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Phentermine vs Placebo for Weight Loss in Obese Patients, Diabetes, Obesity, and Metabolism (2010) [PubMed abstract]
  • The trial enrolled 74 obese patients with an average BMI of 33
Main inclusion criteria
  • BMI ≥ 30 or BMI 27 - 30 and treated for type 2 diabetes, hypertension, or dyslipidemia
Main exclusion criteria
  • HgA1C > 7.5%
  • SBP ≥ 140, DBP ≥ 90
  • History of weight loss surgery or medications
  • Psychiatric illness
Baseline characteristics
  • Average age 35 years
  • Average BMI - 33
  • Average weight - 191 lbs (87 kg)
  • Female sex - 74%
  • Average blood pressure - 123/80
Randomized treatment groups
  • Group 1 (37 patients) - Phentermine 30 mg once daily for 12 weeks
  • Group 2 (37 patients) - Placebo for 12 weeks
  • Phentermine was given in a diffuse-controlled release (DCR) capsule
  • All patients were instructed to follow a hypocaloric diet (1500 cal/day for men, and 1200 cal/day for women)
Primary outcome: Change in body weight and waist circumference at 12 weeks
Results

Duration: 12 weeks
Outcome Phentermine Placebo Comparisons
Primary outcome (body weight loss) 17.8 lbs (8.1 kg) 3.74 lbs (1.7 kg) p<0.001
% weight loss 10.7% 1.9% p<0.001
Primary outcome (decrease in waist circumference) 7.2 cm 2.1 cm p<0.001
Dropout rate 19% 27% N/A
  • Insomnia and dry mouth occurred significantly more in the phentermine group
  • Average blood pressure decreased in both groups over the course of the study, and the difference between groups was not significant [10]

Findings: Short-term phentermine DCR treatment resulted in significant reduction in weight and improvement of metabolic parameters, including waist circumference and some lipid profiles, without clinically severe adverse events. Further study is needed to show long-term efficacy and safety of phentermine DCR in Korean patients with obesity.
Diethylpropion vs Placebo for Weight Loss in Obese Patients, Int J of Obesity (2009) [PubMed abstract]
  • The trial enrolled 69 obese patients with an average BMI of 37
Main inclusion criteria
  • BMI ≥ 30 and ≤ 45
Main exclusion criteria
  • Body weight fluctuations > 4 kg in previous 3 months
  • Use of other weight loss medications
  • Diabetes
  • Significant depression, anxiety, or substance abuse disorder
Baseline characteristics
  • Average age 37 years
  • Average BMI - 37
  • Average weight - 211 lbs (96 kg)
  • Female sex - 90%
  • Average blood pressure - 126/72
Randomized treatment groups
  • Group 1 (37 patients) - Diethylpropion SR 50 mg twice a day for six months
  • Group 2 (32 patients) - Placebo for six months
  • All patients were instructed to follow a 600 calorie deficit per day diet
  • EKGs and echocardiograms were performed at baseline, 6 months, and 12 months
Primary outcome: Percent change in body weight at 6 months
Results

Duration: 6 months
Outcome Diethylpropion Placebo Comparisons
Primary outcome (% weight loss) 9.8% 3.2% p<0.0001
Average weight loss at 6 months 20.5 lbs (9.3 kg) 6.8 lbs (3.1 kg) p<0.0001
Dropout rate 19% 31% N/A
Dry mouth (first 3 months) 69.4% 41% p=0.02
Insomnia (first 3 months) 53% 22% p=0.009
  • Average blood pressure decreased in both groups over the course of the study, and the difference between groups was not significant
  • In the diethylpropion group, there were no clinically relevant abnormal findings or worsening of baseline findings in EKGs and echocardiograms over the course of the study
  • At 6 months, patients were enrolled in an open-label extension phase for 6 additional months. At 12 months, the diethylpropion group lost an additional 1.76 lbs (0.8 kg). [2]

Findings: Diethylpropion plus diet produced sustained and clinically significant weight loss over 1 year. It seems to be safe in relation to cardiovascular and psychiatric aspects in a well-selected population.





