WEIGHT LOSS





Acronyms and definitions



IMPORTANT POINTS ABOUT WEIGHT LOSS



STEPS TO WEIGHT LOSS



BODY MASS INDEX (BMI)



BMI Categories
Category BMI
Underweight < 18.5
Normal weight 18.5 - 24.9
Overweight 25 - 29.9
Obese 30 - 39.9
Morbidly obese ≥ 40




LOW-CARB VS LOW-FAT DIETS


RCT
Low-Fat vs Low-Carb Diet for Weight Loss Over 12 Months, JAMA (2018) [PubMed abstract]
  • A trial in the JAMA enrolled 609 overweight adults without diabetes
Main inclusion criteria
  • Age 18 - 50 years
  • BMI 28 - 40
Main exclusion criteria
  • Diabetes
  • Uncontrolled hypertension
  • Taking medication known to affect body weight
Baseline characteristics
  • Average age - 40 years
  • Average BMI - 33
  • Average weight - 213 lbs (97 kg)
Patients were randomized to one of two groups:
  • Group 1 (305 patients): Low-fat diet (study average: carb 48%, fat 29%, protein 21%)
  • Group 2 (304 patients): Low-carbohydrate diet (study average: carb 30%, fat 45%, protein 23%)
  • Both groups were given intensive instructions on consuming high-quality foods and beverages that were to achieve maximal differentiation in intake of fats and carbohydrates between the 2 diet groups
  • No explicit instructions for calorie restriction were given
  • The study had two other factors. In one factor, genetic variants thought to influence a person's response to different diets (low-carb vs low-fat) were measured and evaluated. In the other factor, diet response based on baseline insulin secretion was measured and evaluated.
Primary outcome: Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss
Results

Duration: 12 months
Outcome Low-fat Low-carb Comparisons
Primary outcome (average weight loss) 11.6 lbs 13 lbs Diff 1.54 lbs, 95%CI [-0.21 to 1.60]
Study dropout rate 21% 21% N/A
Average calorie intake (baseline) 2148 kcal/day 2223 kcal/day N/A
Average calorie intake (6 months) 1624 kcal/day 1621 kcal/day N/A
Average calorie intake (12 months) 1716 kcal/day 1697 kcal/day N/A
  • There was no significant interaction between genetic variants thought to influence a person's response to different diets and assigned group
  • There was no significant interaction between baseline insulin secretion and assigned group

Findings: In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.
RCT
Low-Carb vs Low-Fat Diet for Weight Loss over 2 Years, Annals of Internal Medicine (2010) [PubMed abstract]
  • The study enrolled 307 overweight patients
Main inclusion criteria
  • Age 18 - 65 years
  • BMI 30 - 40
  • Body weight < 299 lbs (136 kg)
Main exclusion criteria
  • Type 2 diabetes
  • Taking weight loss medications
  • Taking lipid-lowering medications
  • BP > 140/90 mmHg
Baseline characteristics
  • Average age 45 years
  • Female - 68%
  • Average BMI - 36
  • Average weight - 227 lbs (103 kg)
  • Average BP - 124/75
  • Average LDL - 122 mg/dl
  • Average HDL - 46 mg/dl
Randomized treatment groups
  • Group 1 (153 patients) - Low-carbohydrate diet
    • Diet followed Dr. Atkins' New Diet Revolution plan
    • During the first 12 weeks of treatment, participants were instructed to limit carbohydrate intake to 20 grams/day in the form of low–glycemic index vegetables
    • After the first 12 weeks, participants gradually increased carbohydrate intake (5 grams/day per week) by consuming more vegetables, a limited amount of fruits, and eventually small quantities of whole grains and dairy products, until a stable and desired weight was achieved
  • Group 2 (154 patients) - Low-fat diet
    • Limit calorie intake to 1200 - 1500 calories a day for women, 1500 - 1800 calories a day for men
    • 55% of calories from carbs, 30% from fat, and 15% from protein
  • All participants received comprehensive, in-person group behavioral treatment throughout the study
Primary outcome: Weight loss at 2 years
Results

