 16 (48%) gained >5% weight. Dogs fed a purpose-formulated weight loss diet regained less weight than those switched onto a standard maintenance diet (P=0.0016). Energy intake at the time of follow-up was significantly higher in those dogs fed a standard maintenance diet, compared with those that had remained on a purpose-formulated weight loss diet (P=0.017). These results suggest that weight regain occurs in about half of dogs after successful weight loss. Long-term use of a purpose-formulated weight management diet can significantly limit regain in the follow-up period, likely by limiting food intake.     

The effect of weight loss on lameness in obese dogs with osteoarthritis

This paper describes the effect of weight loss on lameness in obese dogs with osteoarthritis (OA). Fourteen obese client-owned dogs with clinical and radiographic signs of OA participated in an open prospective clinical trial. After a screening visit and a visit for collection of baseline data, the dogs were fed a restricted-calorie diet over a study period of 16 weeks that incorporated six follow-up visits. At each visit, body weight and pelvic circumference were measured and severity of lameness was assessed using a numeric rating scale (NRS), a visual analogue scale (VAS) and kinetic gait analysis. This is the first study to assess both subjectively and objectively, the effect of weight loss alone on lameness in obese dogs with OA. The results indicate that body weight reduction causes a significant decrease in lameness from a weight loss of 6.10% onwards. Kinetic gait analysis supported the results from a body weight reduction of 8.85% onwards. These results confirm that weight loss should be presented as an important treatment modality to owners of obese dogs with OA and that noticeable improvement may be seen after modest weight loss in the region of 6.10 – 8.85% body weight.     

Physical Rehabilitation Alters Body Composition in Chronically Obese Cat

Successful weight loss in obese dogs and cats is difficult, and even more so in pets who don't exercise regularly or are inactive. Over the past 10 years, physical rehabilitation (or physio‐therapy) as a treatment or wellness modality has been gaining popularity in small animal veterinary practice. This case report describes the use of physical rehabilitation to achieve weight loss and a decreased body condition score in a chronically obese cat. A 7‐year old, female‐spayed domestic, short‐haired cat, weighing 15 lbs, was evaluated by the Nutrition Support Service at Michigan State University's Veterinary Teaching Hospital for a weight management consultation. The cat had a history of chronic obesity and the owner reported feeding a variety of reduced or restricted‐calorie foods, both canned and dry versions, over the previous 5 years. The home environment included three other cats, none of which were overweight. All cats were fed once daily in the evening; separate food bowls were provided for each cat, but multiple water bowls and litter boxes were shared. A course of 8 weeks of physio‐therapy was recommended, with a target weight of 12 lbs identified, to which the owner agreed. Body weight, body condition score and circumference measures of axillary, rib and flank areas were taken at the initial visit, and at 3 weeks and 8 weeks. At the beginning of the 8^th week, the cat's body weight had dropped from 15 lbs to 14.2 lbs, and the body condition score shifted down from 9 to 8 out of 9. More dramatically, however, were changes measured in body circumference: from 43 cm to 38.6 cm in the axilla (11% decrease); 50.3 cm to 42.5 cm in the ribs (15.5% decrease); 46 cm to 41 cm in the flank (11% decrease). To the author's knowledge, this is the first report confirming weight loss, reduced body condition score, and altered body composition in a cat as a direct result of physical rehabilitation.     

Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease

AIM: To evaluate the efficacy and tolerance of an extract of green-lipped mussel (GLME) in the management of mild-to-moderate degenerative joint disease (DJD) in dogs. METHODS: Eighty-one dogs presumptively diagnosed with DJD were treated orally daily with either GLME or a placebo for 56 days, in a double-blind, placebo-controlled study. In an uncontrolled open-label extension to the study, all dogs were treated with GLME for an additional 56 days (from Days 57-112). Clinical signs were subjectively scored by the owners, and findings of detailed musculoskeletal examinations were scored by one veterinarian. Efficacy was assessed from a qualitative comparison of the proportion of dogs with improved clinical signs, and a quantitative comparison of the scores of the musculoskeletal examinations, between groups. Haematological and biochemical analyses and reports by owners of possible adverse drug reactions were used to screen for evidence of toxicity. RESULTS: There was close agreement between assessments by the veterinarian and owners. The clinical signs of DJD in both GLME-treated and placebo groups improved significantly over baseline by Day 28; this improvement continued over the entire course of the study. There were no significant differences between groups on Day 28. On Day 56, a higher proportion of dogs in the GLME-treated group had improved clinical signs (p=0.018), and GLME-treated dogs had marginally better (p=0.053) musculoskeletal scores than dogs in the placebo group. The differences between the groups were no longer apparent by Day 112, by which time the former placebo group had been receiving GLME for 56 days in the open-label phase of the study. The proportion of dogs in the former placebo group that had improved by Day 112 (29/32; 91%) was significantly greater (p=0.012) than the proportion improved at Day 56 (15/37; 41%). No signs of toxicity were apparent. CONCLUSIONS AND CLINICAL RELEVANCE: GLME had a beneficial effect on the clinical signs of dogs presumptively diagnosed with mild-to-moderate DJD. Long-term therapy may be required before improvement is apparent.     

Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial

Oral S-adenosylmethionine (SAMe) tosylate supplementation (Novifit tablets, Virbac) was evaluated as a dietary aid for the management of age-related mental impairment in dogs. Thirty-six dogs older than 8 years that had displayed signs of cognitive dysfunction for at least 1 month were selected for the study. The dogs were administered 18 mg/kg SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months. Concurrent behavioral treatment was forbidden. A 14-item standardized questionnaire evaluated behavior and locomotion difficulties. Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01). The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs.     

Evaluation of owner education as a component of obesity treatment programs for dogs

OBJECTIVE: To compare results of a conventional obesity treatment program with those of an obesity treatment program that included education of owners of obese dogs. DESIGN: Nonblinded prospective clinical trial. ANIMALS: 60 obese dogs with a body condition score (BCS) of 8/9 or 9/9. PROCEDURE: Dogs were randomly assigned to control or owner education (EDU) treatment groups. A 6-month weight loss period was followed by an 18-month weight maintenance period. Daily caloric intake to induce loss of 1% of body weight/wk was calculated for each dog after assessment of prior diet history. The daily caloric intake for weight maintenance was estimated to be 20% greater than that calculated for weight loss with adjustments of +/- 5% as required. Weight and BCS were recorded monthly for each dog. Owners of dogs in the EDU group were required to attend monthly classes that addressed nutrition-related topics during the 6-month weight loss period. RESULTS: Dogs in both treatment groups had significantly lower weight at the end of the weight loss period, compared with initial weight. Mean weight loss at 6 months was 14.7% in the control group and 15% in the EDU group; this difference was not significant. During the weight maintenance period, percentage weight loss was maintained in both treatment groups. Mean changes in BCS at 6 months (relative to time 0) were -1.5 in the control group and -1.7 in the EDU group. At 24 months, mean changes in BCS (relative to time 0) were -2.1 in the control group and -2.2 in the EDU group. No significant differences in BCS were identified between treatment groups at either 6 or 24 months. CONCLUSIONS AND CLINICAL RELEVANCE: Mean decrease in BCS of 2 and mean weight loss of 15% were achieved and maintained in all dogs. An obesity treatment program that included dietary changes and monthly weight checks during the weight loss and weight maintenance periods was sufficient to achieve these results.     

Absorption, distribution, metabolism, and excretion of dirlotapide in the dog

Three once-daily oral doses of 0.2 mg/kg [¹⁴C]dirlotapide were administered to beagle dogs to study the absorption, distribution, metabolism, and excretion of dirlotapide. Mean ¹⁴C recovered at 2.5 and 4.5 h after the last dose was 90%. Mean ¹⁴C in urine, bile, and feces was <1%, 1.7%, and 56% of the dose, respectively. In tissues, 26% of the ¹⁴C dose was present in the gastrointestinal tract, 6.0% in liver, and <1% each in kidney, gall bladder, heart, and brain. To further characterize drug disposition, a single 2.5-mg/kg oral dose of [¹⁴C]dirlotapide was administered to beagle dogs. More than 84% of the dose had been eliminated by 72 h in feces, with 21% of the dose present in feces as parent dirlotapide. Less than 1% of the dose was excreted in urine. In bile collected during the first 24-h postdose from three dogs, 32% and 11% of the ¹⁴C dose was present in samples from male and female dogs, respectively. Based upon metabolite profiling of plasma, excreta, and bile samples, dirlotapide was extensively metabolized to more than 20 metabolites. Biliary/fecal excretion and the potential for enterohepatic recycling of metabolites are suggested.     

Quality of life is reduced in obese dogs but improves after successful weight loss

Obesity is thought to affect quality of life, but limited objective data exist to support this supposition. The current study aim was to use a questionnaire to determine health-related quality of life (HRQOL) both before and after weight loss, in obese client-owned dogs. Fifty obese dogs were included, and represented a variety of breeds and genders. Prior to weight loss, owners were asked to complete a validated standardised questionnaire to determine HRQOL. Thirty of the dogs successfully completed their weight loss programme and reached target, and owners then completed a follow-up questionnaire. The completed questionnaire responses were transformed to scores corresponding to each of four factors (vitality, emotional disturbance, anxiety and pain), and scored on a scale of 0-6. Changes in the scores were used to explore the sensitivity of the questionnaire, and scores were correlated with responses to direct questions about quality of life and pain, as well as weight loss. Dogs that failed to complete their weight loss programme had lower vitality and higher emotional disturbance scores than those successfully losing weight (P=0.03 for both). In the 30 dogs that completed, weight loss led to an increased vitality score (P<0.001), and decreased scores for both emotional disturbance (P<0.001) and pain (P<0.001). However, there was no change in anxiety (P=0.09). The change in vitality score was positively associated with percentage weight loss (r(P)=0.43, P=0.02) and percentage body fat loss (r(P)=0.39, P=0.03). These results indicate demonstrable improvement in HRQOL for obese dogs that successfully lose weight.     