CONQUER trial - Qsymia® vs Placebo for Weight Loss in Obese Patients, Lancet (2011) [PubMed abstract]
  • The CONQUER trial enrolled 2487 overweight and obese patients with risk factors for heart disease
Main inclusion criteria
  • BMI 27 - 45
  • Two or more of the following: SBP 140-160, DBP 90-100 or taking ≥ 2 blood pressure medications, triglycerides 200-400 mg/dl or taking ≥ 2 lipid lowering drugs, fasting blood sugar > 100 mg/dl or 2-hour glucose load > 140 mg/dl or type 2 diabetes managed with lifestyle or metformin monotherapy
  • Waist circumference ≥ 42 inches for men and 34.6 inches for women
Main exclusion criteria
  • Blood pressure > 160/100
  • Fasting blood sugar > 240 mg/dl
  • Triglycerides > 400 mg/dl
  • Type 1 diabetes
  • Taking diabetes drug other than metformin
  • History of kidney stones
  • Significant depression
  • Taking tricyclic antidepressant or MAO inhibitor
Baseline characteristics
  • Average age 51 years
  • Average BMI - 36
  • Average weight - 227 lbs (103 kg)
  • Female sex - 70%
  • Average blood pressure - 128/80
  • Diabetes or prediabetes - 68%
Randomized treatment groups
  • Group 1 (994 patients) - Placebo once daily for 56 weeks
  • Group 2 (498 patients) - Phentermine CR 7.5 mg + Topiramate 46 mg once daily (Qsymia®) for 56 weeks
  • Group 3 (995 patients) - Phentermine CR 15 mg + Topiramate 92 mg once daily (Qsymia®) for 56 weeks
  • All patients were given diet counseling with instructions to decrease their caloric intake by 500 calories/day
Primary outcome: Coprimary outcomes were the average percentage change in body weight and the proportion of patients achieving at least 5% weight loss
Results

Duration: 56 weeks
Outcome Placebo Qsy 7.5/46 Qsy 15/92 Comparisons
Primary outcome (% weight loss) 1.2% 7.8% 9.8% 2 or 3 vs 1 p<0.0001
Primary outcome (≥ 5% weight loss) 21% 62% 70% 2 or 3 vs 1 p<0.0001
Weight loss at 1 year 3 lbs 17.82 lbs 22.4 lbs N/A
Dropout rate 43% 31% 36% N/A
Dry mouth 2% 13% 21% 2 or 3 vs 1 p<0.0001
Paresthesia 2% 14% 21% 2 or 3 vs 1 p<0.0001
Taste perversion 1% 7% 10% 2 or 3 vs 1 p<0.0001
Insomnia 5% 6% 10% 3 vs 1 p<0.0001
Dizziness 3% 7% 10% 2 or 3 vs 1 p<0.05
Disturbance in attention <1% 2% 4% 2 or 3 vs 1 p<0.05
  • Blood pressure decreased in all 3 groups over the course of the study. The decrease in the Qsymia groups was significantly greater than the placebo group.

Findings: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors.
Qsymia vs Placebo for Weight Loss in Obese Adolescents, NEJM Evidence (2022) [NEJM abstract]
  • The trial enrolled 223 obese adolescents aged 12 - 17 years
Main inclusion criteria
  • Age 12 - 17 years
  • BMI ≥ 95th percentile
Main exclusion criteria
  • Stimulant use
  • Congenital heart disease
  • Elevated blood pressure
  • History of bipolar or depression
Baseline characteristics
  • Average age 14 years
  • Female - 54%
  • Average weight - 233 lbs (106 kg)
  • Average BMI - 37.8
Randomized treatment groups
  • Group 1 (56 patients): Placebo
  • Group 2 (54 patients): Qsymia 7.5/46 mg once daily
  • Group 3 (113 patients): Qsymia 15/92 mg once daily
  • All participants were instructed to follow a 500-kilocalorie/day deficit diet plan and lifestyle modifications
Primary outcome: Mean percent change in BMI from randomization to week 56
Results

Duration: 56 weeks
Outcome Placebo Qsy 7.5/46 Qsy 15/92 Comparisons
% BMI change +3.3% -4.8% -7.1% p<0.001 for both doses
Weight change +14.5 lbs (6.57 kg) -12 lbs (5.5 kg) -20 lbs (9.2 kg) p<0.05 for both doses
Psychiatric disorders 1.8% 7.4% 8.8% N/A
Dropouts 43% 24% 35% N/A
  • Besides psychiatric disorders, side effects were similar between groups, and adverse events leading to discontinuation were rare (< 2%)
  • There was no significant difference between groups in SBP and heart rate changes from baseline
  • The authors attribute much of the high dropout rate to the fact that the study took place during the height of the COVID-19 pandemic

Findings: Phentermine/topiramate at both the mid and top doses offered a statistically significant reduction in BMI and favorably impacted triglyceride and HDL-C levels in adolescents with obesity.