Duration: 2 years
Outcome Low-carb Low-fat Comparisons
Primary outcome 13.9 lbs 16.2 lbs p=0.41
Weight loss at 3 months 20.9 lbs 18.4 lbs p=0.019
Weight loss at 12 months 23.9 lbs 23.8 lbs p=0.95
Decrease in LDL at 2 years 4.78 mg/dl 8.01 mg/dl p=0.25
Increase in HDL at 2 years 7.75 mg/dl 4.64 mg/dl p=0.008
Study dropout rate 42% 32% N/A

Findings: Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years.
RCT
Weight Loss with Diets of Different Fat, Protein, and Carbohydrate Composition, NEJM (2009) [PubMed abstract]
  • A study in the NEJM enrolled 811 overweight adults
Main inclusion criteria
  • Age 30 - 70 years
  • BMI 25 - 40
Main exclusion criteria
  • Diabetes
  • Unstable cardiovascular disease
  • Use of medications that affect body weight
Baseline characteristics
  • Average age 51 years
  • Average BMI - 33
  • Female sex - 64%
  • Average weight - 205 lbs (93 kg)
Randomized treatment groups
  • Diet 1 - Low-fat, average-protein (204 patients) - 20% fat, 15% protein, and 65% carbohydrates
  • Diet 2 - Low-fat, high-protein (202 patients) - 20% fat, 25% protein, and 55% carbohydrates
  • Diet 3 - High-fat, average-protein (204 patients) - 40% fat, 15% protein, and 45% carbohydrates
  • Diet 4 - High-fat, high-protein (201 patients) - 40% fat, 25% protein, and 35% carbohydrates
  • Participants received continuous dietary counseling via group and individual sessions throughout the study. Daily meal plans were provided.
  • Participants were given individual caloric goals that provided a 750 kcal/day deficit
  • The study had a 2X2 factorial design that compared the low vs high fat diets and average vs high protein diets
Primary outcome: Weight loss at 2 years
Results

Duration: 2 years
Outcome High-protein Average-protein High-fat Low-fat Comparisons
Primary outcome 7.9 lbs 6.6 lbs 7.2 lbs 7.2 lbs p=0.22 for protein | p=0.94 for fat
  • There was no difference between the diets in patient reported cravings, fullness, hunger, and diet satisfaction scores
  • Participants in all groups did not reach their target macronutrient composition but did have changes in biomarkers (urinary nitrogen, respiratory quotient) from baseline that showed they modified their macronutrient intake in the direction of their goals
  • 80% of the participants completed the study

Findings: Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize
RCT
Low-carb vs Low-fat vs Low Glycemic Index Diets for Energy Expenditure, JAMA (2012) [PubMed abstract]
  • A crossover trial in the JAMA enrolled 24 people who were overweight
Main inclusion criteria
  • Age 18 - 40 years
  • BMI ≥ 27
Main exclusion criteria
  • Body weight ≥ 352 lbs (160 kg)
  • Diabetes
  • Smoker
  • Change in body weight +/- 10% within 1 year
Baseline characteristics
  • Average age 30 years
  • Average BMI - 34
  • Average weight - 231 lbs (105 kg)
  • Male - 62%
Diets
  • Low-fat diet: Carb 60%, Fat 20%, Protein 20%
  • Low-glycemic index diet: Carb 40%, Fat 40%, Protein 20%
  • Very low-carb (Atkins) diet: Carb 10%, Fat 60%, Protein 30%
  • Subjects were first placed on a calorie-restricted diet for 16 weeks where they lost an average of 13.6% of their body weight. Subjects were then randomized to 1 of 3 diets (low-fat, low-glycemic index, very low-carb) for 4 weeks at a time. After 4 weeks on one diet, each subject crossed over to another diet until they had spent 4 weeks on all 3 diets.
  • The diets were designed to maintain weight loss meaning calories-in were equal to expected calories burned
  • Metabolic rates were measured on each diet using indirect calorimetry and doubly-labeled water (techniques that measure carbon dioxide production as an indirect measure of metabolism)
Primary outcome: Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components
Results