Clinical Results Following Nonoperative Management for Rupture of the Cranial Cruciate Ligament in Dogs

Eighty-five dogs were diagnosed as having rupture of the cranial cruciate ligament. They were managed by restriction of activity to leash walks for 3 to 6 weeks, weight loss if indicated, and analgesic medication as needed. Twenty-four of 28 dogs that had a body weight of 15 kg or less (85.7%) were considered to be clinically normal (no lameness and normal range of motion in stifle, 21 dogs) or improved (3 dogs) after an average follow-up period of 36.6 months. Lameness in the remaining four dogs persisted or worsened over an average period of 8.2 months (minimum 6 months), and surgical replacement of the cruciate ligament was performed. Eleven of 57 dogs that had a body weight of 15 kg or greater (19.3%) were classified as normal (4 dogs) or improved (7 dogs) after an average follow-up period of 49.1 months. Lameness in the remaining 46 dogs persisted or worsened over an average period of 10.2 months (minimum 6 months), and surgical replacement of the cruciate ligament was performed.     

Canine obesity – an overview

Canine patients are generally regarded as being clinically obese when their body weight is at least 15% above ideal. The incidence of obesity in dogs is thought to be in the range of 20–40% of the general population and, since obesity is known to predispose or exacerbate a range of serious medical conditions, its importance cannot be overstated. Management of obesity through dietary restriction and increased exercise is often difficult to achieve and dependent upon owner compliance. Until recently there has been no authorized therapeutic medication available for weight reduction in dogs, and drugs used in people have proved unsuitable. However, with the development of microsomal triglyceride transfer protein inhibitors for canine use, such as dirlotapide, the veterinarian has a novel method with which to augment traditional weight control programmes. This approach has the additional advantage that weight loss is achieved without dietary restriction or change in exercise regimen, providing encouragement for the owner to comply with subsequent dietary and exercise recommendations, thereby increasing the likelihood for long-term success.     

Evaluation of thyroid function in obese dogs and in dogs undergoing a weight loss protocol

Obesity and weight loss have been shown to alter thyroid hormone homeostasis in humans. In dogs, obesity is the most common nutritional problem encountered and weight loss is the cornerstone of its treatment. Therefore, it is important to clarify how obesity and weight loss can affect thyroid function test results in that species. The objectives of this study were to compare thyroid function in obese dogs and in lean dogs and to explore the effects of caloric restriction and weight loss on thyroid hormone serum concentrations in obese dogs. In the first experiment, 12 healthy lean beagles and 12 obese beagles were compared. Thyroid function was evaluated by measuring serum concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), and reverse triiodothyronine (rT3) as well as a TSH stimulation test using 75 microg i.v. of recombinant human TSH. In the second experiment, eight obese beagles were fed an energy-restricted diet [average 63% maintenance energy requirement (MER)] until optimal weight was obtained. Blood samples for determination of TT4, FT4, TT3, TSH and rT3, were taken at the start and then weekly during weight loss. Only TT3 and TT4 serum concentrations were significantly higher in obese dogs as compared to lean dogs. In the second experiment, weight loss resulted in a significant decrease in TT3 and TSH serum concentrations. Thus obesity and energy restriction significantly alter thyroid homeostasis in dogs, but the observed changes are unlikely to affect interpretation of thyroid function test results in clinics.     

Beta3-adrenoceptor agonist AJ-9677 reduces body fat in obese beagles

A selective beta3-adrenoceptor agonist, AJ-9677, was reported to ameliorate obesity and insulin resistance in KK-Ay mice. We examined the acute and chronic effects of AJ-9677 on obese dogs. Oral administration of AJ-9677 (0.01 or 0.1 mg/kg) to overnight fasted obese beagles produced a dose-dependent rise in the plasma levels of non-esterified fatty acids and insulin in 1h, followed by a gradual drop of the plasma glucose level. It produced no apparent abnormal behaviors, but easily detectable cutaneous flushing. Daily treatment of AJ-9677 at a lower dose (0.01 mg/kg) for three weeks produced no notable change in body weight, but at a higher dose (0.1 mg/kg) it reduced the body weight compared to a placebo treatment after seven weeks. Computed tomographic examinations revealed a remarkable reduction of body fat after the AJ treatment, being consistent with the histological observations that the adipose tissue of AJ-9677-treated dogs consisted of smaller and some multilocular adipocytes. The plasma levels of leptin and adiponectin were decreased and increased, respectively, after the AJ treatment, reflecting the reduction of adiposity. It was concluded that AJ-9677 is useful for the treatment of obesity in the dog.