The evidences are in favor of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on serum uric acid (sUA), achieving sUA target and gout attacks, respectively.

Gout is the oldest known type of arthritis, with a global prevalence of 0.08% and is higher in developed countries. Gout is characterized by painful swelling and inflammation in one or more joints caused due to crystal-deposition of monosodium urate (MSU) or raised in level of serum uric acid (sUA) in the body. The general principle to manage the increased sUA levels is by allowing MSU crystals to dissolve, thereby reducing acute attacks or disappearance of tophi (deposits of UA). Literature suggest that excessive amount of weight in adulthood were more likely to develop gout later in life. Therefore, weight loss is strongly recommended treatment for the gout. While, those who already suffered from type 2 diabetes are more likely to have high level of UA in the blood which is root cause of the gout. Therefore, improving the insulin level in the blood may results in decreased sUA in overweight patients. The information for effectiveness of weight loss in clinical studies has not been previously evaluated in any systematic review. Therefore, this systematic review determined the pros and cons associated with weight loss in overweight and obese individuals with gout. In addition, the effect of weight loss on the dose-response relationship was assessed.

Rationale behind the research:

• In the previous systemic reviews, no evidence for the effectiveness of weight loss in gout patients is reported
• Therefore, in this study evaluated the risk and benefits associated with weight loss in overweight and obese patients with gout

Objective:

To assess the benefits and harms associated with weight loss in overweight and obese patients with gout.

Study outcome measures:

• Joint pain
• Tophus/tophi
• Physical function
• Health-related quality of life (HRQoL)
• sUA change
• Achieving sUA target (ie, sUA reduction to<360 μmol/L (6 mg/dL))
• Serious adverse events (SAEs, defined as adverse events that are fatal, life-threatening or require hospitalization)
• Withdrawals due to adverse events (WddtAEs)
• Patient global assessment o Body weight change
• Gout attacks (any measure)
• Assessment of risk of bias in included studies: Reviewers were assessed risk of bias using the tool risk of bias in non-randomized studies of interventions and for evaluation of the risk of bias in non-randomized studies and compared health effects of two or more interventions

Time points:

Short-term (<3 months), medium (3–12 months) and long-term (>12 months)

Study Outcomes

• Study characteristics: The studies were consisting of one RCT and nine non-randomized studies. Only three studies were reported with subgroup of Gout patients, out of which, one study included only non-gout patients initially, but later on during follow up, they did a sub-analysis on recurrent gout patients. Between 12 to 408 patients including 0-75% females were included in the studies. The average age and BMI ranged from 49 to 63.3 years, and 26.0 to 49.6 kg/m2, respectively. Besides overweight other co-morbidities like type 2 diabetes, hypertension, and high cardiovascular risk profile were selected in the studies. The actions taken included intentional weight loss from dietary changes with or without increased physical activity, bariatric surgery and unintentional weight loss from high protein diet, diuretics and metformin. Three studies were classified according to the reduction in weight or BMI, using no reduction as control. Follow-up ranged from 4 weeks to 7 years, and a mean weight loss of 3–34 kg at latest follow-up was reported.
• Effect of weight loss: There was no data available for joint pain, health related quality of life (HRQoL) or patient global assessment. Only one study provided data on tophi and one study provided data on physical function measured by Short Form-36 physical functioning domain, reporting diminished function with the values 43.3 (SD 21.8), 24.6 (SD 28.2), 10.8 (SD 12.8) at baseline, 6 months and 1.5 years, respectively. One study reported four withdrawals due to adverse events (WDdtAEs) from metformin, and one study did not report any SAEs in gout patients. There were eight (sUA), five (achieving sUA target) and eight (gout attacks) studies providing the data.
• Effect on sUA: At the latest follow-up, the mean sUA ranged from −168 μmol/L to 30 μmol/L (−2.8 mg/dL to 0.5 mg/dL). Furthermore, Zhu et al showed a dose–response relationship with a weight loss of ≥10 kg being associated with a change in sUA of −37 μmol/L. Similarly, Dalbeth et al reported a mean sUA of 510 (SD 130) μmol/L immediate postoperative, i.e an increase of 70 μmol/L from bariatric surgery, and it was dropped to 330 (SD 90) μmol/L at latest follow-up. During this follow up period, three out of seven patients stop taking urate-lowering medication, that is, the decrease may truly be larger. Ruiz et al, Perez-Ruiz et al and Dalbeth et al were the three studies showed no effect on sUA. On the other hand, Barskova et al showed a decrease in sUA from a weight loss of only 3 kg. 
• Risk of bias assessment: ‘Bias due to confounding’ was the most frequent risk of bias with four studies rated critical due to studying one group without adjustment for con-founders. Out of which five studies were rated serious, and only the RCT was rated low risk of bias. All studies were rated serious risk for ‘Bias due to departures from intended interventions’. Reporting bias was suspected for two studies reporting change in BMI instead of change in weight. Protocols were only found for two sub-studies of one main study and three studies reported no published protocol.
  

In conclusion, the available results are in favor of weight loss for overweight gout patients at medium-term/long-term follow-up for sUA, achieving sUA target and gout attacks. The present study suggests that a weight loss of >7 kg and/or >2 kg per week from either surgery or diet results in a beneficial effect on sUA at medium-term/long-term follow-up based on three studies and that weight loss of >3.5 kg showed beneficial effects on gout attacks at medium-term/long-term follow-up based on six studies. However, two studies reported that weight loss from bariatric surgery results is temporarily increased in sUA levels and gout attacks at short term.

A study conducted by Kang et al compared the gout patients who suffered gout attacks after the surgery with those who did not. They found that the first group had higher presurgical sUA and a more rapid and larger decrease in sUA 3 days after the surgery. Another study conducted by Dalbeth et al reported an extreme increase in sUA after 2 weeks from surgery, which may be due to renal dysfunction or metabolic effects from fasting or rapid weight loss (catabolic state). It is suggested that increase in sUA is linked to decrease in the estimated glomerular filtration rate (eGFR), thus affecting blood pressure due increased vascular stiffness. Therefore, reducing sUA may have beneficial effect on cardiovascular disease and diminished renal function. Gout attacks is also not well defined and was reported in various ways and over various follow-up times in earlier studies. Therefore, stating fewer gout attacks following weight loss is not very specific and not necessarily assessable in smaller sample sizes, or when attacks were not systematically assessed. Three studies did not focus at reduced frequency of attacks, of which Friedman et al did not report any baseline and Perez-Ruizet al did show less increase compared with control. Other studies can mask increasing number of attacks by reporting number of patients experiencing ≥1 attack over various follow-ups. Therefore, one could consider rating the evidence for gout attacks further down for indirectness.