Duration: 4 weeks on each diet
Outcome Low-fat Low GI Low-carb Comparisons
REE 1576 kcal/day 1614 kcal/day 1643 kcal/day p=0.03 overall
TEE 2812 kcal/day 2937 kcal/day 3137 kcal/day p=0.003 overall
Average body weight on each diet 91.5 kg 91.1 kg 91.2 p=0.80 overall
  • For REE, Low-carb was significantly better than Low-fat but not Low GI

Findings: Among overweight and obese young adults compared with pre–weight loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low–glycemic index diet, and least with the very low-carbohydrate diet.





HCG DIET


RCT
HCG Injections vs Placebo for Weight Loss, Amer J of Clinical Nutrition (1976) [PubMed abstract]
  • The study enrolled 51 overweight women
Main inclusion criteria
  • Between 20 and 60 pounds over ideal body weight as defined by Metropolitan Life Insurance Tables
Main exclusion criteria
  • Previous treatment with HCG
  • Took appetite suppressant within 3 months
  • Weight fluctuation of > 10 lbs in previous 3 months
  • Taking medications other than estrogens and birth control pills
Baseline characteristics
  • Average age 33 years
  • Average weight - 166 lbs
Randomized treatment groups
  • Group 1 (25 patients) - Intramuscular HCG 125 units daily, 6 days out of the week for a total of 28 injections
  • Group 2 (26 patients) - Placebo injection
  • All patients were given a 500 calorie/day diet to follow and encouraged to drink 8 - 10 glasses of water daily
Primary outcome: Weight loss at 32 days
Results

Duration: 32 days
Outcome HCG Placebo Comparisons
Primary outcome 15.8 lbs 15.5 lbs p>0.05
Percent body weight lost 9.5% 9.3% p>0.05
Study dropout rate 20% 19% N/A
  • There was no significant difference between the groups in the reported amount of hunger

Findings: HCG does not appear to enhance the effectiveness of a rigidly imposed regimen for weight reduction




INTERMITTENT FASTING


RCT
Intermittent Fasting vs None With a Calorie-Restricted Diet, NEJM (2022) [PubMed abstract]
  • The study enrolled 139 adults with a BMI between 28 and 45
Main inclusion criteria
  • Age 18 - 75 years
  • BMI 28 - 45
Main exclusion criteria
  • Diabetes
  • Taking weight-loss medications
Baseline characteristics
  • Average age 32 years
  • Male sex - 51%
  • Average weight - 194 lbs (88 kg)
  • Average BMI - 31
  • Average calorie intake - 2070 kcal/day
  • Average body fat mass - 73 lbs (33 kg)
Randomized treatment groups
  • Group 1 (69 patients): Intermittent fasting (instructed to eat between 8AM and 4PM only)
  • Group 2 (70 patients): Usual eating (no restriction on when to eat)
  • During the 12 months of the trial, the men were instructed to follow a diet of 1500 to 1800 kcal/day and the women to follow a diet of 1200 to 1500 kcal/day
  • Both diets included a combination of 40 - 55% of calories from carbohydrates, 15 - 20% from protein, and 20 - 30% from fat
  • Participants were provided with one protein shake (Nutriease) per day for the first 6 months to help improve adherence to the permitted calorie intake
  • All participants received dietary counseling
Primary outcome: Difference between the two groups in the change from baseline in body weight at 12 months
Results

Duration: 12 months
Outcome Intermittent fasting Usual eating Comparisons
Primary outcome (12 months) -17.6 lbs (8 kg) -13.9 lbs (6.3 kg) p=0.11
Weight loss (6 months) -20.7 lbs (9.4 kg) -19.6 lbs (8.9 kg) N/A
Body fat mass (12 months) -13 lbs (5.9 kg) -10 lbs (4.5 kg) N/A
Adherence 84% 83% N/A
  • Changes in blood pressure, glucose levels, and lipid levels were similar between groups

Findings: Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction.






