TABLE 2.
Clinical Trials Investigating the Effect of Leptin Administration in Common Obesity
| First Author (Year) (Ref. #) | Study Design | Subjects | N | Type of Leptin | Duration | Dose | Leptin Weight Loss | Other Effects |
|---|---|---|---|---|---|---|---|---|
| Heymsfield et al. (1999) (116) | RCT, double blind placebo controlled | Overweight/obese BMI 27.6–36 kg/m2 | 12 6 8 13 8 |
r-met hu leptin | 24 weeks | Placebo 0.01 mg/kg/day 0.03 mg/kg/day 0.10 mg/kg/day 0.30 mg/kg/day +hypocaloric diet (−500 kcal) |
−1.3 kg/m2 (4.9 kg) −0.7 kg/m2 (5.4 kg) −1.4 kg/m2 (4.1 kg) −2.4 kg/m2 (5.5 kg) −7.1 kg/m2 (8.5 kg) |
• No significant differences in weight loss between treatment groups reported • Linear regression models: reduction of weight and fat mass but not fat free mass with increasing dose |
| Moon et al. (2011) (36) | RCT, double blind placebo controlled | Obese with T2D BMI 33.2 ± 3.8 kg/m2 | 71 | r-met hu leptin | 16 weeks | Placebo 10 mg twice daily |
−0.5 ± 0.2 kg/m2
−0.7 ± 0.1 kg/m2 => No significant effect of leptin on weight loss |
• HbA1c slightly reduced (p = 0.03) Placebo: 8.01 ± 0.93%; leptin: 7.96 ± 1.12% • No changes in inflammatory markers • All metreleptin signaling pathways saturable at 50 ng/ml of free leptin |
| Mittendorfer et al. (2011) (119) | RCT, placebo controlled | Obese with newly diagnosed T2D | 18 | r-met hu leptin | 14 days | Placebo 15 mg twice daily 40 mg twice daily |
=> No changes in BMI in all groups | • No effect on total body mass, fat mass, fat free mass, % of body fat • No effects on insulin sensitivity on hyperinsulinemic-euglycemic clamp |
| Lejeune et al. (2003) (123) | RCT, double blind placebo controlled | Overweight/obese BMI 25–32 kg/m2 | 24 | PEG-OB | 6 weeks of treatment with VLCD followed by 8 weeks of follow-up | VLCD + placebo 80 mg/week for 6 weeks | 0–6 weeks of treatment: −3.6 kg/m2 −4.3 kg/m2 => Reduction (p = 0.049) of body weight with leptin Follow-up: +0.6 kg/m2 +1.1 kg/m2 => Increase of body weight in subjects previously treated with leptin during weight maintenance |
• 0–6 weeks of treatment: no effect of leptin on fat mass, % of body fat, fat-free mass, REE, RQ, hunger • Follow up: no effect of leptin on total body mass, fat mass, fat-free mass, % of fat mass, hunger |
| Hukshorn et al. (2000) (118) | RCT, double blind placebo controllec | Overweight/obese BMI ≥27 kg/m2 | 30 | PEG-OB | 12 weeks | Placebo 20 mg/week +hypocaloric diet (−500 kcal) | −6.4 kg −4.3 kg => No changes in weight |
• No effect on body fat %, 24-h EE, SMR, RQ, appetite (ad libitum evening meal) • No effect on glucose, insulin, glucose disappearance rate, FFAs, glycerol, TGs, TC, LDL-C, HDL-C |
| Hukshorn et al. (2002) (120) | RCT, double blind placebo controlled | Overweight/obese BMI ≥27 kg/m2 + loss of ≥1.75 kg after a 4-week lead-in diet period | 28 | PEG-OB | 4 weeks of diet followed by 8 weeks of treatment | Placebo 60 mg/week | −3.8 kg −4.8 kg => No changes in body weight |
• No effects on glucose, insulin, HOMA-IR, FFAs, glycerol, TGs, TC • No effects on inflammatory markers (sTNF, CRP) |
| Zelissen et al. (2005) (121) | RCT, double blind placebo controlled | Overweight/obese BMI 27.5–37.5 kg/m2 + loss of 0–5 kg and BMI >25 kg/m2 after a 3 week lead-in diet period | 284 | r-met hu leptin | 3 weeks of diet followed by 12 weeks of treatment | Placebo 10 mg every morning 10 mg every night 10 mg twice daily |
−2.6 kg −2.8 kg −2.7 kg −3.4 kg => No changes in body weight |
• No change in SBP, DBP, heart rate, TGs, TCs, LDL-C, HDL-C, fasting glucose, fasting insulin |
| Rosenbaum et al. (2005) (125) | Single-arm open label stud | 3 nonobese, 7 obese | 10 | r-met hu leptin | Diet until 10% weight loss achieved followed by 5 weeks treatment | Dose calculated to maintain blood leptin concentrations at levels prior to weight loss | −2.1 kg compared with treatment start | • 1.0 kg fat mass loss and 1.1 kg free fat mass loss compared with treatment start • Returned of nonresting EE, SNS tone to pre-weight loss levels |
| Rosenbaum et al. (2008) (133) Kissileff etal (2012) (124) |
Single-blind placebo-controlled crossover study design | Obese subjects | 10 | r-met hu Leptin | Diet until 10% weight loss achieved followed by 5 weeks treatment | Placebo Leptin dose calculated to maintain blood leptin concentrations at levels prior to weight loss | No significant changes in weight between leptin and placebo (−1.8-kg difference). | • EE and VAS for satiation were lower in the placebo group than in the leptin group • Leptin reverses changes in neural activity in response to visual food stimuli due to weight loss |
| Korner et al. (2013) (122) | RCT double-blind placebo-controlled crossover study design | Post-RYGB, weight-stable, relative hypoleptinemic subjects | 27 | r-met hu Leptin | 16 weeks | Placebo 0.05 mg/kg twice daily |
No differences in body weight | • No effect of leptin on fat mass, REE, thyroid hormones, cortisol levels |
| Chrysafi et al. (2020) (34) | Crossover study design |
5 obese men, 5 lean men, 5 lean women | 15 | r-met hu Leptin |
(a) 24 h (fed state) (b) 72 h (fasting) Leptin administrated at 8 AM/day [1 dose in (a), 4 doses in (b)] |
0.01 mg/kg 0.1 mg/kg 0.3 mg/kg (total 9 visits for each subject) |
No differences in body weight with escalating leptin doses | • No effect of leptin on energy expenditure, SNS activity, adrenal hormones, lipid utilization. |
CRP = C-reactive protein; DBP = diastolic blood pressure; EE = energy expenditure; FFA = free fatty acid; HbA1c, glycosylated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; LDL-C = low-density lipoprotein cholesterol; PEG-OB = •••; RCT = randomized clinical trial; REE = resting energy expenditure; RQ = respiratory quotient; RYGB = Roux-en-Y gastric bypass; SBP = systolic blood pressure; SMR = sleeping metabolic rate; sTNF, soluble tumor necrosis factor; T2D, type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; VAS = •••; VLCD = very low-caloric diet (provided 2.1 MJ/day).