GLYCEMIC INDEX DIETS


RCT
High Glycemic Index Diet vs Low Glycemic Index Diet for Weight Loss, Archives of Internal Medicine (2006) [PubMed abstract]
  • A study in the Archives of Internal Medicine enrolled 129 overweight or obese adults
Main inclusion criteria
  • Age 18 - 40 years
  • BMI ≥ 25
  • Body weight < 330 lbs (150 kg)
  • Weight fluctuations < 11 lbs in previous 2 months
Main exclusion criteria
  • Chronic illness
  • Medications other than birth control pills
  • Special diets
Baseline characteristics
  • Average age 32 years
  • Female sex - 75%
  • Average weight - 191 lbs (87 kg)
  • Average BMI - 31
Randomized treatment groups
  • Diet 1 (32 patients) - High carbohydrate/High Glycemic index diet (GI - 70, GL - 129)
  • Diet 2 (32 patients) - High carbohydrate/Low Glycemic index diet (GI - 45, GL - 89)
  • Diet 3 (32 patients) - High protein/High glycemic index (GI - 59, GL - 75)
  • Diet 4 (33 patients) - High protein/Low glycemic index (GI - 44, GL - 59)
  • Diets for women and men were designed to provide 1400 kcal/day and 1900 kcal/day, respectively
  • All key carbohydrate and protein foods were provided along with some pre prepared meals
  • Change in body composition was measured with dual energy x-ray absorptiometry
Primary outcome: Change in body weight and body composition at 12 weeks
Results

Duration: 12 weeks
Outcome Diet 1 Diet 2 Diet 3 Diet 4 Comparisons
Primary outcome (weight loss) 8.1 lbs 10.6 lbs 11.7 lbs 9.7 lbs p=0.17 for difference among groups
Primary outcome (% weight loss) 4.2% 5.5% 6.2% 4.8% p=0.09 for difference among groups
Decrease in fat mass 6.2 lbs 9.9 lbs 9.5 lbs 8.1 lbs p=0.08 for difference among groups
Study dropout rate 16% 6.3% 3.1% 15.2% N/A

Findings: Both high-protein and low-GI regimens increase body fat loss, but cardiovascular risk reduction is optimized by a high-carbohydrate, low-GI diet.
RCT
Low-Glycemic Load Diet vs Low-Fat Diet for Weight Loss in Obese Adults, JAMA (2007) [PubMed abstract]
  • A study in JAMA enrolled 73 obese adults
Main inclusion criteria
  • Age 18 - 35 years
  • BMI ≥ 30
Main exclusion criteria
  • Body weight > 308 lbs (140 kg)
  • Smoker
  • Diabetes
  • Use of medications that could affect weight loss or insulin sensitivity
  • Major medical condition
Baseline characteristics
  • Average age 27 years
  • Average weight - 227 lbs (103 kg)
  • Average % body fat - 40%
Randomized treatment groups
  • Diet 1 (36 patients) - Low-glycemic load diet
  • Diet 2 (37 patients) - Low-fat diet
  • For Diet 1, participants were counseled to consume low–glycemic load foods (particularly non starchy vegetables, legumes, and temperate fruits) and to limit intake of high–glycemic load foods (such as refined grains, starchy vegetables, fruit juices, and sweets)
  • For Diet 2, participants were counseled to consume low-fat grains, vegetables, fruits, and legumes and to limit intake of added fats, sweets, and high-fat snacks
  • Participants were not given specific calorie goals
Primary outcome: Change in body weight and body fat percentage as determined by dual energy x-ray absorptiometry at 6, 12, and 18 months
Results

Duration: 18 months
Outcome Low-GI Low-fat Comparisons
Primary outcome (weight loss at 18 months) 4.4 lbs 4.4 lbs p=0.99
Primary outcome (decrease in % body fat at 18 months) 1.5% 1.1% p=0.50
  • Fasting glucose and fasting insulin levels did not differ significantly between the two groups at 6 and 18 months [34]

Findings: Variability in dietary weight loss trials may be partially attributable to differences in hormonal response. Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration.



WEIGHT LOSS MEDICATIONS



  • References [PMID: 32202076, 33625476, 28017964, 19564877, 21481449, 26132939, 10678259, 20673995, 30421844, 35658024]
Average weight loss for obesity treatments
Treatment % weight loss from baseline
(length of follow-up)
BPD/DS 35 - 40%
(> 10 years)
Gastric bypass 30 - 35%
(> 10 years)
Gastric sleeve 25 - 30%
(> 10 years)
Gastric banding 20 - 25%
(> 10 years)
Zepbound (tirzepatide) 21%
(72 weeks)
Wegovy (semaglutide) 16%
(68 weeks)
Endoscopic sleeve gastroplasty 11.4%
(104 weeks)
Intragastric balloon 10%
(6 months)
Appetite suppressants (e.g. phentermine) 10%
(6 months)
Qsymia (topiramate + phentermine) 10%
(56 weeks)
Saxenda (Liraglutide) 8%
(56 weeks)
Xenical (orlistat) 7.6%
(2 years)
Plenity (hydrogel) 6.4%
(24 weeks)
Contrave (naltrexone + bupropion) 6.1%
(56 weeks)



PLENITY®








RCT
GLOW study - Plenity vs Placebo for Weight Loss in Overweight Patients, Obesity (2019) [PubMed abstract]
  • The GLOW study enrolled 436 adults with a BMI of 27 - 40.
Main inclusion criteria
  • Age 22 - 65 years
  • BMI 27 - 40
  • Fasting blood sugar 90 - 145 mg/dl
Main exclusion criteria
  • Type 1 diabetes
  • History of eating disorder
  • Significant GI disorder
  • Gastric bypass or other GI surgery
  • Required to take meds with meals
Baseline characteristics
  • Average age 48 years
  • Average weight - 218 lbs (99 kg)
  • Average BMI - 34
  • Type 2 diabetes - 10%
Randomized treatment groups
  • Group 1 (223 patients): Plenity 3 capsules 20 to 30 minutes before lunch and dinner
  • Group 2 (213 patients): Placebo
  • All patients were prescribed a hypocaloric diet of 300 kcal/d below their calculated energy requirement (with 45% to 50% of daily calorie intake from carbohydrates, ≤ 30% from fat, and 20% to 25% from protein)
  • All patients were instructed to perform daily moderate-intensity exercise (e.g. 30 minutes of walking/day) and maintain their smoking habits during the study
Primary outcome: The co-primary efficacy endpoints were the percent change in body weight from baseline (visit 2) to day 171 (visit 13) and the percent of patients who lost ≥ 5% body weight from baseline to day 171
Results

Duration: 24 weeks
Outcome Plenity Placebo Comparisons
Percent change in body weight -6.4% -4.4% p=0.0007
≥ 5% weight loss 59% 42% p=0.0008
≥ 10% weight loss 27% 15% p=0.0107
Study dropout rate 23% 29% N/A
Diarrhea 12.6% 8.5% p=0.21
Abdominal distension 11.7% 6.6% p=0.09
Infrequent bowel movements 9.4% 4.7% p=0.064
Flatulence 8.5% 5.2% p=0.19
Abdominal pain 5.4% 2.8% p=0.23
Constipation 5.4% 5.2% p=1.0
Dyspepsia 4% 0.9% p=0.063

Findings: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile



MACRONUTRIENTS



BIBLIOGRAPHY